10. Brain Structure Biomarkers at the Psychosis/Nonpsychosis Interphase: Findings From the Bipolar–Schizophrenia Network for Intermediate Phenotypes

Abstract

Background: The study presents whole brain and regional gray matter density (GMD) characteristics contrasted along the psychosis/nonpsychosis interface in (1) schizophrenia—schizoaffective—psychotic bipolar—nonpsychotic bipolar probands, and (2) their first-degree relatives organized by lifetime psychosis expression, from the B–SNIP consortium sample. Methods: A total of 1652 3Tesla T1-weighted MPRAGE or IR-SPGR scans were analyzed using Voxel-Based Morphometry (SPM8/VBM8/DARTEL) with subsequent subject-level regional GMD characterization. Results: Among probands, individuals with schizophrenia (mean d = 0.66) and schizoaffective disorder (mean d = 0.73) showed overlapping and diffusely distributed GMD reductions spanning cortical and subcortical regions, with the largest effects in the frontotemporal, cingulate, and insular cortices, compared to healthy controls. Probands with psychotic bipolar disorder contrasted with controls showed modest GMD reductions (mean d = 0.54), primarily localized to anterior limbic regions. The data for nonpsychotic bipolar probands will be also reported; we predict normal/near-normal GMD characteristics, relative to controls. Among relatives organized by lifetime psychosis manifestations, relatives with DSM-IV Axis I psychotic disorders and Axis II psychosis spectrum personality disorders (schizoid, paranoid, and schizotypal) showed GMD reductions intermediate in magnitude between the psychosis probands and healthy controls, primarily localized to bilateral frontal regions. In contrast, relatives without lifetime Axis I/II psychotic disorders showed GMD not different from healthy controls. No effect of concurrent medications (antipsychotics, mood stabilizers, antidepressants) on GMD outcomes was detected in probands; the majority of relatives were unmedicated. Conclusion: Our findings indicate divergent GMD characteristics for psychotic versus nonpsychotic phenotypes among probands with severe mental illness and their biological relatives and suggest that GMD alterations may serve as a biomarker unique to psychosis.