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Machine learning of brain gray matter differentiates sex in a large forensic sample

HUMAN BRAIN MAPPING 2019年第5期40卷 1496-1506页

作者： Anderson, Nathaniel E. Harenski, Keith A. Harenski, Carla L. Koenigs, Michael R. Decety, Jean Calhoun, Vince D. Kiehl, Kent A. Mind Res Network Albuquerque NM 87106 USA Lovelace Biomed & Environm Res Inst Albuquerque NM 87108 USA Univ Wisconsin Madison WI USA Univ Chicago Chicago IL 60637 USA Univ New Mexico Albuquerque NM 87131 USA

Differences between males and females have been extensively documented in biological, psychological, and behavioral domains. Among these, sex differences in the rate and typology of antisocial behavior remains one of the most conspicuous and enduring patterns among humans. However, the nature and extent of sexual dimorphism in the brain among antisocial populations remains mostly unexplored. Here, we seek to understand sex differences in brain structure between incarcerated males and females in a large sample (n=1,300) using machine learning. We apply source-based morphometry, a contemporary multivariate approach for quantifying gray matter measured with magnetic resonance imaging, and carry these parcellations forward using machine learning to classify sex. Models using components of brain gray matter volume and concentration were able to differentiate between males and females with greater than 93% generalizable accuracy. Highly differentiated components include orbitofrontal and frontopolar regions, proportionally larger in females, and anterior medial temporal regions proportionally larger in males. We also provide a complimentary analysis of a nonforensic healthy control sample and replicate our 93% sex discrimination. These findings demonstrate that the brains of males and females are highly distinguishable. Understanding sex differences in the brain has implications for elucidating variability in the incidence and progression of disease, psychopathology, and differences in psychological traits and behavior. The reliability of these differences confirms the importance of sex as a moderator of individual differences in brain structure and suggests future research should consider sex specific models.

关键词： antisocial behavior gender machine learning MRI sex source-based morphometry

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Common variation in ZNF804A (rs1344706) is not associated with brain morphometry in schizophrenia or healthy participants

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PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY 2018年 82卷 12-20页

作者： Quide, Yann Matosin, Natalie Atkins, Joshua R. Fitzsimmons, Chantel Cairns, Murray J. Carr, Vaughan J. Green, Melissa J. UNSW Sch Psychiat Randwick NSW Australia Neurosci Res Australia Randwick NSW Australia Max Planck Inst Psychiat Dept Translat Res Psychiat Munich Germany Univ Newcastle Sch Biomed Sci & Pharm Callaghan NSW Australia Monash Univ Sch Clin Sci Dept Psychiat Clayton Vic Australia Macquarie Univ ARC Ctr Cognit & Its Disorders CCD Sydney NSW Australia

Background: The single nucleotide polymorphism (SNP) rs1344706 [A > C] within intron 2 of the zinc finger protein 804A gene (ZNF804A) is associated with schizophrenia at the genome-wide level, but its function in relation to the development of psychotic disorders, including its influence on brain morphology remains unclear. Methods: Using both univariate (voxel-based morphometry, VBM;cortical thickness) and multivariate (sourcebased morphometry, SBM) approaches, we examined the effects of variation of the rs1344706 polymorphism on grey matter integrity in 214 Caucasian schizophrenia cases and 94 Caucasian healthy individuals selected from the Australian Schizophrenia Research Bank. Results: Neither univariate nor multivariate analyses showed any associations between indices of grey matter and rs1344706 variation in schizophrenia or healthy participants. This was revealed in the context of the typical pattern of decreased grey matter integrity in schizophrenia compared to healthy individuals, including: (1) large grey matter volume reductions in the orbitofrontal and anterior cingulate cortices and the left fusiform/inferior temporal gyri;(2) decreased cortical thickness in the left inferior temporal and fusiform gyri, the left orbitofrontal gyrus, as well as in the right pars opercularis/precentral gyrus;and (3) decreased covariation of grey matter concentration in frontal and limbic brain regions emerging from the SBM analyses. Conclusions: Contrary to some - but not all - previous findings, this study of a large sample of schizophrenia cases and healthy controls reveals no evidence for association between grey matter alterations and variation in rs1344706 (ZNF804A). Differences in sample sizes and ethnicities may account for discrepant findings between the present and previous studies.

