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1. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author: Kelly, S, Jahanshad, N, Zalesky, A, Kochunov, P, Agartz, I, Alloza, C, Andreassen, OA, Arango, C, Banaj, N, Bouix, S, Bousman, CA, Brouwer, RM, Bruggemann, J, Bustillo, J, Cahn, W, Calhoun, V, Cannon, D, Carr, V, Catts, S, Chen, J, Chen, J-X, Chen, X, Chiapponi, C, Cho, Kl K, Ciullo, V, Corvin, AS, Crespo-Facorro, B, Cropley, V, De Rossi, P, Diaz-Caneja, CM, Dickie, EW, Ehrlich, S, Fan, F-M, Faskowitz, J, Fatouros-Bergman, H, Flyckt, L, Ford, JM, Fouche, J-P, Fukunaga, M, Gill, M, Glahn, DC, Gollub, R, Goudzwaard, ED, Guo, H, Gur, RE, Gur, RC, Gurholt, TP, Hashimoto, R, Hatton, SN, Henskens, FA, Hibar, DP, Hickie, IB, Hong, LE, Horacek, J, Howells, FM, Hulshoff Pol, HE, Hyde, CL, Isaev, D, Jablensky, A, Jansen, PR, Janssen, J, Jönsson, EG, Jung, LA, Kahn, RS, Kikinis, Z, Liu, K, Klauser, P, Knöchel, C, Kubicki, M, Lagopoulos, J, Langen, C, Lawrie, S, Lenroot, RK, Lim, KO, Lopez-Jaramillo, C, Lyall, A, Magnotta, V, Mandl, RCW, Mathalon, DH, McCarley, RW, McCarthy-Jones, S, McDonald, C, McEwen, S, McIntosh, A, Melicher, T, Mesholam-Gately, RI, Michie, PT, Mowry, B, Mueller, BA, Newell, DT, O'Donnell, P, Oertel-Knöchel, V, Oestreich, L, Paciga, SA, Pantelis, C, Pasternak, O, Pearlson, G, Pellicano, GR, Pereira, A, and Pineda Zapata, J
Subjects: Neurosciences, Brain Disorders, Mental Health, Serious Mental Illness, Biomedical Imaging, Schizophrenia, Clinical Research, Mental health, Adult, Aged, Aged, 80 and over, Brain, Cohort Studies, Corpus Callosum, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, White Matter, Young Adult, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
Published: 2018

2. Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium.

Author: Walton, E, Hibar, DP, van Erp, TGM, Potkin, SG, Roiz-Santiañez, R, Crespo-Facorro, B, Suarez-Pinilla, P, van Haren, NEM, de Zwarte, SMC, Kahn, RS, Cahn, W, Doan, NT, Jørgensen, KN, Gurholt, TP, Agartz, I, Andreassen, OA, Westlye, LT, Melle, I, Berg, AO, Morch-Johnsen, L, Færden, A, Flyckt, L, Fatouros-Bergman, H, Karolinska Schizophrenia Project Consortium (KaSP), Jönsson, EG, Hashimoto, R, Yamamori, H, Fukunaga, M, Jahanshad, N, De Rossi, P, Piras, F, Banaj, N, Spalletta, G, Gur, RE, Gur, RC, Wolf, DH, Satterthwaite, TD, Beard, LM, Sommer, IE, Koops, S, Gruber, O, Richter, A, Krämer, B, Kelly, S, Donohoe, G, McDonald, C, Cannon, DM, Corvin, A, Gill, M, Di Giorgio, A, Bertolino, A, Lawrie, S, Nickson, T, Whalley, HC, Neilson, E, Calhoun, VD, Thompson, PM, Turner, JA, and Ehrlich, S
Subjects: Karolinska Schizophrenia Project Consortium, Prefrontal Cortex, Humans, Magnetic Resonance Imaging, Linear Models, Schizophrenia, Psychiatric Status Rating Scales, Schizophrenic Psychology, Internationality, Image Processing, Computer-Assisted, Adult, Female, Male, Functional Laterality, Cortical thickness, ENIGMA, FreeSurfer, MRI, PANSS, SANS, medial orbitofrontal cortex, negative symptoms, schizophrenia, Image Processing, Computer-Assisted, Psychiatry, Psychology, Public Health and Health Services, Neurosciences
Abstract: BackgroundOur understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.MethodsThis study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).ResultsMeta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.ConclusionsUsing an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Published: 2018

3. Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium

Author: Walton, E, Hibar, DP, Erp, TGM, Potkin, SG, Roiz‐Santiañez, R, Crespo‐Facorro, B, Suarez‐Pinilla, P, Van Haren, NEM, Zwarte, SMC, Kahn, RS, Cahn, W, Doan, NT, Jørgensen, KN, Gurholt, TP, Agartz, I, Andreassen, OA, Westlye, LT, Melle, I, Berg, AO, Mørch‐Johnsen, L, Færden, A, Flyckt, L, Fatouros‐Bergman, H, Consortium, Karolinska Schizophrenia Project, Jönsson, EG, Hashimoto, R, Yamamori, H, Fukunaga, M, Preda, A, De Rossi, P, Piras, F, Banaj, N, Ciullo, V, Spalletta, G, Gur, RE, Gur, RC, Wolf, DH, Satterthwaite, TD, Beard, LM, Sommer, IE, Koops, S, Gruber, O, Richter, A, Krämer, B, Kelly, S, Donohoe, G, McDonald, C, Cannon, DM, Corvin, A, Gill, M, Di Giorgio, A, Bertolino, A, Lawrie, S, Nickson, T, Whalley, HC, Neilson, E, Calhoun, VD, Thompson, PM, Turner, JA, and Ehrlich, S
Subjects: Schizophrenia, Mental Health, Brain Disorders, Mental health, Good Health and Well Being, Adult, Brain Mapping, Female, Humans, Magnetic Resonance Imaging, Male, Prospective Studies, Psychiatric Status Rating Scales, Schizophrenic Psychology, Temporal Lobe, schizophrenia, positive symptoms, superior temporal gyrus, cortical thickness, ENIGMA, FreeSurfer, MRI, scale for the assessment of positive symptoms, positive and negative syndrome scale, Karolinska Schizophrenia Project Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: ObjectiveBased on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia.MethodThis prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness.ResultsPositive symptom severity was negatively related to STG thickness in both hemispheres (left: βstd = -0.052; P = 0.021; right: βstd = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness.ConclusionOur findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia.
Published: 2017

4. Subcortical volumetric abnormalities in bipolar disorder.

Author: Hibar, DP, Westlye, LT, van Erp, TGM, Rasmussen, J, Leonardo, CD, Faskowitz, J, Haukvik, UK, Hartberg, CB, Doan, NT, Agartz, I, Dale, AM, Gruber, O, Krämer, B, Trost, S, Liberg, B, Abé, C, Ekman, CJ, Ingvar, M, Landén, M, Fears, SC, Freimer, NB, Bearden, CE, Costa Rica/Colombia Consortium for Genetic Investigation of Bipolar Endophenotypes, Sprooten, E, Glahn, DC, Pearlson, GD, Emsell, L, Kenney, J, Scanlon, C, McDonald, C, Cannon, DM, Almeida, J, Versace, A, Caseras, X, Lawrence, NS, Phillips, ML, Dima, D, Delvecchio, G, Frangou, S, Satterthwaite, TD, Wolf, D, Houenou, J, Henry, C, Malt, UF, Bøen, E, Elvsåshagen, T, Young, AH, Lloyd, AJ, Goodwin, GM, Mackay, CE, Bourne, C, Bilderbeck, A, Abramovic, L, Boks, MP, van Haren, NEM, Ophoff, RA, Kahn, RS, Bauer, M, Pfennig, A, Alda, M, Hajek, T, Mwangi, B, Soares, JC, Nickson, T, Dimitrova, R, Sussmann, JE, Hagenaars, S, Whalley, HC, McIntosh, AM, Thompson, PM, and Andreassen, OA
Subjects: Costa Rica/Colombia Consortium for Genetic Investigation of Bipolar Endophenotypes, Brain, Humans, Magnetic Resonance Imaging, Organ Size, Case-Control Studies, Retrospective Studies, Bipolar Disorder, Adult, Middle Aged, Female, Male, Clinical Research, Mental Health, Brain Disorders, Serious Mental Illness, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Mental health, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10-7) and thalamus (d=-0.148; P=4.27 × 10-3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10-5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.
Published: 2016

5. Brain Age Prediction Reveals Aberrant Brain White Matter in Schizophrenia and Bipolar Disorder: A Multisample Diffusion Tensor Imaging Study

Author: Farde, L., Flyckt, L., Engberg, G., Erhardt, S., Fatouros-Bergman, H., Cervenka, S., Schwieler, L., Piehl, F., Agartz, I., Collste, K., Victorsson, P., Malmqvist, A., Hedberg, M., Orhan, F., Sellgren, C., Tønnesen, Siren, Kaufmann, Tobias, de Lange, Ann-Marie G., Richard, Geneviève, Doan, Nhat Trung, Alnæs, Dag, van der Meer, Dennis, Rokicki, Jaroslav, Moberget, Torgeir, Maximov, Ivan I., Agartz, Ingrid, Aminoff, Sofie R., Beck, Dani, Barch, Deanna M., Beresniewicz, Justyna, Cervenka, Simon, Fatouros-Bergman, Helena, Craven, Alexander R., Flyckt, Lena, Gurholt, Tiril P., Haukvik, Unn K., Hugdahl, Kenneth, Johnsen, Erik, Jönsson, Erik G., Kolskår, Knut K., Kroken, Rune Andreas, Lagerberg, Trine V., Løberg, Else-Marie, Nordvik, Jan Egil, Sanders, Anne-Marthe, Ulrichsen, Kristine, Andreassen, Ole A., and Westlye, Lars T.
Published: 2020
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6. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium

Author: van Erp, TGM, Hibar, DP, Rasmussen, JM, Glahn, DC, Pearlson, GD, Andreassen, OA, Agartz, I, Westlye, LT, Haukvik, UK, Dale, AM, Melle, I, Hartberg, CB, Gruber, O, Kraemer, B, Zilles, D, Donohoe, G, Kelly, S, McDonald, C, Morris, DW, Cannon, DM, Corvin, A, Machielsen, MWJ, Koenders, L, de Haan, L, Veltman, DJ, Satterthwaite, TD, Wolf, DH, Gur, RC, Gur, RE, Potkin, SG, Mathalon, DH, Mueller, BA, Preda, A, Macciardi, F, Ehrlich, S, Walton, E, Hass, J, Calhoun, VD, Bockholt, HJ, Sponheim, SR, Shoemaker, JM, van Haren, NEM, Pol, HEH, Ophoff, RA, Kahn, RS, Roiz-Santiañez, R, Crespo-Facorro, B, Wang, L, Alpert, KI, Jönsson, EG, Dimitrova, R, Bois, C, Whalley, HC, McIntosh, AM, Lawrie, SM, Hashimoto, R, Thompson, PM, and Turner, JA
Subjects: Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Serious Mental Illness, Brain Disorders, Schizophrenia, Clinical Research, Neurosciences, Mental Health, Biomedical Imaging, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Adult, Brain, Brain Mapping, Case-Control Studies, Female, Functional Laterality, Humans, Image Processing, Computer-Assisted, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Prospective Studies, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract: The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.
Published: 2016

7. No progressive brain changes during a 1-year follow-up of patients with first-episode psychosis

Author: Haukvik, UK, Hartberg, CB, Nerland, S, Jørgensen, KN, Lange, EH, Simonsen, C, Nesvåg, R, Dale, AM, Andreassen, OA, Melle, I, and Agartz, I
Subjects: Biological Psychology, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Mental Health, Biomedical Imaging, Neurosciences, Schizophrenia, Clinical Research, Serious Mental Illness, Mental health, Adolescent, Adult, Antipsychotic Agents, Bipolar Disorder, Case-Control Studies, Cerebral Cortex, Disease Progression, Female, Follow-Up Studies, Humans, Linear Models, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Norway, Psychotic Disorders, Young Adult, Bipolar disorder, longitudinal studies, magnetic resonance imaging, schizophrenia, Public Health and Health Services, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract: BackgroundFirst-episode psychosis (FEP) patients show structural brain abnormalities. Whether the changes are progressive or not remain under debate, and the results from longitudinal magnetic resonance imaging (MRI) studies are mixed. We investigated if FEP patients showed a different pattern of regional brain structural change over a 1-year period compared with healthy controls, and if putative changes correlated with clinical characteristics and outcome.MethodMRIs of 79 FEP patients [SCID-I-verified diagnoses: schizophrenia, psychotic bipolar disorder, or other psychoses, mean age 27.6 (s.d. = 7.7) years, 66% male] and 82 healthy controls [age 29.3 (s.d. = 7.2) years, 66% male] were acquired from the same 1.5 T scanner at baseline and 1-year follow-up as part of the Thematically Organized Psychosis (TOP) study, Oslo, Norway. Scans were automatically processed with the longitudinal stream in FreeSurfer that creates an unbiased within-subject template image. General linear models were used to analyse longitudinal change in a wide range of subcortical volumes and detailed thickness and surface area estimates across the entire cortex, and associations with clinical characteristics.ResultsFEP patients and controls did not differ significantly in annual percentage change in cortical thickness or area in any cortical region, or in any of the subcortical structures after adjustment for multiple comparisons. Within the FEP group, duration of untreated psychosis, age at illness onset, antipsychotic medication use and remission at follow-up were not related to longitudinal brain change.ConclusionsWe found no significant longitudinal brain changes over a 1-year period in FEP patients. Our results do not support early progressive brain changes in psychotic disorders.
Published: 2016

8. Pre- and perinatal hypoxia associated with hippocampus/amygdala volume in bipolar disorder

Author: Haukvik, UK, McNeil, T, Lange, EH, Melle, I, Dale, AM, Andreassen, OA, and Agartz, I
Subjects: Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Biomedical Imaging, Mental Health, Serious Mental Illness, Schizophrenia, Neurosciences, Clinical Research, Pediatric, Perinatal Period - Conditions Originating in Perinatal Period, Brain Disorders, 2.3 Psychological, social and economic factors, Aetiology, 2.1 Biological and endogenous factors, Mental health, Adolescent, Adult, Amygdala, Asphyxia Neonatorum, Bipolar Disorder, Comorbidity, Female, Fetal Hypoxia, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Norway, Registries, Young Adult, MRI, neurodevelopment, neuroimaging, obstetric complications, psychosis, Public Health and Health Services, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract: BackgroundPre- and perinatal adversities may increase the risk for schizophrenia and bipolar disorder. Hypoxia-related obstetric complications (OCs) are associated with brain anatomical abnormalities in schizophrenia, but their association with brain anatomy variation in bipolar disorder is unknown.MethodMagnetic resonance imaging brain scans, clinical examinations and data from the Medical Birth Registry of Norway were obtained for 219 adults, including 79 patients with a DSM-IV diagnosis of bipolar disorder (age 29.4 years, s.d. = 11.8 years, 39% male) and 140 healthy controls (age 30.8 years, s.d. = 12.0 years, 53% male). Severe hypoxia-related OCs throughout pregnancy/birth and perinatal asphyxia were each studied in relation to a priori selected brain volumes (hippocampus, lateral ventricles and amygdala, obtained with FreeSurfer), using linear regression models covarying for age, sex, medication use and intracranial volume. Multiple comparison adjustment was applied.ResultsPerinatal asphyxia was associated with smaller left amygdala volume (t = -2.59, p = 0.012) in bipolar disorder patients, but not in healthy controls. Patients with psychotic bipolar disorder showed distinct associations between perinatal asphyxia and smaller left amygdala volume (t = -2.69, p = 0.010), whereas patients with non-psychotic bipolar disorder showed smaller right hippocampal volumes related to both perinatal asphyxia (t = -2.60, p = 0.015) and severe OCs (t = -3.25, p = 0.003). No associations between asphyxia or severe OCs and the lateral ventricles were found.ConclusionsPre- and perinatal hypoxia-related OCs are related to brain morphometry in bipolar disorder in adulthood, with specific patterns in patients with psychotic versus non-psychotic illness.
Published: 2014

9. TCF4 sequence variants and mRNA levels are associated with neurodevelopmental characteristics in psychotic disorders.

Author: Wirgenes, KV, Sønderby, IE, Haukvik, UK, Mattingsdal, M, Tesli, M, Athanasiu, L, Sundet, K, Røssberg, JI, Dale, AM, Brown, AA, Agartz, I, Melle, I, Djurovic, S, and Andreassen, OA
Subjects: Brain, Humans, Transcription Factors, RNA, Messenger, Sequence Analysis, DNA, Affective Disorders, Psychotic, Psychotic Disorders, Schizophrenia, Neuropsychological Tests, Psychometrics, Schizophrenic Psychology, Linkage Disequilibrium, Phenotype, Polymorphism, Single Nucleotide, Alleles, Adult, Middle Aged, Female, Male, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Genetic Variation, Transcription Factor 4, bipolar disorder, mRNA, neurodevelopment, psychotic phenotypes, schizophrenia, transcription factor 4, RNA, Messenger, Sequence Analysis, DNA, Affective Disorders, Psychotic, Polymorphism, Single Nucleotide, Psychology, Clinical Sciences, Public Health and Health Services
Abstract: TCF4 is involved in neurodevelopment, and intergenic and intronic variants in or close to the TCF4 gene have been associated with susceptibility to schizophrenia. However, the functional role of TCF4 at the level of gene expression and relationship to severity of core psychotic phenotypes are not known. TCF4 mRNA expression level in peripheral blood was determined in a large sample of patients with psychosis spectrum disorders (n = 596) and healthy controls (n = 385). The previously identified TCF4 risk variants (rs12966547 (G), rs9960767 (C), rs4309482 (A), rs2958182 (T) and rs17512836 (C)) were tested for association with characteristic psychosis phenotypes, including neurocognitive traits, psychotic symptoms and structural magnetic resonance imaging brain morphometric measures, using a linear regression model. Further, we explored the association of additional 59 single nucleotide polymorphisms (SNPs) covering the TCF4 gene to these phenotypes. The rs12966547 and rs4309482 risk variants were associated with poorer verbal fluency in the total sample. There were significant associations of other TCF4 SNPs with negative symptoms, verbal learning, executive functioning and age at onset in psychotic patients and brain abnormalities in total sample. The TCF4 mRNA expression level was significantly increased in psychosis patients compared with controls and positively correlated with positive- and negative-symptom levels. The increase in TCF4 mRNA expression level in psychosis patients and the association of TCF4 SNPs with core psychotic phenotypes across clinical, cognitive and brain morphological domains support that common TCF4 variants are involved in psychosis pathology, probably related to abnormal neurodevelopment.
Published: 2012

10. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium.

