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Psychotic symptoms and gray matter deficits in clinical pediatric populations.

ABSTRACT: BACKGROUND:Neuroanatomic studies have not yet addressed how subtle phenotypic distinctions in psychosis alter the underlying brain changes, and whether there is evidence for psychosis as a dimensional construct. We explored the relationship of cortical GM thickness to psychotic phenotypes in children. METHODS:Cross-sectional comparison of anatomic brain imaging between patients referred as childhood-onset schizophrenia (COS) but ruled out after a drug free inpatient observation. Groups included: patients with no evidence of psychosis (n=22) after drug free observation, patients with psychosis not otherwise specified (PNOS; total n=29) further divided into those without other axis I diagnoses (n=13) and those with other axis I comorbidities (n=16), age/sex matched COS patients (n=48), and 51 matched healthy controls. GM cortical thickness was compared between the groups, and regressed on patients' SAPS, SANS and GAS scores. RESULTS:Patients with no evidence of psychosis showed no cortical GM deficits. Presence of psychosis (PNOS with or without co-morbidities) showed some areas of temporal and prefrontal deficits, more subtle compared to the extensive bilateral cortical deficits seen for COS. GAS SAPS and SANS scores showed a relationship with cortical GM thickness although it did not survive adjustment for multiple comparisons. CONCLUSIONS:These results highlight the need for careful phenotypic characterization, as subtle diagnostic distinctions appear to reflect distinct underlying patterns of brain deficits. The incremental nature of cortical deficits from no psychosis to PNOS to COS may further support dimensional model for psychosis.

SUBMITTER: Gogtay N

PROVIDER: S-EPMC3448116 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Psychotic symptoms and gray matter deficits in clinical pediatric populations.

Gogtay Nitin N Weisinger Brian B Bakalar Jennifer L JL Stidd Reva R Fernandez de la Vega Oscar O Miller Rachel R Clasen Liv L Greenstein Deanna D Rapoport Judith L JL

Schizophrenia research 20120724 1-3

<h4>Background</h4>Neuroanatomic studies have not yet addressed how subtle phenotypic distinctions in psychosis alter the underlying brain changes, and whether there is evidence for psychosis as a dimensional construct. We explored the relationship of cortical GM thickness to psychotic phenotypes in children.<h4>Methods</h4>Cross-sectional comparison of anatomic brain imaging between patients referred as childhood-onset schizophrenia (COS) but ruled out after a drug free inpatient observation. G ...[more]

PMID: 22835806

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Project description:Abnormal neuroanatomic brain networks have been reported in schizophrenia, but their characterization across patients with psychotic disorders, and their potential alterations in nonpsychotic relatives, remain to be clarified. Participants recruited by the Bipolar and Schizophrenia Network for Intermediate Phenotypes consortium included 326 probands with psychotic disorders (107 with schizophrenia (SZ), 87 with schizoaffective disorder (SAD), 132 with psychotic bipolar disorder (BD)), 315 of their nonpsychotic first-degree relatives and 202 healthy controls. Single-subject gray matter graphs were extracted from structural MRI scans, and whole-brain neuroanatomic organization was compared across the participant groups. Compared with healthy controls, psychotic probands showed decreased nodal efficiency mainly in bilateral superior temporal regions. These regions had altered morphological relationships primarily with frontal lobe regions, and their network-level alterations were associated with positive symptoms of psychosis. Nonpsychotic relatives showed lower nodal centrality metrics in the prefrontal cortex and subcortical regions, and higher nodal centrality metrics in the left cingulate cortex and left thalamus. Diagnosis-specific analysis indicated that individuals with SZ had lower nodal efficiency in bilateral superior temporal regions than controls, probands with SAD only exhibited lower nodal efficiency in the left superior and middle temporal gyrus, and individuals with psychotic BD did not show significant differences from healthy controls. Our findings provide novel evidence of clinically relevant disruptions in the anatomic association of the superior temporal lobe with other regions of whole-brain networks in patients with psychotic disorders, but not in their unaffected relatives, suggesting that it is a disease-related trait. Network disorganization primarily involving frontal lobe and subcortical regions in nonpsychotic relatives may be related to familial illness risk.

Project description:INTRODUCTION: Substantial heterogeneity remains across studies investigating changes in gray matter in schizophrenia. Differences in methodology, heterogeneous symptom patterns and symptom trajectories may contribute to inconsistent findings. To address this problem, we recently proposed to group patients by symptom dimensions, which map on the language, the limbic and the motor systems. The aim of the present study was to investigate whether patients with prevalent symptoms of emotional dysregulation would show structural neuronal abnormalities in the limbic system. METHOD: 43 right-handed medicated patients with schizophrenia were assessed with the Bern Psychopathology Scale (BPS). The patients and a control group of 34 healthy individuals underwent structural imaging at a 3T MRI scanner. Whole brain voxel-based morphometry (VBM) was compared between patient subgroups with different severity of emotional dysregulation. Group comparisons (comparison between patients with severe emotional dysregulation, patients with mild emotional dysregulation, patients with no emotional dysregulation and healthy controls) were performed using a one way ANOVA and ANCOVA respectively. RESULTS: Patients with severe emotional dysregulation had significantly decreased gray matter density in a large cluster including the right ventral striatum and the head of the caudate compared to patients without emotional dysregulation. Comparing patients with severe emotional dysregulation and healthy controls, several clusters of significant decreased GM density were detected in patients, including the right ventral striatum, head of the caudate, left hippocampus, bilateral thalamus, dorsolateral prefrontal and orbitofrontal cortex. The significant effect in the ventral striatum was lost when patients with and without emotional dysregulation were pooled and compared with controls. DISCUSSION: Decreased gray matter density in a large cluster including the right ventral striatum was associated with severe symptoms of emotional dysregulation in patients with schizophrenia. The ventral striatum is an important part of the limbic system, and was indicated to be involved in the generation of incentive salience and psychotic symptoms. Only patients with severe emotional dysregulation had decreased gray matter in several brain structures associated with emotion and reward processing compared to healthy controls. The results support the hypothesis that grouping patients according to specific clinical symptoms matched to the limbic system allows identifying patient subgroups with structural abnormalities in the limbic network.

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Psychotic symptoms and gray matter deficits in clinical pediatric populations.

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Psychotic symptoms and gray matter deficits in clinical pediatric populations.

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