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1. Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy

Author

Wang, Hui, Chang, Timothy S, Dombroski, Beth A, Cheng, Po-Liang, Patil, Vishakha, Valiente-Banuet, Leopoldo, Farrell, Kurt, Mclean, Catriona, Molina-Porcel, Laura, Rajput, Alex, De Deyn, Peter Paul, Le Bastard, Nathalie, Gearing, Marla, Kaat, Laura Donker, Van Swieten, John C, Dopper, Elise, Ghetti, Bernardino F, Newell, Kathy L, Troakes, Claire, de Yébenes, Justo G, Rábano-Gutierrez, Alberto, Meller, Tina, Oertel, Wolfgang H, Respondek, Gesine, Stamelou, Maria, Arzberger, Thomas, Roeber, Sigrun, Müller, Ulrich, Hopfner, Franziska, Pastor, Pau, Brice, Alexis, Durr, Alexandra, Le Ber, Isabelle, Beach, Thomas G, Serrano, Geidy E, Hazrati, Lili-Naz, Litvan, Irene, Rademakers, Rosa, Ross, Owen A, Galasko, Douglas, Boxer, Adam L, Miller, Bruce L, Seeley, Willian W, Van Deerlin, Vivanna M, Lee, Edward B, White, Charles L, Morris, Huw, de Silva, Rohan, Crary, John F, Goate, Alison M, Friedman, Jeffrey S, Leung, Yuk Yee, Coppola, Giovanni, Naj, Adam C, Wang, Li-San, Dalgard, Clifton, Dickson, Dennis W, Höglinger, Günter U, Schellenberg, Gerard D, Geschwind, Daniel H, and Lee, Wan-Ping

Subjects
Biological Sciences, Genetics, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Acquired Cognitive Impairment, Frontotemporal Dementia (FTD), Rare Diseases, Neurosciences, Dementia, Human Genome, Brain Disorders, Biotechnology, Aging, Alzheimer's Disease Related Dementias (ADRD), Alzheimer's Disease, 2.1 Biological and endogenous factors, Neurological, Progressive Supranuclear Palsy, Whole-Genome Sequencing, Genome-Wide Association Study, Structural Variants, Apolipoprotein E, P. S. P. genetics study group, Humans, Supranuclear Palsy, Progressive, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Aged, Aged, 80 and over, Middle Aged, Female, Male, Whole Genome Sequencing, Clinical Sciences, Neurology & Neurosurgery, Biochemistry and cell biology
Abstract

BackgroundProgressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of aggregated tau proteins in astrocytes, neurons, and oligodendrocytes. Previous genome-wide association studies for PSP were based on genotype array, therefore, were inadequate for the analysis of rare variants as well as larger mutations, such as small insertions/deletions (indels) and structural variants (SVs).MethodIn this study, we performed whole genome sequencing (WGS) and conducted association analysis for single nucleotide variants (SNVs), indels, and SVs, in a cohort of 1,718 cases and 2,944 controls of European ancestry. Of the 1,718 PSP individuals, 1,441 were autopsy-confirmed and 277 were clinically diagnosed.ResultsOur analysis of common SNVs and indels confirmed known genetic loci at MAPT, MOBP, STX6, SLCO1A2, DUSP10, and SP1, and further uncovered novel signals in APOE, FCHO1/MAP1S, KIF13A, TRIM24, TNXB, and ELOVL1. Notably, in contrast to Alzheimer's disease (AD), we observed the APOE ε2 allele to be the risk allele in PSP. Analysis of rare SNVs and indels identified significant association in ZNF592 and further gene network analysis identified a module of neuronal genes dysregulated in PSP. Moreover, seven common SVs associated with PSP were observed in the H1/H2 haplotype region (17q21.31) and other loci, including IGH, PCMT1, CYP2A13, and SMCP. In the H1/H2 haplotype region, there is a burden of rare deletions and duplications (P = 6.73 × 10-3) in PSP.ConclusionsThrough WGS, we significantly enhanced our understanding of the genetic basis of PSP, providing new targets for exploring disease mechanisms and therapeutic interventions.

Published
2024

2. Correction: Whole-genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy

Author

Wang, Hui, Chang, Timothy S., Dombroski, Beth A., Cheng, Po-Liang, Patil, Vishakha, Valiente-Banuet, Leopoldo, Farrell, Kurt, Mclean, Catriona, Molina-Porcel, Laura, Rajput, Alex, De Deyn, Peter Paul, Le Bastard, Nathalie, Gearing, Marla, Kaat, Laura Donker, Van Swieten, John C., Dopper, Elise, Ghetti, Bernardino F., Newell, Kathy L., Troakes, Claire, de Yébenes, Justo G., Rábano-Gutierrez, Alberto, Meller, Tina, Oertel, Wolfgang H., Respondek, Gesine, Stamelou, Maria, Arzberger, Thomas, Roeber, Sigrun, Müller, Ulrich, Hopfner, Franziska, Pastor, Pau, Brice, Alexis, Durr, Alexandra, Le Ber, Isabelle, Beach, Thomas G., Serrano, Geidy E., Hazrati, Lili-Naz, Litvan, Irene, Rademakers, Rosa, Ross, Owen A., Galasko, Douglas, Boxer, Adam L., Miller, Bruce L., Seeley, Willian W., Van Deerlin, Vivanna M., Lee, Edward B., White, III, Charles L., Morris, Huw, de Silva, Rohan, Crary, John F., Goate, Alison M., Friedman, Jeffrey S., Leung, Yuk Yee, Coppola, Giovanni, Naj, Adam C., Wang, Li-San, Dalgard, Clifton, Dickson, Dennis W., Höglinger, Günter U., Schellenberg, Gerard D., Geschwind, Daniel H., and Lee, Wan-Ping

Published
2024
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4. Factor analysis of lifetime psychopathology and its brain morphometric and genetic correlates in a transdiagnostic sample

Author

Krug, Axel, Stein, Frederike, David, Friederike S., Schmitt, Simon, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Meller, Tina, Thomas-Odenthal, Florian, Meinert, Susanne, Thiel, Katharina, Winter, Alexandra, Waltemate, Lena, Lemke, Hannah, Grotegerd, Dominik, Opel, Nils, Repple, Jonathan, Hahn, Tim, Streit, Fabian, Witt, Stephanie H., Rietschel, Marcella, Andlauer, Till F. M., Nöthen, Markus M., Philipsen, Alexandra, Nenadić, Igor, Dannlowski, Udo, Kircher, Tilo, and Forstner, Andreas J.

Published
2024
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6. Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants.

