Search

Your search keyword '"Mathalon DH"' showing total 566 results
Start Over Author "Mathalon DH"
566 results on '"Mathalon DH"'

1. Identifying canonical and replicable multi‐scale intrinsic connectivity networks in 100k+ resting‐state fMRI datasets

Author

Iraji, A, Fu, Z, Faghiri, A, Duda, M, Chen, J, Rachakonda, S, DeRamus, T, Kochunov, P, Adhikari, BM, Belger, A, Ford, JM, Mathalon, DH, Pearlson, GD, Potkin, SG, Preda, A, Turner, JA, van Erp, TGM, Bustillo, JR, Yang, K, Ishizuka, K, Faria, A, Sawa, A, Hutchison, K, Osuch, EA, Theberge, J, Abbott, C, Mueller, BA, Zhi, D, Zhuo, C, Liu, S, Xu, Y, Salman, M, Liu, J, Du, Y, Sui, J, Adali, T, and Calhoun, VD

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Cognitive and Computational Psychology, Neurosciences, Psychology, Bioengineering, Clinical Research, Neurological, Humans, Brain Mapping, Magnetic Resonance Imaging, Reproducibility of Results, Nerve Net, Brain, functional connectivity, functional templates, independent component analysis, intrinsic connectivity networks, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

Despite the known benefits of data-driven approaches, the lack of approaches for identifying functional neuroimaging patterns that capture both individual variations and inter-subject correspondence limits the clinical utility of rsfMRI and its application to single-subject analyses. Here, using rsfMRI data from over 100k individuals across private and public datasets, we identify replicable multi-spatial-scale canonical intrinsic connectivity network (ICN) templates via the use of multi-model-order independent component analysis (ICA). We also study the feasibility of estimating subject-specific ICNs via spatially constrained ICA. The results show that the subject-level ICN estimations vary as a function of the ICN itself, the data length, and the spatial resolution. In general, large-scale ICNs require less data to achieve specific levels of (within- and between-subject) spatial similarity with their templates. Importantly, increasing data length can reduce an ICN's subject-level specificity, suggesting longer scans may not always be desirable. We also find a positive linear relationship between data length and spatial smoothness (possibly due to averaging over intrinsic dynamics), suggesting studies examining optimized data length should consider spatial smoothness. Finally, consistency in spatial similarity between ICNs estimated using the full data and subsets across different data lengths suggests lower within-subject spatial similarity in shorter data is not wholly defined by lower reliability in ICN estimates, but may be an indication of meaningful brain dynamics which average out as data length increases.

Published
2023

2. Spatial Dynamic Subspaces Encode Sex-Specific Schizophrenia Disruptions in Transient Network Overlap and its Links to Genetic Risk

Author

Iraji, A, Chen, J, Lewis, N, Faghiri, A, Fu, Z, Agcaoglu, O, Kochunov, P, Adhikari, BM, Mathalon, DH, Pearlson, GD, Macciardi, F, Preda, A, van Erp, TGM, Bustillo, JR, Díaz-Caneja, CM, Andrés-Camazón, P, Dhamala, M, Adali, T, and Calhoun, VD

Subjects
Biological Psychology, Physical Sciences, Psychology, Schizophrenia, Human Genome, Mental Illness, Genetics, Mental Health, Neurosciences, Clinical Research, Brain Disorders, Polygenic Risk Score, Sex Differences, Single Nucleotide Polymorphism, Spatial Dynamics, Spatially Dynamic Covariance, Time-Resolved Referenced-Informed Network Estimation Techniques
Abstract

BACKGROUND: Recent advances in resting-state fMRI allow us to study spatial dynamics, the phenomenon of brain networks spatially evolving over time. However, most dynamic studies still use subject-specific, spatially-static nodes. As recent studies have demonstrated, incorporating time-resolved spatial properties is crucial for precise functional connectivity estimation and gaining unique insights into brain function. Nevertheless, estimating time-resolved networks poses challenges due to the low signal-to-noise ratio, limited information in short time segments, and uncertain identification of corresponding networks within and between subjects. METHODS: We adapt a reference-informed network estimation technique to capture time-resolved spatial networks and their dynamic spatial integration and segregation. We focus on time-resolved spatial functional network connectivity (spFNC), an estimate of network spatial coupling, to study sex-specific alterations in schizophrenia and their links to multi-factorial genomic data. RESULTS: Our findings are consistent with the dysconnectivity and neurodevelopment hypotheses and align with the cerebello-thalamo-cortical, triple-network, and frontoparietal dysconnectivity models, helping to unify them. The potential unification offers a new understanding of the underlying mechanisms. Notably, the posterior default mode/salience spFNC exhibits sex-specific schizophrenia alteration during the state with the highest global network integration and correlates with genetic risk for schizophrenia. This dysfunction is also reflected in high-dimensional (voxel-level) space in regions with weak functional connectivity to corresponding networks. CONCLUSIONS: Our method can effectively capture spatially dynamic networks, detect nuanced SZ effects, and reveal the intricate relationship of dynamic information to genomic data. The results also underscore the potential of dynamic spatial dependence and weak connectivity in the clinical landscape.

Published
2023

3. Moving beyond the 'CAP' of the Iceberg: Intrinsic connectivity networks in fMRI are continuously engaging and overlapping.

Author

Iraji, A, Faghiri, A, Fu, Z, Kochunov, P, Adhikari, BM, Belger, A, Ford, JM, McEwen, S, Mathalon, DH, Pearlson, GD, Potkin, SG, Preda, A, Turner, JA, Van Erp, TGM, Chang, C, and Calhoun, VD

Subjects
Brain, Nerve Net, Humans, Magnetic Resonance Imaging, Brain Mapping, Functional Neuroimaging, Activation spatial map, Co-activation patterns, Event absent time points, Event present time points, Functional connectivity, Independent component analysis, Intrinsic connectivity networks, Brain Disorders, Neurosciences, Biomedical Imaging, 1.1 Normal biological development and functioning, Underpinning research, Mental health, Neurological, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Resting-state functional magnetic resonance imaging is currently the mainstay of functional neuroimaging and has allowed researchers to identify intrinsic connectivity networks (aka functional networks) at different spatial scales. However, little is known about the temporal profiles of these networks and whether it is best to model them as continuous phenomena in both space and time or, rather, as a set of temporally discrete events. Both categories have been supported by series of studies with promising findings. However, a critical question is whether focusing only on time points presumed to contain isolated neural events and disregarding the rest of the data is missing important information, potentially leading to misleading conclusions. In this work, we argue that brain networks identified within the spontaneous blood oxygenation level-dependent (BOLD) signal are not limited to temporally sparse burst moments and that these event present time points (EPTs) contain valuable but incomplete information about the underlying functional patterns. We focus on the default mode and show evidence that is consistent with its continuous presence in the BOLD signal, including during the event absent time points (EATs), i.e., time points that exhibit minimum activity and are the least likely to contain an event. Moreover, our findings suggest that EPTs may not contain all the available information about their corresponding networks. We observe distinct default mode connectivity patterns obtained from all time points (AllTPs), EPTs, and EATs. We show evidence of robust relationships with schizophrenia symptoms that are both common and unique to each of the sets of time points (AllTPs, EPTs, EATs), likely related to transient patterns of connectivity. Together, these findings indicate the importance of leveraging the full temporal data in functional studies, including those using event-detection approaches.

Published
2022

4. Anatomical and fMRI-network comparison of multiple DLPFC targeting strategies for repetitive transcranial magnetic stimulation treatment of depression

Author

Cardenas, VA, Bhat, JV, Horwege, AM, Ehrlich, TJ, Lavacot, J, Mathalon, DH, Glover, GH, Roach, BJ, Badran, BW, Forman, SD, George, MS, Thase, ME, Yesavage, JA, Yurgelun-Todd, D, and Rosen, AC

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Mental Health, Neurosciences, Clinical Research, Depression, Assistive Technology, Biomedical Imaging, Bioengineering, Mental health, Neurological, Depressive Disorder, Treatment-Resistant, Humans, Magnetic Resonance Imaging, Prefrontal Cortex, Transcranial Magnetic Stimulation, Functional connectivity, HCP atlas, Yeo atlas, TMS targeting, Medical and Health Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundThe efficacy of repetitive transcranial magnetic stimulation (rTMS) for depression may vary depending on the subregion stimulated within the dorsolateral prefrontal cortex (DLPFC). Clinical TMS typically uses scalp-based landmarks for DLPFC targeting, rather than individualized MRI guidance.ObjectiveIn rTMS patients, determine the brain systems targeted by multiple DLPFC stimulation rules by computing several surrogate measures: underlying brain targets labeled with connectivity-based atlases, subgenual cingulate anticorrelation strength, and functionally connected networks.MethodsForty-nine patients in a randomized controlled trial of rTMS therapy for treatment resistant major depression underwent structural and functional MRI. DLPFC rules were applied virtually using MR-image guidance. Underlying cortical regions were labeled, and connectivity with the subgenual cingulate and whole-brain computed.ResultsScalp-targeting rules applied post hoc to these MRIs that adjusted for head size, including Beam F3, were comparably precise, successful in directly targeting classical DLPFC and frontal networks, and anticorrelated with the subgenual cingulate. In contrast, all rules involving fixed distances introduced variability in regions and networks targeted. The 5 cm rule targeted a transitional DLPFC region with a different connectivity profile from the adjusted rules. Seed-based connectivity analyses identified multiple regions, such as posterior cingulate and inferior parietal lobe, that warrant further study in order to understand their potential contribution to clinical response.ConclusionEEG-based rules consistently targeted DLPFC brain regions with resting-state fMRI features known to be associated with depression response. These results provide a bridge from lab to clinic by enabling clinicians to relate scalp-targeting rules to functionally connected brain systems.

Published
2022

5. Targeting location relates to treatment response in active but not sham rTMS stimulation

Author

Rosen, AC, Bhat, JV, Cardenas, VA, Ehrlich, TJ, Horwege, AM, Mathalon, DH, Roach, BJ, Glover, GH, Badran, BW, Forman, SD, George, MS, Thase, ME, Yurgelun-Todd, D, Sughrue, ME, Doyen, SP, Nicholas, PJ, Scott, JC, Tian, L, and Yesavage, JA

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Biomedical Imaging, Mental Health, Clinical Trials and Supportive Activities, Brain Disorders, Clinical Research, Rehabilitation, Mental health, Brain, Depressive Disorder, Treatment-Resistant, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prefrontal Cortex, Transcranial Magnetic Stimulation, Treatment Outcome, rTMS, Resting-state fMRI networks, Depression, Subgenual cingulate, Targeting, Dorsolateral prefrontal cortex, Medical and Health Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundPrecise targeting of brain functional networks is believed critical for treatment efficacy of rTMS (repetitive pulse transcranial magnetic stimulation) in treatment resistant major depression.ObjectiveTo use imaging data from a "failed" clinical trial of rTMS in Veterans to test whether treatment response was associated with rTMS coil location in active but not sham stimulation, and compare fMRI functional connectivity between those stimulation locations.MethodsAn imaging substudy of 49 Veterans (mean age, 56 years; range, 27-78 years; 39 male) from a randomized, sham-controlled, double-blinded clinical trial of rTMS treatment, grouping participants by clinical response, followed by group comparisons of treatment locations identified by individualized fiducial markers on structural MRI and resting state fMRI derived networks.ResultsThe average stimulation location for responders versus nonresponders differed in the active but not in the sham condition (P = .02). The average responder location derived from the active condition showed significant negative functional connectivity with the subgenual cingulate (P

Published
2021

6. Persistent negative symptoms in youth at clinical high risk for psychosis: A longitudinal study

Author

Devoe, DJ, Lu, L, Cannon, TD, Cadenhead, KS, Cornblatt, BA, McGlashan, TH, Perkins, DO, Seidman, LJ, Tsuang, MT, Woods, SW, Walker, EF, Mathalon, DH, Bearden, CE, and Addington, J

Subjects
Mental Health, Brain Disorders, Prevention, Behavioral and Social Science, Schizophrenia, Clinical Research, Pediatric, Serious Mental Illness, Mental health, Adolescent, Cognition Disorders, Humans, Longitudinal Studies, Prodromal Symptoms, Psychotic Disorders, Persistent negative symptoms, Clinical high risk, Psychosis, Functioning, Negative-self schemas, Defeatist beliefs, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundSeverity of negative symptoms has been associated with poor functioning, cognitive deficits, and defeatist beliefs in schizophrenia patients. However, one area that remains understudied is persistent negative symptoms (PNS). Negative symptoms, including PNS, have been observed in those at clinical high-risk (CHR) for psychosis. The aim of this study was to determine if PNS were associated with functioning, neurocognition, and defeatist beliefs in a CHR sample.MethodCHR participants (n = 764) were recruited for the North American Prodrome Longitudinal Study. Negative symptoms were rated on the Scale of Psychosis-risk Symptoms. Generalized linear mixed models for repeated measures were used to examine changes over time between and within groups (PNS vs non-PNS).ResultsThe PNS group (n = 67) had significant deficits in functioning at baseline, 6, 12, 18, and 24-months compared to the non-PNS group (n = 673). Functioning improved over time in the non-PNS group, while functioning in the PNS group remained relatively stable and poor over a two-year period. A consistent trend emerged demonstrating higher defeatist beliefs in the PNS group; however, this result was lost when controlling for persistent depressive symptoms. There were no significant differences between the groups on neurocognition, social cognition, and transition to psychosis.ConclusionsPNS exist in youth at CHR for psychosis, resulting in significant and persistent functional impairment, which remains when controlling for persistent depressive symptoms. PNS remain even in CHR youth who do not transition to psychosis. Thus, PNS may represent an unmet therapeutic need in CHR populations for which there are currently no effective treatments.

