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Structural brain alterations in youth with psychosis and bipolar spectrum symptoms

By Maria Jalbrzikowski, David Freedman, Catherine E Hegarty, Eva Mennigen, Katherine H Karlsgodt, Loes M Olde Loohuis, Roel A. Ophoff, Raquel E Gur, Carrie E Bearden

Posted 26 Sep 2018
bioRxiv DOI: 10.1101/427609 (published DOI: 10.1016/j.jaac.2018.11.012)

Objective: Adults with established diagnoses of serious mental illness (bipolar disorder and schizophrenia) exhibit structural brain abnormalities, yet less is known about how such abnormalities manifest earlier in development. Methods: We analyzed the data publicly available from the Philadelphia Neurodevelopmental Cohort (PNC). Structural magnetic resonance neuroimaging data (sMRI) were collected on a subset of the PNC (N=989, ages 9-22 years old). We calculated measures of cortical thickness (CT) and surface area (SA), along with subcortical volumes. Study participants were assessed for psychiatric symptomatology via structured interview and the following groups were created: typically developing (TD, N=376), psychosis spectrum (PS, N=113), bipolar spectrum (BP, N=117), and BP + PS (N=109). We examined group and developmental differences in sMRI measures. We also examined to what extent any structural aberration was related to neurocognition, global functioning, and clinical symptomatology. Results: In comparison to all other groups, PS youth exhibited significantly reduced SA in orbitofrontal, cingulate, precentral, and postcentral regions. PS youth also exhibited reduced thalamic volume in comparison to all other groups. Strongest effects for precentral and posterior cingulate SA reductions were seen during early adolescence (ages 13-15) in PS youth. Strongest effects for reductions in thalamic volume and orbitofrontal and postcentral SA were observed in mid-adolescence (16-18 years) in PS youth. Across groups, better overall functioning was associated with increased lateral orbitofrontal SA. Increased postcentral SA was associated with better executive cognition and less severe negative symptoms in the entire sample. Conclusion: In a community-based sample, we found that reduced cortical SA and thalamic volume are present early in adolescent development in youth with psychosis spectrum symptoms, but not in youth with bipolar spectrum symptoms, or with both bipolar and psychosis spectrum symptoms. These findings point to potential biological distinctions between psychosis and bipolar spectrum conditions, which may suggest additional biomarkers relevant to early identification.

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