Author

Fullerton, Janice, Goikolea, Jose, Goltermann, Janik, Grotegerd, Dominik, Haarman, Bartholomeus, Hahn, Tim, Howells, Fleur, Ingvar, Martin, Jahanshad, Neda, Kircher, Tilo, Krug, Axel, Kuplicki, Rayus, Landén, Mikael, Lemke, Hannah, Liberg, Benny, Lopez-Jaramillo, Carlos, Malt, Ulrik, Martyn, Fiona, Mazza, Elena, McDonald, Colm, McPhilemy, Genevieve, Meier, Sandra, Meinert, Susanne, Meller, Tina, Melloni, Elisa, Mitchell, Philip, Nabulsi, Leila, Nenadic, Igor, Opel, Nils, Ophoff, Roel, Overs, Bronwyn, Pfarr, Julia-Katharina, Pineda-Zapata, Julian, Pomarol-Clotet, Edith, Raduà, Joaquim, Repple, Jonathan, Richter, Maike, Ringwald, Kai, Roberts, Gloria, Ross, Alex, Salvador, Raymond, Savitz, Jonathan, Schmitt, Simon, Schofield, Peter, Sim, Kang, Stein, Dan, Stein, Frederike, Temmingh, Henk, Thiel, Katharina, Thomopoulos, Sophia, van Haren, Neeltje, Vargas, Cristian, Vieta, Eduard, Vreeker, Annabel, Waltemate, Lena, Yatham, Lakshmi, Ching, Christopher, Andreassen, Ole, Thompson, Paul, Hajek, Tomas, McWhinney, Sean, Abé, Christoph, Alda, Martin, Benedetti, Francesco, Bøen, Erlend, Del Mar Bonnin, Caterina, Borgers, Tiana, Brosch, Katharina, Canales-Rodríguez, Erick, Cannon, Dara, Dannlowski, Udo, Diaz-Zuluaga, Ana, Dietze, Lorielle, Elvsåshagen, Torbjørn, and Eyler, Lisa

Subjects
Body mass index, antipsychotics, bipolar disorders, cortical thickness, heterogeneity, lithium, obesity, surface area
Abstract

BACKGROUND: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. METHODS: We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. RESULTS: BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. CONCLUSIONS: We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

Published
2023

7. Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness-ENIGMA study in 2436 individuals.

Author

McWhinney, Sean, Abé, Christoph, Alda, Martin, Benedetti, Francesco, Bøen, Erlend, Del Mar Bonnin, Caterina, Borgers, Tiana, Brosch, Katharina, Canales-Rodríguez, Erick, Cannon, Dara, Dannlowski, Udo, Diaz-Zuluaga, Ana, Dietze, Lorielle, Elvsåshagen, Torbjørn, Fullerton, Janice, Goikolea, Jose, Goltermann, Janik, Grotegerd, Dominik, Haarman, Bartholomeus, Hahn, Tim, Howells, Fleur, Ingvar, Martin, Kircher, Tilo, Krug, Axel, Kuplicki, Rayus, Landén, Mikael, Lemke, Hannah, Liberg, Benny, Lopez-Jaramillo, Carlos, Malt, Ulrik, Martyn, Fiona, Mazza, Elena, McDonald, Colm, McPhilemy, Genevieve, Meier, Sandra, Meinert, Susanne, Meller, Tina, Melloni, Elisa, Mitchell, Philip, Nabulsi, Leila, Nenadic, Igor, Opel, Nils, Overs, Bronwyn, Pfarr, Julia-Katharina, Pineda-Zapata, Julian, Pomarol-Clotet, Edith, Raduà, Joaquim, Repple, Jonathan, Richter, Maike, Ringwald, Kai, Roberts, Gloria, Ross, Alex, Salvador, Raymond, Savitz, Jonathan, Schmitt, Simon, Schofield, Peter, Sim, Kang, Stein, Dan, Stein, Frederike, Temmingh, Henk, Thiel, Katharina, Thomopoulos, Sophia, van Haren, Neeltje, Van Gestel, Holly, Vargas, Cristian, Vieta, Eduard, Vreeker, Annabel, Waltemate, Lena, Yatham, Lakshmi, Ching, Christopher, Andreassen, Ole, Thompson, Paul, Hajek, Tomas, Ophoff, Roel, and Eyler, Lisa

Subjects
bipolar disorders, body mass index, cortical thickness, heterogeneity, obesity, surface area, Bipolar Disorder, Body Mass Index, Cluster Analysis, Humans, Magnetic Resonance Imaging, Obesity, Temporal Lobe
Abstract

AIMS: Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry. METHODS: We obtained body mass index (BMI) and magnetic resonance imaging-derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14 sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles. RESULTS: We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex. CONCLUSIONS: We provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD-associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD.

Published
2022

10. Altered brain dynamic in major depressive disorder: state and trait features

Author

Javaheripour, Nooshin, Colic, Lejla, Opel, Nils, Li, Meng, Maleki Balajoo, Somayeh, Chand, Tara, Van der Meer, Johan, Krylova, Marina, Izyurov, Igor, Meller, Tina, Goltermann, Janik, Winter, Nils R., Meinert, Susanne, Grotegerd, Dominik, Jansen, Andreas, Alexander, Nina, Usemann, Paula, Thomas-Odenthal, Florian, Evermann, Ulrika, Wroblewski, Adrian, Brosch, Katharina, Stein, Frederike, Hahn, Tim, Straube, Benjamin, Krug, Axel, Nenadić, Igor, Kircher, Tilo, Croy, Ilona, Dannlowski, Udo, Wagner, Gerd, and Walter, Martin

Published
2023
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11. A Network Control Theory Approach to Longitudinal Symptom Dynamics in Major Depressive Disorder

Author

Hahn, Tim, Jamalabadi, Hamidreza, Emden, Daniel, Goltermann, Janik, Ernsting, Jan, Winter, Nils R., Fisch, Lukas, Leenings, Ramona, Sarink, Kelvin, Holstein, Vincent, Gruber, Marius, Grotegerd, Dominik, Meinert, Susanne, Dohm, Katharina, Leehr, Elisabeth J., Richter, Maike, Sindermann, Lisa, Enneking, Verena, Lemke, Hannah, Witt, Stephanie, Rietschel, Marcella, Brosch, Katharina, Pfarr, Julia-Katharina, Meller, Tina, Ringwald, Kai Gustav, Schmitt, Simon, Stein, Frederike, Nenadic, Igor, Kircher, Tilo, Müller-Myhsok, Bertram, Andlauer, Till F. M., Repple, Jonathan, Dannlowski, Udo, and Opel, Nils

Subjects
Electrical Engineering and Systems Science - Systems and Control, Quantitative Biology - Neurons and Cognition
Abstract

Background: The evolution of symptoms over time is at the heart of understanding and treating mental disorders. However, a principled, quantitative framework explaining symptom dynamics remains elusive. Here, we propose a Network Control Theory of Psychopathology allowing us to formally derive a theoretical control energy which we hypothesize quantifies resistance to future symptom improvement in Major Depressive Disorder (MDD). We test this hypothesis and investigate the relation to genetic and environmental risk as well as resilience. Methods: We modelled longitudinal symptom-network dynamics derived from N=2,059 Beck Depression Inventory measurements acquired over a median of 134 days in a sample of N=109 patients suffering from MDD. We quantified the theoretical energy required for each patient and time-point to reach a symptom-free state given individual symptom-network topology (E 0 ) and 1) tested if E 0 predicts future symptom improvement and 2) whether this relationship is moderated by Polygenic Risk Scores (PRS) of mental disorders, childhood maltreatment experience, and self-reported resilience. Outcomes: We show that E 0 indeed predicts symptom reduction at the next measurement and reveal that this coupling between E 0 and future symptom change increases with higher genetic risk and childhood maltreatment while it decreases with resilience. Interpretation: Our study provides a mechanistic framework capable of predicting future symptom improvement based on individual symptom-network topology and clarifies the role of genetic and environmental risk as well as resilience. Our control-theoretic framework makes testable, quantitative predictions for individual therapeutic response and provides a starting-point for the theory-driven design of personalized interventions. Funding: German Research Foundation and Interdisciplinary Centre for Clinical Research, M\"unster, Comment: 21 pages, 2 figures