Published
2021

7. Longitudinal changes in social cognition in individuals at clinical high risk for psychosis: An outcome based analysis.

Author

Shakeel, MK, Lu, L, Cannon, TD, Cadenhead, KS, Cornblatt, BA, McGlashan, TH, Perkins, DO, Seidman, LJ, Tsuang, MT, Woods, SW, Walker, EF, Mathalon, DH, Bearden, CE, and Addington, J

Subjects
Humans, Disease Progression, Facial Expression, Remission Induction, Risk, Longitudinal Studies, Emotions, Social Perception, Psychotic Disorders, Adult, Female, Male, Young Adult, Theory of Mind, Prodromal Symptoms, Facial Recognition, Clinical high risk, Emotion perception, Psychosis, Social cognition, Social perception, Theory of mind, Serious Mental Illness, Mental Health, Clinical Research, Behavioral and Social Science, Prevention, Brain Disorders, Basic Behavioral and Social Science, Mental health, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Social cognition deficits have been observed in individuals at clinical high risk (CHR) for psychosis. Longitudinal change in social cognition were analyzed in CHR individuals from the North American Prodrome Longitudinal Study (NAPLS2) based on outcome at 24 months. Individuals (n = 359) were classified into remission, symptomatic, prodromal progression and transition to psychosis (CHR-T) groups. Social cognition was assessed using theory of mind, emotion perception, and social perception tasks. There were no differences at baseline or 24 months between the groups on social cognition. Non-transition groups improved significantly over time on social cognition, but CHR-T did not show this effect.

Published
2019

8. Decreased hemispheric connectivity and decreased intra- and inter- hemisphere asymmetry of resting state functional network connectivity in schizophrenia

Author

Agcaoglu, O, Miller, R, Damaraju, E, Rashid, B, Bustillo, J, Cetin, MS, Van Erp, TGM, McEwen, S, Preda, A, Ford, JM, Lim, KO, Manoach, DS, Mathalon, DH, Potkin, SG, and Calhoun, VD

Subjects
Schizophrenia, Mental Health, Clinical Research, Neurosciences, Brain Disorders, Mental health, Adolescent, Adult, Brain, Brain Mapping, Female, Functional Laterality, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Rest, Young Adult, Functional network connectivity, Laterality, Hemisphere, Lateral connectivity, Heterotopic connectivity, Homotopic connectivity, Medical and Health Sciences, Psychology and Cognitive Sciences, Experimental Psychology
Abstract

Many studies have shown that schizophrenia patients have aberrant functional network connectivity (FNC) among brain regions, suggesting schizophrenia manifests with significantly diminished (in majority of the cases) connectivity. Schizophrenia is also associated with a lack of hemispheric lateralization. Hoptman et al. (2012) reported lower inter-hemispheric connectivity in schizophrenia patients compared to controls using voxel-mirrored homotopic connectivity. In this study, we merge these two points of views together using a group independent component analysis (gICA)-based approach to generate hemisphere-specific timecourses and calculate intra-hemisphere and inter-hemisphere FNC on a resting state fMRI dataset consisting of age- and gender-balanced 151 schizophrenia patients and 163 healthy controls. We analyzed the group differences between patients and healthy controls in each type of FNC measures along with age and gender effects. The results reveal that FNC in schizophrenia patients shows less hemispheric asymmetry compared to that of the healthy controls. We also found a decrease in connectivity in all FNC types such as intra-left (L_FNC), intra-right (R_FNC) and inter-hemisphere (Inter_FNC) in the schizophrenia patients relative to healthy controls, but general patterns of connectivity were preserved in patients. Analyses of age and gender effects yielded results similar to those reported in whole brain FNC studies.

Published
2018

9. 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

11. Intranasal oxytocin increases facial expressivity, but not ratings of trustworthiness, in patients with schizophrenia and healthy controls

Author

Woolley, JD, Chuang, B, Fussell, C, Scherer, S, Biagianti, B, Fulford, D, Mathalon, DH, and Vinogradov, S

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Social and Personality Psychology, Psychology, Pharmacology and Pharmaceutical Sciences, Neurosciences, Serious Mental Illness, Brain Disorders, Clinical Research, Behavioral and Social Science, Schizophrenia, Mental Health, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Mental health, Administration, Intranasal, Adult, Cross-Over Studies, Double-Blind Method, Facial Expression, Facial Recognition, Female, Humans, Male, Middle Aged, Neuropeptides, Oxytocin, Social Perception, Trust, Young Adult, Blunted affect, facial expressivity, oxytocin, schizophrenia, social cognition, trustworthiness, Public Health and Health Services, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

BackgroundBlunted facial affect is a common negative symptom of schizophrenia. Additionally, assessing the trustworthiness of faces is a social cognitive ability that is impaired in schizophrenia. Currently available pharmacological agents are ineffective at improving either of these symptoms, despite their clinical significance. The hypothalamic neuropeptide oxytocin has multiple prosocial effects when administered intranasally to healthy individuals and shows promise in decreasing negative symptoms and enhancing social cognition in schizophrenia. Although two small studies have investigated oxytocin's effects on ratings of facial trustworthiness in schizophrenia, its effects on facial expressivity have not been investigated in any population.MethodWe investigated the effects of oxytocin on facial emotional expressivity while participants performed a facial trustworthiness rating task in 33 individuals with schizophrenia and 35 age-matched healthy controls using a double-blind, placebo-controlled, cross-over design. Participants rated the trustworthiness of presented faces interspersed with emotionally evocative photographs while being video-recorded. Participants' facial expressivity in these videos was quantified by blind raters using a well-validated manualized approach (i.e. the Facial Expression Coding System; FACES).ResultsWhile oxytocin administration did not affect ratings of facial trustworthiness, it significantly increased facial expressivity in individuals with schizophrenia (Z = -2.33, p = 0.02) and at trend level in healthy controls (Z = -1.87, p = 0.06).ConclusionsThese results demonstrate that oxytocin administration can increase facial expressivity in response to emotional stimuli and suggest that oxytocin may have the potential to serve as a treatment for blunted facial affect in schizophrenia.

Published
2017

12. Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis

Author

Haas, SS, Ge, R, Agartz, I, Amminger, GP, Andreassen, OA, Bachman, P, Baeza, I, Choi, S, Colibazzi, T, Cropley, VL, de la Fuente-Sandoval, C, Ebdrup, BH, Fortea, A, Fusar-Poli, P, Glenthoj, BY, Glenthoj, LB, Haut, KM, Hayes, RA, Heekeren, K, Hooker, CI, Hwang, WJ, Jahanshad, N, Kaess, M, Kasai, K, Katagiri, N, Kim, M, Kindler, J, Koike, S, Kristensen, TD, Kwon, JS, Lawrie, SM, Lebedeva, I, Lee, J, Lemmers-Jansen, ILJ, Lin, A, Ma, X, Mathalon, DH, McGuire, P, Michel, C, Mizrahi, R, Mizuno, M, Moller, P, Mora-Duran, R, Nelson, B, Nemoto, T, Nordentoft, M, Nordholm, D, Omelchenko, MA, Pantelis, C, Pariente, JC, Raghava, J, Reyes-Madrigal, F, Rossberg, JI, Rossler, W, Salisbury, DF, Sasabayashi, D, Schall, U, Smigielski, L, Sugranyes, G, Suzuki, M, Takahashi, T, Tamnes, CK, Theodoridou, A, Thomopoulos, SI, Thompson, PM, Tomyshev, AS, Uhlhaas, PJ, Vaernes, TG, van Amelsvoort, TAMJ, van Erp, TGM, Waltz, JA, Wenneberg, C, Westlye, LT, Wood, SJ, Zhou, JH, Hernaus, D, Jalbrzikowski, M, Kahn, RS, Corcoran, CM, Frangou, S, Haas, SS, Ge, R, Agartz, I, Amminger, GP, Andreassen, OA, Bachman, P, Baeza, I, Choi, S, Colibazzi, T, Cropley, VL, de la Fuente-Sandoval, C, Ebdrup, BH, Fortea, A, Fusar-Poli, P, Glenthoj, BY, Glenthoj, LB, Haut, KM, Hayes, RA, Heekeren, K, Hooker, CI, Hwang, WJ, Jahanshad, N, Kaess, M, Kasai, K, Katagiri, N, Kim, M, Kindler, J, Koike, S, Kristensen, TD, Kwon, JS, Lawrie, SM, Lebedeva, I, Lee, J, Lemmers-Jansen, ILJ, Lin, A, Ma, X, Mathalon, DH, McGuire, P, Michel, C, Mizrahi, R, Mizuno, M, Moller, P, Mora-Duran, R, Nelson, B, Nemoto, T, Nordentoft, M, Nordholm, D, Omelchenko, MA, Pantelis, C, Pariente, JC, Raghava, J, Reyes-Madrigal, F, Rossberg, JI, Rossler, W, Salisbury, DF, Sasabayashi, D, Schall, U, Smigielski, L, Sugranyes, G, Suzuki, M, Takahashi, T, Tamnes, CK, Theodoridou, A, Thomopoulos, SI, Thompson, PM, Tomyshev, AS, Uhlhaas, PJ, Vaernes, TG, van Amelsvoort, TAMJ, van Erp, TGM, Waltz, JA, Wenneberg, C, Westlye, LT, Wood, SJ, Zhou, JH, Hernaus, D, Jalbrzikowski, M, Kahn, RS, Corcoran, CM, and Frangou, S

Abstract

IMPORTANCE: The lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in individuals at psychosis risk may be nested within the range observed in healthy individuals. OBJECTIVE: To quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder. DESIGN, SETTING, AND PARTICIPANTS: This case-control study used clinical-, IQ-, and neuroimaging software (FreeSurfer)-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1340 individuals with CHR-P and 1237 healthy individuals pooled from 29 international sites participating in the Enhancing Neuroimaging Genetics Through Meta-analysis (ENIGMA) Clinical High Risk for Psychosis Working Group. Healthy individuals and individuals with CHR-P were matched on age and sex within each recruitment site. Data were analyzed between September 1, 2021, and November 30, 2022. MAIN OUTCOMES AND MEASURES: For each regional morphometric measure, deviation scores were computed as z scores indexing the degree of deviation from their normative means from a healthy reference population. Average deviation scores (ADS) were also calculated for regional CT, SA, and SV measures and globally across all measures. Regression analyses quantified the association of deviation scores with clinical severity and cognition, and 2-proportion z tests identified case-control differences in the proportion of individuals with infranormal (z < -1.96) or supranormal (z > 1.96) scores. RESULTS: Among 1340 individuals with CHR-P, 709 (52.91%) were male, and the mean (SD) age was 20.75 (4.74) years. Among 1237 healthy individuals, 684 (55.30%) were male, and the mean (SD

Published
2024

13. Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS

Author

Woods, SW, Parker, S, Kerr, MJ, Walsh, BC, Wijtenburg, SA, Prunier, N, Nunez, AR, Buccilli, K, Mourgues-Codern, C, Brummitt, K, Kinney, KS, Trankler, C, Szacilo, J, Colton, B-L, Ali, M, Haidar, A, Billah, T, Huynh, K, Ahmed, U, Adery, LL, Marcy, PJ, Allott, K, Amminger, P, Arango, C, Broome, MR, Cadenhead, KS, Chen, EYH, Choi, J, Conus, P, Cornblatt, BA, Glenthoj, LB, Horton, LE, Kambeitz, J, Kapur, T, Keshavan, MS, Koutsouleris, N, Langbein, K, Lavoie, S, Diaz-Caneja, CM, Mathalon, DH, Mittal, VA, Nordentoft, M, Pasternak, O, Pearlson, GD, Gaspar, PA, Shah, JL, Smesny, S, Stone, WS, Strauss, GP, Wang, J, Corcoran, CM, Perkins, DO, Schiffman, J, Perez, J, Mamah, D, Ellman, LM, Powers, AR, Coleman, MJ, Anticevic, A, Fusar-Poli, P, Kane, JM, Kahn, RS, McGorry, PD, Bearden, CE, Shenton, ME, Nelson, B, Calkins, ME, Hendricks, L, Bouix, S, Addington, J, McGlashan, TH, Yung, AR, Clark, SR, Lewandowski, KE, Torous, J, Woods, SW, Parker, S, Kerr, MJ, Walsh, BC, Wijtenburg, SA, Prunier, N, Nunez, AR, Buccilli, K, Mourgues-Codern, C, Brummitt, K, Kinney, KS, Trankler, C, Szacilo, J, Colton, B-L, Ali, M, Haidar, A, Billah, T, Huynh, K, Ahmed, U, Adery, LL, Marcy, PJ, Allott, K, Amminger, P, Arango, C, Broome, MR, Cadenhead, KS, Chen, EYH, Choi, J, Conus, P, Cornblatt, BA, Glenthoj, LB, Horton, LE, Kambeitz, J, Kapur, T, Keshavan, MS, Koutsouleris, N, Langbein, K, Lavoie, S, Diaz-Caneja, CM, Mathalon, DH, Mittal, VA, Nordentoft, M, Pasternak, O, Pearlson, GD, Gaspar, PA, Shah, JL, Smesny, S, Stone, WS, Strauss, GP, Wang, J, Corcoran, CM, Perkins, DO, Schiffman, J, Perez, J, Mamah, D, Ellman, LM, Powers, AR, Coleman, MJ, Anticevic, A, Fusar-Poli, P, Kane, JM, Kahn, RS, McGorry, PD, Bearden, CE, Shenton, ME, Nelson, B, Calkins, ME, Hendricks, L, Bouix, S, Addington, J, McGlashan, TH, Yung, AR, Clark, SR, Lewandowski, KE, and Torous, J

Abstract

AIM: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). METHODS: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. RESULTS: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. CONCLUSIONS: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.