关键词： Schizophrenia ZNF804A Voxel-based morphometry Surface-based morphometry source-based morphometry Imaging genetics

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Mindfulness-based interventions modulate structural network strength in patients with opioid dependence

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ADDICTIVE BEHAVIORS 2018年第0期82卷 50-56页

作者： Fahmy, Reham Wasfi, Maha Mamdouh, Rania Moussa, Kareem Wahba, Ahmed Wittemann, Miriam Hirjak, Dusan Kubera, Katharina M. Wolf, Nadine D. Sambataro, Fabio Wolf, Robert Christian Cairo Univ Kasralainy Fac Med Dept Psychiat Giza Egypt Cairo Univ Kasralainy Fac Med Dept Radiol Giza Egypt Psychiat Hosp Rickling Rickling Germany Saarland Univ Dept Psychiat & Psychotherapy Homburg Germany Heidelberg Univ Med Fac Mannheim Cent Inst Mental Hlth Dept Psychiat & Psychotherapy Heidelberg Germany Udine Univ Dept Med DAME Udine Italy Heidelberg Univ Ctr Psychosocial Med Dept Gen Psychiat Vossstr 4 D-69115 Heidelberg Germany

Mindfulness-based interventions (MBI) are increasingly used in the treatment of patients with mental disorders, in particular in individuals presenting with affective disorders or in patients exhibiting abnormal levels of impulsive behavior. MBI have been also offered to patients with substance use disorders, where such treatment options may yield considerable clinical effects. Neural effects associated with MBI have been increasingly acknowledged, but is unknown whether MBI exert specific effects on brain structure in patients with substance use disorders. In this study, we investigated 19 inpatients with opioid dependence receiving treatment-as-usual (TAU, n = 9) or additional MBI (n = 10). Structural magnetic resonance imaging data were acquired before and after four weeks of treatment. source-based morphometry was used to investigate modulation of structural networks after treatment. Both treatment modalities led to significant clinical improvement. Patients receiving MBI showed a significant change in distress tolerance levels. An increase in bilateral striatal/insular and prefrontal/cingulate network strength was found in patients receiving MBI compared to individuals receiving TAU. Prefrontal/cingulate cortical network strength was associated with impulsivity levels. These findings suggest that MBI can have a recognizable role in treatment of substance use disorders and that neural effects of MBI may be captured in terms of frontostriatal structural network change.

关键词： MRI Opiates source-based morphometry Frontal cortex Striatum Impulsivity

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Regional gray matter volume and structural network strength in somatic vs. non-somatic delusional disorders

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PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY 2018年 82卷 115-122页

作者： Huber, Markus Wolf, Robert Christian Lepping, Peter Kirchler, Erwin Karner, Martin Sambataro, Fabio Herrnberger, Baerbel Corlett, Philip R. Freudenmann, Roland W. Gen Hosp Bruneck Dept Psychiat South Tyrol Italy Heidelberg Univ Ctr Psychosocial Med Dept Gen Psychiat Vosstr 4 D-69115 Heidelberg Germany Betsi Cadwaladr Univ Hlth Board Maelor Hosp Ctr Mental Hlth & Soc Wrexham Wales Gen Hosp Bruneck Dept Radiol South Tyrol Italy Udine Univ Dept Expt & Clin Med Sci Udine Italy Ulm Univ Dept Psychiat & Psychotherapy 3 Ulm Germany Yale Univ Dept Psychiat Connecticut Mental Hlth Ctr New Haven CT 06520 USA