Published
2021

13. Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study

Author

Kirschner, Matthias, Hodzic-Santor, Benazir, Antoniades, Mathilde, Nenadic, Igor, Kircher, Tilo, Krug, Axel, Meller, Tina, Grotegerd, Dominik, Fornito, Alex, Arnatkeviciute, Aurina, Bellgrove, Mark A, Tiego, Jeggan, Dannlowski, Udo, Koch, Katharina, Hülsmann, Carina, Kugel, Harald, Enneking, Verena, Klug, Melissa, Leehr, Elisabeth J, Böhnlein, Joscha, Gruber, Marius, Mehler, David, DeRosse, Pamela, Moyett, Ashley, Baune, Bernhard T, Green, Melissa, Quidé, Yann, Pantelis, Christos, Chan, Raymond, Wang, Yi, Ettinger, Ulrich, Debbané, Martin, Derome, Melodie, Gaser, Christian, Besteher, Bianca, Diederen, Kelly, Spencer, Tom J, Fletcher, Paul, Rössler, Wulf, Smigielski, Lukasz, Kumari, Veena, Premkumar, Preethi, Park, Haeme RP, Wiebels, Kristina, Lemmers-Jansen, Imke, Gilleen, James, Allen, Paul, Kozhuharova, Petya, Marsman, Jan-Bernard, Lebedeva, Irina, Tomyshev, Alexander, Mukhorina, Anna, Kaiser, Stefan, Fett, Anne-Kathrin, Sommer, Iris, Schuite-Koops, Sanne, Paquola, Casey, Larivière, Sara, Bernhardt, Boris, Dagher, Alain, Grant, Phillip, van Erp, Theo GM, Turner, Jessica A, Thompson, Paul M, Aleman, André, and Modinos, Gemma

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Neurosciences, Serious Mental Illness, Schizophrenia, Clinical Research, Mental Health, Mental health, Good Health and Well Being, Bipolar Disorder, Female, Humans, Magnetic Resonance Imaging, Male, Psychotic Disorders, Schizotypal Personality Disorder, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = -0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = -0.690, pspin = 0.006), BD (rho = -0.672, pspin = 0.009), and MDD (rho = -0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.

Published
2022

14. Characterisation of age and polarity at onset in bipolar disorder.

Author

Kalman, Janos L, Olde Loohuis, Loes M, Vreeker, Annabel, McQuillin, Andrew, Stahl, Eli A, Ruderfer, Douglas, Grigoroiu-Serbanescu, Maria, Panagiotaropoulou, Georgia, Ripke, Stephan, Bigdeli, Tim B, Stein, Frederike, Meller, Tina, Meinert, Susanne, Pelin, Helena, Streit, Fabian, Papiol, Sergi, Adams, Mark J, Adolfsson, Rolf, Adorjan, Kristina, Agartz, Ingrid, Aminoff, Sofie R, Anderson-Schmidt, Heike, Andreassen, Ole A, Ardau, Raffaella, Aubry, Jean-Michel, Balaban, Ceylan, Bass, Nicholas, Baune, Bernhard T, Bellivier, Frank, Benabarre, Antoni, Bengesser, Susanne, Berrettini, Wade H, Boks, Marco P, Bromet, Evelyn J, Brosch, Katharina, Budde, Monika, Byerley, William, Cervantes, Pablo, Chillotti, Catina, Cichon, Sven, Clark, Scott R, Comes, Ashley L, Corvin, Aiden, Coryell, William, Craddock, Nick, Craig, David W, Croarkin, Paul E, Cruceanu, Cristiana, Czerski, Piotr M, Dalkner, Nina, Dannlowski, Udo, Degenhardt, Franziska, Del Zompo, Maria, DePaulo, J Raymond, Djurovic, Srdjan, Edenberg, Howard J, Eissa, Mariam Al, Elvsåshagen, Torbjørn, Etain, Bruno, Fanous, Ayman H, Fellendorf, Frederike, Fiorentino, Alessia, Forstner, Andreas J, Frye, Mark A, Fullerton, Janice M, Gade, Katrin, Garnham, Julie, Gershon, Elliot, Gill, Michael, Goes, Fernando S, Gordon-Smith, Katherine, Grof, Paul, Guzman-Parra, Jose, Hahn, Tim, Hasler, Roland, Heilbronner, Maria, Heilbronner, Urs, Jamain, Stephane, Jimenez, Esther, Jones, Ian, Jones, Lisa, Jonsson, Lina, Kahn, Rene S, Kelsoe, John R, Kennedy, James L, Kircher, Tilo, Kirov, George, Kittel-Schneider, Sarah, Klöhn-Saghatolislam, Farah, Knowles, James A, Kranz, Thorsten M, Lagerberg, Trine Vik, Landen, Mikael, Lawson, William B, Leboyer, Marion, Li, Qingqin S, Maj, Mario, Malaspina, Dolores, Manchia, Mirko, and Mayoral, Fermin

Subjects
Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics, Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Humans, Bipolar Disorder, Depressive Disorder, Major, Age of Onset, Multifactorial Inheritance, Genome-Wide Association Study, Autism Spectrum Disorder, Bipolar disorder, GWAS, age at onset, polarity at onset, polygenic score, Genetics, Mental Health, Prevention, Brain Disorders, Serious Mental Illness, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundStudying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = -0.34 years, s.e. = 0.08), major depression (β = -0.34 years, s.e. = 0.08), schizophrenia (β = -0.39 years, s.e. = 0.08), and educational attainment (β = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Published
2021

15. Association between body mass index and subcortical brain volumes in bipolar disorders–ENIGMA study in 2735 individuals

Author

McWhinney, Sean R, Abé, Christoph, Alda, Martin, Benedetti, Francesco, Bøen, Erlend, del Mar Bonnin, Caterina, Borgers, Tiana, Brosch, Katharina, Canales-Rodríguez, Erick J, Cannon, Dara M, Dannlowski, Udo, Díaz-Zuluaga, Ana M, Elvsåshagen, Torbjørn, Eyler, Lisa T, Fullerton, Janice M, Goikolea, Jose M, Goltermann, Janik, Grotegerd, Dominik, Haarman, Bartholomeus CM, Hahn, Tim, Howells, Fleur M, Ingvar, Martin, Kircher, Tilo TJ, Krug, Axel, Kuplicki, Rayus T, Landén, Mikael, Lemke, Hannah, Liberg, Benny, Lopez-Jaramillo, Carlos, Malt, Ulrik F, Martyn, Fiona M, Mazza, Elena, McDonald, Colm, McPhilemy, Genevieve, Meier, Sandra, Meinert, Susanne, Meller, Tina, Melloni, Elisa MT, Mitchell, Philip B, Nabulsi, Leila, Nenadic, Igor, Opel, Nils, Ophoff, Roel A, Overs, Bronwyn J, Pfarr, Julia-Katharina, Pineda-Zapata, Julian A, Pomarol-Clotet, Edith, Raduà, Joaquim, Repple, Jonathan, Richter, Maike, Ringwald, Kai G, Roberts, Gloria, Salvador, Raymond, Savitz, Jonathan, Schmitt, Simon, Schofield, Peter R, Sim, Kang, Stein, Dan J, Stein, Frederike, Temmingh, Henk S, Thiel, Katharina, van Haren, Neeltje EM, Gestel, Holly Van, Vargas, Cristian, Vieta, Eduard, Vreeker, Annabel, Waltemate, Lena, Yatham, Lakshmi N, Ching, Christopher RK, Andreassen, Ole, Thompson, Paul M, and Hajek, Tomas

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Mental Health, Biomedical Imaging, Nutrition, Brain Disorders, Obesity, Neurosciences, Clinical Research, Prevention, Mental health, Amygdala, Bipolar Disorder, Body Mass Index, Brain, Humans, Magnetic Resonance Imaging, ENIGMA Bipolar Disorders Working Group, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles  and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.