Published
2024

14. Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

Author

Wannan, CMJ, Nelson, B, Addington, J, Allott, K, Anticevic, A, Arango, C, Baker, JT, Bearden, CE, Billah, T, Bouix, S, Broome, MR, Buccilli, K, Cadenhead, KS, Calkins, ME, Cannon, TD, Cecci, G, Chen, EYH, Cho, KIK, Choi, J, Clark, SR, Coleman, MJ, Conus, P, Corcoran, CM, Cornblatt, BA, Diaz-Caneja, CM, Dwyer, D, Ebdrup, BH, Ellman, LM, Fusar-Poli, P, Galindo, L, Gaspar, PA, Gerber, C, Glenthoj, LB, Glynn, R, Harms, MP, Horton, LE, Kahn, RS, Kambeitz, J, Kambeitz-Ilankovic, L, Kane, JM, Kapur, T, Keshavan, MS, Kim, S-W, Koutsouleris, N, Kubicki, M, Kwon, JS, Langbein, K, Lewandowski, KE, Light, GA, Mamah, D, Marcy, PJ, Mathalon, DH, McGorry, PD, Mittal, VA, Nordentoft, M, Nunez, A, Pasternak, O, Pearlson, GD, Perez, J, Perkins, DO, Powers, AR, Roalf, DR, Sabb, FW, Schiffman, J, Shah, JL, Smesny, S, Spark, J, Stone, WS, Strauss, GP, Tamayo, Z, Torous, J, Upthegrove, R, Vangel, M, Verma, S, Wang, J, Winter-van Rossum, I, Wolf, DH, Wolff, P, Wood, SJ, Yung, AR, Agurto, C, Alvarez-Jimenez, M, Amminger, P, Armando, M, Asgari-Targhi, A, Cahill, J, Carrion, RE, Castro, E, Cetin-Karayumak, S, Chakravarty, MM, Cho, YT, Cotter, D, D'Alfonso, S, Ennis, M, Fadnavis, S, Fonteneau, C, Gao, C, Gupta, T, Gur, RE, Gur, RC, Hamilton, HK, Hoftman, GD, Jacobs, GR, Jarcho, J, Ji, JL, Kohler, CG, Lalousis, PA, Lavoie, S, Lepage, M, Liebenthal, E, Mervis, J, Murty, V, Nicholas, SC, Ning, L, Penzel, N, Poldrack, R, Polosecki, P, Pratt, DN, Rabin, R, Eichi, HR, Rathi, Y, Reichenberg, A, Reinen, J, Rogers, J, Ruiz-Yu, B, Scott, I, Seitz-Holland, J, Srihari, VH, Srivastava, A, Thompson, A, Turetsky, BI, Walsh, BC, Whitford, T, Wigman, JTW, Yao, B, Yuen, HP, Ahmed, U, Byun, AJS, Chung, Y, Do, K, Hendricks, L, Huynh, K, Jeffries, C, Lane, E, Langholm, C, Lin, E, Mantua, V, Santorelli, G, Ruparel, K, Zoupou, E, Adasme, T, Addamo, L, Adery, L, Ali, M, Auther, A, Aversa, S, Baek, S-H, Bates, K, Bathery, A, Bayer, JMM, Beedham, R, Bilgrami, Z, Birch, S, Bonoldi, I, Borders, O, Borgatti, R, Brown, L, Bruna, A, Carrington, H, Castillo-Passi, RI, Chen, J, Cheng, N, Ching, AE, Clifford, C, Colton, B-L, Contreras, P, Corral, S, Damiani, S, Done, M, Estrade, A, Etuka, BA, Formica, M, Furlan, R, Geljic, M, Germano, C, Getachew, R, Goncalves, M, Haidar, A, Hartmann, J, Jo, A, John, O, Kerins, S, Kerr, M, Kesselring, I, Kim, H, Kim, N, Kinney, K, Krcmar, M, Kotler, E, Lafanechere, M, Lee, C, Llerena, J, Markiewicz, C, Matnejl, P, Maturana, A, Mavambu, A, Mayol-Troncoso, R, McDonnell, A, McGowan, A, McLaughlin, D, McIlhenny, R, McQueen, B, Mebrahtu, Y, Mensi, M, Hui, CLM, Suen, YN, Wong, SMY, Morrell, N, Omar, M, Partridge, A, Phassouliotis, C, Pichiecchio, A, Politi, P, Porter, C, Provenzani, U, Prunier, N, Raj, J, Ray, S, Rayner, V, Reyes, M, Reynolds, K, Rush, S, Salinas, C, Shetty, J, Snowball, C, Tod, S, Turra-Farina, G, Valle, D, Veale, S, Whitson, S, Wickham, A, Youn, S, Zamorano, F, Zavaglia, E, Zinberg, J, Woods, SW, Shenton, ME, Wannan, CMJ, Nelson, B, Addington, J, Allott, K, Anticevic, A, Arango, C, Baker, JT, Bearden, CE, Billah, T, Bouix, S, Broome, MR, Buccilli, K, Cadenhead, KS, Calkins, ME, Cannon, TD, Cecci, G, Chen, EYH, Cho, KIK, Choi, J, Clark, SR, Coleman, MJ, Conus, P, Corcoran, CM, Cornblatt, BA, Diaz-Caneja, CM, Dwyer, D, Ebdrup, BH, Ellman, LM, Fusar-Poli, P, Galindo, L, Gaspar, PA, Gerber, C, Glenthoj, LB, Glynn, R, Harms, MP, Horton, LE, Kahn, RS, Kambeitz, J, Kambeitz-Ilankovic, L, Kane, JM, Kapur, T, Keshavan, MS, Kim, S-W, Koutsouleris, N, Kubicki, M, Kwon, JS, Langbein, K, Lewandowski, KE, Light, GA, Mamah, D, Marcy, PJ, Mathalon, DH, McGorry, PD, Mittal, VA, Nordentoft, M, Nunez, A, Pasternak, O, Pearlson, GD, Perez, J, Perkins, DO, Powers, AR, Roalf, DR, Sabb, FW, Schiffman, J, Shah, JL, Smesny, S, Spark, J, Stone, WS, Strauss, GP, Tamayo, Z, Torous, J, Upthegrove, R, Vangel, M, Verma, S, Wang, J, Winter-van Rossum, I, Wolf, DH, Wolff, P, Wood, SJ, Yung, AR, Agurto, C, Alvarez-Jimenez, M, Amminger, P, Armando, M, Asgari-Targhi, A, Cahill, J, Carrion, RE, Castro, E, Cetin-Karayumak, S, Chakravarty, MM, Cho, YT, Cotter, D, D'Alfonso, S, Ennis, M, Fadnavis, S, Fonteneau, C, Gao, C, Gupta, T, Gur, RE, Gur, RC, Hamilton, HK, Hoftman, GD, Jacobs, GR, Jarcho, J, Ji, JL, Kohler, CG, Lalousis, PA, Lavoie, S, Lepage, M, Liebenthal, E, Mervis, J, Murty, V, Nicholas, SC, Ning, L, Penzel, N, Poldrack, R, Polosecki, P, Pratt, DN, Rabin, R, Eichi, HR, Rathi, Y, Reichenberg, A, Reinen, J, Rogers, J, Ruiz-Yu, B, Scott, I, Seitz-Holland, J, Srihari, VH, Srivastava, A, Thompson, A, Turetsky, BI, Walsh, BC, Whitford, T, Wigman, JTW, Yao, B, Yuen, HP, Ahmed, U, Byun, AJS, Chung, Y, Do, K, Hendricks, L, Huynh, K, Jeffries, C, Lane, E, Langholm, C, Lin, E, Mantua, V, Santorelli, G, Ruparel, K, Zoupou, E, Adasme, T, Addamo, L, Adery, L, Ali, M, Auther, A, Aversa, S, Baek, S-H, Bates, K, Bathery, A, Bayer, JMM, Beedham, R, Bilgrami, Z, Birch, S, Bonoldi, I, Borders, O, Borgatti, R, Brown, L, Bruna, A, Carrington, H, Castillo-Passi, RI, Chen, J, Cheng, N, Ching, AE, Clifford, C, Colton, B-L, Contreras, P, Corral, S, Damiani, S, Done, M, Estrade, A, Etuka, BA, Formica, M, Furlan, R, Geljic, M, Germano, C, Getachew, R, Goncalves, M, Haidar, A, Hartmann, J, Jo, A, John, O, Kerins, S, Kerr, M, Kesselring, I, Kim, H, Kim, N, Kinney, K, Krcmar, M, Kotler, E, Lafanechere, M, Lee, C, Llerena, J, Markiewicz, C, Matnejl, P, Maturana, A, Mavambu, A, Mayol-Troncoso, R, McDonnell, A, McGowan, A, McLaughlin, D, McIlhenny, R, McQueen, B, Mebrahtu, Y, Mensi, M, Hui, CLM, Suen, YN, Wong, SMY, Morrell, N, Omar, M, Partridge, A, Phassouliotis, C, Pichiecchio, A, Politi, P, Porter, C, Provenzani, U, Prunier, N, Raj, J, Ray, S, Rayner, V, Reyes, M, Reynolds, K, Rush, S, Salinas, C, Shetty, J, Snowball, C, Tod, S, Turra-Farina, G, Valle, D, Veale, S, Whitson, S, Wickham, A, Youn, S, Zamorano, F, Zavaglia, E, Zinberg, J, Woods, SW, and Shenton, ME

Abstract

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.

Published
2024

16. 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

17. Error-related brain activity dissociates hoarding disorder from obsessive-compulsive disorder.

Author

Mathews, CA, Perez, VB, Roach, BJ, Fekri, S, Vigil, O, Kupferman, E, and Mathalon, DH

Subjects
Brain, Humans, Electroencephalography, Case-Control Studies, Task Performance and Analysis, Obsessive-Compulsive Disorder, Adolescent, Adult, Aged, Middle Aged, Female, Male, Young Adult, Hoarding Disorder, Electroencephalography/event-related potentials, error monitoring, error-related negativity, hoarding, neurophysiological, obsessive-compulsive disorder, Mental Health, Serious Mental Illness, Neurosciences, Brain Disorders, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Public Health and Health Services, Psychology, Psychiatry
Abstract

BackgroundObsessive-compulsive disorder (OCD) is associated with an abnormally large error-related negativity (ERN), an electrophysiological measure of error monitoring in response to performance errors, but it is unclear if hoarding disorder (HD) also shows this abnormality. This study aimed to determine whether the neurophysiological mechanisms underlying error monitoring are similarly compromised in HD and OCD.MethodWe used a visual flanker task to assess ERN in response to performance errors in 14 individuals with HD, 27 with OCD, 10 with HD+OCD, and 45 healthy controls (HC). Age-corrected performance and ERN amplitudes were examined using analyses of variance and planned pairwise group comparisons.ResultsA main effect of hoarding on ERN (p = 0.031) was observed, indicating ERN amplitudes were attenuated in HD relative to non-HD subjects. A group × age interaction effect on ERN was also evident. In HD-positive subjects, ERN amplitude deficits were significantly greater in younger individuals (r = -0.479, p = 0.018), whereas there were no significant ERN changes with increasing age in OCD and HC participants.ConclusionsThe reduced ERN in HD relative to OCD and HC provides evidence that HD is neurobiologically distinct from OCD, and suggests that deficient error monitoring may be a core pathophysiological feature of HD. This effect was particularly prominent in younger HD participants, further suggesting that deficient error monitoring manifests most strongly early in the illness course and/or in individuals with a relatively early illness onset.

Published
2016

19. Oxytocin administration selectively improves olfactory detection thresholds for lyral in patients with schizophrenia.

Author

Woolley, JD, Lam, O, Chuang, B, Ford, JM, Mathalon, DH, and Vinogradov, S

Subjects
Humans, Olfaction Disorders, Aldehydes, Oxytocin, Oxytocics, Cyclic AMP, Administration, Intranasal, Case-Control Studies, Cross-Over Studies, Double-Blind Method, Sensory Thresholds, Smell, Schizophrenia, Signal Transduction, Adult, Middle Aged, Female, Male, Cyclohexenes, Young Adult, Olfaction, Brain Disorders, Clinical Research, Serious Mental Illness, Mental Health, Neurosciences, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Mental health, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundOlfaction plays an important role in mammalian social behavior. Olfactory deficits are common in schizophrenia and correlate with negative symptoms and low social drive. Despite their prominence and possible clinical relevance, little is understood about the pathological mechanisms underlying olfactory deficits in schizophrenia and there are currently no effective treatments for these deficits. The prosocial neuropeptide oxytocin may affect the olfactory system when administered intranasally to humans and there is growing interest in its therapeutic potential in schizophrenia.MethodsTo examine this model, we administered 40IU of oxytocin and placebo intranasally to 31 patients with a schizophrenia spectrum illness and 34 age-matched healthy control participants in a randomized, double-blind, placebo-controlled, cross-over study. On each test day, participants completed an olfactory detection threshold test for two different odors: (1) lyral, a synthetic fragrance compound for which patients with schizophrenia have specific olfactory detection threshold deficits, possibly related to decreased cyclic adenosine 3',5'-monophosphate (cAMP) signaling; and (2) anise, a compound for which olfactory detection thresholds change with menstrual cycle phase in women.ResultsOn the placebo test day, patients with schizophrenia did not significantly differ from healthy controls in detection of either odor. We found that oxytocin administration significantly and selectively improved olfactory detection thresholds for lyral but not for anise in patients with schizophrenia. In contrast, oxytocin had no effect on detection of either odor in healthy controls.DiscussionOur data indicate that oxytocin administration may ameliorate olfactory deficits in schizophrenia and suggest the effects of intranasal oxytocin may extend to influencing the olfactory system. Given that oxytocin has been found to increase cAMP signaling in vitro a possible mechanism for these effects is discussed.

