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Callosal Abnormalities Across the Psychosis Dimension: Bipolar Schizophrenia Network on Intermediate Phenotypes.

ABSTRACT: The corpus callosum has been implicated in the pathogenesis of schizophrenia and bipolar disorder. However, it is unclear whether corpus callosum alterations are related to the underlying familial diathesis for psychotic disorders. We examined the corpus callosum and its subregion volumes and their relationship to cognition, psychotic symptoms, and age in probands with schizophrenia (SZ), psychotic bipolar disorder (PBD), and schizoaffective disorder; their first-degree relatives; and healthy control subjects.We present findings from morphometric and neurocognitive analyses of 1381 subjects (SZ probands, n = 224; PBD probands, n = 190; schizoaffective disorder probands, n = 142; unaffected relatives, n = 483 [SZ relatives, n = 195; PBD relatives, n = 175; schizoaffective disorder relatives, n = 113]; control subjects, n = 342). Magnetization prepared rapid acquisition gradient-echo T1 scans across five sites were obtained using 3-tesla magnets. Image processing was done using FreeSurfer Version 5.1. Neurocognitive function was measured using the Brief Assessment of Cognition in Schizophrenia scale.Anterior and posterior splenial volumes were significantly reduced across the groups. The SZ and PBD probands showed robust and significant reductions, whereas relatives showed significant reductions of intermediate severity. The splenial volumes were positively but differentially correlated with aspects of cognition in the probands and their relatives. Proband groups showed a significant age-related decrease in the volume of the anterior splenium compared with control subjects. Among the psychosis groups, the anterior splenium in probands with PBD showed a stronger correlation with psychotic symptoms, as shown by the Positive and Negative Syndrome Scale. All five subregions showed significantly high familiality.The splenial volumes were significantly reduced across the psychosis dimension. However, this volume reduction impacts cognition and clinical manifestation of the illnesses differentially.

SUBMITTER: Francis AN

PROVIDER: S-EPMC5218825 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Callosal Abnormalities Across the Psychosis Dimension: Bipolar Schizophrenia Network on Intermediate Phenotypes.

Francis Alan N AN Mothi Suraj S SS Mathew Ian T IT Tandon Neeraj N Clementz Brett B Pearlson Godfrey D GD Sweeney John A JA Tamminga Carol A CA Keshavan Matcheri S MS

Biological psychiatry 20160112 8

<h4>Background</h4>The corpus callosum has been implicated in the pathogenesis of schizophrenia and bipolar disorder. However, it is unclear whether corpus callosum alterations are related to the underlying familial diathesis for psychotic disorders. We examined the corpus callosum and its subregion volumes and their relationship to cognition, psychotic symptoms, and age in probands with schizophrenia (SZ), psychotic bipolar disorder (PBD), and schizoaffective disorder; their first-degree relati ...[more]

PMID: 26954565

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Project description:ObjectiveThe study examined gray matter volume across psychosis diagnoses organized by dimensional and DSM-IV categories from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) sample.MethodIn total, 351 probands with psychosis (146 with schizophrenia, 90 with schizoaffective disorder, and 115 with psychotic bipolar I disorder), 369 of their first-degree relatives (134 were relatives of individuals with schizophrenia, 106 of individuals with schizoaffective disorder, and 129 of individuals with psychotic bipolar I disorder), and 200 healthy comparison subjects were assessed. Gray matter volumes from 3-T T1-weighted images were analyzed using the VBM8 toolbox for SPM8, and outcomes were determined at a false discovery rate-corrected threshold of p<0.005.ResultsAcross the psychosis dimension, probands (N=351) and relatives with psychosis spectrum disorders (N=34) showed substantial overlapping gray matter reductions throughout the neocortex, whereas relatives without psychosis spectrum (N=332) had normal gray matter volumes relative to comparison subjects. Across DSM-IV diagnoses, schizophrenia and schizoaffective probands showed overlapping gray matter reductions in numerous cortical and subcortical regions, whereas psychotic bipolar probands showed limited gray matter reductions localized to the frontotemporal cortex relative to comparison subjects. All relative groups had gray matter volumes that did not differ from comparison subjects.ConclusionsAcross the dimensional psychosis categories, these findings indicate extensive neocortical gray matter reductions in psychosis probands and relatives with psychosis spectrum disorders, possibly reflecting lifetime psychosis burden, but normal gray matter in nonpsychotic relatives. Traditional DSM-IV psychosis grouping revealed partially divergent gray matter phenotypes for probands with schizophrenia or schizoaffective disorder (extensive neocortical or subcortical gray matter reductions) relative to those with psychotic bipolar disorder (smaller reductions were limited to frontotemporal regions). The dimensional conceptualization of psychosis appears useful in defining more homogenous disease categories that may help identify underlying psychosis biomarkers and develop a biologically driven diagnostic system and targeted treatments.