Published
2021

18. Data-driven multivariate identification of gyrification patterns in a transdiagnostic patient cohort: A cluster analysis approach

Author

Pfarr, Julia-Katharina, Meller, Tina, Brosch, Katharina, Stein, Frederike, Thomas-Odenthal, Florian, Evermann, Ulrika, Wroblewski, Adrian, Ringwald, Kai G., Hahn, Tim, Meinert, Susanne, Winter, Alexandra, Thiel, Katharina, Flinkenflügel, Kira, Jansen, Andreas, Krug, Axel, Dannlowski, Udo, Kircher, Tilo, Gaser, Christian, and Nenadić, Igor

Published
2023
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19. Investigating the phenotypic and genetic associations between personality traits and suicidal behavior across major mental health diagnoses

Author

Kalman, Janos L., Yoshida, Tomoya, Andlauer, Till F. M., Schulte, Eva C., Adorjan, Kristina, Alda, Martin, Ardau, Raffaela, Aubry, Jean-Michel, Brosch, Katharina, Budde, Monika, Chillotti, Caterina, Czerski, Piotr M., DePaulo, Raymond J., Forstner, Andreas, Goes, Fernando S., Grigoroiu-Serbanescu, Maria, Grof, Paul, Grotegerd, Dominik, Hahn, Tim, Heilbronner, Maria, Hasler, Roland, Heilbronner, Urs, Heilmann-Heimbach, Stefanie, Kapelski, Pawel, Kato, Tadafumi, Kohshour, Mojtaba Oraki, Meinert, Susanne, Meller, Tina, Nenadić, Igor, Nöthen, Markus M., Novak, Tomas, Opel, Nils, Pawlak, Joanna, Pfarr, Julia-Katharina, Potash, James B., Reich-Erkelenz, Daniela, Repple, Jonathan, Richard-Lepouriel, Hélène, Rietschel, Marcella, Ringwald, Kai G., Rouleau, Guy, Schaupp, Sabrina, Senner, Fanny, Severino, Giovanni, Squassina, Alessio, Stein, Frederike, Stopkova, Pavla, Streit, Fabian, Thiel, Katharina, Thomas-Odenthal, Florian, Turecki, Gustavo, Twarowska-Hauser, Joanna, Winter, Alexandra, Zandi, Peter P., Kelsoe, John R., Falkai, Peter, Dannlowski, Udo, Kircher, Tilo, Schulze, Thomas G., and Papiol, Sergi

Published
2022
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21. Reduced hippocampal gray matter volume is a common feature of patients with major depression, bipolar disorder, and schizophrenia spectrum disorders

Author

Brosch, Katharina, Stein, Frederike, Schmitt, Simon, Pfarr, Julia-Katharina, Ringwald, Kai G., Thomas-Odenthal, Florian, Meller, Tina, Steinsträter, Olaf, Waltemate, Lena, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Breuer, Fabian, Thiel, Katharina, Grotegerd, Dominik, Hahn, Tim, Jansen, Andreas, Dannlowski, Udo, Krug, Axel, Nenadić, Igor, and Kircher, Tilo

Published
2022
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22. Brain structural correlates of recurrence following the first episode in patients with major depressive disorder

Author

Lemke, Hannah, Klute, Hannah, Skupski, Jennifer, Thiel, Katharina, Waltemate, Lena, Winter, Alexandra, Breuer, Fabian, Meinert, Susanne, Klug, Melissa, Enneking, Verena, Winter, Nils R., Grotegerd, Dominik, Leehr, Elisabeth J., Repple, Jonathan, Dohm, Katharina, Opel, Nils, Stein, Frederike, Meller, Tina, Brosch, Katharina, Ringwald, Kai G., Pfarr, Julia-Katharina, Thomas-Odenthal, Florian, Hahn, Tim, Krug, Axel, Jansen, Andreas, Heindel, Walter, Nenadić, Igor, Kircher, Tilo, and Dannlowski, Udo

Published
2022
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23. The Course of Disease in Major Depressive Disorder Is Associated With Altered Activity of the Limbic System During Negative Emotion Processing

Author

Lemke, Hannah, Probst, Stefanie, Warneke, Antonia, Waltemate, Lena, Winter, Alexandra, Thiel, Katharina, Meinert, Susanne, Enneking, Verena, Breuer, Fabian, Klug, Melissa, Goltermann, Janik, Hülsmann, Carina, Grotegerd, Dominik, Redlich, Ronny, Dohm, Katharina, Leehr, Elisabeth J., Repple, Jonathan, Opel, Nils, Brosch, Katharina, Meller, Tina, Pfarr, Julia-Katharina, Ringwald, Kai, Schmitt, Simon, Stein, Frederike, Krug, Axel, Jansen, Andreas, Nenadic, Igor, Kircher, Tilo, Hahn, Tim, and Dannlowski, Udo

Published
2022
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24. Association Between Genetic Risk for Type 2 Diabetes and Structural Brain Connectivity in Major Depressive Disorder

Author

Repple, Jonathan, König, Amelie, de Lange, Siemon C., Opel, Nils, Redlich, Ronny, Meinert, Susanne, Grotegerd, Dominik, Mauritz, Marco, Hahn, Tim, Borgers, Tiana, Leehr, Elisabeth J., Winter, Nils, Goltermann, Janik, Enneking, Verena, Fingas, Stella M., Lemke, Hannah, Waltemate, Lena, Dohm, Katharina, Richter, Maike, Mehler, David M.A., Holstein, Vincent, Gruber, Marius, Nenadic, Igor, Krug, Axel, Brosch, Katharina, Schmitt, Simon, Stein, Frederike, Meller, Tina, Jansen, Andreas, Steinsträter, Olaf, Amare, Azmeraw T., Kircher, Tilo, Baune, Bernhard T., van den Heuvel, Martijn P., and Dannlowski, Udo

Published
2022
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25. Association of brain white matter microstructure with cognitive performance in major depressive disorder and healthy controls: a diffusion-tensor imaging study

Author

Meinert, Susanne, Nowack, Nico, Grotegerd, Dominik, Repple, Jonathan, Winter, Nils R., Abheiden, Isabel, Enneking, Verena, Lemke, Hannah, Waltemate, Lena, Stein, Frederike, Brosch, Katharina, Schmitt, Simon, Meller, Tina, Pfarr, Julia-Katharina, Ringwald, Kai, Steinsträter, Olaf, Gruber, Marius, Nenadić, Igor, Krug, Axel, Leehr, Elisabeth J., Hahn, Tim, Thiel, Katharina, Dohm, Katharina, Winter, Alexandra, Opel, Nils, Schubotz, Ricarda I., Kircher, Tilo, and Dannlowski, Udo

Published
2022
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26. Genome-wide interaction study with major depression identifies novel variants associated with cognitive function

Author

Thalamuthu, Anbupalam, Mills, Natalie T., Berger, Klaus, Minnerup, Heike, Grotegerd, Dominik, Dannlowski, Udo, Meinert, Susanne, Opel, Nils, Repple, Jonathan, Gruber, Marius, Nenadić, Igor, Stein, Frederike, Brosch, Katharina, Meller, Tina, Pfarr, Julia-Katharina, Forstner, Andreas J., Hoffmann, Per, Nöthen, Markus M., Witt, Stephanie, Rietschel, Marcella, Kircher, Tilo, Adams, Mark, McIntosh, Andrew M., Porteous, David J., Deary, Ian J., Hayward, Caroline, Campbell, Archie, Grabe, Hans Jörgen, Teumer, Alexander, Homuth, Georg, van der Auwera-Palitschka, Sandra, Oliver Schubert, K., and Baune, Bernhard T.