Published
2015

21. Oxytocin administration enhances controlled social cognition in patients with schizophrenia.

Author

Woolley, JD, Chuang, B, Lam, O, Lai, W, O'Donovan, A, Rankin, KP, Mathalon, DH, and Vinogradov, S

Subjects
Humans, Oxytocin, Administration, Intranasal, Cross-Over Studies, Double-Blind Method, Social Behavior, Cognition, Awareness, Social Perception, Schizophrenia, Neuropsychological Tests, Schizophrenic Psychology, Adult, Middle Aged, Male, Social cognition, Basic Behavioral and Social Science, Clinical Trials and Supportive Activities, Behavioral and Social Science, Brain Disorders, Serious Mental Illness, Neurosciences, Clinical Research, Mental Health, 1.2 Psychological and socioeconomic processes, Mental health, Psychiatry, Medical and Health Sciences, Psychology and Cognitive Sciences
Abstract

BackgroundIndividuals with schizophrenia have functionally significant deficits in automatic and controlled social cognition, but no currently available pharmacologic treatments reduce these deficits. The neuropeptide oxytocin has multiple prosocial effects when administered intranasally in humans and there is growing interest in its therapeutic potential in schizophrenia.MethodsWe administered 40 IU of oxytocin and saline placebo intranasally to 29 male subjects with schizophrenia and 31 age-matched, healthy controls in a randomized, double-blind, placebo-controlled, cross-over study. Social cognition was assessed with The Awareness of Social Inference Test (TASIT) and the Reading the Mind in the Eyes Test (RMET). We examined the effects of oxytocin administration on automatic social cognition (the ability to rapidly interpret and understand emotional cues from the voice, face, and body); controlled social cognition (the ability to comprehend indirectly expressed emotions, thoughts, and intentions through complex deliberations over longer time periods); and a control task (the ability to comprehend truthful dialog and perform general task procedures) in individuals with and without schizophrenia using mixed factorial analysis of variance models.ResultsPatients with schizophrenia showed significant impairments in automatic and controlled social cognition compared to healthy controls, and administration of oxytocin significantly improved their controlled, but not automatic, social cognition, F(1, 58)=8.75; p=0.004. Conversely, oxytocin administration had limited effects on social cognition in healthy participants. Patients and controls performed equally well and there were no effects of oxytocin administration on the control task.DiscussionIntact social cognitive abilities are associated with better functional outcomes in individuals with schizophrenia. Our data highlight the potentially complex effects of oxytocin on some but not all aspects of social cognition, and support the exploration of intranasal oxytocin as a potential adjunct treatment to improve controlled social cognition in schizophrenia.

Published
2014

22. Effects of nicotine on the neurophysiological and behavioral effects of ketamine in humans

Author

Mathalon, Daniel, Mathalon, DH, Ahn, KH, Perry, EB, Cho, HS, Roach, BJ, Blais, RK, Bhakta, S, Ranganathan, M, Ford, JM, and D'Souza, DC

Abstract

Background: N-methyl-d-aspartate (NMDA) receptor hypofunction has been implicated in the pathophysiology of schizophrenia and its associated neurocognitive impairments. The high rate of cigarette smoking in schizophrenia raises questions about how nicotine

Published
2014

23. Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia

Author

Damaraju, E, Allen, EA, Belger, A, Ford, JM, McEwen, S, Mathalon, DH, Mueller, BA, Pearlson, GD, Potkin, SG, Preda, A, Turner, JA, Vaidya, JG, van Erp, TG, and Calhoun, VD

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Serious Mental Illness, Schizophrenia, Mental Health, Neurosciences, Clinical Research, Underpinning research, 1.1 Normal biological development and functioning, Mental health, Adult, Brain, Brain Mapping, Female, Humans, Image Interpretation, Computer-Assisted, Magnetic Resonance Imaging, Male, Neural Pathways, Biological psychology, Clinical and health psychology
Abstract

Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical-subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences.

Published
2014

24. Auditory cortex processes variation in our own speech

Author

Mathalon, Daniel, Ford, Judith, Houde, John, Sitek, KR, Mathalon, DH, Roach, BJ, Houde, JF, Niziolek, CA, and Ford, JM

Abstract

As we talk, we unconsciously adjust our speech to ensure it sounds the way we intend it to sound. However, because speech production involves complex motor planning and execution, no two utterances of the same sound will be exactly the same. Here, we show

Published
2013

25. Deficient suppression of default mode regions during working memory in individuals with early psychosis and at clinical high-risk for psychosis

Author

Mathalon, Daniel, Fryer, SL, Woods, SW, Kiehl, KA, Calhoun, VD, Pearlson, GD, Roach, BJ, Ford, JM, Srihari, VH, McGlashan, TH, and Mathalon, DH

Abstract

Background: The default mode network (DMN) is a set of brain regions typically activated at rest and suppressed during extrinsic cognition. Schizophrenia has been associated with deficient DMN suppression, though the extent to which DMN dysfunction predate

Published
2013

26. Chapter 11 Converging evidence for gamma synchrony deficits in schizophrenia

Author

Roach, BJ, Ford, JM, Hoffman, RE, and Mathalon, DH

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Schizophrenia, Brain Disorders, Serious Mental Illness, Mental Health, Mental health, Acoustic Stimulation, Adult, Analysis of Variance, Auditory Perceptual Disorders, Brain Mapping, Brain Waves, Case-Control Studies, Electroencephalography, Evoked Potentials, Auditory, Female, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, Psychoacoustics, Reaction Time, Time Factors, Young Adult
Abstract

BackgroundIn electroencephalogram (EEG) studies of auditory steady-state responses (ASSRs), patients with schizophrenia show a deficit in power and/or phase-locking, particularly at the 40 Hz frequency where these responses resonate. In addition, studies of the transient gamma-band response (GBR) elicited by single tones have revealed deficits in gamma power and phase-locking in schizophrenia. We examined the degree to which the 40 Hz ASSR and the transient GBR to single tones are correlated and whether they assess overlapping or distinct gamma-band abnormalities in schizophrenia.MethodsEEG was recorded during 40 Hz ASSR and auditory oddball paradigms from 28 patients with schizophrenia or schizoaffective disorder (SZ) and 25 age- and gender-matched healthy controls (HC). The ASSR was elicited by 500 ms click trains, and the transient GBR was elicited by the standard tones from the oddball paradigm. Gamma phase and magnitude values, calculated using Morlet wavelet transformations, were used to derive total power and phase-locking measures.ResultsRelative to HC, SZ patients had significant deficits in total gamma power and phase-locking for both ASSR- and GBR-based measures. Within both groups, the 40 Hz ASSR and GBR phase-locking measures were significantly correlated, with a similar trend evident for the total power measures. Moreover, co-varying for GBR substantially reduced 40 Hz ASSR power and phase-locking differences between the groups.Conclusions40 Hz ASSR and transient GBR measures provide very similar information about auditory gamma abnormalities in schizophrenia, despite the overall enhancement of 40 Hz ASSR total power and phase-locking values relative to the corresponding GBR values.

Published
2013

27. Neurobiology of schizophrenia: Search for the elusive correlation with symptoms

Author

Mathalon, Daniel, Mathalon, DH, and Ford, JM

Abstract

In the last half-century, human neuroscience methods provided a way to study schizophrenia in vivo, and established that it is associated with subtle abnormalities in brain structure and function. However, efforts to understand the neurobiological bases of

Published
2012

28. Neurobiology of schizophrenia: Search for the elusive correlation with symptoms

Author

Mathalon, DH and Ford, JM

Subjects
Experimental Psychology, Neurosciences, Psychology, Cognitive Sciences
Abstract

In the last half-century, human neuroscience methods provided a way to study schizophrenia in vivo, and established that it is associated with subtle abnormalities in brain structure and function. However, efforts to understand the neurobiological bases of the clinical symptoms that the diagnosis is based on have been largely unsuccessful. In this paper, we provide an overview of the conceptual and methodological obstacles that undermine efforts to link the severity of specific symptoms to specific neurobiological measures. These obstacles include small samples, questionable reliability and validity of measurements, medication confounds, failure to distinguish state and trait effects, correlation-causation ambiguity, and the absence of compelling animal models of specific symptoms to test mechanistic hypotheses derived from brain-symptom correlations. We conclude with recommendations to promote progress in establishing brain-symptom relationships. © 2012 Mathalon and Ford.

Published
2012

29. Advanced brain age correlates with greater rumination and less mindfulness in schizophrenia

Author

Abram, S, Roach, BJ, Hua, JPY, Han, LKM, Mathalon, DH, Ford, JM, Fryer, SL, Abram, S, Roach, BJ, Hua, JPY, Han, LKM, Mathalon, DH, Ford, JM, and Fryer, SL

Abstract

BACKGROUND: Individual variation in brain aging trajectories is linked with several physical and mental health outcomes. Greater stress levels, worry, and rumination correspond with advanced brain age, while other individual characteristics, like mindfulness, may be protective of brain health. Multiple lines of evidence point to advanced brain aging in schizophrenia (i.e., neural age estimate > chronological age). Whether psychological dimensions such as mindfulness, rumination, and perceived stress contribute to brain aging in schizophrenia is unknown. METHODS: We estimated brain age from high-resolution anatomical scans in 54 healthy controls (HC) and 52 individuals with schizophrenia (SZ) and computed the brain predicted age difference (BrainAGE-diff), i.e., the delta between estimated brain age and chronological age. Emotional well-being summary scores were empirically derived to reflect individual differences in trait mindfulness, rumination, and perceived stress. Core analyses evaluated relationships between BrainAGE-diff and emotional well-being, testing for slopes differences across groups. RESULTS: HC showed higher emotional well-being (greater mindfulness and less rumination/stress), relative to SZ. We observed a significant group difference in the relationship between BrainAge-diff and emotional well-being, explained by BrainAGE-diff negatively correlating with emotional well-being scores in SZ, and not in HC. That is, SZ with younger appearing brains (predicted age < chronological age) had emotional summary scores that were more like HC, a relationship that endured after accounting for several demographic and clinical variables. CONCLUSIONS: These data reveal clinically relevant aspects of brain age heterogeneity among SZ and point to case-control differences in the relationship between advanced brain aging and emotional well-being.

Published
2023

30. 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, Pol, HEH, Kahn, RS, Ayesa-Arriola, R, de la Foz, VO-G, Tordesillas-Gutierrez, D, Vazquez-Bourgon, J, Crespo-Facorro, B, Alnaes, D, Dahl, A, Westlye, LT, Agartz, I, Andreassen, OA, Jonsson, EG, Kochunov, P, Bruggemann, JM, Catts, SV, Michie, PT, Mowry, BJ, Quide, 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, Nenadic, I, Kramer, 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, Sarro, 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, Diaz-Caneja, CM, Janssen, J, Lois, NG, Arango, C, Tomyshev, AS, Lebedeva, I, Cervenkav, S, Sellgrenv, CM, Georgiadis, F, Kirschner, M, Kaiser, S, Hajek, T, Skoch, A, Spaniel, F, Kim, M, Bin Kwak, Y, Oh, S, Kwon, JS, James, A, Bakker, G, Knochel, C, Stablein, M, Oertel, V, Uhlmann, A, Howells, FM, Stein, DJ, Temmingh, HS, Diaz-Zuluaga, AM, Pineda-Zapata, JA, Lopez-Jaramillo, C, Homan, S, Ji, E, Surbeck, W, Homan, P, Fishera, 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, Pol, HEH, Kahn, RS, Ayesa-Arriola, R, de la Foz, VO-G, Tordesillas-Gutierrez, D, Vazquez-Bourgon, J, Crespo-Facorro, B, Alnaes, D, Dahl, A, Westlye, LT, Agartz, I, Andreassen, OA, Jonsson, EG, Kochunov, P, Bruggemann, JM, Catts, SV, Michie, PT, Mowry, BJ, Quide, 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, Nenadic, I, Kramer, 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, Sarro, 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, Diaz-Caneja, CM, Janssen, J, Lois, NG, Arango, C, Tomyshev, AS, Lebedeva, I, Cervenkav, S, Sellgrenv, CM, Georgiadis, F, Kirschner, M, Kaiser, S, Hajek, T, Skoch, A, Spaniel, F, Kim, M, Bin Kwak, Y, Oh, S, Kwon, JS, James, A, Bakker, G, Knochel, C, Stablein, M, Oertel, V, Uhlmann, A, Howells, FM, Stein, DJ, Temmingh, HS, Diaz-Zuluaga, AM, Pineda-Zapata, JA, Lopez-Jaramillo, C, Homan, S, Ji, E, Surbeck, W, Homan, P, Fishera, 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

31. 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

32. 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

33. 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

ENIGMA Clinical High Risk for Psychosis Working Group, 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, Esther Via Virgili, 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, Suzuki M, Theodoridou A, Tomyshev AS, Tor J, Værnes TG, Velakoulis D, Venegoni GD, Vinogradov S, Wenneberg C, Westlye LT, Yamasue H, Yuan L, Yung AR, van Amelsvoort TAMJ, Turner JA, van Erp TGM, Thompson PM, and Hernaus D

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 the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (? = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (? = 0.43; 95% CI, 0.20 to 0.61; P = .001). CONCLUSIONS AND RELEVANCE: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.