Background: Monothematic delusional disorders are characterized by a single tenacious belief. They provide a great opportunity to study underlying brain structures in the absence of confounding symptoms that accompany delusions in schizophrenia. Delusional beliefs include persecution, jealousy or somatic delusions including infestation. It is unclear whether specific delusional content is associated with distinct neural substrates. Methods: We used magnetic resonance imaging in patients presenting with somatic vs. non-somatic delusional disorders. Patients with delusional infestation (DI, n = 18), and individuals with non-somatic delusional disorders (n = 19) were included, together with healthy volunteers (n = 20). Uni-and multivariate techniques for structural data analysis were applied to provide a comprehensive characterization of abnormal brain volume at both the regional and neural network level. Results: Patients with DI showed lower gray matter volume in thalamic, striatal (putamen), insular and medial prefrontal brain regions in contrast to non-somatic delusional disorders and healthy controls. Importantly, these differences were consistently detected at regional and network level. Compared to healthy controls, patients with delusional disorders other than DI showed lower gray matter volume in temporal cortical regions. Conclusion: The data support the notion that dysfunctional somatosensory and peripersonal networks could mediate somatic delusions in patients with DI in contrast to delusional disorders without somatic content. The data also suggest putative content-specific neural signatures in delusional disorders and in delusion formation per se.

关键词： Delusional disorders Somatic delusions MRI, voxel-based morphometry source-based morphometry Peripersonal space

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Testing the expanded continuum hypothesis of schizophrenia and bipolar disorder. Neural and psychological evidence for shared and distinct mechanisms

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NEUROIMAGE-CLINICAL 2019年 23卷 101854-000页

作者： Sorellad, Sara Lapomarda, Gaia Messina, Irene Frederickson, Jon Julius Siugzdaite, Roma Job, Remo Grecucci, Alessandro Univ Trento Dept Psychol & Cognit Sci DiPSCo Rovereto Italy Univ Mercatorum Rome Italy Washington Sch Psychiat Washington DC USA Univ Ghent Fac Psychol & Pedag Sci Dept Expt Psychol Ghent Belgium

Despite the traditional view of Schizophrenia (SZ) and Bipolar disorder (BD) as separate diagnostic categories, the validity of such a categorical approach is challenging. In recent years, the hypothesis of a continuum between Schizophrenia (SZ) and Bipolar disorder (BD), postulating a common pathophysiologic mechanism, has been proposed. Although appealing, this unifying hypothesis may be too simplistic when looking at cognitive and affective differences these patients display. In this paper, we aim to test an expanded version of the continuum hypothesis according to which the continuum extends over three clusters: the psychotic, the cognitive, and the affective. We applied an innovative approach known as source-based morphometry (SBM) to the structural images of 46 individuals diagnosed with SZ, 46 with BD and 66 healthy controls (HC). We also analyzed the psychological profiles of the three groups using cognitive, affective, and clinical tests. At a neural level, we found evidence for a shared psychotic core in a distributed network involving portions of the medial parietal and temporo-occipital areas, as well as parts of the cerebellum and the middle frontal gyrus. We also found evidence of a cognitive core more compromised in SZ, including alterations in a fronto-parietal circuit, and mild evidence of an affective core more compromised in BD, including portions of the temporal and occipital lobes, cerebellum, and frontal gyrus. Such differences were confirmed by the psychological profiles, with SZ patients more impaired in cognitive tests, while BD in affective ones. On the bases of these results we put forward an expanded view of the continuum hypothesis, according to which a common psychotic core exists between SZ and BD patients complemented by two separate cognitive and affective cores that are both impaired in the two patients' groups, although to different degrees.

关键词： Schizophrenia Bipolar disorder source-based morphometry Psychosis Continuum hypothesis

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Associations between brain structural networks and neurological soft signs in healthy adults

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PSYCHIATRY RESEARCH-NEUROIMAGING 2019年 293卷 110989-000页

作者： Wang, Xingsong Herold, Christina J. Kong, Li Schroeder, Johannes Shanghai Normal Univ Coll Educ 100 Guilin Rd Shanghai 200234 Peoples R China Heidelberg Univ Dept Psychiat Sect Geriatr Psychiat Vossstr 4 DE-69115 Heidelberg Germany