Published
2022
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27. Multiscale characterization of cortical signatures in positive and negative schizotypy: A worldwide ENIGMA study

Author

Kirschner, Matthias, primary, Hodzic-Santor, Benazir, additional, Kennedy, Leda, additional, Hansen, Justine Y, additional, Antoniades, Mathilde, additional, Nenadic, Igor, additional, Kircher, Tilo, additional, Krug, Alex, additional, Meller, Tina, additional, Dannlowski, Udo, additional, Grotegerd, Dominik, additional, Flinkenfluegel, Kira, additional, Meinert, Susanne, additional, Borgers, Tiana, additional, Goltermann, Janik, additional, Hahn, Tim, additional, Boehnlein, Joscha, additional, Leehr, Elisabeth Johanna, additional, Barkhau, Carlotta, additional, Fornito, Alex, additional, Arnatkeviciute, Aurina, additional, Bellgrove, Mark, additional, Tiego, Jeggan, additional, DeRosse, Pamela, additional, Green, Melissa, additional, Quide, Yann, additional, Pantelis, Christos, additional, Chan, Raymond C K, additional, Wang, Yi, additional, Ettinger, Ulrich, additional, Debbane, Martin, additional, Derome, Melodie, additional, Gaser, Christian, additional, Besteher, Bianca, additional, Diederen, Kelly, additional, Spencer, Thomas J, additional, Houenou, Josselin, additional, Pomarol-Clotet, Edith, additional, Salvador, Raymond, additional, Roessler, Wulf, additional, Smigielski, Lukasz, additional, Kumari, Veena, additional, Premkumar, Preethi, additional, Park, Haeme, additional, Wiebels, Kristina, additional, Lemmers-Jansen, Imke, additional, Gilleen, James, additional, Allen, Paul H, additional, Marsman, Jan-Bernard, additional, Lebedeva, Irina, additional, Tomyshev, Alexander, additional, Fett, Anne-Kathrin, additional, Sommer, Iris, additional, Koops, Sanne, additional, Grant, Phillip, additional, Begue, Indrit, additional, Hernaus, Dennis, additional, Jalbrzikowski, Maria, additional, Paquola, Casey, additional, Lariviere, Sara, additional, Bernhardt, Boris, additional, Valk, Sofie L, additional, Misic, Bratislav, additional, van Erp, Theo GM, additional, Turner, Jessica A, additional, Thompson, Paul M, additional, Aleman, Andre, additional, Dagher, Alain, additional, Kaiser, Stefan, additional, and Modinos, Gemma, additional

Published
2024
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28. Identification of transdiagnostic psychiatric disorder subtypes using unsupervised learning

Author

Pelin, Helena, Ising, Marcus, Stein, Frederike, Meinert, Susanne, Meller, Tina, Brosch, Katharina, Winter, Nils R., Krug, Axel, Leenings, Ramona, Lemke, Hannah, Nenadić, Igor, Heilmann-Heimbach, Stefanie, Forstner, Andreas J., Nöthen, Markus M., Opel, Nils, Repple, Jonathan, Pfarr, Julia, Ringwald, Kai, Schmitt, Simon, Thiel, Katharina, Waltemate, Lena, Winter, Alexandra, Streit, Fabian, Witt, Stephanie, Rietschel, Marcella, Dannlowski, Udo, Kircher, Tilo, Hahn, Tim, Müller-Myhsok, Bertram, and Andlauer, Till F. M.

Published
2021
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31. Apolipoprotein E homozygous ε4 allele status: Effects on cortical structure and white matter integrity in a young to mid-age sample

Author

Goltermann, Janik, Repple, Jonathan, Redlich, Ronny, Dohm, Katharina, Flint, Claas, Grotegerd, Dominik, Waltemate, Lena, Lemke, Hannah, Fingas, Stella Mercedes, Meinert, Susanne, Enneking, Verena, Hahn, Tim, Bauer, Jochen, Schmitt, Simon, Meller, Tina, Stein, Frederike, Brosch, Katharina, Steinsträter, Olaf, Jansen, Andreas, Krug, Axel, Nenadić, Igor, Baune, Bernhard T., Rietschel, Marcella, Witt, Stephanie, Forstner, Andreas J., Nöthen, Markus, Johnen, Andreas, Alferink, Judith, Kircher, Tilo, Dannlowski, Udo, and Opel, Nils

Published
2021
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32. Social support and hippocampal volume are negatively associated in adults with previous experience of childhood maltreatment

Author

Forster, Katharina, Danzer, Lorenz, Redlich, Ronny, Opel, Nils, Grotegerd, Dominik, Leehr, Elisabeth J., Dohm, Katharina, Enneking, Verena, Meinert, Susanne, Goltermann, Janik, Lemke, Hannah, Waltemate, Lena, Thiel, Katharina, Behnert, Katja, Brosch, Katharina, Stein, Frederike, Meller, Tina, Ringwald, Kai, Schmitt, Simon, Steinstrater, Olaf, Jansen, Andreas, Krug, Axel, Nenadic, Igor, Kircher, Tilo, Hahn, Tim, Kugel, Harald, Heindel, Walter, Repple, Jonathan, and Dannlowski, Udo

Subjects
Hippocampus (Brain) -- Physiological aspects, Child abuse -- Physiological aspects -- Psychological aspects, Social networks -- Psychological aspects -- Physiological aspects, Health, Psychology and mental health
Abstract

Background: Childhood maltreatment has been associated with reduced hippocampal volume in healthy individuals, whereas social support, a protective factor, has been positively associated with hippocampal volumes. In this study, we investigated how social support is associated with hippocampal volume in healthy people with previous experience of childhood maltreatment. Methods: We separated a sample of 446 healthy participants into 2 groups using the Childhood Trauma Questionnaire: 265 people without maltreatment and 181 people with maltreatment. We measured perceived social support using a short version of the Social Support Questionnaire. We examined hippocampal volume using automated segmentation (Freesurfer). We conducted a social support x group analysis of covariance on hippocampal volumes controlling for age, sex, total intracranial volume, site and verbal intelligence. Results: Our analysis revealed significantly lower left hippocampal volume in people with maltreatment (left [F.sub.1,432] = 5.686, p = 0.018; right [F.sub.1,433] = 3.371, p = 0.07), but no main effect of social support emerged. However, we did find a significant social support x group interaction for left hippocampal volume (left [F.sub.1,432] = 5.712, p = 0.017; right [F.sub.1,433] = 3.480, p = 0.06). In people without maltreatment, we observed a trend toward a positive association between social support and hippocampal volume. In contrast, social support was negatively associated with hippocampal volume in people with maltreatment. Limitations: Because of the correlative nature of our study, we could not infer causal relationships between social support, maltreatment and hippocampal volume. Conclusion: Our results point to a complex dynamic between environmental risk, protective factors and brain structure--in line with previous evidence--suggesting a detrimental effect of maltreatment on hippocampal development., Introduction Childhood maltreatment is an adverse social experience and is a risk factor for many mental disorders. (1) It is also associated with neuroendocrine dysregulation (e.g., hypercortisolism) and alterations in [...]