Published
2021

34. 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

35. The association between migrant status and transition in an ultra-high risk for psychosis population

Author

O'Donoghue, B, Geros, H, Sizer, H, Addington, J, Amminger, GP, Beaden, CE, Cadenhead, KS, Cannon, TD, Cornblatt, BA, Berger, GE, Chen, EYH, de Haan, L, Hartmann, JA, Hickie, IB, Ising, HK, Lavoie, S, Lin, A, Markulev, C, Mathalon, DH, McGlashan, TH, Mifsud, NG, Mossaheb, N, Nieman, DH, Nordentoft, M, Perkins, DO, Riecher-Roessler, A, Schaefer, MR, Schloegelhofer, M, Seidman, LJ, Smesny, S, Thompson, A, Tsuang, MT, van der Gaag, M, Verma, S, Walker, EF, Wood, SJ, Woods, SW, Yuen, HP, Yung, AR, McGorry, PD, Nelson, B, O'Donoghue, B, Geros, H, Sizer, H, Addington, J, Amminger, GP, Beaden, CE, Cadenhead, KS, Cannon, TD, Cornblatt, BA, Berger, GE, Chen, EYH, de Haan, L, Hartmann, JA, Hickie, IB, Ising, HK, Lavoie, S, Lin, A, Markulev, C, Mathalon, DH, McGlashan, TH, Mifsud, NG, Mossaheb, N, Nieman, DH, Nordentoft, M, Perkins, DO, Riecher-Roessler, A, Schaefer, MR, Schloegelhofer, M, Seidman, LJ, Smesny, S, Thompson, A, Tsuang, MT, van der Gaag, M, Verma, S, Walker, EF, Wood, SJ, Woods, SW, Yuen, HP, Yung, AR, McGorry, PD, and Nelson, B

Abstract

PURPOSE: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. METHODS: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. RESULTS: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147-756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62-1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70-1.51). CONCLUSIONS: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics.

Published
2021

36. Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

Author

Patel, Y, Parker, N, Shin, J, Howard, D, French, L, Thomopoulos, SI, Pozzi, E, Abe, Y, Abe, C, Anticevic, A, Alda, M, Aleman, A, Alloza, C, Alonso-Lana, S, Ameis, SH, Anagnostou, E, McIntosh, AA, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Ayesa-Arriola, R, Bakker, G, Banaj, N, Banaschewski, T, Bandeira, CE, Baranov, A, Bargallo, N, Bau, CHD, Baumeister, S, Baune, BT, Bellgrove, MA, Benedetti, F, Bertolino, A, Boedhoe, PSW, Boks, M, Bollettini, I, del Mar Bonnin, C, Borgers, T, Borgwardt, S, Brandeis, D, Brennan, BP, Bruggemann, JM, Bulow, R, Busatto, GF, Calderoni, S, Calhoun, VD, Calvo, R, Canales-Rodriguez, EJ, Cannon, DM, Carr, VJ, Cascella, N, Cercignani, M, Chaim-Avancini, TM, Christakou, A, Coghill, D, Conzelmann, A, Crespo-Facorro, B, Cubillo, AI, Cullen, KR, Cupertino, RB, Daly, E, Dannlowski, U, Davey, CG, Denys, D, Deruelle, C, Di Giorgio, A, Dickie, EW, Dima, D, Dohm, K, Ehrlich, S, Ely, BA, Erwin-Grabner, T, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Fatjo-Vilas, M, Fedor, JM, Fitzgerald, KD, Ford, JM, Frodl, T, Fu, CHY, Fullerton, JM, Gabel, MC, Glahn, DC, Roberts, G, Gogberashvili, T, Goikolea, JM, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Green, MJ, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Guerrero-Pedraza, A, Gur, RE, Gur, RC, Haar, S, Haarman, BCM, Haavik, J, Hahn, T, Hajek, T, Harrison, BJ, Harrison, NA, Hartman, CA, Whalley, HC, Heslenfeld, DJ, Hibar, DP, Hilland, E, Hirano, Y, Ho, TC, Hoekstra, PJ, Hoekstra, L, Hohmann, S, Hong, LE, Hoschl, C, Hovik, MF, Howells, FM, Nenadic, I, Jalbrzikowski, M, James, AC, Janssen, J, Jaspers-Fayer, F, Xu, J, Jonassen, R, Karkashadze, G, King, JA, Kircher, T, Kirschner, M, Koch, K, Kochunov, P, Kohls, G, Konrad, K, Kramer, B, Krug, A, Kuntsi, J, Kwon, JS, Landen, M, Landro, NI, Lazaro, L, Lebedeva, IS, Leehr, EJ, Lera-Miguel, S, Lesch, K-P, Lochner, C, Louza, MR, Luna, B, Lundervold, AJ, MacMaster, FP, Maglanoc, LA, Malpas, CB, Portella, MJ, Marsh, R, Martyn, FM, Mataix-Cols, D, Mathalon, DH, McCarthy, H, McDonald, C, McPhilemy, G, Meinert, S, Menchon, JM, Minuzzi, L, Mitchell, PB, Moreno, C, Morgado, P, Muratori, F, Murphy, CM, Murphy, D, Mwangi, B, Nabulsi, L, Nakagawa, A, Nakamae, T, Namazova, L, Narayanaswamy, J, Jahanshad, N, Nguyen, DD, Nicolau, R, O'Gorman Tuura, RL, O'Hearn, K, Oosterlaan, J, Opel, N, Ophoff, RA, Oranje, B, Garcia de la Foz, VO, Overs, BJ, Paloyelis, Y, Pantelis, C, Parellada, M, Pauli, P, Pico-Perez, M, Picon, FA, Piras, F, Plessen, KJ, Pomarol-Clotet, E, Preda, A, Puig, O, Quide, Y, Radua, J, Ramos-Quiroga, JA, Rasser, PE, Rauer, L, Reddy, J, Redlich, R, Reif, A, Reneman, L, Repple, J, Retico, A, Richarte, V, Richter, A, Rosa, PGP, Rubia, KK, Hashimoto, R, Sacchet, MD, Salvador, R, Santonja, J, Sarink, K, Sarro, S, Satterthwaite, TD, Sawa, A, Schall, U, Schofield, PR, Schrantee, A, Seitz, J, Serpa, MH, Setien-Suero, E, Shaw, P, Shook, D, Silk, TJ, Sim, K, Simon, S, Simpson, HB, Singh, A, Skoch, A, Skokauskas, N, Soares, JC, Soreni, N, Soriano-Mas, C, Spalletta, G, Spaniel, F, Lawrie, SM, Stern, ER, Stewart, SE, Takayanagi, Y, Temmingh, HS, Tolin, DF, Tomecek, D, Tordesillas-Gutierrez, D, Tosetti, M, Uhlmann, A, van Amelsvoort, T, van der Wee, NJA, van der Werff, SJA, van Haren, NEM, van Wingen, GA, Vance, A, Vazquez-Bourgon, J, Vecchio, D, Venkatasubramanian, G, Vieta, E, Vilarroya, O, Vives-Gilabert, Y, Voineskos, AN, Volzke, H, von Polier, GG, Walton, E, Weickert, TW, Weickert, CS, Weideman, AS, Wittfeld, K, Wolf, DH, Wu, M-J, Yang, TT, Yang, K, Yoncheva, Y, Yun, J-Y, Cheng, Y, Zanetti, MV, Ziegler, GC, Franke, B, Hoogman, M, Buitelaar, JK, van Rooij, D, Andreassen, OA, Ching, CRK, Veltman, DJ, Schmaal, L, Stein, DJ, van den Heuvel, OA, Turner, JA, van Erp, TGM, Pausova, Z, Thompson, PM, Paus, T, Patel, Y, Parker, N, Shin, J, Howard, D, French, L, Thomopoulos, SI, Pozzi, E, Abe, Y, Abe, C, Anticevic, A, Alda, M, Aleman, A, Alloza, C, Alonso-Lana, S, Ameis, SH, Anagnostou, E, McIntosh, AA, Arango, C, Arnold, PD, Asherson, P, Assogna, F, Auzias, G, Ayesa-Arriola, R, Bakker, G, Banaj, N, Banaschewski, T, Bandeira, CE, Baranov, A, Bargallo, N, Bau, CHD, Baumeister, S, Baune, BT, Bellgrove, MA, Benedetti, F, Bertolino, A, Boedhoe, PSW, Boks, M, Bollettini, I, del Mar Bonnin, C, Borgers, T, Borgwardt, S, Brandeis, D, Brennan, BP, Bruggemann, JM, Bulow, R, Busatto, GF, Calderoni, S, Calhoun, VD, Calvo, R, Canales-Rodriguez, EJ, Cannon, DM, Carr, VJ, Cascella, N, Cercignani, M, Chaim-Avancini, TM, Christakou, A, Coghill, D, Conzelmann, A, Crespo-Facorro, B, Cubillo, AI, Cullen, KR, Cupertino, RB, Daly, E, Dannlowski, U, Davey, CG, Denys, D, Deruelle, C, Di Giorgio, A, Dickie, EW, Dima, D, Dohm, K, Ehrlich, S, Ely, BA, Erwin-Grabner, T, Ethofer, T, Fair, DA, Fallgatter, AJ, Faraone, SV, Fatjo-Vilas, M, Fedor, JM, Fitzgerald, KD, Ford, JM, Frodl, T, Fu, CHY, Fullerton, JM, Gabel, MC, Glahn, DC, Roberts, G, Gogberashvili, T, Goikolea, JM, Gotlib, IH, Goya-Maldonado, R, Grabe, HJ, Green, MJ, Grevet, EH, Groenewold, NA, Grotegerd, D, Gruber, O, Gruner, P, Guerrero-Pedraza, A, Gur, RE, Gur, RC, Haar, S, Haarman, BCM, Haavik, J, Hahn, T, Hajek, T, Harrison, BJ, Harrison, NA, Hartman, CA, Whalley, HC, Heslenfeld, DJ, Hibar, DP, Hilland, E, Hirano, Y, Ho, TC, Hoekstra, PJ, Hoekstra, L, Hohmann, S, Hong, LE, Hoschl, C, Hovik, MF, Howells, FM, Nenadic, I, Jalbrzikowski, M, James, AC, Janssen, J, Jaspers-Fayer, F, Xu, J, Jonassen, R, Karkashadze, G, King, JA, Kircher, T, Kirschner, M, Koch, K, Kochunov, P, Kohls, G, Konrad, K, Kramer, B, Krug, A, Kuntsi, J, Kwon, JS, Landen, M, Landro, NI, Lazaro, L, Lebedeva, IS, Leehr, EJ, Lera-Miguel, S, Lesch, K-P, Lochner, C, Louza, MR, Luna, B, Lundervold, AJ, MacMaster, FP, Maglanoc, LA, Malpas, CB, Portella, MJ, Marsh, R, Martyn, FM, Mataix-Cols, D, Mathalon, DH, McCarthy, H, McDonald, C, McPhilemy, G, Meinert, S, Menchon, JM, Minuzzi, L, Mitchell, PB, Moreno, C, Morgado, P, Muratori, F, Murphy, CM, Murphy, D, Mwangi, B, Nabulsi, L, Nakagawa, A, Nakamae, T, Namazova, L, Narayanaswamy, J, Jahanshad, N, Nguyen, DD, Nicolau, R, O'Gorman Tuura, RL, O'Hearn, K, Oosterlaan, J, Opel, N, Ophoff, RA, Oranje, B, Garcia de la Foz, VO, Overs, BJ, Paloyelis, Y, Pantelis, C, Parellada, M, Pauli, P, Pico-Perez, M, Picon, FA, Piras, F, Plessen, KJ, Pomarol-Clotet, E, Preda, A, Puig, O, Quide, Y, Radua, J, Ramos-Quiroga, JA, Rasser, PE, Rauer, L, Reddy, J, Redlich, R, Reif, A, Reneman, L, Repple, J, Retico, A, Richarte, V, Richter, A, Rosa, PGP, Rubia, KK, Hashimoto, R, Sacchet, MD, Salvador, R, Santonja, J, Sarink, K, Sarro, S, Satterthwaite, TD, Sawa, A, Schall, U, Schofield, PR, Schrantee, A, Seitz, J, Serpa, MH, Setien-Suero, E, Shaw, P, Shook, D, Silk, TJ, Sim, K, Simon, S, Simpson, HB, Singh, A, Skoch, A, Skokauskas, N, Soares, JC, Soreni, N, Soriano-Mas, C, Spalletta, G, Spaniel, F, Lawrie, SM, Stern, ER, Stewart, SE, Takayanagi, Y, Temmingh, HS, Tolin, DF, Tomecek, D, Tordesillas-Gutierrez, D, Tosetti, M, Uhlmann, A, van Amelsvoort, T, van der Wee, NJA, van der Werff, SJA, van Haren, NEM, van Wingen, GA, Vance, A, Vazquez-Bourgon, J, Vecchio, D, Venkatasubramanian, G, Vieta, E, Vilarroya, O, Vives-Gilabert, Y, Voineskos, AN, Volzke, H, von Polier, GG, Walton, E, Weickert, TW, Weickert, CS, Weideman, AS, Wittfeld, K, Wolf, DH, Wu, M-J, Yang, TT, Yang, K, Yoncheva, Y, Yun, J-Y, Cheng, Y, Zanetti, MV, Ziegler, GC, Franke, B, Hoogman, M, Buitelaar, JK, van Rooij, D, Andreassen, OA, Ching, CRK, Veltman, DJ, Schmaal, L, Stein, DJ, van den Heuvel, OA, Turner, JA, van Erp, TGM, Pausova, Z, Thompson, PM, and Paus, T

Abstract

IMPORTANCE: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. OBJECTIVE: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. MAIN OUTCOMES AND MEASURES: Interregional profiles of group difference in cortical thickness between cases and controls. RESULTS: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene

