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 firstly, that claustrum volumes are lower in schizophrenia and secondarily, that potentially lower volumes mediate patients' attention deficits.

Methods: Based on T1-weighted MRI, advanced automated claustrum segmentation, and attention symbol coding task (SCT) in 90 patients with schizophrenia and 96 healthy controls from two independent sites, the COBRE open-source database and MUNICH dataset, we compared total-intracranial-volume-normalized claustrum volumes and SCT scores across groups via ANCOVA and related variables via correlation and mediation analysis.

Results: Patients had lower claustrum volumes of about 13 % (p<0.001, Hedges g=0.63), which not only correlated with (r=0.24, p=0.014) but also mediated lower SCT scores (indirect effect ab = -1.30 ± 0.69; CI [-3.73; -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.