Claustrum Volumes Are Lower in Schizophrenia and Mediate Patients’ Attentional Deficits

Background: While the last decade of extensive research revealed the prominent role of the claustrum for mammalian forebrain organization (i.e., widely distributed claustral-cortical circuits coordinate basic cognitive functions such as attention), it is poorly understood whether the claustrum is relevant for schizophrenia and related cognitive symptoms. We hypothesized that claustrum volumes are lower in schizophrenia and also that potentially lower volumes mediate patients’ attention deficits. Methods: Based on T1-weighted magnetic resonance imaging, advanced automated claustrum segmentation, and attention symbol coding task in 90 patients with schizophrenia and 96 healthy control participants from 2 independent sites, the COBRE open-source database and Munich dataset, we compared total intracranial volume–normalized claustrum volumes and symbol coding task scores across groups via analysis of covariance and related variables via correlation and mediation analysis. Results: Patients had lower claustrum volumes of about 13% (p < .001, Hedges’ g = 0.63), which not only correlated with (r = 0.24, p = .014) but also mediated lower symbol coding task scores (indirect effect ab = −1.30 ± 0.69; 95% CI, −3.73 to −1.04). Results were not confounded by age, sex, global and claustrum-adjacent gray matter changes, scanner site, smoking, and medication. Conclusions: Results demonstrate lower claustrum volumes that mediate patients’ attention deficits in schizophrenia. Data indicate the claustrum as being relevant for schizophrenia pathophysiology and cognitive functioning.