Published
2021

37. Genetic and clinical analyses of psychosis spectrum symptoms in a large multiethnic youth cohort reveal significant link with ADHD

Author

Loohuis, LMO, Mennigen, E, Ori, APS, Perkins, D, Robinson, E, Addington, J, Cadenhead, KS, Cornblatt, BA, Mathalon, DH, McGlashan, TH, Seidman, LJ, Keshavan, MS, Stone, WS, Tsuang, MT, Walker, EF, Woods, SW, Cannon, TD, Gur, RC, Gur, RE, Bearden, CE, Ophoff, Roel, Loohuis, LMO, Mennigen, E, Ori, APS, Perkins, D, Robinson, E, Addington, J, Cadenhead, KS, Cornblatt, BA, Mathalon, DH, McGlashan, TH, Seidman, LJ, Keshavan, MS, Stone, WS, Tsuang, MT, Walker, EF, Woods, SW, Cannon, TD, Gur, RC, Gur, RE, Bearden, CE, and Ophoff, Roel

Abstract

Psychotic symptoms are not only an important feature of severe neuropsychiatric disorders, but are also common in the general population, especially in youth. The genetic etiology of psychosis symptoms in youth remains poorly understood. To characterize genetic risk for psychosis spectrum symptoms (PS), we leverage a community-based multiethnic sample of children and adolescents aged 8–22 years, the Philadelphia Neurodevelopmental Cohort (n = 7225, 20% PS). Using an elastic net regression model, we aim to classify PS status using polygenic scores (PGS) based on a range of heritable psychiatric and brain-related traits in a multi-PGS model. We also perform univariate PGS associations and evaluate age-specific effects. The multi-PGS analyses do not improve prediction of PS status over univariate models, but reveal that the attention deficit hyperactivity disorder (ADHD) PGS is robustly and uniquely associated with PS (OR 1.12 (1.05, 1.18) P = 0.0003). This association is driven by subjects of European ancestry (OR = 1.23 (1.14, 1.34), P = 4.15 × 10−7) but is not observed in African American subjects (P = 0.65). We find a significant interaction of ADHD PGS with age (P = 0.01), with a stronger association in younger children. The association is independent of phenotypic overlap between ADHD and PS, not indirectly driven by substance use or childhood trauma, and appears to be specific to PS rather than reflecting general psychopathology in youth. In an independent sample, we replicate an increased ADHD PGS in 328 youth at clinical high risk for psychosis, compared to 216 unaffected controls (OR 1.06, CI(1.01, 1.11), P = 0.02). Our findings suggest that PS in youth may reflect a different genetic etiology than psychotic symptoms in adulthood, one more akin to ADHD, and shed light on how genetic risk can be investigated across early disease trajectories.

Published
2021

38. The genetic architecture of the human cerebral cortex

Author

Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Ching, CRK, McMahon, MAB, Shatokhina, N, Zsembik, LCP, Thomopoulos, SI, Zhu, AH, Strike, LT, Agartz, I, Alhusaini, S, Almeida, MAA, Alnaes, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-Koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bulow, R, Burger, C, Cannon, DM, Chakravarty, M, Chen, Q, Cheung, JW, Couvy-Duchesne, B, Dale, AM, Dalvie, S, de Araujo, TK, de Zubicaray, GI, de Zwarte, SMC, den Braber, A, Nhat, TD, Dohm, K, Ehrlich, S, Engelbrecht, H-R, Erk, S, Fan, CC, Fedko, IO, Foley, SF, Ford, JM, Fukunaga, M, Garrett, ME, Ge, T, Giddaluru, S, Goldman, AL, Green, MJ, Groenewold, NA, Grotegerd, D, Gurholt, TP, Gutman, BA, Hansell, NK, Harris, MA, Harrison, MB, Haswell, CC, Hauser, M, Herms, S, Heslenfeld, DJ, Ho, NF, Hoehn, D, Hoffmann, P, Holleran, L, Hoogman, M, Hottenga, J-J, Ikeda, M, Janowitz, D, Jansen, IE, Jia, T, Jockwitz, C, Kanai, R, Karama, S, Kasperaviciute, D, Kaufmann, T, Kelly, S, Kikuchi, M, Klein, M, Knapp, M, Knodt, AR, Kramer, B, Lam, M, Lancaster, TM, Lee, PH, Lett, TA, Lewis, LB, Lopes-Cendes, I, Luciano, M, Macciardi, F, Marquand, AF, Mathias, SR, Melzer, TR, Milaneschi, Y, Mirza-Schreiber, N, Moreira, JCV, Muhleisen, TW, Mueller-Myhsok, B, Najt, P, Nakahara, S, Nho, K, Loohuis, LMO, Orfanos, DP, Pearson, JF, Pitcher, TL, Putz, B, Quide, Y, Ragothaman, A, Rashid, FM, Reay, WR, Redlich, R, Reinbold, CS, Repple, J, Richard, G, Riedel, BC, Risacher, SL, Rocha, CS, Mota, NR, Salminen, L, Saremi, A, Saykin, AJ, Schlag, F, Schmaal, L, Schofield, PR, Secolin, R, Shapland, CY, Shen, L, Shin, J, Shumskaya, E, Sonderby, IE, Sprooten, E, Tansey, KE, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Turner, JA, Uhlmann, A, Vallerga, CL, van der Meer, D, van Donkelaar, MMJ, van Eijk, L, van Erp, TGM, van Haren, NEM, van Rooij, D, van Tol, M-J, Veldink, JH, Verhoef, E, Walton, E, Wang, M, Wang, Y, Wardlaw, JM, Wen, W, Westlye, LT, Whelan, CD, Witt, SH, Wittfeld, K, Wolf, C, Wolfers, T, Wu, JQ, Yasuda, CL, Zaremba, D, Zhang, Z, Zwiers, MP, Artiges, E, Assareh, AA, Ayesa-Arriola, R, Belger, A, Brandt, CL, Brown, GG, Cichon, S, Curran, JE, Davies, GE, Degenhardt, F, Dennis, MF, Dietsche, B, Djurovic, S, Doherty, CP, Espiritu, R, Garijo, D, Gil, Y, Gowland, PA, Green, RC, Hausler, AN, Heindel, W, Ho, B-C, Hoffmann, WU, Holsboer, F, Homuth, G, Hosten, N, Jack, CR, Jang, M, Jansen, A, Kimbrel, NA, Kolskar, K, Koops, S, Krug, A, Lim, KO, Luykx, JJ, Mathalon, DH, Mather, KA, Mattay, VS, Matthews, S, Van Son, JM, McEwen, SC, Melle, I, Morris, DW, Mueller, BA, Nauck, M, Nordvik, JE, Noethen, MM, O'Leary, DS, Opel, N, Martinot, M-LP, Pike, GB, Preda, A, Quinlan, EB, Rasser, PE, Ratnakar, V, Reppermund, S, Steen, VM, Tooney, PA, Torres, FR, Veltman, DJ, Voyvodic, JT, Whelan, R, White, T, Yamamori, H, Adams, HHH, Bis, JC, Debette, S, Decarli, C, Fornage, M, Gudnason, V, Hofer, E, Ikram, MA, Launer, L, Longstreth, WT, Lopez, OL, Mazoyer, B, Mosley, TH, Roshchupkin, GV, Satizabal, CL, Schmidt, R, Seshadri, S, Yang, Q, Alvim, MKM, Ames, D, Anderson, TJ, Andreassen, OA, Arias-Vasquez, A, Bastin, ME, Baune, BT, Beckham, JC, Blangero, J, Boomsma, DI, Brodaty, H, Brunner, HG, Buckner, RL, Buitelaar, JK, Bustillo, JR, Cahn, W, Cairns, MJ, Calhoun, V, Carr, VJ, Caseras, X, Caspers, S, Cavalleri, GL, Cendes, F, Corvin, A, Crespo-Facorro, B, Dalrymple-Alford, JC, Dannlowski, U, de Geus, EJC, Deary, IJ, Delanty, N, Depondt, C, Desrivieres, S, Donohoe, G, Espeseth, T, Fernandez, G, Fisher, SE, Flor, H, Forstner, AJ, Francks, C, Franke, B, Glahn, DC, Gollub, RL, Grabe, HJ, Gruber, O, Haberg, AK, Hariri, AR, Hartman, CA, Hashimoto, R, Heinz, A, Henskens, FA, Hillegers, MHJ, Hoekstra, PJ, Holmes, AJ, Hong, LE, Hopkins, WD, Pol, HEH, Jernigan, TL, Jonsson, EG, Kahn, RS, Kennedy, MA, Kircher, TTJ, Kochunov, P, Kwok, JBJ, Le Hellard, S, Loughland, CM, Martin, NG, Martinot, J-L, McDonald, C, McMahon, KL, Meyer-Lindenberg, A, Michie, PT, Morey, RA, Mowry, B, Nyberg, L, Oosterlaan, J, Ophoff, RA, Pantelis, C, Paus, T, Pausova, Z, Penninx, BWJH, Polderman, TJC, Posthuma, D, Rietschel, M, Roffman, JL, Rowland, LM, Sachdev, PS, Samann, PG, Schall, U, Schumann, G, Scott, RJ, Sim, K, Sisodiya, SM, Smoller, JW, Sommer, IE, St Pourcain, B, Stein, DJ, Toga, AW, Trollor, JN, Van der Wee, NJA, van't Ent, D, Volzke, H, Walter, H, Weber, B, Weinberger, DR, Wright, MJ, Zhou, J, Stein, JL, Thompson, PM, Medland, SE, Grasby, KL, Jahanshad, N, Painter, JN, Colodro-Conde, L, Bralten, J, Hibar, DP, Lind, PA, Pizzagalli, F, Ching, CRK, McMahon, MAB, Shatokhina, N, Zsembik, LCP, Thomopoulos, SI, Zhu, AH, Strike, LT, Agartz, I, Alhusaini, S, Almeida, MAA, Alnaes, D, Amlien, IK, Andersson, M, Ard, T, Armstrong, NJ, Ashley-Koch, A, Atkins, JR, Bernard, M, Brouwer, RM, Buimer, EEL, Bulow, R, Burger, C, Cannon, DM, Chakravarty, M, Chen, Q, Cheung, JW, Couvy-Duchesne, B, Dale, AM, Dalvie, S, de Araujo, TK, de Zubicaray, GI, de Zwarte, SMC, den Braber, A, Nhat, TD, Dohm, K, Ehrlich, S, Engelbrecht, H-R, Erk, S, Fan, CC, Fedko, IO, Foley, SF, Ford, JM, Fukunaga, M, Garrett, ME, Ge, T, Giddaluru, S, Goldman, AL, Green, MJ, Groenewold, NA, Grotegerd, D, Gurholt, TP, Gutman, BA, Hansell, NK, Harris, MA, Harrison, MB, Haswell, CC, Hauser, M, Herms, S, Heslenfeld, DJ, Ho, NF, Hoehn, D, Hoffmann, P, Holleran, L, Hoogman, M, Hottenga, J-J, Ikeda, M, Janowitz, D, Jansen, IE, Jia, T, Jockwitz, C, Kanai, R, Karama, S, Kasperaviciute, D, Kaufmann, T, Kelly, S, Kikuchi, M, Klein, M, Knapp, M, Knodt, AR, Kramer, B, Lam, M, Lancaster, TM, Lee, PH, Lett, TA, Lewis, LB, Lopes-Cendes, I, Luciano, M, Macciardi, F, Marquand, AF, Mathias, SR, Melzer, TR, Milaneschi, Y, Mirza-Schreiber, N, Moreira, JCV, Muhleisen, TW, Mueller-Myhsok, B, Najt, P, Nakahara, S, Nho, K, Loohuis, LMO, Orfanos, DP, Pearson, JF, Pitcher, TL, Putz, B, Quide, Y, Ragothaman, A, Rashid, FM, Reay, WR, Redlich, R, Reinbold, CS, Repple, J, Richard, G, Riedel, BC, Risacher, SL, Rocha, CS, Mota, NR, Salminen, L, Saremi, A, Saykin, AJ, Schlag, F, Schmaal, L, Schofield, PR, Secolin, R, Shapland, CY, Shen, L, Shin, J, Shumskaya, E, Sonderby, IE, Sprooten, E, Tansey, KE, Teumer, A, Thalamuthu, A, Tordesillas-Gutierrez, D, Turner, JA, Uhlmann, A, Vallerga, CL, van der Meer, D, van Donkelaar, MMJ, van Eijk, L, van Erp, TGM, van Haren, NEM, van Rooij, D, van Tol, M-J, Veldink, JH, Verhoef, E, Walton, E, Wang, M, Wang, Y, Wardlaw, JM, Wen, W, Westlye, LT, Whelan, CD, Witt, SH, Wittfeld, K, Wolf, C, Wolfers, T, Wu, JQ, Yasuda, CL, Zaremba, D, Zhang, Z, Zwiers, MP, Artiges, E, Assareh, AA, Ayesa-Arriola, R, Belger, A, Brandt, CL, Brown, GG, Cichon, S, Curran, JE, Davies, GE, Degenhardt, F, Dennis, MF, Dietsche, B, Djurovic, S, Doherty, CP, Espiritu, R, Garijo, D, Gil, Y, Gowland, PA, Green, RC, Hausler, AN, Heindel, W, Ho, B-C, Hoffmann, WU, Holsboer, F, Homuth, G, Hosten, N, Jack, CR, Jang, M, Jansen, A, Kimbrel, NA, Kolskar, K, Koops, S, Krug, A, Lim, KO, Luykx, JJ, Mathalon, DH, Mather, KA, Mattay, VS, Matthews, S, Van Son, JM, McEwen, SC, Melle, I, Morris, DW, Mueller, BA, Nauck, M, Nordvik, JE, Noethen, MM, O'Leary, DS, Opel, N, Martinot, M-LP, Pike, GB, Preda, A, Quinlan, EB, Rasser, PE, Ratnakar, V, Reppermund, S, Steen, VM, Tooney, PA, Torres, FR, Veltman, DJ, Voyvodic, JT, Whelan, R, White, T, Yamamori, H, Adams, HHH, Bis, JC, Debette, S, Decarli, C, Fornage, M, Gudnason, V, Hofer, E, Ikram, MA, Launer, L, Longstreth, WT, Lopez, OL, Mazoyer, B, Mosley, TH, Roshchupkin, GV, Satizabal, CL, Schmidt, R, Seshadri, S, Yang, Q, Alvim, MKM, Ames, D, Anderson, TJ, Andreassen, OA, Arias-Vasquez, A, Bastin, ME, Baune, BT, Beckham, JC, Blangero, J, Boomsma, DI, Brodaty, H, Brunner, HG, Buckner, RL, Buitelaar, JK, Bustillo, JR, Cahn, W, Cairns, MJ, Calhoun, V, Carr, VJ, Caseras, X, Caspers, S, Cavalleri, GL, Cendes, F, Corvin, A, Crespo-Facorro, B, Dalrymple-Alford, JC, Dannlowski, U, de Geus, EJC, Deary, IJ, Delanty, N, Depondt, C, Desrivieres, S, Donohoe, G, Espeseth, T, Fernandez, G, Fisher, SE, Flor, H, Forstner, AJ, Francks, C, Franke, B, Glahn, DC, Gollub, RL, Grabe, HJ, Gruber, O, Haberg, AK, Hariri, AR, Hartman, CA, Hashimoto, R, Heinz, A, Henskens, FA, Hillegers, MHJ, Hoekstra, PJ, Holmes, AJ, Hong, LE, Hopkins, WD, Pol, HEH, Jernigan, TL, Jonsson, EG, Kahn, RS, Kennedy, MA, Kircher, TTJ, Kochunov, P, Kwok, JBJ, Le Hellard, S, Loughland, CM, Martin, NG, Martinot, J-L, McDonald, C, McMahon, KL, Meyer-Lindenberg, A, Michie, PT, Morey, RA, Mowry, B, Nyberg, L, Oosterlaan, J, Ophoff, RA, Pantelis, C, Paus, T, Pausova, Z, Penninx, BWJH, Polderman, TJC, Posthuma, D, Rietschel, M, Roffman, JL, Rowland, LM, Sachdev, PS, Samann, PG, Schall, U, Schumann, G, Scott, RJ, Sim, K, Sisodiya, SM, Smoller, JW, Sommer, IE, St Pourcain, B, Stein, DJ, Toga, AW, Trollor, JN, Van der Wee, NJA, van't Ent, D, Volzke, H, Walter, H, Weber, B, Weinberger, DR, Wright, MJ, Zhou, J, Stein, JL, Thompson, PM, and Medland, SE