Author: Schijven, Dick, Postema, M.C., Fukunaga, M., Matsumoto, J., Miura, K., Zwarte, S.M.C. de, Haren, N.E.M. van, Cahn, W., Hulshoff Pol, H.E., Kahn, R.S., Ayesa-Arriola, R., Ortoz-García de la Foz, V., Tordesillas-Gutierrez, D., Vázquez-Bourgon, J., Crespo-Facorro, B., Alnæs, D., Dahl, A., Westlye, L.T., Agartz, I., Andreassen, O.A., Jönsson, E.G., Kochunov, P., Bruggemann, J.M., Catts, S.V., Michie, P.T., Mowry, B.J., Quidé, Y., Rasser, P.E., Schall, U., Scott, R.J., Carr, V.J., Green, M.J., Henskens, F.A., Loughland, C.M., Pantelis, C., Weickert, C.S., Weickert, T.W., Haan, L. de, Brosch, K., Pfarr, J.K., Ringwald, K.G., Stein, F., Jansen, Andreas, Kircher, T.T.J., Nenadić, I., Krämer, Bernd, Gruber, O., Satterthwaite, T.D., Bustillo, J., Mathalon, D.H., Preda, A., Calhoun, V.D., Ford, J.M., Potkin, S.G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, F., Ehrlich, S., Fuentes-Claramonte, P., Garcia-Leon, M.A., Guerrero-Pedraza, A., Salvador, R., Sarró, S., Pomarol-Clotet, E., Ciullo, V., Piras, F., Vecchio, D., Banaj, N., Spalletta, G., Michielse, S., Amelsvoort, T. van, Dickie, E.W., Voineskos, A.N., Sim, K., Ciufolini, S., Dazzan, P., Murray, R.M., Kim, W.S., Chung, Y.C., Andreou, C., Schmidt, A, Borgwardt, S., McIntosh, A.M., Whalley, H.C., Lawrie, S.M., Plessis, S. du, Luckhoff, H.K., Scheffler, F., Emsley, R., Grotegerd, D., Lencer, R., Dannlowski, U., Edmond, J.T., Rootes-Murdy, K., Stephen, J.M., Mayer, A.R., Antonucci, L.A., Fazio, L., Pergola, G., Bertolino, A., Díaz-Caneja, C.M., Janssen, J, Lois, N.G., Arango, C., Tomyshev, A.S., Lebedeva, I., Cervenka, S., Sellgren, C.M., Georgiadis, F., Kirschner, M., Kaiser, S., Hajek, T., Skoch, A., Spaniel, F., Kim, M., Kwak, Y.B., Oh, S., Kwon, J.S., James, A., Bakker, G., Knöchel, C., Stäblein, M., Oertel, V., Uhlmann, A., Howells, F.M., Stein, D.J., Temmingh, H.S., Diaz-Zuluaga, A.M., Pineda-Zapata, J.A., López-Jaramillo, C., Homan, S., Ji, E., Surbeck, W., Homan, P., Fisher, S.E., Franke, B., Glahn, D.C., Gur, R.C., Hashimoto, R., Jahanshad, N., Luders, E., Medland, S.E., Thompson, P.M., Turner, J.A., Erp, T.G. van, Francks, C., Schijven, Dick, Postema, M.C., Fukunaga, M., Matsumoto, J., Miura, K., Zwarte, S.M.C. de, Haren, N.E.M. van, Cahn, W., Hulshoff Pol, H.E., Kahn, R.S., Ayesa-Arriola, R., Ortoz-García de la Foz, V., Tordesillas-Gutierrez, D., Vázquez-Bourgon, J., Crespo-Facorro, B., Alnæs, D., Dahl, A., Westlye, L.T., Agartz, I., Andreassen, O.A., Jönsson, E.G., Kochunov, P., Bruggemann, J.M., Catts, S.V., Michie, P.T., Mowry, B.J., Quidé, Y., Rasser, P.E., Schall, U., Scott, R.J., Carr, V.J., Green, M.J., Henskens, F.A., Loughland, C.M., Pantelis, C., Weickert, C.S., Weickert, T.W., Haan, L. de, Brosch, K., Pfarr, J.K., Ringwald, K.G., Stein, F., Jansen, Andreas, Kircher, T.T.J., Nenadić, I., Krämer, Bernd, Gruber, O., Satterthwaite, T.D., Bustillo, J., Mathalon, D.H., Preda, A., Calhoun, V.D., Ford, J.M., Potkin, S.G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, F., Ehrlich, S., Fuentes-Claramonte, P., Garcia-Leon, M.A., Guerrero-Pedraza, A., Salvador, R., Sarró, S., Pomarol-Clotet, E., Ciullo, V., Piras, F., Vecchio, D., Banaj, N., Spalletta, G., Michielse, S., Amelsvoort, T. van, Dickie, E.W., Voineskos, A.N., Sim, K., Ciufolini, S., Dazzan, P., Murray, R.M., Kim, W.S., Chung, Y.C., Andreou, C., Schmidt, A, Borgwardt, S., McIntosh, A.M., Whalley, H.C., Lawrie, S.M., Plessis, S. du, Luckhoff, H.K., Scheffler, F., Emsley, R., Grotegerd, D., Lencer, R., Dannlowski, U., Edmond, J.T., Rootes-Murdy, K., Stephen, J.M., Mayer, A.R., Antonucci, L.A., Fazio, L., Pergola, G., Bertolino, A., Díaz-Caneja, C.M., Janssen, J, Lois, N.G., Arango, C., Tomyshev, A.S., Lebedeva, I., Cervenka, S., Sellgren, C.M., Georgiadis, F., Kirschner, M., Kaiser, S., Hajek, T., Skoch, A., Spaniel, F., Kim, M., Kwak, Y.B., Oh, S., Kwon, J.S., James, A., Bakker, G., Knöchel, C., Stäblein, M., Oertel, V., Uhlmann, A., Howells, F.M., Stein, D.J., Temmingh, H.S., Diaz-Zuluaga, A.M., Pineda-Zapata, J.A., López-Jaramillo, C., Homan, S., Ji, E., Surbeck, W., Homan, P., Fisher, S.E., Franke, B., Glahn, D.C., Gur, R.C., Hashimoto, R., Jahanshad, N., Luders, E., Medland, S.E., Thompson, P.M., Turner, J.A., Erp, T.G. van, and Francks, C.
Abstract: Item does not contain fulltext, Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Published: 2023

11. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium.

Author: Schijven, D, Postema, MC, Fukunaga, M, Matsumoto, J, Miura, K, de Zwarte, SMC, van Haren, NEM, Cahn, W, Hulshoff Pol, HE, Kahn, RS, Ayesa-Arriola, R, Ortiz-García de la Foz, V, Tordesillas-Gutierrez, D, Vázquez-Bourgon, J, Crespo-Facorro, B, Alnæs, D, Dahl, A, Westlye, LT, Agartz, I, Andreassen, OA, Jönsson, EG, Kochunov, P, Bruggemann, JM, Catts, SV, Michie, PT, Mowry, BJ, Quidé, Y, Rasser, PE, Schall, U, Scott, RJ, Carr, VJ, Green, MJ, Henskens, FA, Loughland, CM, Pantelis, C, Weickert, CS, Weickert, TW, de Haan, L, Brosch, K, Pfarr, J-K, Ringwald, KG, Stein, F, Jansen, A, Kircher, TTJ, Nenadić, I, Krämer, B, Gruber, O, Satterthwaite, TD, Bustillo, J, Mathalon, DH, Preda, A, Calhoun, VD, Ford, JM, Potkin, SG, Chen, J, Tan, Y, Wang, Z, Xiang, H, Fan, F, Bernardoni, F, Ehrlich, S, Fuentes-Claramonte, P, Garcia-Leon, MA, Guerrero-Pedraza, A, Salvador, R, Sarró, S, Pomarol-Clotet, E, Ciullo, V, Piras, F, Vecchio, D, Banaj, N, Spalletta, G, Michielse, S, van Amelsvoort, T, Dickie, EW, Voineskos, AN, Sim, K, Ciufolini, S, Dazzan, P, Murray, RM, Kim, W-S, Chung, Y-C, Andreou, C, Schmidt, A, Borgwardt, S, McIntosh, AM, Whalley, HC, Lawrie, SM, du Plessis, S, Luckhoff, HK, Scheffler, F, Emsley, R, Grotegerd, D, Lencer, R, Dannlowski, U, Edmond, JT, Rootes-Murdy, K, Stephen, JM, Mayer, AR, Antonucci, LA, Fazio, L, Pergola, G, Bertolino, A, Díaz-Caneja, CM, Janssen, J, Lois, NG, Arango, C, Tomyshev, AS, Lebedeva, I, Cervenka, S, Sellgren, CM, Georgiadis, F, Kirschner, M, Kaiser, S, Hajek, T, Skoch, A, Spaniel, F, Kim, M, Kwak, YB, Oh, S, Kwon, JS, James, A, Bakker, G, Knöchel, C, Stäblein, M, Oertel, V, Uhlmann, A, Howells, FM, Stein, DJ, Temmingh, HS, Diaz-Zuluaga, AM, Pineda-Zapata, JA, López-Jaramillo, C, Homan, S, Ji, E, Surbeck, W, Homan, P, Fisher, SE, Franke, B, Glahn, DC, Gur, RC, Hashimoto, R, Jahanshad, N, Luders, E, Medland, SE, Thompson, PM, Turner, JA, van Erp, TGM, Francks, C, Schijven, D, Postema, MC, Fukunaga, M, Matsumoto, J, Miura, K, de Zwarte, SMC, van Haren, NEM, Cahn, W, Hulshoff Pol, HE, Kahn, RS, Ayesa-Arriola, R, Ortiz-García de la Foz, V, Tordesillas-Gutierrez, D, Vázquez-Bourgon, J, Crespo-Facorro, B, Alnæs, D, Dahl, A, Westlye, LT, Agartz, I, Andreassen, OA, Jönsson, EG, Kochunov, P, Bruggemann, JM, Catts, SV, Michie, PT, Mowry, BJ, Quidé, Y, Rasser, PE, Schall, U, Scott, RJ, Carr, VJ, Green, MJ, Henskens, FA, Loughland, CM, Pantelis, C, Weickert, CS, Weickert, TW, de Haan, L, Brosch, K, Pfarr, J-K, Ringwald, KG, Stein, F, Jansen, A, Kircher, TTJ, Nenadić, I, Krämer, B, Gruber, O, Satterthwaite, TD, Bustillo, J, Mathalon, DH, Preda, A, Calhoun, VD, Ford, JM, Potkin, SG, Chen, J, Tan, Y, Wang, Z, Xiang, H, Fan, F, Bernardoni, F, Ehrlich, S, Fuentes-Claramonte, P, Garcia-Leon, MA, Guerrero-Pedraza, A, Salvador, R, Sarró, S, Pomarol-Clotet, E, Ciullo, V, Piras, F, Vecchio, D, Banaj, N, Spalletta, G, Michielse, S, van Amelsvoort, T, Dickie, EW, Voineskos, AN, Sim, K, Ciufolini, S, Dazzan, P, Murray, RM, Kim, W-S, Chung, Y-C, Andreou, C, Schmidt, A, Borgwardt, S, McIntosh, AM, Whalley, HC, Lawrie, SM, du Plessis, S, Luckhoff, HK, Scheffler, F, Emsley, R, Grotegerd, D, Lencer, R, Dannlowski, U, Edmond, JT, Rootes-Murdy, K, Stephen, JM, Mayer, AR, Antonucci, LA, Fazio, L, Pergola, G, Bertolino, A, Díaz-Caneja, CM, Janssen, J, Lois, NG, Arango, C, Tomyshev, AS, Lebedeva, I, Cervenka, S, Sellgren, CM, Georgiadis, F, Kirschner, M, Kaiser, S, Hajek, T, Skoch, A, Spaniel, F, Kim, M, Kwak, YB, Oh, S, Kwon, JS, James, A, Bakker, G, Knöchel, C, Stäblein, M, Oertel, V, Uhlmann, A, Howells, FM, Stein, DJ, Temmingh, HS, Diaz-Zuluaga, AM, Pineda-Zapata, JA, López-Jaramillo, C, Homan, S, Ji, E, Surbeck, W, Homan, P, Fisher, SE, Franke, B, Glahn, DC, Gur, RC, Hashimoto, R, Jahanshad, N, Luders, E, Medland, SE, Thompson, PM, Turner, JA, van Erp, TGM, and Francks, C
Abstract: Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Published: 2023

12. Cytomegalovirus infection associated with smaller cerebellum in severe mental illness

Author: Andreou, D., primary, Jørgensen, K. N., additional, Nerland, S., additional, Andreassen, O. A., additional, Yolken, R. H., additional, and Agartz, I., additional
Published: 2023
Full Text: View/download PDF

13. Linking menopause, history of depression, and proxies of biological aging in the UK Biobank cohort

Author: Crestol, A., primary, Subramaniapillai, S., additional, Schindler, L.S., additional, De Lange, A.M.G., additional, Andreassen, O.A., additional, Westlye, L.T., additional, Agartz, I., additional, Tamnes, C.K., additional, and Barth, C., additional
Published: 2023
Full Text: View/download PDF

14. Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not

Author: Aas, M., Melle, I., Bettella, F., Djurovic, S., Le Hellard, S., Bjella, T., Ringen, P. A., Lagerberg, T. V., Smeland, O. B., Agartz, I., Andreassen, O. A., and Tesli, M.
Published: 2018
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15. Persistent increase in TNF and IL‐1 markers in severe mental disorders suggests trait‐related inflammation: a one year follow‐up study

Author: Mørch, R. H., Dieset, I., Færden, A., Hope, S., Aas, M., Nerhus, M., Gardsjord, E. S., Haram, M., Falk, R. S., Joa, I., Morken, G., Agartz, I., Aukrust, P., Djurovic, S., Melle, I., Ueland, T., and Andreassen, O. A.
Published: 2017
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16. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years

Author: Dima, D., Modabbernia, A., Papachristou, E., Doucet, G.E., Agartz, I., Aghajani, M., Akudjedu, T.N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K.I., Andersson, M., Andreasen, N.C., Andreassen, O.A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D.I., Borgwardt, S., Bourque, J., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R.M., Buitelaar, J.K., Busatto, G.F., Buckner, R.L., Calhoun, V., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Castellanos, F.X., Cervenka, S., Chaim-Avancini, T.M., Ching, C.R., Chubar, V., Clark, V.P., Conrod, P., Conzelmann, A., Crespo-Facorro, B., Crivello, F., Crone, E.A.M., Dannlowski, U., Dale, A.M., Davey, C., Geus, E.J. de, Haan, L. de, Zubicaray, G.I. de, Braber, A., Dickie, E.W., Giorgio, A. Di, Doan, N.T., Dørum, E.S., Ehrlich, S., Erk, S., Espeseth, T., Fatouros-Bergman, H., Fisher, S.E., Fouche, J.P., Franke, B., Frodl, T., Fuentes-Claramonte, P., Glahn, D.C., Gotlib, I.H., Grabe, H.J., Grimm, O., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Gur, R.E., Gur, R.C., Hahn, T., Harrison, B.J., Hartman, Catharina A., Hatton, S.N., Heinz, A., Heslenfeld, D.J., Hibar, D.P., Hickie, I.B., Ho, B.C.H., Hoekstra, P.J., Hohmann, S., Holmes, A.J., Hoogman, M., Hosten, N., Howells, F.M., Pol, H.E.H., Huyser, C., Jahanshad, N., James, A., Jernigan, T.L., Jiang, J., Jönsson, E.G., Joska, J.A., Kahn, R., Kalnin, A., Naaijen, J., Klein, M., Thompson, P.M., Frangou, S., Dima, D., Modabbernia, A., Papachristou, E., Doucet, G.E., Agartz, I., Aghajani, M., Akudjedu, T.N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K.I., Andersson, M., Andreasen, N.C., Andreassen, O.A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D.I., Borgwardt, S., Bourque, J., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R.M., Buitelaar, J.K., Busatto, G.F., Buckner, R.L., Calhoun, V., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Castellanos, F.X., Cervenka, S., Chaim-Avancini, T.M., Ching, C.R., Chubar, V., Clark, V.P., Conrod, P., Conzelmann, A., Crespo-Facorro, B., Crivello, F., Crone, E.A.M., Dannlowski, U., Dale, A.M., Davey, C., Geus, E.J. de, Haan, L. de, Zubicaray, G.I. de, Braber, A., Dickie, E.W., Giorgio, A. Di, Doan, N.T., Dørum, E.S., Ehrlich, S., Erk, S., Espeseth, T., Fatouros-Bergman, H., Fisher, S.E., Fouche, J.P., Franke, B., Frodl, T., Fuentes-Claramonte, P., Glahn, D.C., Gotlib, I.H., Grabe, H.J., Grimm, O., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Gur, R.E., Gur, R.C., Hahn, T., Harrison, B.J., Hartman, Catharina A., Hatton, S.N., Heinz, A., Heslenfeld, D.J., Hibar, D.P., Hickie, I.B., Ho, B.C.H., Hoekstra, P.J., Hohmann, S., Holmes, A.J., Hoogman, M., Hosten, N., Howells, F.M., Pol, H.E.H., Huyser, C., Jahanshad, N., James, A., Jernigan, T.L., Jiang, J., Jönsson, E.G., Joska, J.A., Kahn, R., Kalnin, A., Naaijen, J., Klein, M., Thompson, P.M., and Frangou, S.
Abstract: Contains fulltext : 245411.pdf (Publisher’s version ) (Open Access), Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
Published: 2022

17. Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years

Author: Frangou, S., Modabbernia, A., Williams, S.C.R., Papachristou, E., Doucet, G.E., Agartz, I., Aghajani, M., Akudjedu, T.N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K.I., Andersson, M., Andreasen, N.C., Andreassen, O.A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D.I., Borgwardt, S., Bourque, J., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R.M., Buitelaar, J.K., Busatto, G.F., Buckner, R.L., Calhoun, V., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Castellanos, F.X., Cervenka, S., Chaim-Avancini, T.M., Ching, C.R., Chubar, V., Clark, V.P., Conrod, P., Conzelmann, A., Crespo-Facorro, B., Crivello, F., Crone, E.A.M., Dale, A.M., Dannlowski, U., Davey, C., Geus, E.J. de, Haan, L. de, Zubicaray, G.I. de, Braber, A., Dickie, E.W., Giorgio, A. Di, Doan, N.T., Dørum, E.S., Ehrlich, S., Erk, S., Espeseth, T., Fatouros-Bergman, H., Fisher, S.E., Fouche, J.P., Franke, B., Frodl, T., Fuentes-Claramonte, P., Glahn, D.C., Gotlib, I.H., Grabe, H.J., Grimm, O., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Gur, R.E., Gur, R.C., Hahn, T., Harrison, B.J., Hartman, Catharina A., Hatton, S.N., Heinz, A., Heslenfeld, D.J., Hibar, D.P., Hickie, I.B., Ho, B.C.H., Hoekstra, P.J., Hohmann, S., Holmes, A.J., Hoogman, M., Hosten, N., Howells, F.M., Pol, H.E.H., Huyser, C., Jahanshad, N., James, A., Jernigan, T.L., Jiang, J., Jönsson, E.G., Joska, J.A., Kahn, R., Klein, M., Frangou, S., Modabbernia, A., Williams, S.C.R., Papachristou, E., Doucet, G.E., Agartz, I., Aghajani, M., Akudjedu, T.N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K.I., Andersson, M., Andreasen, N.C., Andreassen, O.A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D.I., Borgwardt, S., Bourque, J., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R.M., Buitelaar, J.K., Busatto, G.F., Buckner, R.L., Calhoun, V., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Castellanos, F.X., Cervenka, S., Chaim-Avancini, T.M., Ching, C.R., Chubar, V., Clark, V.P., Conrod, P., Conzelmann, A., Crespo-Facorro, B., Crivello, F., Crone, E.A.M., Dale, A.M., Dannlowski, U., Davey, C., Geus, E.J. de, Haan, L. de, Zubicaray, G.I. de, Braber, A., Dickie, E.W., Giorgio, A. Di, Doan, N.T., Dørum, E.S., Ehrlich, S., Erk, S., Espeseth, T., Fatouros-Bergman, H., Fisher, S.E., Fouche, J.P., Franke, B., Frodl, T., Fuentes-Claramonte, P., Glahn, D.C., Gotlib, I.H., Grabe, H.J., Grimm, O., Groenewold, N.A., Grotegerd, D., Gruber, O., Gruner, P., Gur, R.E., Gur, R.C., Hahn, T., Harrison, B.J., Hartman, Catharina A., Hatton, S.N., Heinz, A., Heslenfeld, D.J., Hibar, D.P., Hickie, I.B., Ho, B.C.H., Hoekstra, P.J., Hohmann, S., Holmes, A.J., Hoogman, M., Hosten, N., Howells, F.M., Pol, H.E.H., Huyser, C., Jahanshad, N., James, A., Jernigan, T.L., Jiang, J., Jönsson, E.G., Joska, J.A., Kahn, R., and Klein, M.
Abstract: Contains fulltext : 245396.pdf (Publisher’s version ) (Open Access), Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
Published: 2022

18. Reproducibility in the absence of selective reporting: An illustration from large‐scale brain asymmetry research

Author: Kong, X.Z., Francks, C., Mathias, S.R., Guadalupe, T.M., Abé, C., Agartz, I., Buitelaar, J.K., Luijten, M., Fisher, S.E., Orhan, F., Sellgren, C., Kong, X.Z., Francks, C., Mathias, S.R., Guadalupe, T.M., Abé, C., Agartz, I., Buitelaar, J.K., Luijten, M., Fisher, S.E., Orhan, F., and Sellgren, C.
Abstract: Contains fulltext : 227140.pdf (publisher's version ) (Open Access), The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p-hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left-right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta-analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an "ideal publishing environment," that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically-used sample sizes.
Published: 2022