Neurological soft signs (NSS), as minor neurological deficits, have been identified in several psychiatric disorders, especially in schizophrenia. However, ifs unclear how the neuropathological processes of the disease affect NSS related brain morphological changes and whether it is confounded by the use of medication. As NSS also exist in healthy people, the potential confounding effects of psychopathology or medication will be excluded if NSS are investigated in healthy people. Therefore, we applied a novel multivariate approach, source-based morphometry (SBM), to study structural networks in relation to NSS in healthy adults based on structural magnetic resonance imaging (MRI) data. The Heidelberg Scale was applied to evaluate NSS. Using SBM, we constructed structural networks and investigated their associations with NSS in healthy adults. Six grey matter (GM) structural networks were identified. Sensory integration subscores were associated with the cerebellar component and the cortico-basal ganglia-thalamic component. Motor coordination subscores and total NSS scores were associated with the sensorimotor component. The present findings indicated that structural network abnormalities in cerebellar, subcortical and cortical sensorimotor areas contribute to NSS performance in healthy adults.

关键词： Neurological soft signs Healthy adults source-based morphometry Cerebellum Sensorimotor areas Structural networks

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Early Socioemotional Intervention Mediates Long-Term Effects of Atypical Rearing on Structural Covariation in Gray Matter in Adult Chimpanzees

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PSYCHOLOGICAL SCIENCE 2018年第4期29卷 594-603页

作者： Bard, Kim A. Hopkins, William D. Univ Portsmouth Dept Psychol King Henry I StKing Henry Bldg Portsmouth PO1 2DY Hants England Georgia State Univ Neurosci Inst Atlanta GA 30303 USA

Atypical rearing has deleterious effects on chimpanzee behavior during development, some of which can be ameliorated with a responsive care intervention (RCI). Here, we obtained in vivo magnetic resonance images of adult brains of 27 chimpanzees given institutional care, with and without RCI, and compared them with those of 16 chimpanzees mother-reared from birth. We found significant long-term rearing effects on structural covariation and gray matter volume, specifically in the basal forebrain (i.e., caudate, putamen, nucleus accumbens, rectus gyrus, and orbital prefrontal cortex), indicating that RCI prevented brain changes due to atypical rearing. A significant correlation between covariation in these brain areas and caregiver nurturing, experienced in the first month of life, suggests a possible developmental mechanism for the effect of early experience on brain networks. We identified an early intervention that prevents changes in the basal forebrain that otherwise emerge as a consequence of institutionalized rearing without species-typical socioemotional experiences.

关键词： great apes brain institutionalization nurturing experiences source-based morphometry

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Common and distinct structural network abnormalities in major depressive disorder and borderline personality disorder

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PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY 2016年 65卷 127-133页

作者： Depping, Malte S. Wolf, Nadine D. Vasic, Nenad Sambataro, Fabio Thomann, Philipp A. Wolf, R. Christian Heidelberg Univ Dept Gen Psychiat Ctr Psychosocial Med D-69115 Heidelberg Germany Univ Saarland Dept Psychiat Psychotherapy & Psychosomat D-66421 Homburg Germany Univ Ulm Dept Forens Psychiat & Psychotherapy Dist Hosp Gunzburg D-89069 Ulm Germany Univ Udine Dept Expt & Clin Med Sci DISM I-33100 Udine Italy

Major depressive disorder (MDD) and borderline personality disorder (BPD) show substantial overlap in both affective symptom expression and in regional brain volume reduction. To address the specificity of structural brain change for the respective diagnostic category, we investigated structural networks in MDD and BPD to identify shared and distinct patterns of abnormal brain volume associated with these phenotypically related disorders. Using magnetic resonance imaging at 3 T, we studied 22 females with MDD, 17 females with BPD and without comorbid posttraumatic stress disorder, and 22 age-matched female healthy controls. We used "source-based morphometry" (SBM) to investigate naturally grouping patterns of gray matter volume variation (i.e. "structural networks") and the magnitude of their expression between groups. SBM identified three distinct structural networks which showed a significant group effect (p < 0.05, FDR-corrected). A bilateral frontostriatal network showed reduced volume in MDD compared to both controls and BPD patients. A medial temporal/medial frontal network was found to be significantly reduced in BPD compared to both controls and MDD patients. Decreased cingulate and lateral prefrontal volume was found in both MDD and BPD when compared to healthy individuals. In MDD significant relationships were found between depressive symptoms and a cingulate/lateral prefrontal structural pattern. In contrast, overall BPD symptoms and impulsivity scores were significantly associated with medial temporal/medial frontal network volume. The data suggest both distinct and common patterns of abnormal brain volume in MDD and BPD. Alterations of distinct structural networks differentially modulate clinical symptom expression in these disorders. (C) 2015 Elsevier Inc. All rights reserved.