Abstract

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Published
2020

39. Advanced Diffusion Imaging in Psychosis Risk: a cross-sectional and longitudinal study of white matter development

Author

Di Biase, M, Karayumak, SC, Zalesky, A, Kubicki, M, Rathi, Y, Lyons, MG, Bouix, S, Billah, T, Higger, M, Anticevic, A, Addington, J, Bearden, CE, Cornblatt, BA, Keshavan, MS, Mathalon, DH, McGlashan, TH, Perkins, DO, Cadenhead, KS, Tsuang, MT, Woods, SW, Seidman, LJ, Stone, WS, Shenton, ME, Cannon, TD, Pasternak, O, Di Biase, M, Karayumak, SC, Zalesky, A, Kubicki, M, Rathi, Y, Lyons, MG, Bouix, S, Billah, T, Higger, M, Anticevic, A, Addington, J, Bearden, CE, Cornblatt, BA, Keshavan, MS, Mathalon, DH, McGlashan, TH, Perkins, DO, Cadenhead, KS, Tsuang, MT, Woods, SW, Seidman, LJ, Stone, WS, Shenton, ME, Cannon, TD, and Pasternak, O

Abstract

Background: Studies in individuals at clinical high risk (CHR) for psychosis provide a powerful means to predict outcomes and inform putative mechanisms underlying conversion to psychosis. In previous work, we applied advanced diffusion imaging methods to reveal that white matter pathology in a CHR population is characterized by cellular-specific changes in white matter, suggesting a preexisting neurodevelopmental anomaly. However, it remains unknown whether these deficits relate to clinical symptoms and/or conversion to frank psychosis. To address this gap, we examined cross-sectional and longitudinal white matter maturation in the largest imaging population of CHR individuals to date, obtained from the North American Prodrome Longitudinal Study (NAPLS-3). Methods: Multi-shell diffusion magnetic resonance imaging (MRI) data were collected across multiple timepoints (1–6 at ~2 month intervals) in 286 subjects (age range=12–32 years). These were 230 unmedicated CHR subjects, including 11% (n=25) who transitioned to psychosis (CHR-converters), as well as 56 age and sex-matched healthy controls. Raw diffusion signals were harmonized to remove scanner/site-induced effects, yielding a unified imaging dataset. Fractional anisotropy of cellular tissue (FAt) and the volume fraction of extracellular free-water (FW) were assessed in 12 major tracts from the IIT Human Brain Atlas (v.5.0). Linear mixed effects (LME) models were fitted to infer developmental trajectories of FAt and FW across age for CHR-converters, CHR-nonconverters and control groups, while accounting for the repeated measurements on each individual. Results: The rate at which FAt changed with age significantly differed between the three groups across commissural and association tracts (5 in total; p<0.05). In these tracts, FAt increased with age in controls (0.002% change per year) and in CHR-nonconverters, albeit at a slower rate (0.00074% per year). In contrast, FAt declined with age in CHR-converters at a r

Published
2020

41. Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

Author

van Erp, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Clark, VP, Mueller, BA, de Zwarte, SMC, Ophoff, RA, van Haren, NEM, Andreassen, OA, Gurholt, TP, Gruber, O, Kraemer, B, Richter, A, Calhoun, VD, Crespo-Facorro, B, Roiz-Santiañez, R, Tordesillas-Gutiérrez, D, Loughland, C, Catts, S, Fullerton, JM, Green, MJ, Henskens, F, Jablensky, A, Mowry, BJ, Pantelis, C, Quidé, Y, Schall, U, Scott, RJ, Cairns, MJ, Seal, M, Tooney, PA, Rasser, PE, Cooper, G, Shannon Weickert, C, Weickert, TW, Hong, E, Kochunov, P, Gur, RE, Gur, RC, Ford, JM, Macciardi, F, Mathalon, DH, Potkin, SG, Preda, A, Fan, F, Ehrlich, S, King, MD, De Haan, L, Veltman, DJ, Assogna, F, Banaj, N, de Rossi, P, Iorio, M, Piras, F, Spalletta, G, Pomarol-Clotet, E, Kelly, S, Ciufolini, S, Radua, J, Murray, R, Marques, TR, Simmons, A, Borgwardt, S, Schönborn-Harrisberger, F, Riecher-Rössler, A, Smieskova, R, Alpert, KI, Bertolino, A, Bonvino, A, Di Giorgio, A, Neilson, E, Mayer, AR, Yun, JY, Cannon, DM, Lebedeva, I, Tomyshev, AS, Akhadov, T, Kaleda, V, Fatouros-Bergman, H, Flyckt, L, Farde, L, Cervenka, S, Agartz, I, Collste, K, Victorsson, P, Engberg, G, Erhardt, S, Schwieler, L, Malmqvist, A, Hedberg, M, Orhan, F, van Erp, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Clark, VP, Mueller, BA, de Zwarte, SMC, Ophoff, RA, van Haren, NEM, Andreassen, OA, Gurholt, TP, Gruber, O, Kraemer, B, Richter, A, Calhoun, VD, Crespo-Facorro, B, Roiz-Santiañez, R, Tordesillas-Gutiérrez, D, Loughland, C, Catts, S, Fullerton, JM, Green, MJ, Henskens, F, Jablensky, A, Mowry, BJ, Pantelis, C, Quidé, Y, Schall, U, Scott, RJ, Cairns, MJ, Seal, M, Tooney, PA, Rasser, PE, Cooper, G, Shannon Weickert, C, Weickert, TW, Hong, E, Kochunov, P, Gur, RE, Gur, RC, Ford, JM, Macciardi, F, Mathalon, DH, Potkin, SG, Preda, A, Fan, F, Ehrlich, S, King, MD, De Haan, L, Veltman, DJ, Assogna, F, Banaj, N, de Rossi, P, Iorio, M, Piras, F, Spalletta, G, Pomarol-Clotet, E, Kelly, S, Ciufolini, S, Radua, J, Murray, R, Marques, TR, Simmons, A, Borgwardt, S, Schönborn-Harrisberger, F, Riecher-Rössler, A, Smieskova, R, Alpert, KI, Bertolino, A, Bonvino, A, Di Giorgio, A, Neilson, E, Mayer, AR, Yun, JY, Cannon, DM, Lebedeva, I, Tomyshev, AS, Akhadov, T, Kaleda, V, Fatouros-Bergman, H, Flyckt, L, Farde, L, Cervenka, S, Agartz, I, Collste, K, Victorsson, P, Engberg, G, Erhardt, S, Schwieler, L, Malmqvist, A, Hedberg, M, and Orhan, F

Published
2019

42. Efference copy/corollary discharge function and targeted cognitive training in patients with schizophrenia

Author

Roach, B, Ford, J, Biagianti, B, Hamilton, H, Ramsay, I, Fisher, M, Loewy, R, Vinogradov, S, Mathalon, D, Roach BJ, Ford JM, Biagianti B, Hamilton HK, Ramsay IS, Fisher M, Loewy R, Vinogradov S, Mathalon DH, Roach, B, Ford, J, Biagianti, B, Hamilton, H, Ramsay, I, Fisher, M, Loewy, R, Vinogradov, S, Mathalon, D, Roach BJ, Ford JM, Biagianti B, Hamilton HK, Ramsay IS, Fisher M, Loewy R, Vinogradov S, and Mathalon DH

Abstract

Introduction: During vocalization, efference copy/corollary discharge mechanisms suppress the auditory cortical response to self-generated sounds as reflected in the N1 component of the auditory event-related potential (ERP). N1 suppression during talking is reduced in patients with schizophrenia. We hypothesized that these deficits would recover with auditory training that targets the speech processing system. Methods: Forty-nine individuals early in the course of a schizophrenia-spectrum illness (ESZ) were randomly assigned to 40 h of Targeted Auditory Training (TAT; n = 23) or Computer Games (CG; n = 26). The N1 ERP component was elicited during production (Talk) and playback (Listen) of vocalization. Effects of Treatment on Global Cognition, N1 suppression (Talk-Listen), N1 during Talking and Listening were assessed. Simple effects of the passage of time were also assessed in the HC after 28 weeks. Results: There was a Treatment × Time interaction revealing that N1 suppression was improved with TAT, but not with CG. TAT, but not CG, also improved Global Cognition. However, TAT and CG groups differed in their pre-treatment N1 suppression, and greater N1-suppression abnormalities were strongly associated with greater improvement in N1 suppression. Conclusions: In this sample of ESZ individuals, targeted auditory training appeared to improve the function of the efference copy/corollary discharge mechanism which tended to deteriorate with computer games. It remains to be determined if baseline N1 suppression abnormalities are necessary for TAT treatment to have a positive effect on efference copy/corollary discharge function or if improvements observed in this study represent a regression to the mean N1 suppression in ESZ.