Project description:BackgroundThe current definitions of psychotic illness lack biological validity, motivating alternative biomarker-driven disease entities. Building on experimental constructs-Biotypes-that were previously developed from cognitive and neurophysiologic measures, we contrast brain anatomy characteristics across Biotypes alongside conventional diagnoses, examining gray matter density (GMD) as an independent validator for the Biotypes.MethodsWhole brain GMD measures were examined in probands, their relatives, and healthy subjects organized by Biotype and then by DSM-IV-TR diagnosis (n = 1409) using voxel-based morphometry with subsequent subject-level regional characterization and distribution analyses.ResultsProbands grouped by Biotype versus healthy controls showed a stepwise pattern of GMD reductions as follows: Biotype1, extensive and diffusely distributed GMD loss, with the largest effects in frontal, anterior/middle cingulate cortex, and temporal regions; Biotype2, intermediate and more localized reductions, with the largest effects in insula and frontotemporal regions; and Biotype3, small reductions localized to anterior limbic regions. Relatives showed regionally distinct GMD reductions versus healthy controls, with primarily anterior (frontotemporal) effects in Biotype1; posterior (temporo-parieto-cerebellar) in Biotype2; and normal GMD in Biotype3. Schizophrenia and schizoaffective probands versus healthy controls showed overlapping GMD reductions, with the largest effects in frontotemporal and parietal regions; psychotic bipolar probands had small reductions, primarily in frontal regions. GMD changes in relatives followed regional patterns observed in probands, albeit less extensive. Biotypes showed stronger between-group separation based on GMD than the conventional diagnoses and were the strongest predictor of GMD change.ConclusionsGMD biomarkers depicted unique brain structure characteristics within Biotypes, consistent with their cognitive and sensorimotor profiles, and provided stronger discrimination for biologically driven biotypes than symptom-based diagnoses.

Project description:BACKGROUND:Difficulty recognizing facial emotions is an important social-cognitive deficit associated with psychotic disorders. It also may reflect a familial risk for psychosis in schizophrenia-spectrum disorders and bipolar disorder. OBJECTIVE:The objectives of this study from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium were to: 1) compare emotion recognition deficits in schizophrenia, schizoaffective disorder and bipolar disorder with psychosis, 2) determine the familiality of emotion recognition deficits across these disorders, and 3) evaluate emotion recognition deficits in nonpsychotic relatives with and without elevated Cluster A and Cluster B personality disorder traits. METHOD:Participants included probands with schizophrenia (n=297), schizoaffective disorder (depressed type, n=61; bipolar type, n=69), bipolar disorder with psychosis (n=248), their first-degree relatives (n=332, n=69, n=154, and n=286, respectively) and healthy controls (n=380). All participants completed the Penn Emotion Recognition Test, a standardized measure of facial emotion recognition assessing four basic emotions (happiness, sadness, anger and fear) and neutral expressions (no emotion). RESULTS:Compared to controls, emotion recognition deficits among probands increased progressively from bipolar disorder to schizoaffective disorder to schizophrenia. Proband and relative groups showed similar deficits perceiving angry and neutral faces, whereas deficits on fearful, happy and sad faces were primarily isolated to schizophrenia probands. Even non-psychotic relatives without elevated Cluster A or Cluster B personality disorder traits showed deficits on neutral and angry faces. Emotion recognition ability was moderately familial only in schizophrenia families. CONCLUSIONS:Emotion recognition deficits are prominent but somewhat different across psychotic disorders. These deficits are reflected to a lesser extent in relatives, particularly on angry and neutral faces. Deficits were evident in non-psychotic relatives even without elevated personality disorder traits. Deficits in facial emotion recognition may reflect an important social-cognitive deficit in patients with psychotic disorders.

Dataset Information

Callosal Abnormalities Across the Psychosis Dimension: Bipolar Schizophrenia Network on Intermediate Phenotypes.

Publications

Callosal Abnormalities Across the Psychosis Dimension: Bipolar Schizophrenia Network on Intermediate Phenotypes.

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