19. Greater male than female variability in regional brain structure across the lifespan

Author: Wierenga, L.M., Doucet, G.E., Dima, D., Agartz, I., Aghajani, M., Akudjedu, T.N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K.I., Andreassen, O.A., Anticevic, A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D.I., Borgwardt, S., Bourque, J., Braber, A., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R.M., Buitelaar, J.K., Busatto, G.F., Calhoun, V.D., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Castellanos, F.X., Chaim-Avancini, T.M., Ching, C.R., Clark, V.P., Conrod, P.J., Conzelmann, A., Crivello, F., Davey, C.G., Dickie, E.W., Ehrlich, S., Ent, D. van 't, Fisher, S.E., Fouche, J.P., Franke, B., Fuentes-Claramonte, P., Geus, E.J. de, Giorgio, A. Di, Glahn, D.C., Gotlib, I.H., Grabe, H.J., Gruber, O., Gruner, P., Gur, R.E., Gur, R.C., Gurholt, T.P., Haan, L. de, Haatveit, B., Harrison, B.J., Hartman, C.A., Hatton, S.N., Heslenfeld, D.J., Heuvel, O.A. van den, Hickie, I.B., Hoekstra, P.J., Hohmann, S., Holmes, A.J., Hoogman, M., Hosten, N., Howells, F.M., Pol, H.E.H., Huyser, C., Jahanshad, N., James, A.C., Jiang, J., Jönsson, E.G., Joska, J.A., Kalnin, A.J., Klein, M., Koenders, L., Kolskår, K.K., Krämer, B., Kuntsi, J., Lagopoulos, J., Lazaro, L., Lebedeva, I.S., Lee, Phil H., Lochner, C., Machielsen, M.W., Maingault, S., Martin, N.G., Martínez-Zalacaín, I., Mataix-Cols, D., Mazoyer, B., McDonald, B.C., McDonald, C., McIntosh, A.M., McMahon, K.L., McPhilemy, G., Naaijen, J., Frangou, S., Tamnes, C.K., Wierenga, L.M., Doucet, G.E., Dima, D., Agartz, I., Aghajani, M., Akudjedu, T.N., Albajes-Eizagirre, A., Alnaes, D., Alpert, K.I., Andreassen, O.A., Anticevic, A., Asherson, P., Banaschewski, T., Bargallo, N., Baumeister, S., Baur-Streubel, R., Bertolino, A., Bonvino, A., Boomsma, D.I., Borgwardt, S., Bourque, J., Braber, A., Brandeis, D., Breier, A., Brodaty, H., Brouwer, R.M., Buitelaar, J.K., Busatto, G.F., Calhoun, V.D., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Castellanos, F.X., Chaim-Avancini, T.M., Ching, C.R., Clark, V.P., Conrod, P.J., Conzelmann, A., Crivello, F., Davey, C.G., Dickie, E.W., Ehrlich, S., Ent, D. van 't, Fisher, S.E., Fouche, J.P., Franke, B., Fuentes-Claramonte, P., Geus, E.J. de, Giorgio, A. Di, Glahn, D.C., Gotlib, I.H., Grabe, H.J., Gruber, O., Gruner, P., Gur, R.E., Gur, R.C., Gurholt, T.P., Haan, L. de, Haatveit, B., Harrison, B.J., Hartman, C.A., Hatton, S.N., Heslenfeld, D.J., Heuvel, O.A. van den, Hickie, I.B., Hoekstra, P.J., Hohmann, S., Holmes, A.J., Hoogman, M., Hosten, N., Howells, F.M., Pol, H.E.H., Huyser, C., Jahanshad, N., James, A.C., Jiang, J., Jönsson, E.G., Joska, J.A., Kalnin, A.J., Klein, M., Koenders, L., Kolskår, K.K., Krämer, B., Kuntsi, J., Lagopoulos, J., Lazaro, L., Lebedeva, I.S., Lee, Phil H., Lochner, C., Machielsen, M.W., Maingault, S., Martin, N.G., Martínez-Zalacaín, I., Mataix-Cols, D., Mazoyer, B., McDonald, B.C., McDonald, C., McIntosh, A.M., McMahon, K.L., McPhilemy, G., Naaijen, J., Frangou, S., and Tamnes, C.K.
Abstract: Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access), For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
Published: 2022

20. Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working Group

Author: Abé, C, Ching, CRK, Liberg, B, Lebedev, AV, Agartz, I, Akudjedu, TN, Alda, M, Alnæs, D, Alonso-Lana, S, Benedetti, F, Berk, Michael, Bøen, E, Bonnin, CDM, Breuer, F, Brosch, K, Brouwer, RM, Canales-Rodríguez, EJ, Cannon, DM, Chye, Y, Dahl, A, Dandash, O, Dannlowski, U, Dohm, K, Elvsåshagen, T, Fisch, L, Fullerton, JM, Goikolea, JM, Grotegerd, D, Haatveit, B, Hahn, T, Hajek, T, Heindel, W, Ingvar, M, Sim, K, Kircher, TTJ, Lenroot, RK, Malt, UF, McDonald, C, McWhinney, SR, Melle, I, Meller, T, Melloni, EMT, Mitchell, PB, Nabulsi, L, Nenadić, I, Opel, N, Overs, BJ, Panicalli, F, Pfarr, JK, Poletti, S, Pomarol-Clotet, E, Radua, J, Repple, J, Ringwald, KG, Roberts, G, Rodriguez-Cano, E, Salvador, R, Sarink, K, Sarró, S, Schmitt, S, Stein, F, Suo, C, Thomopoulos, SI, Tronchin, G, Vieta, E, Westlye, LT, White, AG, Yatham, LN, Zak, N, Thompson, PM, Andreassen, OA, Landén, M, Abé, C, Ching, CRK, Liberg, B, Lebedev, AV, Agartz, I, Akudjedu, TN, Alda, M, Alnæs, D, Alonso-Lana, S, Benedetti, F, Berk, Michael, Bøen, E, Bonnin, CDM, Breuer, F, Brosch, K, Brouwer, RM, Canales-Rodríguez, EJ, Cannon, DM, Chye, Y, Dahl, A, Dandash, O, Dannlowski, U, Dohm, K, Elvsåshagen, T, Fisch, L, Fullerton, JM, Goikolea, JM, Grotegerd, D, Haatveit, B, Hahn, T, Hajek, T, Heindel, W, Ingvar, M, Sim, K, Kircher, TTJ, Lenroot, RK, Malt, UF, McDonald, C, McWhinney, SR, Melle, I, Meller, T, Melloni, EMT, Mitchell, PB, Nabulsi, L, Nenadić, I, Opel, N, Overs, BJ, Panicalli, F, Pfarr, JK, Poletti, S, Pomarol-Clotet, E, Radua, J, Repple, J, Ringwald, KG, Roberts, G, Rodriguez-Cano, E, Salvador, R, Sarink, K, Sarró, S, Schmitt, S, Stein, F, Suo, C, Thomopoulos, SI, Tronchin, G, Vieta, E, Westlye, LT, White, AG, Yatham, LN, Zak, N, Thompson, PM, Andreassen, OA, and Landén, M
Published: 2022

21. In vivo hippocampal subfield volumes in bipolar disorder—A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group

Author: Haukvik, UK, Gurholt, TP, Nerland, S, Elvsåshagen, T, Akudjedu, TN, Alda, M, Alnæs, D, Alonso-Lana, S, Bauer, J, Baune, BT, Benedetti, F, Berk, Michael, Bettella, F, Bøen, E, Bonnín, CM, Brambilla, P, Canales-Rodríguez, EJ, Cannon, DM, Caseras, X, Dandash, O, Dannlowski, U, Delvecchio, G, Díaz-Zuluaga, AM, van Erp, TGM, Fatjó-Vilas, M, Foley, SF, Förster, K, Fullerton, JM, Goikolea, JM, Grotegerd, D, Gruber, O, Haarman, BCM, Haatveit, B, Hajek, T, Hallahan, B, Harris, M, Hawkins, EL, Howells, FM, Hülsmann, C, Jahanshad, N, Jørgensen, KN, Kircher, T, Krämer, B, Krug, A, Kuplicki, R, Lagerberg, TV, Lancaster, TM, Lenroot, RK, Lonning, V, López-Jaramillo, C, Malt, UF, McDonald, C, McIntosh, AM, McPhilemy, G, van der Meer, D, Melle, I, Melloni, EMT, Mitchell, PB, Nabulsi, L, Nenadić, I, Oertel, V, Oldani, L, Opel, N, Otaduy, MCG, Overs, BJ, Pineda-Zapata, JA, Pomarol-Clotet, E, Radua, J, Rauer, L, Redlich, R, Repple, J, Rive, MM, Roberts, G, Ruhe, HG, Salminen, LE, Salvador, R, Sarró, S, Savitz, J, Schene, AH, Sim, K, Soeiro-de-Souza, MG, Stäblein, M, Stein, DJ, Stein, F, Tamnes, CK, Temmingh, HS, Thomopoulos, SI, Veltman, DJ, Vieta, E, Waltemate, L, Westlye, LT, Whalley, HC, Sämann, PG, Thompson, PM, Ching, CRK, Andreassen, OA, Agartz, I, Haukvik, UK, Gurholt, TP, Nerland, S, Elvsåshagen, T, Akudjedu, TN, Alda, M, Alnæs, D, Alonso-Lana, S, Bauer, J, Baune, BT, Benedetti, F, Berk, Michael, Bettella, F, Bøen, E, Bonnín, CM, Brambilla, P, Canales-Rodríguez, EJ, Cannon, DM, Caseras, X, Dandash, O, Dannlowski, U, Delvecchio, G, Díaz-Zuluaga, AM, van Erp, TGM, Fatjó-Vilas, M, Foley, SF, Förster, K, Fullerton, JM, Goikolea, JM, Grotegerd, D, Gruber, O, Haarman, BCM, Haatveit, B, Hajek, T, Hallahan, B, Harris, M, Hawkins, EL, Howells, FM, Hülsmann, C, Jahanshad, N, Jørgensen, KN, Kircher, T, Krämer, B, Krug, A, Kuplicki, R, Lagerberg, TV, Lancaster, TM, Lenroot, RK, Lonning, V, López-Jaramillo, C, Malt, UF, McDonald, C, McIntosh, AM, McPhilemy, G, van der Meer, D, Melle, I, Melloni, EMT, Mitchell, PB, Nabulsi, L, Nenadić, I, Oertel, V, Oldani, L, Opel, N, Otaduy, MCG, Overs, BJ, Pineda-Zapata, JA, Pomarol-Clotet, E, Radua, J, Rauer, L, Redlich, R, Repple, J, Rive, MM, Roberts, G, Ruhe, HG, Salminen, LE, Salvador, R, Sarró, S, Savitz, J, Schene, AH, Sim, K, Soeiro-de-Souza, MG, Stäblein, M, Stein, DJ, Stein, F, Tamnes, CK, Temmingh, HS, Thomopoulos, SI, Veltman, DJ, Vieta, E, Waltemate, L, Westlye, LT, Whalley, HC, Sämann, PG, Thompson, PM, Ching, CRK, Andreassen, OA, and Agartz, I
Published: 2022

22. Intracranial and subcortical volumes in adolescents with early-onset psychosis: A multisite mega-analysis from the ENIGMA consortium

Author: Gurholt, TP, Lonning, V, Nerland, S, Jørgensen, KN, Haukvik, UK, Alloza, C, Arango, C, Barth, C, Bearden, CE, Berk, Michael, Bohman, H, Dandash, O, Díaz-Caneja, CM, Edbom, CT, van Erp, TGM, Fett, AKJ, Frangou, S, Goldstein, BI, Grigorian, A, Jahanshad, N, James, AC, Janssen, J, Johannessen, C, Karlsgodt, KH, Kempton, MJ, Kochunov, P, Krabbendam, L, Kyriakopoulos, M, Lundberg, M, MacIntosh, BJ, Rund, BR, Smelror, RE, Sultan, A, Tamnes, CK, Thomopoulos, SI, Vajdi, A, Wedervang-Resell, K, Myhre, AM, Andreassen, OA, Thompson, PM, Agartz, I, Gurholt, TP, Lonning, V, Nerland, S, Jørgensen, KN, Haukvik, UK, Alloza, C, Arango, C, Barth, C, Bearden, CE, Berk, Michael, Bohman, H, Dandash, O, Díaz-Caneja, CM, Edbom, CT, van Erp, TGM, Fett, AKJ, Frangou, S, Goldstein, BI, Grigorian, A, Jahanshad, N, James, AC, Janssen, J, Johannessen, C, Karlsgodt, KH, Kempton, MJ, Kochunov, P, Krabbendam, L, Kyriakopoulos, M, Lundberg, M, MacIntosh, BJ, Rund, BR, Smelror, RE, Sultan, A, Tamnes, CK, Thomopoulos, SI, Vajdi, A, Wedervang-Resell, K, Myhre, AM, Andreassen, OA, Thompson, PM, and Agartz, I
Published: 2022

23. Reproducibility in the absence of selective reporting: An illustration from large-scale brain asymmetry research

Author: Kong, XZ, Francks, C, Mathias, SR, Guadalupe, T, Abé, C, Agartz, I, Akudjedu, TN, Aleman, A, Alhusaini, S, Allen, NB, Ames, D, Andreassen, OA, Vasquez, AA, Armstrong, NJ, Asherson, P, Bergo, F, Bastin, ME, Batalla, A, Bauer, J, Baune, BT, Baur-Streubel, R, Biederman, J, Blaine, SK, Boedhoe, P, Bøen, E, Bose, A, Bralten, J, Brandeis, D, Brem, S, Brodaty, H, Yüksel, D, Brooks, SJ, Buitelaar, J, Bürger, C, Bülow, R, Calhoun, V, Calvo, A, Canales-Rodríguez, EJ, Cannon, DM, Caparelli, EC, Castellanos, FX, Cendes, F, Chaim-Avancini, TM, Chantiluke, K, Chen, QL, Chen, X, Cheng, Y, Christakou, A, Clark, VP, Coghill, D, Connolly, CG, Conzelmann, A, Córdova-Palomera, A, Cousijn, J, Crow, T, Cubillo, A, Dannlowski, U, de Bruttopilo, SA, de Zeeuw, P, Deary, IJ, Demeter, DV, Di Martino, A, Dickie, EW, Dietsche, B, Doan, NT, Doherty, CP, Doyle, A, Durston, S, Earl, E, Ehrlich, S, Ekman, CJ, Elvsåshagen, T, Epstein, JN, Fair, DA, Faraone, SV, Fernández, G, Flint, C, Filho, GB, Förster, K, Fouche, JP, Foxe, JJ, Frodl, T, Fuentes-Claramonte, P, Fullerton, JM, Garavan, H, do Santos Garcia, D, Gotlib, IH, Goudriaan, AE, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Gurholt, T, Haavik, J, Hahn, T, Hansell, NK, Harris, MA, Hartman, CA, del Carmen Valdés Hernández, M, Kong, XZ, Francks, C, Mathias, SR, Guadalupe, T, Abé, C, Agartz, I, Akudjedu, TN, Aleman, A, Alhusaini, S, Allen, NB, Ames, D, Andreassen, OA, Vasquez, AA, Armstrong, NJ, Asherson, P, Bergo, F, Bastin, ME, Batalla, A, Bauer, J, Baune, BT, Baur-Streubel, R, Biederman, J, Blaine, SK, Boedhoe, P, Bøen, E, Bose, A, Bralten, J, Brandeis, D, Brem, S, Brodaty, H, Yüksel, D, Brooks, SJ, Buitelaar, J, Bürger, C, Bülow, R, Calhoun, V, Calvo, A, Canales-Rodríguez, EJ, Cannon, DM, Caparelli, EC, Castellanos, FX, Cendes, F, Chaim-Avancini, TM, Chantiluke, K, Chen, QL, Chen, X, Cheng, Y, Christakou, A, Clark, VP, Coghill, D, Connolly, CG, Conzelmann, A, Córdova-Palomera, A, Cousijn, J, Crow, T, Cubillo, A, Dannlowski, U, de Bruttopilo, SA, de Zeeuw, P, Deary, IJ, Demeter, DV, Di Martino, A, Dickie, EW, Dietsche, B, Doan, NT, Doherty, CP, Doyle, A, Durston, S, Earl, E, Ehrlich, S, Ekman, CJ, Elvsåshagen, T, Epstein, JN, Fair, DA, Faraone, SV, Fernández, G, Flint, C, Filho, GB, Förster, K, Fouche, JP, Foxe, JJ, Frodl, T, Fuentes-Claramonte, P, Fullerton, JM, Garavan, H, do Santos Garcia, D, Gotlib, IH, Goudriaan, AE, Grabe, HJ, Groenewold, NA, Grotegerd, D, Gruber, O, Gurholt, T, Haavik, J, Hahn, T, Hansell, NK, Harris, MA, Hartman, CA, and del Carmen Valdés Hernández, M
Published: 2022

24. Genetic variants associated with longitudinal changes in brain structure across the lifespan

Author: Brouwer, RM, Klein, M, Grasby, KL, Schnack, HG, Jahanshad, N, Teeuw, J, Thomopoulos, SI, Sprooten, E, Franz, CE, Gogtay, N, Kremen, WS, Panizzon, MS, Olde Loohuis, LM, Whelan, CD, Aghajani, M, Alloza, C, Alanaes, D, Artiges, E, Ayesa-Arriola, R, Barker, GJ, Bastin, ME, Blok, E, Boen, E, Breukelaar, IA, Bright, JK, Buimer, EEL, Bulow, R, Cannon, DM, Ciufolini, S, Crossley, NA, Damatac, CG, Dazzan, P, de Mol, CL, de Zwarte, SMC, Desrivieres, S, Diaz-Caneja, CM, Doan, NT, Dohm, K, Froehner, JH, Goltermann, J, Grigis, A, Grotegerd, D, Han, LKM, Harris, MA, Hartman, CA, Heany, SJ, Heindel, W, Heslenfeld, DJ, Hohmann, S, Ittermann, B, Jansen, PR, Janssen, J, Jia, T, Jiang, J, Jockwitz, C, Karali, T, Keeser, D, Koevoets, MGJC, Lenroot, RK, Malchow, B, Mandl, RCW, Medel, V, Meinert, S, Morgan, CA, Muehleisen, TW, Nabulsi, L, Opel, N, de la Foz, VO-G, Overs, BJ, Paillere Martinot, M-L, Redlich, R, Marques, TR, Repple, J, Roberts, G, Roshchupkin, GV, Setiaman, N, Shumskaya, E, Stein, F, Sudre, G, Takahashi, S, Thalamuthu, A, Tordesillas-Gutierrez, D, van der Lugt, A, van Haren, NEM, Wardlaw, JM, Wen, W, Westeneng, H-J, Wittfeld, K, Zhu, AH, Zugman, A, Armstrong, NJ, Bonfiglio, G, Bralten, J, Dalvie, S, Davies, G, Di Forti, M, Ding, L, Donohoe, G, Forstner, AJ, Gonzalez-Penas, J, Guimaraes, JPOFT, Homuth, G, Hottenga, J-J, Knol, MJ, Kwok, JBJ, Le Hellard, S, Mather, KA, Milaneschi, Y, Morris, DW, Noethen, MM, Papiol, S, Rietschel, M, Santoro, ML, Steen, VM, Stein, JL, Streit, F, Tankard, RM, Teumer, A, van 't Ent, D, van der Meer, D, van Eijk, KR, Vassos, E, Vazquez-Bourgon, J, Witt, SH, Adams, HHH, Agartz, I, Ames, D, Amunts, K, Andreassen, OA, Arango, C, Banaschewski, T, Baune, BT, Belangero, SI, Bokde, ALW, Boomsma, DI, Bressan, RA, Brodaty, H, Buitelaar, JK, Cahn, W, Caspers, S, Cichon, S, Crespo-Facorro, B, Cox, SR, Dannlowski, U, Elvsashagen, T, Espeseth, T, Falkai, PG, Fisher, SE, Flor, H, Fullerton, JM, Garavan, H, Gowland, PA, Grabe, HJ, Hahn, T, Heinz, A, Hillegers, M, Hoare, J, Hoekstra, PJ, Ikram, MA, Jackowski, AP, Jansen, A, Jonsson, EG, Kahn, RS, Kircher, T, Korgaonkar, MS, Krug, A, Lemaitre, H, Malt, UF, Martinot, J-L, McDonald, C, Mitchell, PB, Muetzel, RL, Murray, RM, Nees, F, Nenadic, I, Oosterlaan, J, Ophoff, RA, Pan, PM, Penninx, BWJH, Poustka, L, Sachdev, PS, Salum, GA, Schofield, PR, Schumann, G, Shaw, P, Sim, K, Smolka, MN, Stein, DJ, Trollor, JN, van den Berg, LH, Veldink, JH, Walter, H, Westlye, LT, Whelan, R, White, T, Wright, MJ, Medland, SE, Franke, B, Thompson, PM, Hulshoff Pol, HE, Brouwer, RM, Klein, M, Grasby, KL, Schnack, HG, Jahanshad, N, Teeuw, J, Thomopoulos, SI, Sprooten, E, Franz, CE, Gogtay, N, Kremen, WS, Panizzon, MS, Olde Loohuis, LM, Whelan, CD, Aghajani, M, Alloza, C, Alanaes, D, Artiges, E, Ayesa-Arriola, R, Barker, GJ, Bastin, ME, Blok, E, Boen, E, Breukelaar, IA, Bright, JK, Buimer, EEL, Bulow, R, Cannon, DM, Ciufolini, S, Crossley, NA, Damatac, CG, Dazzan, P, de Mol, CL, de Zwarte, SMC, Desrivieres, S, Diaz-Caneja, CM, Doan, NT, Dohm, K, Froehner, JH, Goltermann, J, Grigis, A, Grotegerd, D, Han, LKM, Harris, MA, Hartman, CA, Heany, SJ, Heindel, W, Heslenfeld, DJ, Hohmann, S, Ittermann, B, Jansen, PR, Janssen, J, Jia, T, Jiang, J, Jockwitz, C, Karali, T, Keeser, D, Koevoets, MGJC, Lenroot, RK, Malchow, B, Mandl, RCW, Medel, V, Meinert, S, Morgan, CA, Muehleisen, TW, Nabulsi, L, Opel, N, de la Foz, VO-G, Overs, BJ, Paillere Martinot, M-L, Redlich, R, Marques, TR, Repple, J, Roberts, G, Roshchupkin, GV, Setiaman, N, Shumskaya, E, Stein, F, Sudre, G, Takahashi, S, Thalamuthu, A, Tordesillas-Gutierrez, D, van der Lugt, A, van Haren, NEM, Wardlaw, JM, Wen, W, Westeneng, H-J, Wittfeld, K, Zhu, AH, Zugman, A, Armstrong, NJ, Bonfiglio, G, Bralten, J, Dalvie, S, Davies, G, Di Forti, M, Ding, L, Donohoe, G, Forstner, AJ, Gonzalez-Penas, J, Guimaraes, JPOFT, Homuth, G, Hottenga, J-J, Knol, MJ, Kwok, JBJ, Le Hellard, S, Mather, KA, Milaneschi, Y, Morris, DW, Noethen, MM, Papiol, S, Rietschel, M, Santoro, ML, Steen, VM, Stein, JL, Streit, F, Tankard, RM, Teumer, A, van 't Ent, D, van der Meer, D, van Eijk, KR, Vassos, E, Vazquez-Bourgon, J, Witt, SH, Adams, HHH, Agartz, I, Ames, D, Amunts, K, Andreassen, OA, Arango, C, Banaschewski, T, Baune, BT, Belangero, SI, Bokde, ALW, Boomsma, DI, Bressan, RA, Brodaty, H, Buitelaar, JK, Cahn, W, Caspers, S, Cichon, S, Crespo-Facorro, B, Cox, SR, Dannlowski, U, Elvsashagen, T, Espeseth, T, Falkai, PG, Fisher, SE, Flor, H, Fullerton, JM, Garavan, H, Gowland, PA, Grabe, HJ, Hahn, T, Heinz, A, Hillegers, M, Hoare, J, Hoekstra, PJ, Ikram, MA, Jackowski, AP, Jansen, A, Jonsson, EG, Kahn, RS, Kircher, T, Korgaonkar, MS, Krug, A, Lemaitre, H, Malt, UF, Martinot, J-L, McDonald, C, Mitchell, PB, Muetzel, RL, Murray, RM, Nees, F, Nenadic, I, Oosterlaan, J, Ophoff, RA, Pan, PM, Penninx, BWJH, Poustka, L, Sachdev, PS, Salum, GA, Schofield, PR, Schumann, G, Shaw, P, Sim, K, Smolka, MN, Stein, DJ, Trollor, JN, van den Berg, LH, Veldink, JH, Walter, H, Westlye, LT, Whelan, R, White, T, Wright, MJ, Medland, SE, Franke, B, Thompson, PM, and Hulshoff Pol, HE
Abstract: Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.
Published: 2022

