Abstract Background: Schizophrenia is characterized by impairments in the fronto–striatal network. Underlying these impairments may be disruptions in anatomical pathways connecting frontal and striatal regions. However, the specifics of these disruptions remain unclear and whether these impairments are related to the genetic vulnerability of schizophrenia is not known. Methods: Here, we investigated fronto–striatal tract connections in 24 schizophrenia patients, 30 unaffected siblings, and 58 healthy controls using diffusion tensor imaging. Mean fractional anisotropy (FA) was calculated for tracts connecting the striatum with frontal cortex regions including the dorsolateral prefrontal cortex (DLPFC), medial orbital frontal cortex, and inferior frontal gyrus. Specifically, the striatum was divided into three subregions (caudate nucleus, putamen, and nucleus accumbens) and mean FA was computed for tracts originating from these striatal subregions. Results: We found no differences between patients, siblings, and controls in mean FA when taking the whole striatum as a seed region. However, subregion analyses showed reduced FA in the tract connecting the left nucleus accumbens and left DLPFC in both patients (P=0.0003) and siblings (P=0.0008) compared with controls. Conclusions: The result of reduced FA in the tract connecting the left nucleus accumbens and left DLPFC indicates a possible reduction of white matter integrity, commonly associated with schizophrenia. As both patients and unaffected siblings show reduced FA, this may represent a vulnerability factor for schizophrenia.