Reduced resting state functional connectivity in the hippocampus-midbrain-striatum network of schizophrenia patients

Contemporary preclinical models suggest that abnormal functioning of a brain network consisting of the hippocampus, midbrain and striatum plays a critical role in the pathophysiology of schizophrenia. Previous neuroimaging studies examined individual aspects of this model in schizophrenia patients and individuals at clinical high risk for psychosis. However, this exact preclinical brain network has not been translated to human neuroimaging studies with schizophrenia patients and therefore it is currently unknown how functioning of this network is altered in patients. Here we investigated resting state functional connectivity in the hippocampus-midbrain-striatum network of schizophrenia patients, using functional Magnetic Resonance Imaging. Based on preclinical models, a network of functionally validated brain regions comprising the anterior subiculum (SUB), limbic striatum (LS), ventral tegmental area (VTA) and associative striatum (AS) was examined in 47 schizophrenia patients and 51 healthy controls. Schizophrenia patients demonstrated significantly lower functional connectivity in this hippocampus-midbrain-striatum network compared with healthy controls (p = 0.036). Particular reductions in connectivity were found between the SUB and LS (0.002 +/- 0.315 and 0.116 +/- 0.224, p = 0.040) and between the VTA and AS (0.230 +/- 0.268 and 0.356 +/- 0.285, p = 0.026). In patients, functional connectivity was not significantly associated with positive, negative or general symptom scores. Reduced connectivity is consistent with the concept of functional brain dysconnectivity as a key feature of the disorder. Our results support the notion that functioning of the hippocampus-midbrain-striatum network is significantly altered in the pathophysiology of schizophrenia.