25. In vivo hippocampal subfield volumes in bipolar disorder-A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group

Author: Haukvik, U.K., Gurholt, T.P., Nerland, S., Elvsåshagen, T., Akudjedu, T.N., Alda, M., Alnaes, D., Alonso-Lana, S., Bauer, J., Baune, B.T., Benedetti, F. De, Berk, M., Bettella, F., Bøen, E., Bonnín, C.M., Brambilla, P., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Dandash, O., Dannlowski, U., Delvecchio, G., Díaz-Zuluaga, A.M., Erp, T.G. van, Fatjó-Vilas, M., Foley, S.F., Förster, K., Fullerton, J.M., Goikolea, J.M., Grotegerd, D., Gruber, O., Haarman, B.C.M., Haatveit, B., Hajek, T., Hallahan, B., Harris, M., Hawkins, E.L., Howells, F.M., Hülsmann, C., Jahanshad, N., Jørgensen, K.N., Kircher, T., Krämer, B., Krug, A., Kuplicki, R., Lagerberg, T.V., Lancaster, T.M., Lenroot, R.K., Lonning, V., López-Jaramillo, C., Malt, U.F., McDonald, C., McIntosh, A.M., McPhilemy, G., Meer, D. van der, Melle, I., Melloni, E.M.T., Mitchell, P.B., Nabulsi, L., Nenadić, I., Oertel, V., Oldani, L., Opel, N., Otaduy, M.C.G., Overs, B.J., Pineda-Zapata, J.A., Pomarol-Clotet, E., Radua, J., Rauer, L., Redlich, R., Repple, J., Rive, M.M., Roberts, G., Ruhe, H.G., Salminen, L.E., Salvador, R., Sarró, S., Savitz, J., Schene, A.H., Sim, K., Soeiro-de-Souza, M.G., Stäblein, M., Stein, D.J., Stein, F., Tamnes, C.K., Temmingh, H.S., Thomopoulos, S.I., Veltman, D.J., Vieta, E., Waltemate, L., Westlye, L.T., Whalley, H.C., Sämann, P.G., Thompson, P.M., Ching, C.R., Andreassen, O.A., Agartz, I., Haukvik, U.K., Gurholt, T.P., Nerland, S., Elvsåshagen, T., Akudjedu, T.N., Alda, M., Alnaes, D., Alonso-Lana, S., Bauer, J., Baune, B.T., Benedetti, F. De, Berk, M., Bettella, F., Bøen, E., Bonnín, C.M., Brambilla, P., Canales-Rodríguez, E.J., Cannon, D.M., Caseras, X., Dandash, O., Dannlowski, U., Delvecchio, G., Díaz-Zuluaga, A.M., Erp, T.G. van, Fatjó-Vilas, M., Foley, S.F., Förster, K., Fullerton, J.M., Goikolea, J.M., Grotegerd, D., Gruber, O., Haarman, B.C.M., Haatveit, B., Hajek, T., Hallahan, B., Harris, M., Hawkins, E.L., Howells, F.M., Hülsmann, C., Jahanshad, N., Jørgensen, K.N., Kircher, T., Krämer, B., Krug, A., Kuplicki, R., Lagerberg, T.V., Lancaster, T.M., Lenroot, R.K., Lonning, V., López-Jaramillo, C., Malt, U.F., McDonald, C., McIntosh, A.M., McPhilemy, G., Meer, D. van der, Melle, I., Melloni, E.M.T., Mitchell, P.B., Nabulsi, L., Nenadić, I., Oertel, V., Oldani, L., Opel, N., Otaduy, M.C.G., Overs, B.J., Pineda-Zapata, J.A., Pomarol-Clotet, E., Radua, J., Rauer, L., Redlich, R., Repple, J., Rive, M.M., Roberts, G., Ruhe, H.G., Salminen, L.E., Salvador, R., Sarró, S., Savitz, J., Schene, A.H., Sim, K., Soeiro-de-Souza, M.G., Stäblein, M., Stein, D.J., Stein, F., Tamnes, C.K., Temmingh, H.S., Thomopoulos, S.I., Veltman, D.J., Vieta, E., Waltemate, L., Westlye, L.T., Whalley, H.C., Sämann, P.G., Thompson, P.M., Ching, C.R., Andreassen, O.A., and Agartz, I.
Abstract: Contains fulltext : 252169.pdf (Publisher’s version ) (Open Access), The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.
Published: 2022

26. What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group

Author: Ching, C.R., Hibar, D.P., Gurholt, T.P., Nunes, A., Thomopoulos, S.I., Abé, C., Agartz, I., Brouwer, R.M., Cannon, D.M., Zwarte, S.M.C. de, Eyler, L.T., Favre, P., Hajek, T., Haukvik, U.K., Houenou, J., Landén, M., Lett, T.A., McDonald, C., Nabulsi, L., Patel, Y., Pauling, M.E., Paus, T., Radua, J., Soeiro-de-Souza, M.G., Tronchin, G., Haren, N.E.M. van, Vieta, E., Walter, H., Zeng, L.L., Alda, M., Almeida, J., Alnaes, D., Alonso-Lana, S., Altimus, C., Bauer, M, Baune, B.T., Bearden, C.E., Bellani, M., Benedetti, F. De, Berk, M., Bilderbeck, A.C., Blumberg, H.P., Bøen, E., Bollettini, I., Bonnin, C. Del Mar, Brambilla, P., Canales-Rodríguez, E.J., Caseras, X., Dandash, O., Dannlowski, U., Delvecchio, G., Díaz-Zuluaga, A.M., Dima, D., Duchesnay, É., Elvsåshagen, T., Fears, S.C., Frangou, S., Fullerton, J.M., Glahn, D.C., Goikolea, J.M., Green, M.J., Grotegerd, D., Gruber, O., Haarman, B.C.M., Henry, C., Howells, F.M., Ives-Deliperi, V., Jansen, Andreas, Kircher, T.T.J., Knöchel, C., Kramer, B., Lafer, B., López-Jaramillo, C., Machado-Vieira, R., MacIntosh, B.J., Melloni, E.M.T., Mitchell, P.B., Nenadic, I., Nery, F., Nugent, A.C., Oertel, V., Ophoff, R.A., Ota, M., Overs, B.J., Pham, D.L., Phillips, M.L., Pineda-Zapata, J.A., Poletti, S., Polosan, M., Pomarol-Clotet, E., Pouchon, A., Quidé, Y., Rive, M.M., Roberts, G., Ruhe, H.G., Salvador, R., Sarró, S., Satterthwaite, T.D., Schene, A.H., Sim, K., Thompson, P.M., Andreassen, O.A., Ching, C.R., Hibar, D.P., Gurholt, T.P., Nunes, A., Thomopoulos, S.I., Abé, C., Agartz, I., Brouwer, R.M., Cannon, D.M., Zwarte, S.M.C. de, Eyler, L.T., Favre, P., Hajek, T., Haukvik, U.K., Houenou, J., Landén, M., Lett, T.A., McDonald, C., Nabulsi, L., Patel, Y., Pauling, M.E., Paus, T., Radua, J., Soeiro-de-Souza, M.G., Tronchin, G., Haren, N.E.M. van, Vieta, E., Walter, H., Zeng, L.L., Alda, M., Almeida, J., Alnaes, D., Alonso-Lana, S., Altimus, C., Bauer, M, Baune, B.T., Bearden, C.E., Bellani, M., Benedetti, F. De, Berk, M., Bilderbeck, A.C., Blumberg, H.P., Bøen, E., Bollettini, I., Bonnin, C. Del Mar, Brambilla, P., Canales-Rodríguez, E.J., Caseras, X., Dandash, O., Dannlowski, U., Delvecchio, G., Díaz-Zuluaga, A.M., Dima, D., Duchesnay, É., Elvsåshagen, T., Fears, S.C., Frangou, S., Fullerton, J.M., Glahn, D.C., Goikolea, J.M., Green, M.J., Grotegerd, D., Gruber, O., Haarman, B.C.M., Henry, C., Howells, F.M., Ives-Deliperi, V., Jansen, Andreas, Kircher, T.T.J., Knöchel, C., Kramer, B., Lafer, B., López-Jaramillo, C., Machado-Vieira, R., MacIntosh, B.J., Melloni, E.M.T., Mitchell, P.B., Nenadic, I., Nery, F., Nugent, A.C., Oertel, V., Ophoff, R.A., Ota, M., Overs, B.J., Pham, D.L., Phillips, M.L., Pineda-Zapata, J.A., Poletti, S., Polosan, M., Pomarol-Clotet, E., Pouchon, A., Quidé, Y., Rive, M.M., Roberts, G., Ruhe, H.G., Salvador, R., Sarró, S., Satterthwaite, T.D., Schene, A.H., Sim, K., Thompson, P.M., and Andreassen, O.A.
Abstract: Contains fulltext : 252204.pdf (Publisher’s version ) (Open Access), MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.
Published: 2022

27. Deep neural networks learn general and clinically relevant representations of the ageing brain

Author: Leonardsen, E.H., Peng, H., Kaufmann, T., Agartz, I., Andreassen, O.A., Celius, E.G., Espeseth, T., Harbo, H.F., Høgestøl, E.A., Lange, Ann-Marie de, Marquand, A.F., Vidal-Piñeiro, D., Roe, J.M., Selbæk, G., Sørensen, Ø., Smith, S.M., Westlye, L.T., Wolfers, T., Wang, Y., Leonardsen, E.H., Peng, H., Kaufmann, T., Agartz, I., Andreassen, O.A., Celius, E.G., Espeseth, T., Harbo, H.F., Høgestøl, E.A., Lange, Ann-Marie de, Marquand, A.F., Vidal-Piñeiro, D., Roe, J.M., Selbæk, G., Sørensen, Ø., Smith, S.M., Westlye, L.T., Wolfers, T., and Wang, Y.
Abstract: Contains fulltext : 251344.pdf (Publisher’s version ) (Open Access), The discrepancy between chronological age and the apparent age of the brain based on neuroimaging data - the brain age delta - has emerged as a reliable marker of brain health. With an increasing wealth of data, approaches to tackle heterogeneity in data acquisition are vital. To this end, we compiled raw structural magnetic resonance images into one of the largest and most diverse datasets assembled (n=53542), and trained convolutional neural networks (CNNs) to predict age. We achieved state-of-the-art performance on unseen data from unknown scanners (n=2553), and showed that higher brain age delta is associated with diabetes, alcohol intake and smoking. Using transfer learning, the intermediate representations learned by our model complemented and partly outperformed brain age delta in predicting common brain disorders. Our work shows we can achieve generalizable and biologically plausible brain age predictions using CNNs trained on heterogeneous datasets, and transfer them to clinical use cases.
Published: 2022

28. Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Author: Patel, Y., Shin, J., Abé, C., Agartz, I., Alloza, C., Alnæs, D., Ambrogi, S., Antonucci, L.A., Arango, C., Arolt, V., Auzias, G., Ayesa-Arriola, R., Banaj, N., Banaschewski, T., Bandeira, C., Başgöze, Z., Cupertino, R.B., Bau, C.H.D., Bauer, J., Baumeister, S., Bernardoni, F., Bertolino, A., Bonnin, C.D.M., Brandeis, D., Brem, S., Bruggemann, J., Bülow, R., Bustillo, J.R., Calderoni, S., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carmona, S., Carr, V.J., Catts, S.V., Chenji, S., Chew, Q.H., Coghill, D., Connolly, C.G., Conzelmann, A., Craven, A.R., Crespo-Facorro, B., Cullen, K., Dahl, A., Dannlowski, U., Davey, C.G., Deruelle, C., Díaz-Caneja, C.M., Dohm, K., Ehrlich, S., Epstein, J., Erwin-Grabner, T., Eyler, L.T., Fedor, J., Fitzgerald, J., Foran, W., Ford, J.M., Fortea, L., Fuentes-Claramonte, P., Fullerton, J., Furlong, L., Gallagher, L., Gao, B., Gao, S., Goikolea, J.M., Gotlib, I., Goya-Maldonado, R., Grabe, H.J., Green, M., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Haavik, J., Hahn, T., Harrison, B.J., Heindel, W., Henskens, F., Heslenfeld, D.J., Hilland, E., Hoekstra, P.J., Hohmann, S., Holz, N., Howells, F.M., Ipser, J.C., Jahanshad, N., Jakobi, B., Jansen, A, Janssen, J., Jonassen, R., Kaiser, A., Kaleda, V., Karantonis, J., King, J.A., Kircher, T., Kochunov, P., Koopowitz, S.M., Landén, M., Landrø, N.I., Hoogman, M., Lawrie, S., Franke, B., Rooij, D. van, Buitelaar, J.K., Thompson, P., Paus, T., Patel, Y., Shin, J., Abé, C., Agartz, I., Alloza, C., Alnæs, D., Ambrogi, S., Antonucci, L.A., Arango, C., Arolt, V., Auzias, G., Ayesa-Arriola, R., Banaj, N., Banaschewski, T., Bandeira, C., Başgöze, Z., Cupertino, R.B., Bau, C.H.D., Bauer, J., Baumeister, S., Bernardoni, F., Bertolino, A., Bonnin, C.D.M., Brandeis, D., Brem, S., Bruggemann, J., Bülow, R., Bustillo, J.R., Calderoni, S., Calvo, R., Canales-Rodríguez, E.J., Cannon, D.M., Carmona, S., Carr, V.J., Catts, S.V., Chenji, S., Chew, Q.H., Coghill, D., Connolly, C.G., Conzelmann, A., Craven, A.R., Crespo-Facorro, B., Cullen, K., Dahl, A., Dannlowski, U., Davey, C.G., Deruelle, C., Díaz-Caneja, C.M., Dohm, K., Ehrlich, S., Epstein, J., Erwin-Grabner, T., Eyler, L.T., Fedor, J., Fitzgerald, J., Foran, W., Ford, J.M., Fortea, L., Fuentes-Claramonte, P., Fullerton, J., Furlong, L., Gallagher, L., Gao, B., Gao, S., Goikolea, J.M., Gotlib, I., Goya-Maldonado, R., Grabe, H.J., Green, M., Grevet, E.H., Groenewold, N.A., Grotegerd, D., Gruber, O., Haavik, J., Hahn, T., Harrison, B.J., Heindel, W., Henskens, F., Heslenfeld, D.J., Hilland, E., Hoekstra, P.J., Hohmann, S., Holz, N., Howells, F.M., Ipser, J.C., Jahanshad, N., Jakobi, B., Jansen, A, Janssen, J., Jonassen, R., Kaiser, A., Kaleda, V., Karantonis, J., King, J.A., Kircher, T., Kochunov, P., Koopowitz, S.M., Landén, M., Landrø, N.I., Hoogman, M., Lawrie, S., Franke, B., Rooij, D. van, Buitelaar, J.K., Thompson, P., and Paus, T.
Abstract: Contains fulltext : 281502.pdf (Publisher’s version ) (Closed access), BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from t
Published: 2022

29. Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs

Author: Sonderby, I.E., Ching, C.R.K., Thomopoulos, S.I., Meer, D. van der, Sun, D., Villalon-Reina, J.E., Agartz, I., Amunts, K., Arango, Celso, Fisher, S.E., et al., Sonderby, I.E., Ching, C.R.K., Thomopoulos, S.I., Meer, D. van der, Sun, D., Villalon-Reina, J.E., Agartz, I., Amunts, K., Arango, Celso, Fisher, S.E., and et al.
Abstract: Contains fulltext : 245367.pdf (Publisher’s version ) (Open Access)
Published: 2022

30. Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis

Author: Baldwin, H, Radua, J, Antoniades, M, Haas, SS, Frangou, S, Agartz, I, Allen, P, Andreassen, OA, Atkinson, K, Bachman, P, Baeza, I, Bartholomeusz, CF, Chee, MWL, Colibazzi, T, Cooper, RE, Corcoran, CM, Cropley, VL, Ebdrup, BH, Fortea, A, Glenthoj, LB, Hamilton, HK, Haut, KM, Hayes, RA, He, Y, Heekeren, K, Kaess, M, Kasai, K, Katagiri, N, Kim, M, Kindler, J, Klaunig, MJ, Koike, S, Koppel, A, Kristensen, TD, Bin Kwak, Y, Kwon, JS, Lawrie, SM, Lebedeva, I, Lee, J, Lin, A, Loewy, RL, Mathalon, DH, Michel, C, Mizrahi, R, Moller, P, Nelson, B, Nemoto, T, Nordholm, D, Omelchenko, MA, Pantelis, C, Raghava, JM, Rossberg, J, Roessler, W, Salisbury, DF, Sasabayashi, D, Schall, U, Smigielski, L, Sugranyes, G, Suzuki, M, Takahashi, T, Tamnes, CK, Tang, J, Theodoridou, A, Thomopoulos, S, Tomyshev, AS, Uhlhaas, PJ, Vaernes, TG, van Amelsvoort, TAMJ, Van Erp, TGM, Waltz, JA, Westlye, LT, Wood, SJ, Zhou, JH, McGuire, P, Thompson, PM, Jalbrzikowski, M, Hernaus, D, Fusar-Poli, P, Baldwin, H, Radua, J, Antoniades, M, Haas, SS, Frangou, S, Agartz, I, Allen, P, Andreassen, OA, Atkinson, K, Bachman, P, Baeza, I, Bartholomeusz, CF, Chee, MWL, Colibazzi, T, Cooper, RE, Corcoran, CM, Cropley, VL, Ebdrup, BH, Fortea, A, Glenthoj, LB, Hamilton, HK, Haut, KM, Hayes, RA, He, Y, Heekeren, K, Kaess, M, Kasai, K, Katagiri, N, Kim, M, Kindler, J, Klaunig, MJ, Koike, S, Koppel, A, Kristensen, TD, Bin Kwak, Y, Kwon, JS, Lawrie, SM, Lebedeva, I, Lee, J, Lin, A, Loewy, RL, Mathalon, DH, Michel, C, Mizrahi, R, Moller, P, Nelson, B, Nemoto, T, Nordholm, D, Omelchenko, MA, Pantelis, C, Raghava, JM, Rossberg, J, Roessler, W, Salisbury, DF, Sasabayashi, D, Schall, U, Smigielski, L, Sugranyes, G, Suzuki, M, Takahashi, T, Tamnes, CK, Tang, J, Theodoridou, A, Thomopoulos, S, Tomyshev, AS, Uhlhaas, PJ, Vaernes, TG, van Amelsvoort, TAMJ, Van Erp, TGM, Waltz, JA, Westlye, LT, Wood, SJ, Zhou, JH, McGuire, P, Thompson, PM, Jalbrzikowski, M, Hernaus, D, and Fusar-Poli, P
Abstract: Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irre
Published: 2022

31. Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Author: Patel, Y, Shin, J, Abe, C, Agartz, I, Alloza, C, Alnaes, D, Ambrogi, S, Antonucci, LA, Arango, C, Arolt, V, Auzias, G, Ayesa-Arriola, R, Banaj, N, Banaschewski, T, Bandeira, C, Basgoze, Z, Cupertino, RB, Bau, CHD, Bauer, J, Baumeister, S, Bernardoni, F, Bertolino, A, del Mar Bonnin, C, Brandeis, D, Brem, S, Bruggemann, J, Bulow, R, Bustillo, JR, Calderoni, S, Calvo, R, Canales-Rodriguez, EJ, Cannon, DM, Carmona, S, Carr, VJ, Catts, SV, Chenji, S, Chew, QH, Coghill, D, Connolly, CG, Conzelmann, A, Craven, AR, Crespo-Facorro, B, Cullen, K, Dahl, A, Dannlowski, U, Davey, CG, Deruelle, C, Diaz-Caneja, CM, Dohm, K, Ehrlich, S, Epstein, J, Erwin-Grabner, T, Eyler, LT, Fedor, J, Fitzgerald, J, Foran, W, Ford, JM, Fortea, L, Fuentes-Claramonte, P, Fullerton, J, Furlong, L, Gallagher, L, Gao, B, Gao, S, Goikolea, JM, Gotlib, I, Goya-Maldonado, R, Grabe, HJ, Green, M, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Haavik, J, Hahn, T, Harrison, BJ, Heindel, W, Henskens, F, Heslenfeld, DJ, Hilland, E, Hoekstra, PJ, Hohmann, S, Holz, N, Howells, FM, Ipser, JC, Jahanshad, N, Jakobi, B, Jansen, A, Janssen, J, Jonassen, R, Kaiser, A, Kaleda, V, Karantonis, J, King, JA, Kircher, T, Kochunov, P, Koopowitz, S-M, Landen, M, Landro, NI, Lawrie, S, Lebedeva, I, Luna, B, Lundervold, AJ, MacMaster, FP, Maglanoc, LA, Mathalon, DH, McDonald, C, McIntosh, A, Meinert, S, Michie, PT, Mitchell, P, Moreno-Alcazar, A, Mowry, B, Muratori, F, Nabulsi, L, Nenadic, I, Tuura, RO, Oosterlaan, J, Overs, B, Pantelis, C, Parellada, M, Pariente, JC, Pauli, P, Pergola, G, Piarulli, FM, Picon, F, Piras, F, Pomarol-Clotet, E, Pretus, C, Quide, Y, Radua, J, Ramos-Quiroga, JA, Rasser, PE, Reif, A, Retico, A, Roberts, G, Rossell, S, Rovaris, DL, Rubia, K, Sacchet, M, Salavert, J, Salvador, R, Sarro, S, Sawa, A, Schall, U, Scott, R, Selvaggi, P, Silk, T, Sim, K, Skoch, A, Spalletta, G, Spaniel, F, Stein, DJ, Steinstrater, O, Stolicyn, A, Takayanagi, Y, Tamm, L, Tavares, M, Teumer, A, Thiel, K, Thomopoulos, SI, Tomecek, D, Tomyshev, AS, Tordesillas-Gutierrez, D, Tosetti, M, Uhlmann, A, Van Rheenen, T, Vazquez-Bourgon, J, Vernooij, MW, Vieta, E, Vilarroya, O, Weickert, C, Weickert, T, Westlye, LT, Whalley, H, Willinger, D, Winter, A, Wittfeld, K, Yang, TT, Yoncheva, Y, Zijlmans, JL, Hoogman, M, Franke, B, van Rooij, D, Buitelaar, J, Ching, CRK, Andreassen, OA, Pozzi, E, Veltman, D, Schmaal, L, van Erp, TGM, Turner, J, Castellanos, FX, Pausova, Z, Thompson, P, Paus, T, Patel, Y, Shin, J, Abe, C, Agartz, I, Alloza, C, Alnaes, D, Ambrogi, S, Antonucci, LA, Arango, C, Arolt, V, Auzias, G, Ayesa-Arriola, R, Banaj, N, Banaschewski, T, Bandeira, C, Basgoze, Z, Cupertino, RB, Bau, CHD, Bauer, J, Baumeister, S, Bernardoni, F, Bertolino, A, del Mar Bonnin, C, Brandeis, D, Brem, S, Bruggemann, J, Bulow, R, Bustillo, JR, Calderoni, S, Calvo, R, Canales-Rodriguez, EJ, Cannon, DM, Carmona, S, Carr, VJ, Catts, SV, Chenji, S, Chew, QH, Coghill, D, Connolly, CG, Conzelmann, A, Craven, AR, Crespo-Facorro, B, Cullen, K, Dahl, A, Dannlowski, U, Davey, CG, Deruelle, C, Diaz-Caneja, CM, Dohm, K, Ehrlich, S, Epstein, J, Erwin-Grabner, T, Eyler, LT, Fedor, J, Fitzgerald, J, Foran, W, Ford, JM, Fortea, L, Fuentes-Claramonte, P, Fullerton, J, Furlong, L, Gallagher, L, Gao, B, Gao, S, Goikolea, JM, Gotlib, I, Goya-Maldonado, R, Grabe, HJ, Green, M, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Haavik, J, Hahn, T, Harrison, BJ, Heindel, W, Henskens, F, Heslenfeld, DJ, Hilland, E, Hoekstra, PJ, Hohmann, S, Holz, N, Howells, FM, Ipser, JC, Jahanshad, N, Jakobi, B, Jansen, A, Janssen, J, Jonassen, R, Kaiser, A, Kaleda, V, Karantonis, J, King, JA, Kircher, T, Kochunov, P, Koopowitz, S-M, Landen, M, Landro, NI, Lawrie, S, Lebedeva, I, Luna, B, Lundervold, AJ, MacMaster, FP, Maglanoc, LA, Mathalon, DH, McDonald, C, McIntosh, A, Meinert, S, Michie, PT, Mitchell, P, Moreno-Alcazar, A, Mowry, B, Muratori, F, Nabulsi, L, Nenadic, I, Tuura, RO, Oosterlaan, J, Overs, B, Pantelis, C, Parellada, M, Pariente, JC, Pauli, P, Pergola, G, Piarulli, FM, Picon, F, Piras, F, Pomarol-Clotet, E, Pretus, C, Quide, Y, Radua, J, Ramos-Quiroga, JA, Rasser, PE, Reif, A, Retico, A, Roberts, G, Rossell, S, Rovaris, DL, Rubia, K, Sacchet, M, Salavert, J, Salvador, R, Sarro, S, Sawa, A, Schall, U, Scott, R, Selvaggi, P, Silk, T, Sim, K, Skoch, A, Spalletta, G, Spaniel, F, Stein, DJ, Steinstrater, O, Stolicyn, A, Takayanagi, Y, Tamm, L, Tavares, M, Teumer, A, Thiel, K, Thomopoulos, SI, Tomecek, D, Tomyshev, AS, Tordesillas-Gutierrez, D, Tosetti, M, Uhlmann, A, Van Rheenen, T, Vazquez-Bourgon, J, Vernooij, MW, Vieta, E, Vilarroya, O, Weickert, C, Weickert, T, Westlye, LT, Whalley, H, Willinger, D, Winter, A, Wittfeld, K, Yang, TT, Yoncheva, Y, Zijlmans, JL, Hoogman, M, Franke, B, van Rooij, D, Buitelaar, J, Ching, CRK, Andreassen, OA, Pozzi, E, Veltman, D, Schmaal, L, van Erp, TGM, Turner, J, Castellanos, FX, Pausova, Z, Thompson, P, and Paus, T
Abstract: BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from t
Published: 2022

32. Alcohol use is associated with thinner cerebral cortex and larger ventricles in schizophrenia, bipolar disorder and healthy controls

Author: Lange, E. H., Nerland, S., Jørgensen, K. N., Mørch-Johnsen, L., Nesvåg, R., Hartberg, C. B., Haukvik, U. K., Osnes, K., Melle, I., Andreassen, O. A., and Agartz, I.
Published: 2017
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33. Childhood trauma is associated with increased brain responses to emotionally negative as compared with positive faces in patients with psychotic disorders

Author: Aas, M., Kauppi, K., Brandt, C. L., Tesli, M., Kaufmann, T., Steen, N. E., Agartz, I., Westlye, L. T., Andreassen, O. A., and Melle, I.
Published: 2017
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34. Brain volume change in first-episode psychosis: an effect of antipsychotic medication independent of BMI change

Author: Jørgensen, K. N., Nesvåg, R., Nerland, S., Mørch-Johnsen, L., Westlye, L. T., Lange, E. H., Haukvik, U. K., Hartberg, C. B., Melle, I., Andreassen, O. A., and Agartz, I.
Published: 2017
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35. P.0766 Sex differences in hippocampal subfield volumes and relationship to testosterone measures in schizophrenia and bipolar disorders

Author: Barth, C., primary, De Lange, A.M.G., additional, Jørgensen, K.N., additional, Nerland, S., additional, Andreassen, O.A., additional, and Agartz, I., additional
Published: 2021
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36. Increased MRI-based cortical grey/white-matter contrast in sensory and motor regions in schizophrenia and bipolar disorder

Author: Jørgensen, K. N., Nerland, S., Norbom, L. B., Doan, N. T., Nesvåg, R., Mørch-Johnsen, L., Haukvik, U. K., Melle, I., Andreassen, O. A., Westlye, L. T., and Agartz, I.
Published: 2016
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37. Common variant at 16p11.2 conferring risk of psychosis

Author: Steinberg, S, de Jong, S, Mattheisen, M, Costas, J, Demontis, D, Jamain, S, Pietiläinen, O P H, Lin, K, Papiol, S, Huttenlocher, J, Sigurdsson, E, Vassos, E, Giegling, I, Breuer, R, Fraser, G, Walker, N, Melle, I, Djurovic, S, Agartz, I, Tuulio-Henriksson, A, Suvisaari, J, Lönnqvist, J, Paunio, T, Olsen, L, Hansen, T, Ingason, A, Pirinen, M, Strengman, E, Hougaard, D M, Ørntoft, T, Didriksen, M, Hollegaard, M V, Nordentoft, M, Abramova, L, Kaleda, V, Arrojo, M, Sanjuán, J, Arango, C, Etain, B, Bellivier, F, Méary, A, Schürhoff, F, Szoke, A, Ribolsi, M, Magni, V, Siracusano, A, Sperling, S, Rossner, M, Christiansen, C, Kiemeney, L A, Franke, B, van den Berg, L H, Veldink, J, Curran, S, Bolton, P, Poot, M, Staal, W, Rehnstrom, K, Kilpinen, H, Freitag, C M, Meyer, J, Magnusson, P, Saemundsen, E, Martsenkovsky, I, Bikshaieva, I, Martsenkovska, I, Vashchenko, O, Raleva, M, Paketchieva, K, Stefanovski, B, Durmishi, N, Pejovic Milovancevic, M, Lecic Tosevski, D, Silagadze, T, Naneishvili, N, Mikeladze, N, Surguladze, S, Vincent, J B, Farmer, A, Mitchell, P B, Wright, A, Schofield, P R, Fullerton, J M, Montgomery, G W, Martin, N G, Rubino, I A, van Winkel, R, Kenis, G, De Hert, M, Réthelyi, J M, Bitter, I, Terenius, L, Jönsson, E G, Bakker, S, van Os, J, Jablensky, A, Leboyer, M, Bramon, E, Powell, J, Murray, R, Corvin, A, Gill, M, Morris, D, O'Neill, F A, Kendler, K, Riley, B, Craddock, N, Owen, M J, O'Donovan, M C, Thorsteinsdottir, U, Kong, A, Ehrenreich, H, Carracedo, A, Golimbet, V, Andreassen, O A, Børglum, A D, Mors, O, Mortensen, P B, Werge, T, Ophoff, R A, Nöthen, M M, Rietschel, M, Cichon, S, Ruggeri, M, Tosato, S, Palotie, A, St Clair, D, Rujescu, D, Collier, D A, Stefansson, H, and Stefansson, K
Published: 2014
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38. Association between cytokine levels, verbal memory and hippocampus volume in psychotic disorders and healthy controls

Author: Hoseth, E. Z., Westlye, L. T., Hope, S., Dieset, I., Aukrust, P., Melle, I., Haukvik, U. K., Agartz, I., Ueland, T., and Andreassen, O. A.
Published: 2016
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39. Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs

Author: Sonderby, I.E., Ching, C.R.K., Thomopoulos, S.I., Meer, D. van der, Villalon-Reina, J.E., Agartz, I., Amunts, K., Arango, Celso, Fisher, S.E., et al., Sonderby, I.E., Ching, C.R.K., Thomopoulos, S.I., Meer, D. van der, Villalon-Reina, J.E., Agartz, I., Amunts, K., Arango, Celso, Fisher, S.E., and et al.
Abstract: Contains fulltext : 245367.pdf (Publisher’s version ) (Open Access)
Published: 2021

40. Genetic control of variability in subcortical and intracranial volumes

Author: Córdova-Palomera, A., Meer, D. van der, Kaufmann, T., Bettella, F., Wang, Y., Alnæs, D., Doan, N.T., Agartz, I., Bertolino, A., Buitelaar, J.K., Coynel, D., Djurovic, S., Dørum, E.S., Espeseth, T., Fazio, L., Franke, B., Frei, O., Håberg, A., Hellard, S. Le, Jönsson, E.G., Kolskår, K.K., Lund, M.J., Moberget, T., Nordvik, J.E., Nyberg, L., Papassotiropoulos, A., Pergola, G., Quervain, D. de, Rampino, A., Richard, G., Rokicki, J., Sanders, A.M., Schwarz, E., Smeland, O.B., Steen, V.M., Starrfelt, J., Sønderby, I.E., Ulrichsen, K.M., Andreassen, O.A., Westlye, L.T., Córdova-Palomera, A., Meer, D. van der, Kaufmann, T., Bettella, F., Wang, Y., Alnæs, D., Doan, N.T., Agartz, I., Bertolino, A., Buitelaar, J.K., Coynel, D., Djurovic, S., Dørum, E.S., Espeseth, T., Fazio, L., Franke, B., Frei, O., Håberg, A., Hellard, S. Le, Jönsson, E.G., Kolskår, K.K., Lund, M.J., Moberget, T., Nordvik, J.E., Nyberg, L., Papassotiropoulos, A., Pergola, G., Quervain, D. de, Rampino, A., Richard, G., Rokicki, J., Sanders, A.M., Schwarz, E., Smeland, O.B., Steen, V.M., Starrfelt, J., Sønderby, I.E., Ulrichsen, K.M., Andreassen, O.A., and Westlye, L.T.
Abstract: Item does not contain fulltext, Sensitivity to external demands is essential for adaptation to dynamic environments, but comes at the cost of increased risk of adverse outcomes when facing poor environmental conditions. Here, we apply a novel methodology to perform genome-wide association analysis of mean and variance in ten key brain features (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, intracranial volume, cortical surface area, and cortical thickness), integrating genetic and neuroanatomical data from a large lifespan sample (n = 25,575 individuals; 8-89 years, mean age 51.9 years). We identify genetic loci associated with phenotypic variability in thalamus volume and cortical thickness. The variance-controlling loci involved genes with a documented role in brain and mental health and were not associated with the mean anatomical volumes. This proof-of-principle of the hypothesis of a genetic regulation of brain volume variability contributes to establishing the genetic basis of phenotypic variance (i.e., heritability), allows identifying different degrees of brain robustness across individuals, and opens new research avenues in the search for mechanisms controlling brain and mental health.
Published: 2021

41. Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working Group

Author: Abé, C, Ching, CRK, Liberg, B, Lebedev, AV, Agartz, I, Akudjedu, TN, Alda, M, Alnæs, D, Alonso-Lana, S, Benedetti, F, Berk, M, Bøen, E, Bonnin, CDM, Breuer, F, Brosch, K, Brouwer, RM, Canales-Rodríguez, EJ, Cannon, DM, Chye, Y, Dahl, A, Dandash, O, Dannlowski, U, Dohm, K, Elvsåshagen, T, Fisch, L, Fullerton, JM, Goikolea, JM, Grotegerd, D, Haatveit, B, Hahn, T, Hajek, T, Heindel, W, Ingvar, M, Sim, K, Kircher, TTJ, Lenroot, RK, Malt, UF, McDonald, C, McWhinney, SR, Melle, I, Meller, T, Melloni, EMT, Mitchell, PB, Nabulsi, L, Nenadić, I, Opel, N, Overs, BJ, Panicalli, F, Pfarr, J-K, Poletti, S, Pomarol-Clotet, E, Radua, J, Repple, J, Ringwald, KG, Roberts, G, Rodriguez-Cano, E, Salvador, R, Sarink, K, Sarró, S, Schmitt, S, Stein, F, Suo, C, Thomopoulos, SI, Tronchin, G, Vieta, E, Westlye, LT, White, AG, Yatham, LN, Zak, N, Thompson, PM, Andreassen, OA, Landén, M, Abé, C, Ching, CRK, Liberg, B, Lebedev, AV, Agartz, I, Akudjedu, TN, Alda, M, Alnæs, D, Alonso-Lana, S, Benedetti, F, Berk, M, Bøen, E, Bonnin, CDM, Breuer, F, Brosch, K, Brouwer, RM, Canales-Rodríguez, EJ, Cannon, DM, Chye, Y, Dahl, A, Dandash, O, Dannlowski, U, Dohm, K, Elvsåshagen, T, Fisch, L, Fullerton, JM, Goikolea, JM, Grotegerd, D, Haatveit, B, Hahn, T, Hajek, T, Heindel, W, Ingvar, M, Sim, K, Kircher, TTJ, Lenroot, RK, Malt, UF, McDonald, C, McWhinney, SR, Melle, I, Meller, T, Melloni, EMT, Mitchell, PB, Nabulsi, L, Nenadić, I, Opel, N, Overs, BJ, Panicalli, F, Pfarr, J-K, Poletti, S, Pomarol-Clotet, E, Radua, J, Repple, J, Ringwald, KG, Roberts, G, Rodriguez-Cano, E, Salvador, R, Sarink, K, Sarró, S, Schmitt, S, Stein, F, Suo, C, Thomopoulos, SI, Tronchin, G, Vieta, E, Westlye, LT, White, AG, Yatham, LN, Zak, N, Thompson, PM, Andreassen, OA, and Landén, M
Published: 2021

42. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Author: Blokland, GAM, Grove, J, Chen, CY, Cotsapas, C, Tobet, S, Handa, R, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, Hirschhorn, JN, Blokland, GAM, Grove, J, Chen, CY, Cotsapas, C, Tobet, S, Handa, R, Ripke, S, Neale, BM, Corvin, A, Walters, JTR, Farh, KH, Holmans, PA, Lee, P, Bulik-Sullivan, B, Collier, DA, Huang, H, Pers, TH, Agartz, I, Agerbo, E, Albus, M, Alexander, M, Amin, F, Bacanu, SA, Begemann, M, Belliveau, RA, Bene, J, Bergen, SE, Bevilacqua, E, Bigdeli, TB, Black, DW, Bruggeman, R, Buccola, NG, Buckner, RL, Byerley, W, Cahn, W, Cai, G, Campion, D, Cantor, RM, Carr, VJ, Carrera, N, Catts, SV, Chambert, KD, Chan, RCK, Chen, RYL, Chen, EYH, Cheng, W, Cheung, EFC, Chong, SA, Cloninger, CR, Cohen, D, Cohen, N, Cormican, P, Craddock, N, Crowley, JJ, Curtis, D, Davidson, M, Davis, KL, Degenhardt, F, Del Favero, J, Demontis, D, Dikeos, D, Dinan, T, Djurovic, S, Donohoe, G, Drapeau, E, Duan, J, Dudbridge, F, Durmishi, N, Eichhammer, P, Eriksson, J, Escott-Price, V, Essioux, L, Fanous, AH, Farrell, MS, Frank, J, Franke, L, Freedman, R, Freimer, NB, Friedl, M, Friedman, JI, Fromer, M, Genovese, G, Georgieva, L, Giegling, I, Giusti-Rodríguez, P, Godard, S, Goldstein, JI, Golimbet, V, Gopal, S, Gratten, J, de Haan, L, Hammer, C, Hamshere, ML, Hansen, M, Hansen, T, Haroutunian, V, Hartmann, AM, Henskens, FA, Herms, S, and Hirschhorn, JN
Abstract: Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functio
Published: 2021

