In individuals at clinical high risk (CHR) for psychosis, cortical volumetric asymmetry (CVA) development over time reflects the increased risk for psychosis and schizophrenia, according to study results published in Schizophrenia Bulletin.

Cortical volumetric asymmetry has been widely observed in patients with psychosis and has been related to symptom severity, but the precise time course of CVA onset in relation to psychotic illness has not been determined. The objective of this study was to examine CVA manifestation longitudinally using imaging at multiple time points to assess whether changes in CVA are related to risk for psychosis in individuals at CHR compared with healthy control participants and patients with schizophrenia.

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In this study, researchers recruited 233 patients: 112 healthy controls (74 younger controls and 38 older controls), 73 patients with CHR, and 48 patients with schizophrenia. They administered the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders to all participants to diagnose and/or rule out psychotic disorders between groups and to assess history of mood and anxiety disorders. Investigators scanned all participants using 3-T magnetic resonance imaging and collected and analyzed T1- and T2-weighted structural images at baseline and 12-month follow-up.

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Results revealed that in the CHR group (M =−0.43, standard error of the mean [SEM]=0.172), CVA indices were reduced compared with the younger control group (M =0.02, SEM=0.17; P =.04). Cortical volumetric asymmetry indices were also reduced in the schizophrenia group (M =−0.341, SEM=0.29) compared with the older control group (M =0.35, SEM=0.27; P =.04). CVA indices were reduced in the CHR group compared with the older control group (P =.03). CVA indices in the CHR group did not differ significantly from the schizophrenia group (P =.84).

A group by lobe interaction revealed lobe-specific reductions in frontal and cingulate CVA. In the frontal CVA, the CHR group (M =−0.554, SEM=0.175) did not significantly differ from the younger control group (M =−0.363, SEM=0.177; P =.398), and the schizophrenia group (M =−0.855, SEM=0.295; all P >.19) did not significantly differ from any other group. Across sites, the CHR group differed from the older control group (M =0.756, SEM=0.357; P =.036) and the younger group differed from the older control group as well (P =.01).

In the cingulate CVA, the CHR group (M =−3.62, SEM=0.76) demonstrated nonsignificant reductions compared with the healthy control group (M =−1.83, SEM=0.768, P =.068); however, cingulate CVA was significantly reduced in the schizophrenia group (M=−4.380, SEM=1.28, P =.002) compared with the older control group (M = 0.44, SEM = 1.19). Across sites, cingulate CVA in the CHR group did not differ from the schizophrenia group (P =.638), although it was reduced compared with the older control group (P =.009).

This study had a few limitations. The study was underpowered to fully explore the effect of sex on CVA, and only 7 patients with CHR were diagnosed with a psychotic disorder at the 1-year follow-up, resulting in an unknown rate of future conversion. Larger sample sizes in future studies may allow further exploration of conversion and vulnerability for psychosis and further methodological development of longitudinal assessment of CVA.

The study researchers concluded that CVA similarly affects people with schizophrenia and CHR and that, in CHR, the pathogenic development of CVA may reflect increased risk for psychosis over time.


Damme KSF, Vargas T, Calhoun V, Turner J, Mittal VA. Global and specific cortical volume asymmetries in individuals with psychosis risk syndrome and schizophrenia: a mixed cross-sectional and longitudinal perspective [published online October 18, 2019]. Schizophr Bull. doi:10.1093/schbul/sbz096