关键词： Major depressive disorder Borderline personality disorder MRI source-based morphometry Anterior cingulate

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Structural network changes in patients with major depression and schizophrenia treated with electroconvulsive therapy

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EUROPEAN NEUROPSYCHOPHARMACOLOGY 2016年第9期26卷 1465-1474页

作者： Wolf, Robert Christian Nolte, Henrike Maria Hirjak, Dusan Hofer, Stefan Seidl, Ulrich Depping, Matte Sebastian Stieltjes, Bram Maier-Hein, Klaus Sambataro, Fabio Thomann, Philipp Arthur Heidelberg Univ Dept Psychiat Ctr Psychosocial Med D-69115 Heidelberg Germany Univ Saarland Dept Psychiat Psychotherapy & Psychosomat Kirrberger Str 1 D-66421 Homburg Germany Heidelberg Univ Dept Anesthesiol D-69120 Heidelberg Germany Klinikum Stuttgart Ctr Mental Hlth D-70374 Stuttgart Germany Univ Basel Hosp Dept Radiol CH-4031 Basel Switzerland German Canc Res Ctr Div Med & Biol Informat Med Image Comp Grp D-69120 Heidelberg Germany Univ Udine Dept Expt & Clin Med Sci DISM Udine Italy

Electroconvulsive therapy (ECT) is one of the most effective treatments in severe and treatment-resistant major depressive disorder (MDD). In schizophrenia (SZ), ECT is frequently considered in drug-resistant cases, as an augmehtation of antipsychotic treatment or in cases when rapid symptom relief is indicated. Accumulating neuroimaging evidence suggests modulation of medial temporal lobe and prefrontal cortical regions in MDD by ECT. In SZ, ECT-effects on brain structure have not been systematically investigated so far. In this study, we investigated brain volume in 21 ECT-naive patients (12 with MDD, 9 with SZ) who received right sided unilateral ECT. Twenty-one healthy controls were included. Structural magnetic resonance imaging data were acquired before and after ECT. Healthy participants were scanned once. source-based morphometry was used to investigate modulation of structural networks pre/post ECT. ECT had an impact on distinct structural networks in MDD and SZ. In both MDD and SZ SBM revealed a medial temporal lobe (MTL) network (including hippocannpus and parahippocampal cortex) which showed a significant increase after ECT. The increase in MTL network strength was not associated with clinical improvement in either MDD or SZ. In SZ a Lateral prefrontal/cingulate cortical network showed a volume increase after ECT, and this effect was accompanied by clinical improvement. These findings provide preliminary evidence for structural network change in response to ECT in MDD and SZ. The data suggest both diagnosis-specific and transdiagnostic ECT-effects on brain volume. In contrast to SZ, in MDD structural network modulation by ECT was not associated with clinical improvement. (C) 2016 Elsevier B.V. and ECNR All rights reserved.

关键词： Electroconvulsive therapy ECT Depression Schizophrenia source-based morphometry Prefrontal cortex

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Patterns of Gray Matter Abnormalities in Schizophrenia based on an International Mega-analysis

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SCHIZOPHRENIA BULLETIN 2015年第5期41卷 1133-1142页