Published
2021
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33. Childhood maltreatment and cognitive functioning: the role of depression, parental education, and polygenic predisposition

Author

Goltermann, Janik, Redlich, Ronny, Grotegerd, Dominik, Dohm, Katharina, Leehr, Elisabeth J., Böhnlein, Joscha, Förster, Katharina, Meinert, Susanne, Enneking, Verena, Richter, Maike, Repple, Jonathan, DeVillers, Immanuel, Kloecker, Marine, Jansen, Andreas, Krug, Axel, Nenadić, Igor, Brosch, Katharina, Meller, Tina, Stein, Frederike, Schmitt, Simon, Rietschel, Marcella, Streit, Fabian, Witt, Stephanie H., Forstner, Andreas J., Nöthen, Markus M., Baune, Bernhard T., Andlauer, Till F. M., Kircher, Tilo, Opel, Nils, and Dannlowski, Udo

Published
2021
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36. Factor analyses of multidimensional symptoms in a large group of patients with major depressive disorder, bipolar disorder, schizoaffective disorder and schizophrenia

Author

Stein, Frederike, Lemmer, Gunnar, Schmitt, Simon, Brosch, Katharina, Meller, Tina, Fischer, Elena, Kraus, Cynthia, Lenhard, Lutz, Köhnlein, Birgit, Murata, Harumi, Bäcker, Achim, Müller, Matthias, Franz, Michael, Förster, Katharina, Meinert, Susanne, Enneking, Verena, Koch, Katharina, Grotegerd, Dominik, Nagels, Arne, Nenadić, Igor, Dannlowski, Udo, Kircher, Tilo, and Krug, Axel

Published
2020
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37. Severity of current depression and remission status are associated with structural connectome alterations in major depressive disorder

Author

Repple, Jonathan, Mauritz, Marco, Meinert, Susanne, de Lange, Siemon C., Grotegerd, Dominik, Opel, Nils, Redlich, Ronny, Hahn, Tim, Förster, Katharina, Leehr, Elisabeth J., Winter, Nils, Goltermann, Janik, Enneking, Verena, Fingas, Stella M., Lemke, Hannah, Waltemate, Lena, Nenadic, Igor, Krug, Axel, Brosch, Katharina, Schmitt, Simon, Stein, Frederike, Meller, Tina, Jansen, Andreas, Steinsträter, Olaf, Baune, Bernhard T., Kircher, Tilo, Dannlowski, Udo, and van den Heuvel, Martijn P.

Published
2020
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38. Associations of schizophrenia risk genes ZNF804A and CACNA1C with schizotypy and modulation of attention in healthy subjects

Author

Meller, Tina, Schmitt, Simon, Stein, Frederike, Brosch, Katharina, Mosebach, Johannes, Yüksel, Dilara, Zaremba, Dario, Grotegerd, Dominik, Dohm, Katharina, Meinert, Susanne, Förster, Katharina, Redlich, Ronny, Opel, Nils, Repple, Jonathan, Hahn, Tim, Jansen, Andreas, Andlauer, Till F.M., Forstner, Andreas J., Heilmann-Heimbach, Stefanie, Streit, Fabian, Witt, Stephanie H., Rietschel, Marcella, Müller-Myhsok, Bertram, Nöthen, Markus M., Dannlowski, Udo, Krug, Axel, Kircher, Tilo, and Nenadić, Igor

Published
2019
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40. Reduced fractional anisotropy in depressed patients due to childhood maltreatment rather than diagnosis

Author

Meinert, Susanne, Repple, Jonathan, Nenadic, Igor, Krug, Axel, Jansen, Andreas, Grotegerd, Dominik, Förster, Katharina, Enneking, Verena, Dohm, Katharina, Schmitt, Simon, Stein, Frederike, Brosch, Katharina, Meller, Tina, Redlich, Ronny, Böhnlein, Joscha, Sindermann, Lisa, Goltermann, Janik, Leehr, Elisabeth J., Opel, Nils, Aldermann, Leni, Reuter, Andreas, Schubotz, Ricarda I., Hahn, Tim, Kircher, Tilo, and Dannlowski, Udo

Published
2019
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41. State of illness-dependent associations of neuro-cognition and psychopathological syndromes in a large transdiagnostic cohort

Author

Stein, Frederike, primary, Schmitt, Simon, additional, Brosch, Katharina, additional, Meller, Tina, additional, Pfarr, Julia-Katharina, additional, Ringwald, Kai, additional, Lemmer, Gunnar, additional, Philipsen, Alexandra, additional, Meinert, Susanne, additional, Lemke, Hannah, additional, Waltemate, Lena, additional, Thiel, Katharina, additional, Franz, Michael, additional, Preuss, Ulrich W., additional, Metzger, Florian G., additional, Nagels, Arne, additional, Nenadić, Igor, additional, Dannlowski, Udo, additional, Kircher, Tilo, additional, and Krug, Axel, additional

Published
2023
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42. Shared and Specific Patterns of Structural Brain Connectivity Across Affective and Psychotic Disorders

Author

Repple, Jonathan, Gruber, Marius, Mauritz, Marco, de Lange, Siemon C., Winter, Nils Ralf, Opel, Nils, Goltermann, Janik, Meinert, Susanne, Grotegerd, Dominik, Leehr, Elisabeth J., Enneking, Verena, Borgers, Tiana, Klug, Melissa, Lemke, Hannah, Waltemate, Lena, Thiel, Katharina, Winter, Alexandra, Breuer, Fabian, Grumbach, Pascal, Hofmann, Hannes, Stein, Frederike, Brosch, Katharina, Ringwald, Kai G., Pfarr, Julia, Thomas-Odenthal, Florian, Meller, Tina, Jansen, Andreas, Nenadic, Igor, Redlich, Ronny, Bauer, Jochen, Kircher, Tilo, Hahn, Tim, van den Heuvel, Martijn, Dannlowski, Udo, Repple, Jonathan, Gruber, Marius, Mauritz, Marco, de Lange, Siemon C., Winter, Nils Ralf, Opel, Nils, Goltermann, Janik, Meinert, Susanne, Grotegerd, Dominik, Leehr, Elisabeth J., Enneking, Verena, Borgers, Tiana, Klug, Melissa, Lemke, Hannah, Waltemate, Lena, Thiel, Katharina, Winter, Alexandra, Breuer, Fabian, Grumbach, Pascal, Hofmann, Hannes, Stein, Frederike, Brosch, Katharina, Ringwald, Kai G., Pfarr, Julia, Thomas-Odenthal, Florian, Meller, Tina, Jansen, Andreas, Nenadic, Igor, Redlich, Ronny, Bauer, Jochen, Kircher, Tilo, Hahn, Tim, van den Heuvel, Martijn, and Dannlowski, Udo

Abstract

BACKGROUND: Altered brain structural connectivity has been implicated in the pathophysiology of psychiatric disorders including schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). However, it is unknown which part of these connectivity abnormalities are disorder specific and which are shared across the spectrum of psychotic and affective disorders. We investigated common and distinct brain connectivity alterations in a large sample (N = 1743) of patients with SZ, BD, or MDD and healthy control (HC) subjects.METHODS: This study examined diffusion-weighted imaging-based structural connectome topology in 720 patients with MDD, 112 patients with BD, 69 patients with SZ, and 842 HC subjects (mean age of all subjects: 35.7 years). Graph theory-based network analysis was used to investigate connectome organization. Machine learning algorithms were trained to classify groups based on their structural connectivity matrices.RESULTS: Groups differed significantly in the network metrics global efficiency, clustering, present edges, and global connectivity strength with a converging pattern of alterations between diagnoses (e.g., efficiency: HC > MDD > BD > SZ, false discovery rate-corrected p = .028). Subnetwork analysis revealed a common core of edges that were affected across all 3 disorders, but also revealed differences between disorders. Machine learning algorithms could not discriminate between disorders but could discriminate each diagnosis from HC. Furthermore, dysconnectivity patterns were found most pronounced in patients with an early disease onset irrespective of diagnosis.CONCLUSIONS: We found shared and specific signatures of structural white matter dysconnectivity in SZ, BD, and MDD, leading to commonly reduced network efficiency. These results showed a compromised brain communication across a spectrum of major psychiatric disorders.