Published
2019

43. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium

Author

van Erp, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Bustillo, JR, Clark, VP, Agartz, I, Mueller, BA, Cahn, W, de Zwarte, SMC, Hulshoff Pol, HE, Kahn, RS, Ophoff, RA, van Haren, NEM, Andreassen, OA, Dale, AM, Doan, NT, Gurholt, TP, Hartberg, CB, Haukvik, UK, Jørgensen, KN, Lagerberg, TV, Melle, I, Westlye, LT, Gruber, O, Kraemer, B, Richter, A, Zilles, D, Calhoun, VD, Crespo-Facorro, B, Roiz-Santiañez, R, Tordesillas-Gutiérrez, D, Loughland, C, Carr, VJ, Catts, S, Cropley, VL, Fullerton, JM, Green, MJ, Henskens, FA, Jablensky, A, Lenroot, RK, Mowry, BJ, Michie, PT, Pantelis, C, Quidé, Y, Schall, U, Scott, RJ, Cairns, MJ, Seal, M, Tooney, PA, Rasser, PE, Cooper, G, Shannon Weickert, C, Weickert, TW, Morris, DW, Hong, E, Kochunov, P, Beard, LM, Gur, RE, Gur, RC, Satterthwaite, TD, Wolf, DH, Belger, A, Brown, GG, Ford, JM, Macciardi, F, Mathalon, DH, O'Leary, DS, Potkin, SG, Preda, A, Voyvodic, J, Lim, KO, McEwen, S, Yang, F, Tan, Y, Tan, S, Wang, Z, Fan, F, Chen, J, Xiang, H, Tang, S, Guo, H, Wan, P, Wei, D, Bockholt, HJ, Ehrlich, S, Wolthusen, RPF, King, MD, Shoemaker, JM, Sponheim, SR, De Haan, L, Koenders, L, van Erp, TGM, Walton, E, Hibar, DP, Schmaal, L, Jiang, W, Glahn, DC, Pearlson, GD, Yao, N, Fukunaga, M, Hashimoto, R, Okada, N, Yamamori, H, Bustillo, JR, Clark, VP, Agartz, I, Mueller, BA, Cahn, W, de Zwarte, SMC, Hulshoff Pol, HE, Kahn, RS, Ophoff, RA, van Haren, NEM, Andreassen, OA, Dale, AM, Doan, NT, Gurholt, TP, Hartberg, CB, Haukvik, UK, Jørgensen, KN, Lagerberg, TV, Melle, I, Westlye, LT, Gruber, O, Kraemer, B, Richter, A, Zilles, D, Calhoun, VD, Crespo-Facorro, B, Roiz-Santiañez, R, Tordesillas-Gutiérrez, D, Loughland, C, Carr, VJ, Catts, S, Cropley, VL, Fullerton, JM, Green, MJ, Henskens, FA, Jablensky, A, Lenroot, RK, Mowry, BJ, Michie, PT, Pantelis, C, Quidé, Y, Schall, U, Scott, RJ, Cairns, MJ, Seal, M, Tooney, PA, Rasser, PE, Cooper, G, Shannon Weickert, C, Weickert, TW, Morris, DW, Hong, E, Kochunov, P, Beard, LM, Gur, RE, Gur, RC, Satterthwaite, TD, Wolf, DH, Belger, A, Brown, GG, Ford, JM, Macciardi, F, Mathalon, DH, O'Leary, DS, Potkin, SG, Preda, A, Voyvodic, J, Lim, KO, McEwen, S, Yang, F, Tan, Y, Tan, S, Wang, Z, Fan, F, Chen, J, Xiang, H, Tang, S, Guo, H, Wan, P, Wei, D, Bockholt, HJ, Ehrlich, S, Wolthusen, RPF, King, MD, Shoemaker, JM, Sponheim, SR, De Haan, L, and Koenders, L

Abstract

Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. Methods: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11–78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10–87 years; 53% male) assessed with standardized methods at 39 centers worldwide. Results: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = −0.530/−0.516) and smaller surface area (left/right hemisphere: Cohen's d = −0.251/−0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. Conclusions: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

Published
2018

44. Intranasal oxytocin increases facial expressivity, but not ratings of trustworthiness, in patients with schizophrenia and healthy controls

Author

Woolley, J, Chuang, B, Fussell, C, Scherer, S, Biagianti, B, Fulford, D, Mathalon, D, Vinogradov, S, Woolley JD, Chuang B, Fussell C, Scherer S, Biagianti B, Fulford D, Mathalon DH, Vinogradov S, Woolley, J, Chuang, B, Fussell, C, Scherer, S, Biagianti, B, Fulford, D, Mathalon, D, Vinogradov, S, Woolley JD, Chuang B, Fussell C, Scherer S, Biagianti B, Fulford D, Mathalon DH, and Vinogradov S

Abstract

Background Blunted facial affect is a common negative symptom of schizophrenia. Additionally, assessing the trustworthiness of faces is a social cognitive ability that is impaired in schizophrenia. Currently available pharmacological agents are ineffective at improving either of these symptoms, despite their clinical significance. The hypothalamic neuropeptide oxytocin has multiple prosocial effects when administered intranasally to healthy individuals and shows promise in decreasing negative symptoms and enhancing social cognition in schizophrenia. Although two small studies have investigated oxytocin's effects on ratings of facial trustworthiness in schizophrenia, its effects on facial expressivity have not been investigated in any population. Method We investigated the effects of oxytocin on facial emotional expressivity while participants performed a facial trustworthiness rating task in 33 individuals with schizophrenia and 35 age-matched healthy controls using a double-blind, placebo-controlled, cross-over design. Participants rated the trustworthiness of presented faces interspersed with emotionally evocative photographs while being video-recorded. Participants' facial expressivity in these videos was quantified by blind raters using a well-validated manualized approach (i.e. the Facial Expression Coding System; FACES). Results While oxytocin administration did not affect ratings of facial trustworthiness, it significantly increased facial expressivity in individuals with schizophrenia (Z =Â-2.33, p = 0.02) and at trend level in healthy controls (Z =Â-1.87, p = 0.06). Conclusions These results demonstrate that oxytocin administration can increase facial expressivity in response to emotional stimuli and suggest that oxytocin may have the potential to serve as a treatment for blunted facial affect in schizophrenia.

Published
2017

45. Trait aspects of auditory mismatch negativity predict response to auditory training in individuals with early illness schizophrenia

Author

Biagianti, B, Roach, B, Fisher, M, Loewy, R, Ford, J, Vinogradov, S, Mathalon, D, Roach, BJ, Ford, JM, Mathalon, DH, Biagianti, B, Roach, B, Fisher, M, Loewy, R, Ford, J, Vinogradov, S, Mathalon, D, Roach, BJ, Ford, JM, and Mathalon, DH

Abstract

Background: Individuals with schizophrenia have heterogeneous impairments of the auditory processing system that likely mediate differences in the cognitive gains induced by auditory training (AT). Mismatch negativity (MMN) is an event-related potential component reflecting auditory echoic memory, and its amplitude reduction in schizophrenia has been linked to cognitive deficits. Therefore, MMN may predict response to AT and identify individuals with schizophrenia who have the most to gain from AT. Furthermore, to the extent that AT strengthens auditory deviance processing, MMN may also serve as a readout of the underlying changes in the auditory system induced by AT. Methods: Fifty-six individuals early in the course of a schizophrenia-spectrum illness (ESZ) were randomly assigned to 40 h of AT or Computer Games (CG). Cognitive assessments and EEG recordings during a multi-deviant MMN paradigm were obtained before and after AT and CG. Changes in these measures were compared between the treatment groups. Baseline and trait-like MMN data were evaluated as predictors of treatment response. MMN data collected with the same paradigm from a sample of Healthy Controls (HC; n = 105) were compared to baseline MMN data from the ESZ group. Results: Compared to HC, ESZ individuals showed significant MMN reductions at baseline (p = .003). Reduced Double-Deviant MMN was associated with greater general cognitive impairment in ESZ individuals (p = .020). Neither ESZ intervention group showed significant change in MMN. We found high correlations in all MMN deviant types (rs = .59-.68, all ps < .001) between baseline and post-intervention amplitudes irrespective of treatment group, suggesting trait-like stability of the MMN signal. Greater deficits in trait-like Double-Deviant MMN predicted greater cognitive improvements in the AT group (p = .02), but not in the CG group. Conclusions: In this sample of ESZ individuals, AT had no effect on auditory deviance processing as assessed

Published
2017

46. Erratum: Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium (Molecular Psychiatry (2015) DOI:10.1038/mp.2015.63)

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

Published
2016

47. Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain

Author

Forsyth, JK, Bachman, P, Mathalon, DH, Roach, BJ, Asarnow, RF, and Foerde, K

Abstract

Experience-dependent plasticity is a fundamental property of the brain. It is critical for everyday function, is impaired in a range of neurological and psychiatric disorders, and frequently depends on long-term potentiation (LTP). Preclinical studies suggest that augmenting N-methyl-D-aspartate receptor (NMDAR) signaling may promote experience-dependent plasticity; however, a lack of noninvasive methods has limited our ability to test this idea in humans until recently. We examined the effects of enhancing NMDAR signaling using D-cycloserine (DCS) on a recently developed LTP EEG paradigm that uses high-frequency visual stimulation (HFvS) to induce neural potentiation in visual cortex neurons, as well as on three cognitive tasks: a weather prediction task (WPT), an information integration task (IIT), and a n-back task. The WPT and IIT are learning tasks that require practice with feedback to reach optimal performance. The n-back assesses working memory. Healthy adults were randomized to receive DCS (100 mg; n = 32) or placebo (n = 33); groups were similar in IQ and demographic characteristics. Participants who received DCS showed enhanced potentiation of neural responses following repetitive HFvS, as well as enhanced performance on the WPT and IIT. Groups did not differ on the n-back. Augmenting NMDAR signaling using DCS therefore enhanced activity-dependent plasticity in human adults, as demonstrated by lasting enhancement of neural potentiation following repetitive HFvS and accelerated acquisition of two learning tasks. Results highlight the utility of considering cellular mechanisms underlying distinct cognitive functions when investigating potential cognitive enhancers.

Published
2015

48. Neural Oscillations and Synchrony in Brain Dysfunction and Neuropsychiatric Disorders: It's About Time

Author

Mathalon, DH and Sohal, VS

Subjects
Neurons, Time Factors, Other Medical and Health Sciences, Quantitative Biology::Neurons and Cognition, Mental Disorders, 1.1 Normal biological development and functioning, Neurosciences, Brain, Magnetoencephalography, Electroencephalography, Mental Health, Neurological, Humans, Gamma Rhythm, Psychology, Cognitive Sciences, Evoked Potentials
Abstract

Neural oscillations are rhythmic fluctuations over time in the activity or excitability of single neurons, local neuronal populations or "assemblies," and/or multiple regionally distributed neuronal assemblies. Synchronized oscillations among large numbers of neurons are evident in electrocorticographic, electroencephalographic, magnetoencephalographic, and local field potential recordings and are generally understood to depend on inhibition that paces assemblies of excitatory neurons to produce alternating temporal windows of reduced and increased excitability. Synchronization of neural oscillations is supported by the extensive networks of local and long-range feedforward and feedback bidirectional connections between neurons. Here, we review some of the major methods and measures used to characterize neural oscillations, with a focus on gamma oscillations. Distinctions are drawn between stimulus-independent oscillations recorded during resting states or intervals between task events, stimulus-induced oscillations that are time locked but not phase locked to stimuli, and stimulus-evoked oscillations that are both time and phase locked to stimuli. Synchrony of oscillations between recording sites, and between the amplitudes and phases of oscillations of different frequencies (cross-frequency coupling), is described and illustrated. Molecular mechanisms underlying gamma oscillations are also reviewed. Ultimately, understanding the temporal organization of neuronal network activity, including interactions between neural oscillations, is critical for elucidating brain dysfunction in neuropsychiatric disorders.

Published
2015

49. Prodromal Symptom Severity Predicts Accelerated Gray Matter Reduction and Third Ventricle Expansion Among Clinically High Risk Youth Developing Psychotic Disorders

Author

Chung, Y, Jacobson, A, He, G, van Erp, TGM, McEwen, S, Addington, J, Bearden, CE, Cadenhead, K, Cornblatt, B, Mathalon, DH, McGlashan, T, Perkins, D, Seidman, LJ, Tsuang, M, Walker, E, Woods, SW, Heinssen, R, and Cannon, TD

Abstract

A recent prospective longitudinal neuroimaging study of 274 prodromal risk syndrome subjects revealed that those who later developed full-blown psychotic symptoms exhibited accelerated gray matter loss and third ventricle expansion around the time of onset of psychosis. Previous studies also indicate that higher levels of unusual thought content during prodromal states are a significant predictor of psychosis in clinically high-risk youth (CHR). However, the relationship between clinical symptoms and changes in neuroanatomical structure has not been previously examined in the North American Prodrome Longitudinal Study (NAPLS) sample at the atlas level. In this report, we investigated whether symptom severity as measured by the Scale of Prodromal Symptoms (SOPS) predicted the accelerated gray matter decline in 274 CHR cases, including 35 who converted to psychosis. Higher levels of unusual thought content (pre-delusional) symptoms at baseline were associated with a steeper rate of gray matter loss in the prefrontal cortex bilaterally among converters. In contrast, there was no association found among non-converters. Steeper gray matter loss seems to be unique to those (CHR) individuals with higher levels of sub-psychotic pre-delusional symptoms that acutely worsen in the ramp-up to full-blown psychosis, and as such may reflect pathophysiological processes driving emergence of psychosis.

Published
2015

50. Visual hallucinations are associated with hyperconnectivity between the amygdala and visual cortex in people with a diagnosis of schizophrenia

Author

Ford, JM, Palzes, VA, Roach, BJ, Potkin, SG, Van Erp, TGM, Turner, JA, Mueller, BA, Calhoun, VD, Voyvodic, J, Belger, A, Bustillo, J, Vaidya, JG, Preda, A, McEwen, SC, and Mathalon, DH

Abstract

© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.Introduction: While auditory verbal hallucinations (AH) are a cardinal symptom of schizophrenia, people with a diagnosis of schizophrenia (SZ) may also experience visual hallucinations (VH). In a retrospective analysis of a large sample of SZ and healthy controls (HC) studied as part of the functional magnetic resonance imaging (fMRI) Biomedical Informatics Research Network (FBIRN), we asked if SZ who endorsed experiencing VH during clinical interviews had greater connectivity between visual cortex and limbic structures than SZ who did not endorse experiencing VH. Methods: We analyzed resting state fMRI data from 162 SZ and 178 age- and gender-matched HC. SZ were sorted into groups according to clinical ratings on AH and VH: SZ with VH (VH-SZ; n = 45), SZ with AH but no VH (AH-SZ; n = 50), and SZ with neither AH nor VH (NoH-SZ; n = 67). Our primary analysis was seed based, extracting connectivity between visual cortex and the amygdala (because of its role in fear and negative emotion) and visual cortex and the hippocampus (because of its role in memory). Results: Compared with the other groups, VH-SZ showed hyperconnectivity between the amygdala and visual cortex, specifically BA18, with no differences in connectivity among the other groups. In a voxel-wise, whole brain analysis comparing VH-SZ with AH-SZ, the amygdala was hyperconnected to left temporal pole and inferior frontal gyrus in VH-SZ, likely due to their more severe thought broadcasting. Conclusions: VH-SZ have hyperconnectivity between subcortical areas subserving emotion and cortical areas subserving higher order visual processing, providing biological support for distressing VH in schizophrenia.

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results