作者： Gupta, Cota Navin Calhoun, Vince D. Rachakonda, Srinivas Chen, Jiayu Patel, Veena Liu, Jingyu Segall, Judith Franke, Barbara Zwiers, Marcel P. Arias-Vasquez, Alejandro Buitelaar, Jan Fisher, Simon E. Fernandez, Guillen van Erp, Theo G. M. Potkin, Steven Ford, Judith Mathalon, Daniel McEwen, Sarah Lee, Hyo Jong Mueller, Bryon A. Greve, Douglas N. Andreassen, Ole Agartz, Ingrid Gollub, Randy L. Sponheim, Scott R. Ehrlich, Stefan Wang, Lei Pearlson, Godfrey Glahn, David C. Sprooten, Emma Mayer, Andrew R. Stephen, Julia Jung, Rex E. Canive, Jose Bustillo, Juan Turner, Jessica A. Mind Res Network Albuquerque NM USA Univ New Mexico Hlth Sci Ctr Albuquerque NM 87131 USA Univ New Mexico Dept Elect & Comp Engn Albuquerque NM 87131 USA Univ New Mexico Dept Psychiat Albuquerque NM 87131 USA Yale Univ Sch Med Dept Psychiat New Haven CT USA Radboud Univ Nijmegen Med Ctr Dept Psychiat & Human Genet NL-6525 ED Nijmegen Netherlands Radboud Univ Nijmegen Med Ctr Donders Inst Brain Cognit & Behav Dept Cognit Neurosci NL-6525 ED Nijmegen Netherlands Max Planck Inst Psycholinguist Dept Language & Genet Nijmegen Netherlands Univ Calif Irvine Sch Med Dept Psychiat & Human Behav Irvine CA 92717 USA Univ Calif San Francisco Sch Med Dept Psychiat San Francisco CA 94143 USA Univ Calif San Francisco Dept Psychiat & Biobehav Sci San Francisco CA 94143 USA Chonbuk Natl Univ Div Elect & Informat Engn Jeonju South Korea Univ Minnesota Dept Psychiat Minneapolis MN 55455 USA MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi Charlestown MA USA Univ Oslo Inst Clin Med KG Jebsen Ctr Psychosis Res NORMENT Oslo Norway Oslo Univ Hosp Div Mental Hlth & Addict Oslo Norway Karolinska Inst Dept Clin Neurosci Stockholm Sweden Diakonhjemmet Hosp Dept Res Oslo Norway HMS Massachusetts Gen Hosp Dept Psychiat Boston MA USA Minneapolis VA Healthcare Syst Minneapolis MN USA Tech Univ Dresden Univ Hosp Carl Gustav Carus Dept Child & Adolescent Psychiat Dresden Germany Northwestern Univ Dept Psychiat & Behav Sci Chicago IL 60611 USA Northwestern Univ Dept Radiol Chicago IL 60611 USA Hartford Healthcare Corp Inst Living Hartford CT USA Yale Univ Sch Med Dept Neurobiol New Haven CT USA Univ New Mexico Hlth Sci Ctr Dept Neurosurg Albuquerque NM 87131 USA Raymond G Murphy VA Med Ctr Albuquerque NM USA Georgia State Univ Dept Psychol Atlanta GA 30302 USA Georgia State Univ Inst Neurosci Atlanta GA 30302 USA

Analyses of gray matter concentration (GMC) deficits in patients with schizophrenia (Sz) have identified robust changes throughout the cortex. We assessed the relationships between diagnosis, overall symptom severity, and patterns of gray matter in the largest aggregated structural imaging dataset to date. We performed both source-based morphometry (SBM) and voxel-based morphometry (VBM) analyses on GMC images from 784 Sz and 936 controls (Ct) across 23 scanning sites in Europe and the United States. After correcting for age, gender, site, and diagnosis by site interactions, SBM analyses showed 9 patterns of diagnostic differences. They comprised separate cortical, subcortical, and cerebellar regions. Seven patterns showed greater GMC in Ct than Sz, while 2 (brainstem and cerebellum) showed greater GMC for Sz. The greatest GMC deficit was in a single pattern comprising regions in the superior temporal gyrus, inferior frontal gyrus, and medial frontal cortex, which replicated over analyses of data subsets. VBM analyses identified overall cortical GMC loss and one small cluster of increased GMC in Sz, which overlapped with the SBM brainstem component. We found no significant association between the component loadings and symptom severity in either analysis. This mega-analysis confirms that the commonly found GMC loss in Sz in the anterior temporal lobe, insula, and medial frontal lobe form a single, consistent spatial pattern even in such a diverse dataset. The separation of GMC loss into robust, repeatable spatial patterns across multiple datasets paves the way for the application of these methods to identify subtle genetic and clinical cohort effects.

关键词： independent component analysis schizophrenia source-based morphometry symptoms voxel-based morphometry

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