Published
2023
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43. Mega-analysis of association between obesity and cortical morphology in bipolar disorders:ENIGMA study in 2832 participants

Author

Mcwhinney, Sean R., Abé, Christoph, Alda, Martin, Benedetti, Francesco, Boen, Erlend, Del Mar Bonnin, Caterina, Borgers, Tiana, Brosch, Katharina, Canales-Rodríguez, Erick J., Cannon, Dara M., Dannlowski, Udo, Diaz-Zuluaga, Ana M., Dietze, Lorielle M.F., Elvsåshagen, Torbjorn, Eyler, Lisa T., Fullerton, Janice M., Goikolea, Jose M., Goltermann, Janik, Grotegerd, Dominik, Haarman, Bartholomeus C.M., Hahn, Tim, Howells, Fleur M., Ingvar, Martin, Jahanshad, Neda, Kircher, Tilo T.J., Krug, Axel, Kuplicki, Rayus T., Landén, Mikael, Lemke, Hannah, Liberg, Benny, Lopez-Jaramillo, Carlos, Malt, Ulrik F., Martyn, Fiona M., Mazza, Elena, Mcdonald, Colm, Mcphilemy, Genevieve, Meier, Sandra, Meinert, Susanne, Meller, Tina, Melloni, Elisa M.T., Mitchell, Philip B., Nabulsi, Leila, Nenadic, Igor, Opel, Nils, Ophoff, Roel A., Overs, Bronwyn J., Pfarr, Julia Katharina, Pineda-Zapata, Julian A., Pomarol-Clotet, Edith, Raduà, Joaquim, Repple, Jonathan, Richter, Maike, Ringwald, Kai G., Roberts, Gloria, Ross, Alex, Salvador, Raymond, Savitz, Jonathan, Schmitt, Simon, Schofield, Peter R., Sim, Kang, Stein, Dan J., Stein, Frederike, Temmingh, Henk S., Thiel, Katharina, Thomopoulos, Sophia I., Van Haren, Neeltje E.M., Vargas, Cristian, Vieta, Eduard, Vreeker, Annabel, Waltemate, Lena, Yatham, Lakshmi N., Ching, Christopher R.K., Andreassen, Ole A., Thompson, Paul M., Hajek, Tomas, Mcwhinney, Sean R., Abé, Christoph, Alda, Martin, Benedetti, Francesco, Boen, Erlend, Del Mar Bonnin, Caterina, Borgers, Tiana, Brosch, Katharina, Canales-Rodríguez, Erick J., Cannon, Dara M., Dannlowski, Udo, Diaz-Zuluaga, Ana M., Dietze, Lorielle M.F., Elvsåshagen, Torbjorn, Eyler, Lisa T., Fullerton, Janice M., Goikolea, Jose M., Goltermann, Janik, Grotegerd, Dominik, Haarman, Bartholomeus C.M., Hahn, Tim, Howells, Fleur M., Ingvar, Martin, Jahanshad, Neda, Kircher, Tilo T.J., Krug, Axel, Kuplicki, Rayus T., Landén, Mikael, Lemke, Hannah, Liberg, Benny, Lopez-Jaramillo, Carlos, Malt, Ulrik F., Martyn, Fiona M., Mazza, Elena, Mcdonald, Colm, Mcphilemy, Genevieve, Meier, Sandra, Meinert, Susanne, Meller, Tina, Melloni, Elisa M.T., Mitchell, Philip B., Nabulsi, Leila, Nenadic, Igor, Opel, Nils, Ophoff, Roel A., Overs, Bronwyn J., Pfarr, Julia Katharina, Pineda-Zapata, Julian A., Pomarol-Clotet, Edith, Raduà, Joaquim, Repple, Jonathan, Richter, Maike, Ringwald, Kai G., Roberts, Gloria, Ross, Alex, Salvador, Raymond, Savitz, Jonathan, Schmitt, Simon, Schofield, Peter R., Sim, Kang, Stein, Dan J., Stein, Frederike, Temmingh, Henk S., Thiel, Katharina, Thomopoulos, Sophia I., Van Haren, Neeltje E.M., Vargas, Cristian, Vieta, Eduard, Vreeker, Annabel, Waltemate, Lena, Yatham, Lakshmi N., Ching, Christopher R.K., Andreassen, Ole A., Thompson, Paul M., and Hajek, Tomas

Abstract

Background: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. Methods: We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. Results: BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. Conclusions: We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

Published
2023

44. Cognitive performance and brain structural connectome alterations in major depressive disorder

Author

Gruber, Marius, Mauritz, Marco, Meinert, Susanne, Grotegerd, Dominik, de Lange, Siemon C, Grumbach, Pascal, Goltermann, Janik, Winter, Nils Ralf, Waltemate, Lena, Lemke, Hannah, Thiel, Katharina, Winter, Alexandra, Breuer, Fabian, Borgers, Tiana, Enneking, Verena, Klug, Melissa, Brosch, Katharina, Meller, Tina, Pfarr, Julia-Katharina, Ringwald, Kai Gustav, Stein, Frederike, Opel, Nils, Redlich, Ronny, Hahn, Tim, Leehr, Elisabeth J, Bauer, Jochen, Nenadić, Igor, Kircher, Tilo, van den Heuvel, Martijn P, Dannlowski, Udo, Repple, Jonathan, Gruber, Marius, Mauritz, Marco, Meinert, Susanne, Grotegerd, Dominik, de Lange, Siemon C, Grumbach, Pascal, Goltermann, Janik, Winter, Nils Ralf, Waltemate, Lena, Lemke, Hannah, Thiel, Katharina, Winter, Alexandra, Breuer, Fabian, Borgers, Tiana, Enneking, Verena, Klug, Melissa, Brosch, Katharina, Meller, Tina, Pfarr, Julia-Katharina, Ringwald, Kai Gustav, Stein, Frederike, Opel, Nils, Redlich, Ronny, Hahn, Tim, Leehr, Elisabeth J, Bauer, Jochen, Nenadić, Igor, Kircher, Tilo, van den Heuvel, Martijn P, Dannlowski, Udo, and Repple, Jonathan

