F91. REDUCED RESTING STATE FUNCTIONAL CONNECTIVITY IN THE HIPPOCAMPUS-MIDBRAIN-STRIATUM NETWORK OF SCHIZOPHRENIA PATIENTS

Contemporary preclinical models suggest that abnormal functioning of the hippocampal-midbrain-striatum network plays a critical role in the pathophysiology of schizophrenia. Consistently, neuroimaging studies demonstrate significant changes in resting perfusion in these areas in individuals at clinical high risk for the development of psychosis. However, it is currently unknown how functioning of this brain network is altered in patients with schizophrenia. The present study is the first that investigated (1) resting state functional connectivity in the hippocampus-midbrain-striatum network of schizophrenia patients, and (2) how connectivity in this network is related to symptomatology.

47 patients with a schizophrenia spectrum disorder and 51 healthy controls underwent 3T resting state functional magnetic resonance imaging (3D PRESTO-SENSE, 1000 volumes, TR/TE=22.5/33.2ms, flip angle 10°). Groups were matched for age, gender and parental socio-economic status. Based on preclinical models, functional connectivity was examined in a network of brain regions comprising the anterior subiculum, limbic striatum, ventral tegmental area (VTA) and associative striatum. All areas were functionally validated in previous neuroimaging studies. Functional connectivity was assessed using the RESTplus toolkit by correlating time series extracted from these brain regions. In patients, symptomatology was measured with the Positive And Negative Syndrome Scale. Group differences were determined with multivariate analysis of variance (MANOVA) and correlations with multiple regression analysis.

Schizophrenia patients demonstrated significantly lower functional connectivity in the hippocampus-midbrain-striatum network than controls (group effect, p=0.036). In particular, patients showed reduced connectivity between the anterior subiculum and limbic striatum (0.002±0.315 and 0.116±0.224, p=0.040) and between the VTA and associative striatum (0.230±0.268 and 0.356±0.285, p=0.026). Lower functional connectivity in the hippocampus-midbrain-striatum network was significantly correlated with less severe negative symptoms (R2 = 0.205, p=0.019). Specifically, connectivity between the limbic striatum and VTA was a significant predictor for negative symptoms (β = 10.57, p= 0.012). There were no significant associations between functional connectivity and positive or general symptoms (p>0.25).

Schizophrenia patients showed significantly reduced resting state functional connectivity in the hippocampus-midbrain-striatum network, which was related to lower negative symptom scores. These findings are consistent with both preclinical models and neuroimaging findings in individuals at clinical high risk for developing psychosis that indicate that alterations in the hippocampus-midbrain-striatum are significantly involved in schizophrenia. Our findings suggest that a decrease in functional connectivity in a network comprising the hippocampus, midbrain and striatum may be a beneficial mechanism in schizophrenia to diminish debilitating symptoms such as anhedonia and avolition.