43. 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Author: Sønderby, I.E., van der Meer, D., Moreau, C., Kaufmann, T., Walters, G.B., Ellegaard, M., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N.B., Blangero, J., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Bülow, R., Bøen, R., Cahn, W., Calhoun, V.D., Caspers, S., Ching, C.R.K., Cichon, S., Ciufolini, S., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Desrivières, S., Doherty, J.L., Donohoe, G., Draganski, B., Ehrlich, S., Eising, E., Espeseth, T., Fejgin, K., Fisher, S.E., Fladby, T., Frei, O., Frouin, V., Fukunaga, M., Gareau, T., Ge, T., Glahn, D.C., Grabe, H.J., Groenewold, N.A., Gústafsson, Ó., Haavik, J., Håberg, A.K., Hall, J., Hashimoto, R., Hehir-Kwa, J.Y., Hibar, D.P., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Holmes, A.J., Homuth, G., Hottenga, J-J, Hulshoff Pol, H.E., Ikeda, M., Jahanshad, N., Jockwitz, C., Johansson, S., Jönsson, E.G., Jørgensen, N.R., Kikuchi, M., Knowles, E.E.M., Kumar, K., Le Hellard, S., Leu, C., Linden, D.E.J., Liu, J., Lundervold, A., Lundervold, A.J., Maillard, A.M., Martin, N.G., Martin-Brevet, S., Mather, K.A., Mathias, S.R., McMahon, K.L., McRae, A.F., Medland, S.E., Meyer-Lindenberg, A., Moberget, T., Modenato, C., Sánchez, J.M., Morris, D.W., Mühleisen, T.W., Murray, R.M., Nielsen, J., Nordvik, J.E., Nyberg, L., Loohuis, L.M.O., Ophoff, R.A., Owen, M.J., Paus, T., Pausova, Z., Peralta, J.M., Pike, G.B., Prieto, C., Quinlan, E.B., Reinbold, C.S., Marques, T.R., Rucker, J.J.H., Sachdev, P.S., Sando, S.B., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Silva, A.I., Sisodiya, S.M., Steen, V.M., Stein, D.J., Strike, L.T., Suzuki, I.K., Tamnes, C.K., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Uhlmann, A., Ulfarsson, M.O., van ‘t Ent, D., van den Bree, M.B.M., Vanderhaeghen, P., Vassos, E., Wen, W., Wittfeld, K., Wright, M.J., Agartz, I., Djurovic, S., Westlye, L.T., Stefánsson, H., Stefánsson, K., Jacquemont, S., Thompson, P.M., Andreassen, O.A., Sønderby, I.E., van der Meer, D., Moreau, C., Kaufmann, T., Walters, G.B., Ellegaard, M., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N.J., Bernard, M., Blackburn, N.B., Blangero, J., Boomsma, D.I., Brodaty, H., Brouwer, R.M., Bülow, R., Bøen, R., Cahn, W., Calhoun, V.D., Caspers, S., Ching, C.R.K., Cichon, S., Ciufolini, S., Crespo-Facorro, B., Curran, J.E., Dale, A.M., Dalvie, S., Dazzan, P., de Geus, E.J.C., de Zubicaray, G.I., de Zwarte, S.M.C., Desrivières, S., Doherty, J.L., Donohoe, G., Draganski, B., Ehrlich, S., Eising, E., Espeseth, T., Fejgin, K., Fisher, S.E., Fladby, T., Frei, O., Frouin, V., Fukunaga, M., Gareau, T., Ge, T., Glahn, D.C., Grabe, H.J., Groenewold, N.A., Gústafsson, Ó., Haavik, J., Håberg, A.K., Hall, J., Hashimoto, R., Hehir-Kwa, J.Y., Hibar, D.P., Hillegers, M.H.J., Hoffmann, P., Holleran, L., Holmes, A.J., Homuth, G., Hottenga, J-J, Hulshoff Pol, H.E., Ikeda, M., Jahanshad, N., Jockwitz, C., Johansson, S., Jönsson, E.G., Jørgensen, N.R., Kikuchi, M., Knowles, E.E.M., Kumar, K., Le Hellard, S., Leu, C., Linden, D.E.J., Liu, J., Lundervold, A., Lundervold, A.J., Maillard, A.M., Martin, N.G., Martin-Brevet, S., Mather, K.A., Mathias, S.R., McMahon, K.L., McRae, A.F., Medland, S.E., Meyer-Lindenberg, A., Moberget, T., Modenato, C., Sánchez, J.M., Morris, D.W., Mühleisen, T.W., Murray, R.M., Nielsen, J., Nordvik, J.E., Nyberg, L., Loohuis, L.M.O., Ophoff, R.A., Owen, M.J., Paus, T., Pausova, Z., Peralta, J.M., Pike, G.B., Prieto, C., Quinlan, E.B., Reinbold, C.S., Marques, T.R., Rucker, J.J.H., Sachdev, P.S., Sando, S.B., Schofield, P.R., Schork, A.J., Schumann, G., Shin, J., Shumskaya, E., Silva, A.I., Sisodiya, S.M., Steen, V.M., Stein, D.J., Strike, L.T., Suzuki, I.K., Tamnes, C.K., Teumer, A., Thalamuthu, A., Tordesillas-Gutierrez, D., Uhlmann, A., Ulfarsson, M.O., van ‘t Ent, D., van den Bree, M.B.M., Vanderhaeghen, P., Vassos, E., Wen, W., Wittfeld, K., Wright, M.J., Agartz, I., Djurovic, S., Westlye, L.T., Stefánsson, H., Stefánsson, K., Jacquemont, S., Thompson, P.M., and Andreassen, O.A.
Abstract: Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
Published: 2021

44. Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3–90 years

Author: Frangou, S. (Sophia), Modabbernia, A. (Amirhossein), Williams, S.C.R. (Steven C. R.), Papachristou, E. (Efstathios), Doucet, G.E. (Gaelle E.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Akudjedu, T.N. (Theophilus N.), Albajes-Eizagirre, A. (Anton), Alnæs, D. (Dag), Alpert, K. (Kathryn), Andersson, M. (Micael), Andreasen, N.C. (Nancy C.), Andreassen, O.A. (Ole), Asherson, P. (Philip), Banaschewski, T. (Tobias), Bargallo, N. (Nuria), Baumeister, S. (Sarah), Baur-Streubel, R. (Ramona), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Boomsma, D.I. (Dorret I.), Borgwardt, S. (Stefan), Bourque, J. (Josiane), Brandeis, D. (Daniel), Breier, A. (Alan), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan K.), Busatto, G.F. (Geraldo F.), Buckner, M., Calhoun, V.D. (Vince), Canales-Rodríguez, E.J. (Erick J.), Cannon, D.M. (Dara M.), Caseras, X. (Xavier), Castellanos, F.X. (Francisco X.), Cervenka, S. (Simon), Chaim-Avancini, T.M. (Tiffany M.), Ching, C.R.K. (Christopher), Chubar, V. (Victoria), Clark, V.P. (Vincent P.), Conrod, P. (Patricia), Conzelmann, A. (Annette), Crespo-Facorro, B. (Benedicto), Crivello, F. (Fabrice), Crone, E.A. (Eveline), Dale, A.M. (Anders), Davey, C.G. (Christopher), Geus, E.J.C. (Eco) de, Haan, L. (Lieuwe) de, Zubicaray, G.I. (Greig) de, Braber, A. (Anouk) den, Dickie, E.W. (Erin W.), Di Giorgio, A. (Annabella), Doan, N.T. (Nhat Trung), Dørum, E.S. (Erlend S.), Ehrlich, S.M. (Stefan), Erk, S., Espeseth, T. (Thomas), Fatouros-Bergman, H. (Helena), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Franke, B. (Barbara), Frodl, T. (Thomas), Fuentes-Claramonte, P. (Paola), Glahn, D.C. (David), Gotlib, I.H. (Ian H.), Grabe, H.J. (Hans Jörgen), Grimm, O. (Oliver), Groenewold, N.A. (Nynke A.), Grotegerd, D. (Dominik), Gruber, O. (Oliver), Gruner, P. (Patricia), Gur, R.E. (Rachel E.), Gur, R.C. (Ruben C.), Harrison, B.J. (Ben J.), Hartman, C.A. (Catharine A.), Hatton, W., Heinz, A. (Andreas), Heslenfeld, D.J. (Dirk), Hibar, D.P. (Derrek P.), Hickie, I.B. (Ian), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hohmann, S. (Sarah), Holmes, A.J. (Avram J.), Hoogman, M. (Martine), Hosten, N. (Norbert), Howells, F.M. (Fleur M.), Hulshoff Pol, H.E. (Hilleke E.), Huyser, J. (Jochanan), Jahanshad, N. (Neda), James, A., Jernigan, T.L. (Terry L.), Jiang, J. (Jiyang), Jönsson, E.G. (Erik G.), Joska, J.A. (John A.), Kahn, R. (Rene), Kalnin, A. (Andrew), Kanai, R. (Ryota), Klein, M. (Marieke), Klyushnik, T.P. (Tatyana P.), Koenders, L. (Laura), Koops, S. (Sanne), Krämer, B. (Bernd), Kuntsi, J. (Jonna), Lagopoulos, J. (Jim), Lázaro, L. (Luisa), Lebedeva, I. (Irina), Lee, W.H. (Won Hee), Lesch, K.-P. (Klaus-Peter), Lochner, C. (Christine), Machielsen, M.W.J. (Marise), Maingault, S. (Sophie), Martin, N.G. (Nicholas G.), Martínez-Zalacaín, I. (Ignacio), Mataix-Cols, D. (David), Mazoyer, B. (Bernard), McDonald, C. (Colm), McDonald, B.C. (Brenna C.), McIntosh, A.M. (Andrew), McMahon, K.L. (Katie L.), McPhilemy, G. (Genevieve), Menchón, J.M. (José M.), Medland, S.E. (Sarah), Meyer-Lindenberg, A. (Andreas), Naaijen, J. (Jilly), Najt, P. (Pablo), Nakao, T. (Tomohiro), Nordvik, J.E. (Jan E.), Nyberg, L. (Lisa), Oosterlaan, J. (Jaap), de la Foz, V.O.-G. (Víctor Ortiz-García), Paloyelis, Y. (Yannis), Pauli, P. (Paul), Pergola, G. (Giulio), Pomarol-Clotet, E. (Edith), Portella, M.J. (Maria J.), Potkin, S.G. (Steven G.), Radua, J. (Joaquim), Reif, A. (Andreas), Rinker, D.A. (Daniel A.), Roffman, J.L. (Joshua), Rosa, P.G.P. (Pedro G. P.), Sacchet, M.D. (Matthew D.), Sachdev, P.S. (Perminder), Salvador, R. (Raymond), Sánchez-Juan, P. (Pascual), Sarró, S. (Salvador), Satterthwaite, T.D. (Theodore), Saykin, A.J. (Andrew), Serpa, M.H. (Mauricio H.), Schmaal, L. (Lianne), Schnell, K. (Kerry), Schumann, G. (Gunter), Sim, K. (Kang), Smoller, J.W., Sommer, I. (Iris), Soriano-Mas, C. (Carles), Stein, D.J. (Dan J.), Strike, L.T. (Lachlan), Swagerman, S.C. (Suzanne C.), Tamnes, C.K. (Christian K.), Temmingh, H.S. (Henk S.), Thomopoulos, S.I. (Sophia I.), Tomyshev, A.S. (Alexander S.), Tordesillas-Gutierrez, D. (Diana), Trollor, J., Turner, J.A. (Jessica A.), Uhlmann, A. (Anne), Heuvel, O.A. (Odile A.), van den Meer, D. (Dennis), Wee, N.J. (Nic) van der, van Haren, N.E.M. (Neeltje E. M.), Ent, D. (Dennis) van 't, Erp, T.G.M. (Theo G.) van, Veer, I.M. (Ilya), Veltman, D.J. (Dick), Voineskos, A. (Aristotle), Völzke, H. (Henry), Walter, H. (Henrik), Walton, E. (Esther), Wang, L. (Lei), Wang, Y. (Yang), Wassink, A.M.J. (Annemarie), Weber, B. (Bernd), Wen, W. (Wei), West, J.D. (John D.), Westlye, L.T. (Lars), Whalley, H. (Heather), Wierenga, L.M. (Lara M.), Wittfeld, K. (Katharina), Wolf, D.H. (Daniel H.), Worker, A. (Amanda), Wright, M.J. (Margaret J.), Yang, K. (Kun), Yoncheva, Y. (Yulyia), Zanetti, M.V. (Marcus V.), Ziegler, G.C. (Georg C.), Thompson, P.M. (Paul), Dima, D. (Danai), Frangou, S. (Sophia), Modabbernia, A. (Amirhossein), Williams, S.C.R. (Steven C. R.), Papachristou, E. (Efstathios), Doucet, G.E. (Gaelle E.), Agartz, I. (Ingrid), Aghajani, M. (Moji), Akudjedu, T.N. (Theophilus N.), Albajes-Eizagirre, A. (Anton), Alnæs, D. (Dag), Alpert, K. (Kathryn), Andersson, M. (Micael), Andreasen, N.C. (Nancy C.), Andreassen, O.A. (Ole), Asherson, P. (Philip), Banaschewski, T. (Tobias), Bargallo, N. (Nuria), Baumeister, S. (Sarah), Baur-Streubel, R. (Ramona), Bertolino, A. (Alessandro), Bonvino, A. (Aurora), Boomsma, D.I. (Dorret I.), Borgwardt, S. (Stefan), Bourque, J. (Josiane), Brandeis, D. (Daniel), Breier, A. (Alan), Brodaty, H. (Henry), Brouwer, R.M. (Rachel), Buitelaar, J.K. (Jan K.), Busatto, G.F. (Geraldo F.), Buckner, M., Calhoun, V.D. (Vince), Canales-Rodríguez, E.J. (Erick J.), Cannon, D.M. (Dara M.), Caseras, X. (Xavier), Castellanos, F.X. (Francisco X.), Cervenka, S. (Simon), Chaim-Avancini, T.M. (Tiffany M.), Ching, C.R.K. (Christopher), Chubar, V. (Victoria), Clark, V.P. (Vincent P.), Conrod, P. (Patricia), Conzelmann, A. (Annette), Crespo-Facorro, B. (Benedicto), Crivello, F. (Fabrice), Crone, E.A. (Eveline), Dale, A.M. (Anders), Davey, C.G. (Christopher), Geus, E.J.C. (Eco) de, Haan, L. (Lieuwe) de, Zubicaray, G.I. (Greig) de, Braber, A. (Anouk) den, Dickie, E.W. (Erin W.), Di Giorgio, A. (Annabella), Doan, N.T. (Nhat Trung), Dørum, E.S. (Erlend S.), Ehrlich, S.M. (Stefan), Erk, S., Espeseth, T. (Thomas), Fatouros-Bergman, H. (Helena), Fisher, S.E. (Simon), Fouche, J.-P. (Jean-Paul), Franke, B. (Barbara), Frodl, T. (Thomas), Fuentes-Claramonte, P. (Paola), Glahn, D.C. (David), Gotlib, I.H. (Ian H.), Grabe, H.J. (Hans Jörgen), Grimm, O. (Oliver), Groenewold, N.A. (Nynke A.), Grotegerd, D. (Dominik), Gruber, O. (Oliver), Gruner, P. (Patricia), Gur, R.E. (Rachel E.), Gur, R.C. (Ruben C.), Harrison, B.J. (Ben J.), Hartman, C.A. (Catharine A.), Hatton, W., Heinz, A. (Andreas), Heslenfeld, D.J. (Dirk), Hibar, D.P. (Derrek P.), Hickie, I.B. (Ian), Ho, B.-C. (Beng-Choon), Hoekstra, P.J. (Pieter), Hohmann, S. (Sarah), Holmes, A.J. (Avram J.), Hoogman, M. (Martine), Hosten, N. (Norbert), Howells, F.M. (Fleur M.), Hulshoff Pol, H.E. (Hilleke E.), Huyser, J. (Jochanan), Jahanshad, N. (Neda), James, A., Jernigan, T.L. (Terry L.), Jiang, J. (Jiyang), Jönsson, E.G. (Erik G.), Joska, J.A. (John A.), Kahn, R. (Rene), Kalnin, A. (Andrew), Kanai, R. (Ryota), Klein, M. (Marieke), Klyushnik, T.P. (Tatyana P.), Koenders, L. (Laura), Koops, S. (Sanne), Krämer, B. (Bernd), Kuntsi, J. (Jonna), Lagopoulos, J. (Jim), Lázaro, L. (Luisa), Lebedeva, I. (Irina), Lee, W.H. (Won Hee), Lesch, K.-P. (Klaus-Peter), Lochner, C. (Christine), Machielsen, M.W.J. (Marise), Maingault, S. (Sophie), Martin, N.G. (Nicholas G.), Martínez-Zalacaín, I. (Ignacio), Mataix-Cols, D. (David), Mazoyer, B. (Bernard), McDonald, C. (Colm), McDonald, B.C. (Brenna C.), McIntosh, A.M. (Andrew), McMahon, K.L. (Katie L.), McPhilemy, G. (Genevieve), Menchón, J.M. (José M.), Medland, S.E. (Sarah), Meyer-Lindenberg, A. (Andreas), Naaijen, J. (Jilly), Najt, P. (Pablo), Nakao, T. (Tomohiro), Nordvik, J.E. (Jan E.), Nyberg, L. (Lisa), Oosterlaan, J. (Jaap), de la Foz, V.O.-G. (Víctor Ortiz-García), Paloyelis, Y. (Yannis), Pauli, P. (Paul), Pergola, G. (Giulio), Pomarol-Clotet, E. (Edith), Portella, M.J. (Maria J.), Potkin, S.G. (Steven G.), Radua, J. (Joaquim), Reif, A. (Andreas), Rinker, D.A. (Daniel A.), Roffman, J.L. (Joshua), Rosa, P.G.P. (Pedro G. P.), Sacchet, M.D. (Matthew D.), Sachdev, P.S. (Perminder), Salvador, R. (Raymond), Sánchez-Juan, P. (Pascual), Sarró, S. (Salvador), Satterthwaite, T.D. (Theodore), Saykin, A.J. (Andrew), Serpa, M.H. (Mauricio H.), Schmaal, L. (Lianne), Schnell, K. (Kerry), Schumann, G. (Gunter), Sim, K. (Kang), Smoller, J.W., Sommer, I. (Iris), Soriano-Mas, C. (Carles), Stein, D.J. (Dan J.), Strike, L.T. (Lachlan), Swagerman, S.C. (Suzanne C.), Tamnes, C.K. (Christian K.), Temmingh, H.S. (Henk S.), Thomopoulos, S.I. (Sophia I.), Tomyshev, A.S. (Alexander S.), Tordesillas-Gutierrez, D. (Diana), Trollor, J., Turner, J.A. (Jessica A.), Uhlmann, A. (Anne), Heuvel, O.A. (Odile A.), van den Meer, D. (Dennis), Wee, N.J. (Nic) van der, van Haren, N.E.M. (Neeltje E. M.), Ent, D. (Dennis) van 't, Erp, T.G.M. (Theo G.) van, Veer, I.M. (Ilya), Veltman, D.J. (Dick), Voineskos, A. (Aristotle), Völzke, H. (Henry), Walter, H. (Henrik), Walton, E. (Esther), Wang, L. (Lei), Wang, Y. (Yang), Wassink, A.M.J. (Annemarie), Weber, B. (Bernd), Wen, W. (Wei), West, J.D. (John D.), Westlye, L.T. (Lars), Whalley, H. (Heather), Wierenga, L.M. (Lara M.), Wittfeld, K. (Katharina), Wolf, D.H. (Daniel H.), Worker, A. (Amanda), Wright, M.J. (Margaret J.), Yang, K. (Kun), Yoncheva, Y. (Yulyia), Zanetti, M.V. (Marcus V.), Ziegler, G.C. (Georg C.), Thompson, P.M. (Paul), and Dima, D. (Danai)
Abstract: Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
Published: 2021
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45. Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis

