Subcortical brain abnormalities and cognitive function in individuals with psychosis and their unaffected relatives: A normative modeling approach

Previous research has shown subcortical aberrations in individuals with psychosis (probands) and their unaffected first-degree relatives. However, few studies directly evaluated whether the pattern of aberration is similar across multiple subcortical regions and across probands and relatives, and whether the relationship between subcortical aberrations and cognition is similar between probands and unaffected relatives. To address these questions, this study employed a normative modeling approach and examined deviation scores of five subcortical regions from the normative range of 127 probands, 86 unaffected relatives, and 50 controls from the Psychosis Human Connectome Project. Cognitive performance was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS). The pattern of deviations across subcortical regions differed between probands and relatives, such that compared to relatives, probands had more negative deviations in the hippocampus, thalamus and amygdala but not in other subcortical regions. Further, compared to the reference norm, both probands and relatives showed negative hippocampal deviations, but only probands had negative thalamic, amygdala, and nucleus accumbens deviations. In both hippocampus and thalamus, negative deviations were related to poor cognitive performance across both groups. These findings suggest that the pattern of structural aberration is not uniform across subcortical regions across probands and relatives. Negative hippocampal deviations appear to reflect genetic risk to psychosis, whereas negative thalamic, amygdala, and nucleus accumbens deviations may be psychosis specific. Subcortical structural aberrations may contribute to poor cognition in both probands and unaffected relatives.