Striatal Functional Hypoconnectivity in Patients With Schizophrenia Suffering From Negative Symptoms, Longitudinal Findings

Abstract Background Negative symptoms in schizophrenia (SZ), such as apathy and diminished expression, have limited treatments and significantly impact daily life. Our study focuses on the functional division of the striatum: limbic—motivation and reward, associative—cognition, and sensorimotor—sensory and motor processing, aiming to identify potential biomarkers for negative symptoms. Study Design This longitudinal, 2-center resting-state-fMRI (rsfMRI) study examines striatal seeds-to-whole-brain functional connectivity. We examined connectivity aberrations in patients with schizophrenia (PwSZ), focusing on stable group differences across 2-time points using intra-class-correlation and associated these with negative symptoms and measures of cognition. Additionally, in PwSZ, we used negative symptoms to predict striatal connectivity aberrations at the baseline and used the striatal aberration to predict symptoms 9 months later. Study Results A total of 143 participants (77 PwSZ, 66 controls) from 2 centers (Berlin/Geneva) participated. We found sensorimotor-striatum and associative-striatum hypoconnectivity. We identified 4 stable hypoconnectivity findings over 3 months, revealing striatal-fronto-parietal-cerebellar hypoconnectivity in PwSZ. From those findings, we found hypoconnectivity in the bilateral associative striatum with the bilateral paracingulate-gyrus and the anterior cingulate cortex in PwSZ. Additionally, hypoconnectivity between the associative striatum and the superior frontal gyrus was associated with lower cognition scores in PwSZ, and weaker sensorimotor striatum connectivity with the superior parietal lobule correlated negatively with diminished expression and could predict symptom severity 9 months later. Conclusions Importantly, patterns of weaker sensorimotor striatum and superior parietal lobule connectivity fulfilled the biomarker criteria: clinical significance, reflecting underlying pathophysiology, and stability across time and centers.