Abstract

BACKGROUND: Cognitive dysfunction and brain structural connectivity alterations have been observed in major depressive disorder (MDD). However, little is known about their interrelation. The present study follows a network approach to evaluate alterations in cognition-related brain structural networks.METHODS: Cognitive performance of n = 805 healthy and n = 679 acutely depressed or remitted individuals was assessed using 14 cognitive tests aggregated into cognitive factors. The structural connectome was reconstructed from structural and diffusion-weighted magnetic resonance imaging. Associations between global connectivity strength and cognitive factors were established using linear regressions. Network-based statistics were applied to identify subnetworks of connections underlying these global-level associations. In exploratory analyses, effects of depression were assessed by evaluating remission status-related group differences in subnetwork-specific connectivity. Partial correlations were employed to directly test the complete triad of cognitive factors, depressive symptom severity, and subnetwork-specific connectivity strength.RESULTS: All cognitive factors were associated with global connectivity strength. For each cognitive factor, network-based statistics identified a subnetwork of connections, revealing, for example, a subnetwork positively associated with processing speed. Within that subnetwork, acutely depressed patients showed significantly reduced connectivity strength compared to healthy controls. Moreover, connectivity strength in that subnetwork was associated to current depressive symptom severity independent of the previous disease course.CONCLUSIONS: Our study is the first to identify cognition-related structural brain networks in MDD patients, thereby revealing associations between cognitive deficits, depressive symptoms, and reduced structural connectivity. This supports the hypothesis that structural connectome alterati

Published
2023

45. Cognitive performance and brain structural connectome alterations in major depressive disorder

Author

Gruber, Marius, primary, Mauritz, Marco, additional, Meinert, Susanne, additional, Grotegerd, Dominik, additional, de Lange, Siemon C., additional, Grumbach, Pascal, additional, Goltermann, Janik, additional, Winter, Nils Ralf, additional, Waltemate, Lena, additional, Lemke, Hannah, additional, Thiel, Katharina, additional, Winter, Alexandra, additional, Breuer, Fabian, additional, Borgers, Tiana, additional, Enneking, Verena, additional, Klug, Melissa, additional, Brosch, Katharina, additional, Meller, Tina, additional, Pfarr, Julia-Katharina, additional, Ringwald, Kai Gustav, additional, Stein, Frederike, additional, Opel, Nils, additional, Redlich, Ronny, additional, Hahn, Tim, additional, Leehr, Elisabeth J., additional, Bauer, Jochen, additional, Nenadić, Igor, additional, Kircher, Tilo, additional, van den Heuvel, Martijn P., additional, Dannlowski, Udo, additional, and Repple, Jonathan, additional

Published
2023
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46. Morphometry variations of orbitofrontal regions for increased BMI and appetite in major depression

Author

Mehler, David Marc Anton, primary, Opel, Nils, additional, Repple, Jonathan, additional, Kroemer, Nils B., additional, Richter, Maike, additional, Goltermann, Janik, additional, Meinert, Susanne, additional, Waltemate, Lena, additional, Enneking, Verena, additional, Klug, Melissa, additional, Borgers, Tiana, additional, Thiel, Katharina, additional, Winter, Alexandra, additional, Gruber, Marius, additional, Mauritz, Marco, additional, Lemke, Hannah, additional, Grotegerd, Dominik, additional, Edgren, Steffen, additional, Brosch, Katharina, additional, Meller, Tina, additional, Ringwald, Kai, additional, Pfarr, Julia-Katharina, additional, Schmitt, Simon, additional, Stein, Frederike, additional, Jansen, Andreas, additional, Krug, Axel, additional, Nenadic, Igor, additional, Hahn, Tim, additional, Walter, Martin, additional, Kircher, Tilo, additional, and Dannlowski, Udo, additional

Published
2023
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47. Temporal stability and state-dependence of retrospective self-reports of childhood maltreatment in healthy and depressed adults.

Author

Goltermann, Janik, primary, Meinert, Susanne, additional, Hülsmann, Carina, additional, Dohm, Katharina, additional, Grotegerd, Dominik, additional, Redlich, Ronny, additional, Waltemate, Lena, additional, Lemke, Hannah, additional, Thiel, Katharina, additional, Mehler, David M. A., additional, Enneking, Verena, additional, Borgers, Tiana, additional, Repple, Jonathan, additional, Gruber, Marius, additional, Winter, Nils, additional, Hahn, Tim, additional, Brosch, Katharina, additional, Meller, Tina, additional, Ringwald, Kai G., additional, Schmitt, Simon, additional, Stein, Frederike, additional, Pfarr, Julia-Katharina, additional, Krug, Axel, additional, Nenadić, Igor, additional, Kircher, Tilo, additional, Opel, Nils, additional, and Dannlowski, Udo, additional

Published
2023
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48. Shared and Specific Patterns of Structural Brain Connectivity Across Affective and Psychotic Disorders

Author

Repple, Jonathan, primary, Gruber, Marius, additional, Mauritz, Marco, additional, de Lange, Siemon C., additional, Winter, Nils Ralf, additional, Opel, Nils, additional, Goltermann, Janik, additional, Meinert, Susanne, additional, Grotegerd, Dominik, additional, Leehr, Elisabeth J., additional, Enneking, Verena, additional, Borgers, Tiana, additional, Klug, Melissa, additional, Lemke, Hannah, additional, Waltemate, Lena, additional, Thiel, Katharina, additional, Winter, Alexandra, additional, Breuer, Fabian, additional, Grumbach, Pascal, additional, Hofmann, Hannes, additional, Stein, Frederike, additional, Brosch, Katharina, additional, Ringwald, Kai G., additional, Pfarr, Julia, additional, Thomas-Odenthal, Florian, additional, Meller, Tina, additional, Jansen, Andreas, additional, Nenadic, Igor, additional, Redlich, Ronny, additional, Bauer, Jochen, additional, Kircher, Tilo, additional, Hahn, Tim, additional, van den Heuvel, Martijn, additional, and Dannlowski, Udo, additional

Published
2023
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49. Emotion processing in depression with and without comorbid anxiety disorder

Author

Sindermann, Lisa, primary, Leehr, Elisabeth J., additional, Redlich, Ronny, additional, Meinert, Susanne, additional, Böhnlein, Joscha, additional, Grotegerd, Dominik, additional, Pollack, Daniel, additional, Reepen, Marieke, additional, Thiel, Katharina, additional, Winter, Alexandra, additional, Waltemate, Lena, additional, Lemke, Hannah, additional, Enneking, Verena, additional, Borgers, Tiana, additional, Opel, Nils, additional, Repple, Jonathan, additional, Goltermann, Janik, additional, Brosch, Katharina, additional, Meller, Tina, additional, Pfarr, Julia-Katharina, additional, Ringwald, Kai Gustav, additional, Schmitt, Simon, additional, Stein, Frederike, additional, Jansen, Andreas, additional, Krug, Axel, additional, Nenadić, Igor, additional, Kircher, Tilo, additional, and Dannlowski, Udo, additional

Published
2022
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50. Cognitive Performance and Brain Structural Connectome Alterations in Major Depressive Disorder

Author

Gruber, Marius, primary, Mauritz, Marco, additional, Meinert, Susanne, additional, Grotegerd, Dominik, additional, de Lange, Siemon C., additional, Grumbach, Pascal, additional, Goltermann, Janik, additional, Winter, Nils Ralf, additional, Waltemate, Lena, additional, Lemke, Hannah, additional, Thiel, Katharina, additional, Winter, Alexandra, additional, Breuer, Fabian, additional, Borgers, Tiana, additional, Enneking, Verena, additional, Klug, Melissa, additional, Brosch, Katharina, additional, Meller, Tina, additional, Pfarr, Julia-Katharina, additional, Ringwald, Kai Gustav, additional, Stein, Frederike, additional, Opel, Nils, additional, Redlich, Ronny, additional, Hahn, Tim, additional, Leehr, Elisabeth, additional, Bauer, Jochen, additional, Nenadic, Igor, additional, Kircher, Tilo, additional, van den Heuvel, Martijn P., additional, Dannlowski, Udo, additional, and Repple, Jonathan, additional

Published
2022
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