Author: Jalbrzikowski, M., Jalbrzikowski, M., Hayes, R.A., Wood, S.J., Nordholm, D., Zhou, J.H., Fusar-Poli, P., Uhlhaas, P.J., Takahashi, T., Sugranyes, G., Kwak, Y.B., Mathalon, D.H., Katagiri, N., Hooker, C.I., Smigielski, L., Colibazzi, T., Via, E., Tang, J.S., Koike, S., Rasser, P.E., Michel, C., Lebedeva, I., Hegelstad, W.T., de la Fuente-Sandoval, C., Waltz, J.A., Mizrahi, R., Corcoran, C.M., Resch, F., Tamnes, C.K., Haas, S.S., Lemmers-Jansen, I.L.J., Agartz, I., Allen, P., Amminger, G.P., Andreassen, O.A., Atkinson, K., Bachman, P., Baeza, I., Baldwin, H., Bartholomeusz, C.F., Borgwardt, S., Catalano, S., Chee, M.W.L., Chen, X.G., Cho, K.I.K., Cooper, R.E., Cropley, V.L., Dolz, M., Ebdrup, B.H., Fortea, A., Glenthoj, L.B., ENIGMA Clinical High Risk for Psychosis Working Group, Hernaus, Dennis, van Amelsvoort, Thérèse, Jalbrzikowski, M., Jalbrzikowski, M., Hayes, R.A., Wood, S.J., Nordholm, D., Zhou, J.H., Fusar-Poli, P., Uhlhaas, P.J., Takahashi, T., Sugranyes, G., Kwak, Y.B., Mathalon, D.H., Katagiri, N., Hooker, C.I., Smigielski, L., Colibazzi, T., Via, E., Tang, J.S., Koike, S., Rasser, P.E., Michel, C., Lebedeva, I., Hegelstad, W.T., de la Fuente-Sandoval, C., Waltz, J.A., Mizrahi, R., Corcoran, C.M., Resch, F., Tamnes, C.K., Haas, S.S., Lemmers-Jansen, I.L.J., Agartz, I., Allen, P., Amminger, G.P., Andreassen, O.A., Atkinson, K., Bachman, P., Baeza, I., Baldwin, H., Bartholomeusz, C.F., Borgwardt, S., Catalano, S., Chee, M.W.L., Chen, X.G., Cho, K.I.K., Cooper, R.E., Cropley, V.L., Dolz, M., Ebdrup, B.H., Fortea, A., Glenthoj, L.B., ENIGMA Clinical High Risk for Psychosis Working Group, Hernaus, Dennis, and van Amelsvoort, Thérèse
Abstract: IMPORTANCE The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.OBJECTIVE To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).DESIGN, SETTING, AND PARTICIPANTS In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.MAIN OUTCOMES AND MEASURES Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).RESULTS Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in t
Published: 2021

46. Association of Structural Magnetic Resonance Imaging Measures with Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis

Author: Jalbrzikowski, M, Hayes, RA, Wood, SJ, Nordholm, D, Zhou, JH, Fusar-Poli, P, Uhlhaas, PJ, Takahashi, T, Sugranyes, G, Kwak, YB, Mathalon, DH, Katagiri, N, Hooker, CI, Smigielski, L, Colibazzi, T, Via, E, Tang, J, Koike, S, Rasser, PE, Michel, C, Lebedeva, I, Hegelstad, WTV, De La Fuente-Sandoval, C, Waltz, JA, Mizrahi, R, Corcoran, CM, Resch, F, Tamnes, CK, Haas, SS, Lemmers-Jansen, ILJ, Agartz, I, Allen, P, Amminger, GP, Andreassen, OA, Atkinson, K, Bachman, P, Baeza, I, Baldwin, H, Bartholomeusz, CF, Borgwardt, S, Catalano, S, Chee, MWL, Chen, X, Cho, KIK, Cooper, RE, Cropley, VL, Dolz, M, Ebdrup, BH, Fortea, A, Glenthøj, LB, Glenthøj, BY, De Haan, L, Hamilton, HK, Harris, MA, Haut, KM, He, Y, Heekeren, K, Heinz, A, Hubl, D, Hwang, WJ, Kaess, M, Kasai, K, Kim, M, Kindler, J, Klaunig, MJ, Koppel, A, Kristensen, TD, Kwon, JS, Lawrie, SM, Lee, J, León-Ortiz, P, Lin, A, Loewy, RL, Ma, X, McGorry, P, McGuire, P, Mizuno, M, Møller, P, Moncada-Habib, T, Muñoz-Samons, D, Nelson, B, Nemoto, T, Nordentoft, M, Omelchenko, MA, Oppedal, K, Ouyang, L, Pantelis, C, Pariente, JC, Raghava, JM, Reyes-Madrigal, F, Roach, BJ, Røssberg, JI, Rössler, W, Salisbury, DF, Sasabayashi, D, Schall, U, Schiffman, J, Schlagenhauf, F, Schmidt, A, Sørensen, ME, Yung, Alison, Jalbrzikowski, M, Hayes, RA, Wood, SJ, Nordholm, D, Zhou, JH, Fusar-Poli, P, Uhlhaas, PJ, Takahashi, T, Sugranyes, G, Kwak, YB, Mathalon, DH, Katagiri, N, Hooker, CI, Smigielski, L, Colibazzi, T, Via, E, Tang, J, Koike, S, Rasser, PE, Michel, C, Lebedeva, I, Hegelstad, WTV, De La Fuente-Sandoval, C, Waltz, JA, Mizrahi, R, Corcoran, CM, Resch, F, Tamnes, CK, Haas, SS, Lemmers-Jansen, ILJ, Agartz, I, Allen, P, Amminger, GP, Andreassen, OA, Atkinson, K, Bachman, P, Baeza, I, Baldwin, H, Bartholomeusz, CF, Borgwardt, S, Catalano, S, Chee, MWL, Chen, X, Cho, KIK, Cooper, RE, Cropley, VL, Dolz, M, Ebdrup, BH, Fortea, A, Glenthøj, LB, Glenthøj, BY, De Haan, L, Hamilton, HK, Harris, MA, Haut, KM, He, Y, Heekeren, K, Heinz, A, Hubl, D, Hwang, WJ, Kaess, M, Kasai, K, Kim, M, Kindler, J, Klaunig, MJ, Koppel, A, Kristensen, TD, Kwon, JS, Lawrie, SM, Lee, J, León-Ortiz, P, Lin, A, Loewy, RL, Ma, X, McGorry, P, McGuire, P, Mizuno, M, Møller, P, Moncada-Habib, T, Muñoz-Samons, D, Nelson, B, Nemoto, T, Nordentoft, M, Omelchenko, MA, Oppedal, K, Ouyang, L, Pantelis, C, Pariente, JC, Raghava, JM, Reyes-Madrigal, F, Roach, BJ, Røssberg, JI, Rössler, W, Salisbury, DF, Sasabayashi, D, Schall, U, Schiffman, J, Schlagenhauf, F, Schmidt, A, Sørensen, ME, and Yung, Alison
Published: 2021

47. 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Author: Sonderby, IE, van der Meer, D, Moreau, C, Kaufmann, T, Walters, GB, Ellegaard, M, Abdellaoui, A, Ames, D, Amunts, K, Andersson, M, Armstrong, NJ, Bernard, M, Blackburn, NB, Blangero, J, Boomsma, DI, Brodaty, H, Brouwer, RM, Buelow, R, Boen, R, Cahn, W, Calhoun, VD, Caspers, S, Ching, CRK, Cichon, S, Ciufolini, S, Crespo-Facorro, B, Curran, JE, Dale, AM, Dalvie, S, Dazzan, P, de Geus, EJC, de Zubicaray, GI, de Zwarte, SMC, Desrivieres, S, Doherty, JL, Donohoe, G, Draganski, B, Ehrlich, S, Eising, E, Espeseth, T, Fejgin, K, Fisher, SE, Fladby, T, Frei, O, Frouin, V, Fukunaga, M, Gareau, T, Ge, T, Glahn, DC, Grabe, HJ, Groenewold, NA, Gustafsson, O, Haavik, J, Haberg, AK, Hall, J, Hashimoto, R, Hehir-Kwa, JY, Hibar, DP, Hillegers, MHJ, Hoffmann, P, Holleran, L, Holmes, AJ, Homuth, G, Hottenga, J-J, Hulshoff Pol, HE, Ikeda, M, Jahanshad, N, Jockwitz, C, Johansson, S, Joensson, EG, Jorgensen, NR, Kikuchi, M, Knowles, EEM, Kumar, K, Le Hellard, S, Leu, C, Linden, DEJ, Liu, J, Lundervold, A, Lundervold, AJ, Maillard, AM, Martin, NG, Martin-Brevet, S, Mather, KA, Mathias, SR, McMahon, KL, McRae, AF, Medland, SE, Meyer-Lindenberg, A, Moberget, T, Modenato, C, Sanchez, JM, Morris, DW, Muehleisen, TW, Murray, RM, Nielsen, J, Nordvik, JE, Nyberg, L, Loohuis, LMO, Ophoff, RA, Owen, MJ, Paus, T, Pausova, Z, Peralta, JM, Pike, GB, Prieto, C, Quinlan, EB, Reinbold, CS, Marques, TR, Rucker, JJH, Sachdev, PS, Sando, SB, Schofield, PR, Schork, AJ, Schumann, G, Shin, J, Shumskaya, E, Silva, AI, Sisodiya, SM, Steen, VM, Stein, DJ, Strike, LT, Suzuki, IK, Tamnes, CK, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Uhlmann, A, Ulfarsson, MO, van 't Ent, D, van den Bree, MBM, Vanderhaeghen, P, Vassos, E, Wen, W, Wittfeld, K, Wright, MJ, Agartz, I, Djurovic, S, Westlye, LT, Stefansson, H, Stefansson, K, Jacquemont, S, Thompson, PM, Andreassen, OA, Sonderby, IE, van der Meer, D, Moreau, C, Kaufmann, T, Walters, GB, Ellegaard, M, Abdellaoui, A, Ames, D, Amunts, K, Andersson, M, Armstrong, NJ, Bernard, M, Blackburn, NB, Blangero, J, Boomsma, DI, Brodaty, H, Brouwer, RM, Buelow, R, Boen, R, Cahn, W, Calhoun, VD, Caspers, S, Ching, CRK, Cichon, S, Ciufolini, S, Crespo-Facorro, B, Curran, JE, Dale, AM, Dalvie, S, Dazzan, P, de Geus, EJC, de Zubicaray, GI, de Zwarte, SMC, Desrivieres, S, Doherty, JL, Donohoe, G, Draganski, B, Ehrlich, S, Eising, E, Espeseth, T, Fejgin, K, Fisher, SE, Fladby, T, Frei, O, Frouin, V, Fukunaga, M, Gareau, T, Ge, T, Glahn, DC, Grabe, HJ, Groenewold, NA, Gustafsson, O, Haavik, J, Haberg, AK, Hall, J, Hashimoto, R, Hehir-Kwa, JY, Hibar, DP, Hillegers, MHJ, Hoffmann, P, Holleran, L, Holmes, AJ, Homuth, G, Hottenga, J-J, Hulshoff Pol, HE, Ikeda, M, Jahanshad, N, Jockwitz, C, Johansson, S, Joensson, EG, Jorgensen, NR, Kikuchi, M, Knowles, EEM, Kumar, K, Le Hellard, S, Leu, C, Linden, DEJ, Liu, J, Lundervold, A, Lundervold, AJ, Maillard, AM, Martin, NG, Martin-Brevet, S, Mather, KA, Mathias, SR, McMahon, KL, McRae, AF, Medland, SE, Meyer-Lindenberg, A, Moberget, T, Modenato, C, Sanchez, JM, Morris, DW, Muehleisen, TW, Murray, RM, Nielsen, J, Nordvik, JE, Nyberg, L, Loohuis, LMO, Ophoff, RA, Owen, MJ, Paus, T, Pausova, Z, Peralta, JM, Pike, GB, Prieto, C, Quinlan, EB, Reinbold, CS, Marques, TR, Rucker, JJH, Sachdev, PS, Sando, SB, Schofield, PR, Schork, AJ, Schumann, G, Shin, J, Shumskaya, E, Silva, AI, Sisodiya, SM, Steen, VM, Stein, DJ, Strike, LT, Suzuki, IK, Tamnes, CK, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Uhlmann, A, Ulfarsson, MO, van 't Ent, D, van den Bree, MBM, Vanderhaeghen, P, Vassos, E, Wen, W, Wittfeld, K, Wright, MJ, Agartz, I, Djurovic, S, Westlye, LT, Stefansson, H, Stefansson, K, Jacquemont, S, Thompson, PM, and Andreassen, OA
Abstract: Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
Published: 2021

48. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author: Mullins, N, Kang, J, Campos, A, Coleman, JR, Edwards, AC, Galfalvy, H, Levey, DF, Lori, A, Shabalin, A, Starnawska, A, Su, M-H, Watson, HJ, Adams, M, Awasthi, S, Ganda, M, Hafferty, JD, Hishimoto, A, Kim, M, Okazaki, S, Otsuka, I, Ripke, S, Ware, EB, Bergen, AW, Berrettini, WH, Bohus, M, Brandt, H, Chang, X, Chen, WJ, Chen, H-C, Crawford, S, Crow, S, DiBlasi, E, Duriez, P, Fernandez-Aranda, F, Fichter, MM, Gallinger, S, Glatt, SJ, Gorwood, P, Guo, Y, Hakonarson, H, Halmi, KA, Hwu, H-G, Jain, S, Jamain, S, Jimenez-Murcia, S, Johnson, C, Kaplan, AS, Kaye, WH, Keel, PK, Kennedy, JL, Klump, KL, Li, D, Liao, S-C, Lieb, K, Lilenfeld, L, Liu, C-M, Magistretti, PJ, Marshall, CR, Mitchell, JE, Monson, ET, Myers, RM, Pinto, D, Powers, A, Ramoz, N, Roepke, S, Rozanov, V, Scherer, SW, Schmahl, C, Sokolowski, M, Strober, M, Thornton, LM, Treasure, J, Tsuang, MT, Witt, SH, Woodside, DB, Yilmaz, Z, Zillich, L, Adolfsson, R, Agartz, I, Air, TM, Alda, M, Alfredsson, L, Andreassen, OA, Anjorin, A, Appadurai, V, Artigas, MS, Van der Auwera, S, Azevedo, MH, Bass, N, Bau, CHD, Baune, BT, Bellivier, F, Berger, K, Biernacka, JM, Bigdeli, TB, Binder, EB, Boehnke, M, Boks, MP, Bosch, R, Braff, DL, Bryant, R, Budde, M, Byrne, EM, Cahn, W, Casas, M, Castelao, E, Cervilla, JA, Chaumette, B, Cichon, S, Corvin, A, Craddock, N, Craig, D, Degenhardt, F, Djurovic, S, Edenberg, HJ, Fanous, AH, Foo, JC, Forstner, AJ, Frye, M, Fullerton, JM, Gatt, JM, Gejman, P, Giegling, I, Grabe, HJ, Green, MJ, Grevet, EH, Grigoroiu-Serbanescu, M, Gutierrez, B, Guzman-Parra, J, Hamilton, SP, Hamshere, ML, Hartmann, A, Hauser, J, Heilmann-Heimbach, S, Hoffmann, P, Ising, M, Jones, I, Jones, LA, Jonsson, L, Kahn, RS, Kelsoe, JR, Kendler, KS, Kloiber, S, Koenen, KC, Kogevinas, M, Konte, B, Krebs, M-O, Lander, M, Lawrence, J, Leboyer, M, Lee, PH, Levinson, DF, Liao, C, Lissowska, J, Lucae, S, Mayoral, F, McElroy, SL, McGrath, P, McGuffin, P, McQuillin, A, Medland, SE, Mehta, D, Melle, I, Milaneschi, Y, Mitchell, PB, Molina, E, Morken, G, Mortensen, PB, Mueller-Myhsok, B, Nievergelt, C, Nimgaonkar, V, Noethen, MM, O'Donovan, MC, Ophoff, RA, Owen, MJ, Pato, C, Pato, MT, Penninx, BWJH, Pimm, J, Pistis, G, Potash, JB, Power, RA, Preisig, M, Quested, D, Ramos-Quiroga, JA, Reif, A, Ribases, M, Richarte, V, Rietschel, M, Rivera, M, Roberts, A, Roberts, G, Rouleau, GA, Rovaris, DL, Rujescu, D, Sanchez-Mora, C, Sanders, AR, Schofield, PR, Schulze, TG, Scott, LJ, Serretti, A, Shi, J, Shyn, S, Sirignano, L, Sklar, P, Smeland, OB, Smoller, JW, Sonuga-Barke, EJS, Spalletta, G, Strauss, JS, Swiatkowska, B, Trzaskowski, M, Turecki, G, Vilar-Ribo, L, Vincent, JB, Voelzke, H, Walters, JTR, Weickert, CS, Weickert, TW, Weissman, MM, Williams, LM, Wray, NR, Zai, CC, Ashley-Koch, AE, Beckham, JC, Hauser, ER, Hauser, MA, Kimbrel, NA, Lindquist, JH, McMahon, B, Oslin, DW, Qin, X, Agerbo, E, Borglum, AD, Breen, G, Erlangsen, A, Esko, T, Gelernter, J, Hougaard, DM, Kessler, RC, Kranzler, HR, Li, QS, Martin, NG, McIntosh, AM, Mors, O, Nordentoft, M, Olsen, CM, Porteous, D, Ursano, RJ, Wasserman, D, Werge, T, Whiteman, DC, Bulik, CM, Coon, H, Demontis, D, Docherty, AR, Kuo, P-H, Lewis, CM, Mann, JJ, Renteria, ME, Smith, DJ, Stahl, EA, Stein, MB, Streit, F, Willour, V, Ruderfer, DM, Mullins, N, Kang, J, Campos, A, Coleman, JR, Edwards, AC, Galfalvy, H, Levey, DF, Lori, A, Shabalin, A, Starnawska, A, Su, M-H, Watson, HJ, Adams, M, Awasthi, S, Ganda, M, Hafferty, JD, Hishimoto, A, Kim, M, Okazaki, S, Otsuka, I, Ripke, S, Ware, EB, Bergen, AW, Berrettini, WH, Bohus, M, Brandt, H, Chang, X, Chen, WJ, Chen, H-C, Crawford, S, Crow, S, DiBlasi, E, Duriez, P, Fernandez-Aranda, F, Fichter, MM, Gallinger, S, Glatt, SJ, Gorwood, P, Guo, Y, Hakonarson, H, Halmi, KA, Hwu, H-G, Jain, S, Jamain, S, Jimenez-Murcia, S, Johnson, C, Kaplan, AS, Kaye, WH, Keel, PK, Kennedy, JL, Klump, KL, Li, D, Liao, S-C, Lieb, K, Lilenfeld, L, Liu, C-M, Magistretti, PJ, Marshall, CR, Mitchell, JE, Monson, ET, Myers, RM, Pinto, D, Powers, A, Ramoz, N, Roepke, S, Rozanov, V, Scherer, SW, Schmahl, C, Sokolowski, M, Strober, M, Thornton, LM, Treasure, J, Tsuang, MT, Witt, SH, Woodside, DB, Yilmaz, Z, Zillich, L, Adolfsson, R, Agartz, I, Air, TM, Alda, M, Alfredsson, L, Andreassen, OA, Anjorin, A, Appadurai, V, Artigas, MS, Van der Auwera, S, Azevedo, MH, Bass, N, Bau, CHD, Baune, BT, Bellivier, F, Berger, K, Biernacka, JM, Bigdeli, TB, Binder, EB, Boehnke, M, Boks, MP, Bosch, R, Braff, DL, Bryant, R, Budde, M, Byrne, EM, Cahn, W, Casas, M, Castelao, E, Cervilla, JA, Chaumette, B, Cichon, S, Corvin, A, Craddock, N, Craig, D, Degenhardt, F, Djurovic, S, Edenberg, HJ, Fanous, AH, Foo, JC, Forstner, AJ, Frye, M, Fullerton, JM, Gatt, JM, Gejman, P, Giegling, I, Grabe, HJ, Green, MJ, Grevet, EH, Grigoroiu-Serbanescu, M, Gutierrez, B, Guzman-Parra, J, Hamilton, SP, Hamshere, ML, Hartmann, A, Hauser, J, Heilmann-Heimbach, S, Hoffmann, P, Ising, M, Jones, I, Jones, LA, Jonsson, L, Kahn, RS, Kelsoe, JR, Kendler, KS, Kloiber, S, Koenen, KC, Kogevinas, M, Konte, B, Krebs, M-O, Lander, M, Lawrence, J, Leboyer, M, Lee, PH, Levinson, DF, Liao, C, Lissowska, J, Lucae, S, Mayoral, F, McElroy, SL, McGrath, P, McGuffin, P, McQuillin, A, Medland, SE, Mehta, D, Melle, I, Milaneschi, Y, Mitchell, PB, Molina, E, Morken, G, Mortensen, PB, Mueller-Myhsok, B, Nievergelt, C, Nimgaonkar, V, Noethen, MM, O'Donovan, MC, Ophoff, RA, Owen, MJ, Pato, C, Pato, MT, Penninx, BWJH, Pimm, J, Pistis, G, Potash, JB, Power, RA, Preisig, M, Quested, D, Ramos-Quiroga, JA, Reif, A, Ribases, M, Richarte, V, Rietschel, M, Rivera, M, Roberts, A, Roberts, G, Rouleau, GA, Rovaris, DL, Rujescu, D, Sanchez-Mora, C, Sanders, AR, Schofield, PR, Schulze, TG, Scott, LJ, Serretti, A, Shi, J, Shyn, S, Sirignano, L, Sklar, P, Smeland, OB, Smoller, JW, Sonuga-Barke, EJS, Spalletta, G, Strauss, JS, Swiatkowska, B, Trzaskowski, M, Turecki, G, Vilar-Ribo, L, Vincent, JB, Voelzke, H, Walters, JTR, Weickert, CS, Weickert, TW, Weissman, MM, Williams, LM, Wray, NR, Zai, CC, Ashley-Koch, AE, Beckham, JC, Hauser, ER, Hauser, MA, Kimbrel, NA, Lindquist, JH, McMahon, B, Oslin, DW, Qin, X, Agerbo, E, Borglum, AD, Breen, G, Erlangsen, A, Esko, T, Gelernter, J, Hougaard, DM, Kessler, RC, Kranzler, HR, Li, QS, Martin, NG, McIntosh, AM, Mors, O, Nordentoft, M, Olsen, CM, Porteous, D, Ursano, RJ, Wasserman, D, Werge, T, Whiteman, DC, Bulik, CM, Coon, H, Demontis, D, Docherty, AR, Kuo, P-H, Lewis, CM, Mann, JJ, Renteria, ME, Smith, DJ, Stahl, EA, Stein, MB, Streit, F, Willour, V, and Ruderfer, DM
Abstract: BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
Published: 2021

49. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author: Mullins, N, Forstner, AJ, O'Connell, KS, Coombes, B, Coleman, JR, Qiao, Z, Als, TD, Bigdeli, TB, Borte, S, Bryois, J, Charney, AW, Drange, OK, Gandal, MJ, Hagenaars, SP, Ikeda, M, Kamitaki, N, Kim, M, Krebs, K, Panagiotaropoulou, G, Schilder, BM, Sloofman, LG, Steinberg, S, Trubetskoy, V, Winsvold, BS, Won, H-H, Abramova, L, Adorjan, K, Agerbo, E, Al Eissa, M, Albani, D, Alliey-Rodriguez, N, Anjorin, A, Antilla, V, Antoniou, A, Awasthi, S, Baek, JH, Baekvad-Hansen, M, Bass, N, Bauer, M, Beins, EC, Bergen, SE, Birner, A, Pedersen, CB, Boen, E, Boks, MP, Bosch, R, Brum, M, Brumpton, BM, Brunkhorst-Kanaan, N, Budde, M, Bybjerg-Grauholm, J, Byerley, W, Cairns, M, Casas, M, Cervantes, P, Clarke, T-K, Cruceanu, C, Cuellar-Barboza, A, Cunningham, J, Curtis, D, Czerski, PM, Dale, AM, Dalkner, N, David, FS, Degenhardt, F, Djurovic, S, Dobbyn, AL, Douzenis, A, Elvsashagen, T, Escott-Price, V, Ferrier, IN, Fiorentino, A, Foroud, TM, Forty, L, Frank, J, Frei, O, Freimer, NB, Frisen, L, Gade, K, Garnham, J, Gelernter, J, Pedersen, MG, Gizer, IR, Gordon, SD, Gordon-Smith, K, Greenwood, TA, Grove, J, Guzman-Parra, J, Ha, K, Haraldsson, M, Hautzinger, M, Heilbronner, U, Hellgren, D, Herms, S, Hoffmann, P, Holmans, PA, Huckins, L, Jamain, S, Johnson, JS, Kalman, JL, Kamatani, Y, Kennedy, JL, Kittel-Schneider, S, Knowles, JA, Kogevinas, M, Koromina, M, Kranz, TM, Kranzler, HR, Kubo, M, Kupka, R, Kushner, SA, Lavebratt, C, Lawrence, J, Leber, M, Lee, H-J, Lee, PH, Levy, SE, Lewis, C, Liao, C, Lucae, S, Lundberg, M, MacIntyre, DJ, Maier, W, Maihofer, A, Malaspina, D, Maratou, E, Martinsson, L, Mattheisen, M, McCarroll, SA, McGregor, NW, McGuffin, P, McKay, JD, Medeiros, H, Medland, SE, Millischer, V, Montgomery, GW, Moran, JL, Morris, DW, Muhleisen, TW, O'Brien, N, O'Donovan, C, Loohuis, LMO, Oruc, L, Papiol, S, Pardinas, AF, Perry, A, Pfennig, A, Porichi, E, Potash, JB, Quested, D, Raj, T, Rapaport, MH, DePaulo, JR, Regeer, EJ, Rice, JP, Rivas, F, Rivera, M, Roth, J, Roussos, P, Ruderfer, DM, Sanchez-Mora, C, Schulte, EC, Senner, F, Sharp, S, Shilling, PD, Sigurdsson, E, Sirignano, L, Slaney, C, Smeland, OB, Sobell, JL, Hansen, CS, Artigas, MS, Spijker, AT, Stein, DJ, Strauss, JS, Swiatkowska, B, Terao, C, Thorgeirsson, TE, Toma, C, Tooney, P, Tsermpini, E-E, Vawter, MP, Vedder, H, Walters, JTR, Witt, SH, Xi, S, Xu, W, Yang, JMK, Young, AH, Young, H, Zandi, PP, Zhou, H, Zillich, L, Adolfsson, R, Agartz, I, Alda, M, Alfredsson, L, Babadjanova, G, Backlund, L, Baune, BT, Bellivier, F, Bengesser, S, Berrettini, WH, Blackwood, DHR, Boehnke, M, Borglum, AD, Breen, G, Carr, VJ, Catts, S, Corvin, A, Craddock, N, Dannlowski, U, Dikeos, D, Esko, T, Etain, B, Ferentinos, P, Frye, M, Fullerton, JM, Gawlik, M, Gershon, ES, Goes, F, Green, MJ, Grigoroiu-Serbanescu, M, Hauser, J, Henskens, F, Hillert, J, Hong, KS, Hougaard, DM, Hultman, CM, Hveem, K, Iwata, N, Jablensky, A, Jones, I, Jones, LA, Kahn, RS, Kelsoe, JR, Kirov, G, Landen, M, Leboyer, M, Lewis, CM, Li, QS, Lissowska, J, Lochner, C, Loughland, C, Martin, NG, Mathews, CA, Mayoral, F, McElroy, SL, McIntosh, AM, McMahon, FJ, Melle, I, Michie, P, Milani, L, Mitchell, PB, Morken, G, Mors, O, Mortensen, PB, Mowry, B, Muller-Myhsok, B, Myers, RM, Neale, BM, Nievergelt, CM, Nordentoft, M, Nothen, MM, ODonovan, MC, Oedegaard, KJ, Olsson, T, Owen, MJ, Paciga, SA, Pantelis, C, Pato, C, Pato, MT, Patrinos, GP, Perlis, RH, Posthuma, D, Ramos-Quiroga, JA, Reif, A, Reininghaus, EZ, Ribases, M, Rietschel, M, Ripke, S, Rouleau, GA, Saito, T, Schall, U, Schalling, M, Schofield, PR, Schulze, TG, Scott, LJ, Scott, RJ, Serretti, A, Weickert, CS, Smoller, JW, Stefansson, H, Stefansson, K, Stordal, E, Streit, F, Sullivan, PF, Turecki, G, Vaaler, AE, Vieta, E, Vincent, JB, Waldman, ID, Weickert, TW, Werge, T, Wray, NR, Zwart, J, Biernacka, JM, Nurnberger, J, Cichon, S, Edenberg, HJ, Stahl, EA, McQuillin, A, Di Florio, A, Ophoff, RA, Andreassen, OA, Mullins, N, Forstner, AJ, O'Connell, KS, Coombes, B, Coleman, JR, Qiao, Z, Als, TD, Bigdeli, TB, Borte, S, Bryois, J, Charney, AW, Drange, OK, Gandal, MJ, Hagenaars, SP, Ikeda, M, Kamitaki, N, Kim, M, Krebs, K, Panagiotaropoulou, G, Schilder, BM, Sloofman, LG, Steinberg, S, Trubetskoy, V, Winsvold, BS, Won, H-H, Abramova, L, Adorjan, K, Agerbo, E, Al Eissa, M, Albani, D, Alliey-Rodriguez, N, Anjorin, A, Antilla, V, Antoniou, A, Awasthi, S, Baek, JH, Baekvad-Hansen, M, Bass, N, Bauer, M, Beins, EC, Bergen, SE, Birner, A, Pedersen, CB, Boen, E, Boks, MP, Bosch, R, Brum, M, Brumpton, BM, Brunkhorst-Kanaan, N, Budde, M, Bybjerg-Grauholm, J, Byerley, W, Cairns, M, Casas, M, Cervantes, P, Clarke, T-K, Cruceanu, C, Cuellar-Barboza, A, Cunningham, J, Curtis, D, Czerski, PM, Dale, AM, Dalkner, N, David, FS, Degenhardt, F, Djurovic, S, Dobbyn, AL, Douzenis, A, Elvsashagen, T, Escott-Price, V, Ferrier, IN, Fiorentino, A, Foroud, TM, Forty, L, Frank, J, Frei, O, Freimer, NB, Frisen, L, Gade, K, Garnham, J, Gelernter, J, Pedersen, MG, Gizer, IR, Gordon, SD, Gordon-Smith, K, Greenwood, TA, Grove, J, Guzman-Parra, J, Ha, K, Haraldsson, M, Hautzinger, M, Heilbronner, U, Hellgren, D, Herms, S, Hoffmann, P, Holmans, PA, Huckins, L, Jamain, S, Johnson, JS, Kalman, JL, Kamatani, Y, Kennedy, JL, Kittel-Schneider, S, Knowles, JA, Kogevinas, M, Koromina, M, Kranz, TM, Kranzler, HR, Kubo, M, Kupka, R, Kushner, SA, Lavebratt, C, Lawrence, J, Leber, M, Lee, H-J, Lee, PH, Levy, SE, Lewis, C, Liao, C, Lucae, S, Lundberg, M, MacIntyre, DJ, Maier, W, Maihofer, A, Malaspina, D, Maratou, E, Martinsson, L, Mattheisen, M, McCarroll, SA, McGregor, NW, McGuffin, P, McKay, JD, Medeiros, H, Medland, SE, Millischer, V, Montgomery, GW, Moran, JL, Morris, DW, Muhleisen, TW, O'Brien, N, O'Donovan, C, Loohuis, LMO, Oruc, L, Papiol, S, Pardinas, AF, Perry, A, Pfennig, A, Porichi, E, Potash, JB, Quested, D, Raj, T, Rapaport, MH, DePaulo, JR, Regeer, EJ, Rice, JP, Rivas, F, Rivera, M, Roth, J, Roussos, P, Ruderfer, DM, Sanchez-Mora, C, Schulte, EC, Senner, F, Sharp, S, Shilling, PD, Sigurdsson, E, Sirignano, L, Slaney, C, Smeland, OB, Sobell, JL, Hansen, CS, Artigas, MS, Spijker, AT, Stein, DJ, Strauss, JS, Swiatkowska, B, Terao, C, Thorgeirsson, TE, Toma, C, Tooney, P, Tsermpini, E-E, Vawter, MP, Vedder, H, Walters, JTR, Witt, SH, Xi, S, Xu, W, Yang, JMK, Young, AH, Young, H, Zandi, PP, Zhou, H, Zillich, L, Adolfsson, R, Agartz, I, Alda, M, Alfredsson, L, Babadjanova, G, Backlund, L, Baune, BT, Bellivier, F, Bengesser, S, Berrettini, WH, Blackwood, DHR, Boehnke, M, Borglum, AD, Breen, G, Carr, VJ, Catts, S, Corvin, A, Craddock, N, Dannlowski, U, Dikeos, D, Esko, T, Etain, B, Ferentinos, P, Frye, M, Fullerton, JM, Gawlik, M, Gershon, ES, Goes, F, Green, MJ, Grigoroiu-Serbanescu, M, Hauser, J, Henskens, F, Hillert, J, Hong, KS, Hougaard, DM, Hultman, CM, Hveem, K, Iwata, N, Jablensky, A, Jones, I, Jones, LA, Kahn, RS, Kelsoe, JR, Kirov, G, Landen, M, Leboyer, M, Lewis, CM, Li, QS, Lissowska, J, Lochner, C, Loughland, C, Martin, NG, Mathews, CA, Mayoral, F, McElroy, SL, McIntosh, AM, McMahon, FJ, Melle, I, Michie, P, Milani, L, Mitchell, PB, Morken, G, Mors, O, Mortensen, PB, Mowry, B, Muller-Myhsok, B, Myers, RM, Neale, BM, Nievergelt, CM, Nordentoft, M, Nothen, MM, ODonovan, MC, Oedegaard, KJ, Olsson, T, Owen, MJ, Paciga, SA, Pantelis, C, Pato, C, Pato, MT, Patrinos, GP, Perlis, RH, Posthuma, D, Ramos-Quiroga, JA, Reif, A, Reininghaus, EZ, Ribases, M, Rietschel, M, Ripke, S, Rouleau, GA, Saito, T, Schall, U, Schalling, M, Schofield, PR, Schulze, TG, Scott, LJ, Scott, RJ, Serretti, A, Weickert, CS, Smoller, JW, Stefansson, H, Stefansson, K, Stordal, E, Streit, F, Sullivan, PF, Turecki, G, Vaaler, AE, Vieta, E, Vincent, JB, Waldman, ID, Weickert, TW, Werge, T, Wray, NR, Zwart, J, Biernacka, JM, Nurnberger, J, Cichon, S, Edenberg, HJ, Stahl, EA, McQuillin, A, Di Florio, A, Ophoff, RA, and Andreassen, OA
Abstract: Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
Published: 2021

50. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years

Author: Dima, D, Modabbernia, A, Papachristou, E, Doucet, GE, Agartz, I, Aghajani, M, Akudjedu, TN, Albajes-Eizagirre, A, Alnaes, D, Alpert, K, Andersson, M, Andreasen, NC, Andreassen, OA, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Buckner, RL, Calhoun, V, Canales-Rodriguez, EJ, Cannon, DM, Caseras, X, Castellanos, FX, Cervenka, S, Chaim-Avancini, TM, Ching, CRK, Chubar, V, Clark, VP, Conrod, P, Conzelmann, A, Crespo-Facorro, B, Crivello, F, Crone, EA, Dale, AM, Davey, C, de Geus, EJC, de Haan, L, de Zubicaray, G, den Braber, A, Dickie, EW, Di Giorgio, A, Nhat, TD, Dorum, ES, Ehrlich, S, Erk, S, Espeseth, T, Fatouros-Bergman, H, Fisher, SE, Fouche, J-P, Franke, B, Frodl, T, Fuentes-Claramonte, P, Glahn, DC, Gotlib, IH, Grabe, H-J, Grimm, O, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Gur, RE, Gur, RC, Harrison, BJ, Hartman, CA, Hatton, SN, Heinz, A, Heslenfeld, DJ, Hibar, DP, Hickie, IB, Ho, B-C, Hoekstra, PJ, Hohmann, S, Holmes, AJ, Hoogman, M, Hosten, N, Howells, FM, Pol, HEH, Huyser, C, Jahanshad, N, James, A, Jernigan, TL, Jiang, J, Jonsson, EG, Joska, JA, Kahn, R, Kalnin, A, Kanai, R, Klein, M, Klyushnik, TP, Koenders, L, Koops, S, Kraemer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, I, Lee, WH, Lesch, K-P, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, C, McDonald, BC, McIntosh, AM, McMahon, KL, McPhilemy, G, Menchon, JM, Medland, SE, Meyer-Lindenberg, A, Naaijen, J, Najt, P, Nakao, T, Nordvik, JE, Nyberg, L, Oosterlaan, J, Ortiz-Garcia De la Foz, V, Paloyelis, Y, Pauli, P, Pergola, G, Pomarol-Clotet, E, Portella, MJ, Potkin, SG, Radua, J, Reif, A, Rinker, DA, Roffman, JL, Rosa, PGP, Sacchet, MD, Sachdev, PS, Salvador, R, Sanchez-Juan, P, Sarro, S, Satterthwaite, TD, Saykin, AJ, Serpa, MH, Schmaal, L, Schnell, K, Schumann, G, Sim, K, Smoller, JW, Sommer, I, Soriano-Mas, C, Stein, DJ, Strike, LT, Swagerman, SC, Tamnes, CK, Temmingh, HS, Thomopoulos, S, Tomyshev, AS, Tordesillas-Gutierrez, D, Trollor, JN, Turner, JA, Uhlmann, A, van den Heuvel, OA, van den Meer, D, van der Wee, NJA, van Haren, NEM, Van't Ent, D, van Erp, TGM, Veer, IM, Veltman, DJ, Voineskos, A, Voelzke, H, Walter, H, Walton, E, Wang, L, Wang, Y, Wassink, TH, Weber, B, Wen, W, West, JD, Westlye, LT, Whalley, H, Wierenga, LM, Williams, SCR, Wittfeld, K, Wolf, DH, Worker, A, Wright, MJ, Yang, K, Yoncheva, Y, Zanetti, M, Ziegler, GC, Thompson, PM, Frangou, S, Dima, D, Modabbernia, A, Papachristou, E, Doucet, GE, Agartz, I, Aghajani, M, Akudjedu, TN, Albajes-Eizagirre, A, Alnaes, D, Alpert, K, Andersson, M, Andreasen, NC, Andreassen, OA, Asherson, P, Banaschewski, T, Bargallo, N, Baumeister, S, Baur-Streubel, R, Bertolino, A, Bonvino, A, Boomsma, D, Borgwardt, S, Bourque, J, Brandeis, D, Breier, A, Brodaty, H, Brouwer, RM, Buitelaar, JK, Busatto, GF, Buckner, RL, Calhoun, V, Canales-Rodriguez, EJ, Cannon, DM, Caseras, X, Castellanos, FX, Cervenka, S, Chaim-Avancini, TM, Ching, CRK, Chubar, V, Clark, VP, Conrod, P, Conzelmann, A, Crespo-Facorro, B, Crivello, F, Crone, EA, Dale, AM, Davey, C, de Geus, EJC, de Haan, L, de Zubicaray, G, den Braber, A, Dickie, EW, Di Giorgio, A, Nhat, TD, Dorum, ES, Ehrlich, S, Erk, S, Espeseth, T, Fatouros-Bergman, H, Fisher, SE, Fouche, J-P, Franke, B, Frodl, T, Fuentes-Claramonte, P, Glahn, DC, Gotlib, IH, Grabe, H-J, Grimm, O, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Gur, RE, Gur, RC, Harrison, BJ, Hartman, CA, Hatton, SN, Heinz, A, Heslenfeld, DJ, Hibar, DP, Hickie, IB, Ho, B-C, Hoekstra, PJ, Hohmann, S, Holmes, AJ, Hoogman, M, Hosten, N, Howells, FM, Pol, HEH, Huyser, C, Jahanshad, N, James, A, Jernigan, TL, Jiang, J, Jonsson, EG, Joska, JA, Kahn, R, Kalnin, A, Kanai, R, Klein, M, Klyushnik, TP, Koenders, L, Koops, S, Kraemer, B, Kuntsi, J, Lagopoulos, J, Lazaro, L, Lebedeva, I, Lee, WH, Lesch, K-P, Lochner, C, Machielsen, MWJ, Maingault, S, Martin, NG, Martinez-Zalacain, I, Mataix-Cols, D, Mazoyer, B, McDonald, C, McDonald, BC, McIntosh, AM, McMahon, KL, McPhilemy, G, Menchon, JM, Medland, SE, Meyer-Lindenberg, A, Naaijen, J, Najt, P, Nakao, T, Nordvik, JE, Nyberg, L, Oosterlaan, J, Ortiz-Garcia De la Foz, V, Paloyelis, Y, Pauli, P, Pergola, G, Pomarol-Clotet, E, Portella, MJ, Potkin, SG, Radua, J, Reif, A, Rinker, DA, Roffman, JL, Rosa, PGP, Sacchet, MD, Sachdev, PS, Salvador, R, Sanchez-Juan, P, Sarro, S, Satterthwaite, TD, Saykin, AJ, Serpa, MH, Schmaal, L, Schnell, K, Schumann, G, Sim, K, Smoller, JW, Sommer, I, Soriano-Mas, C, Stein, DJ, Strike, LT, Swagerman, SC, Tamnes, CK, Temmingh, HS, Thomopoulos, S, Tomyshev, AS, Tordesillas-Gutierrez, D, Trollor, JN, Turner, JA, Uhlmann, A, van den Heuvel, OA, van den Meer, D, van der Wee, NJA, van Haren, NEM, Van't Ent, D, van Erp, TGM, Veer, IM, Veltman, DJ, Voineskos, A, Voelzke, H, Walter, H, Walton, E, Wang, L, Wang, Y, Wassink, TH, Weber, B, Wen, W, West, JD, Westlye, LT, Whalley, H, Wierenga, LM, Williams, SCR, Wittfeld, K, Wolf, DH, Worker, A, Wright, MJ, Yang, K, Yoncheva, Y, Zanetti, M, Ziegler, GC, Thompson, PM, and Frangou, S
Abstract: Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
Published: 2021

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