Loss of asymmetry in D2 receptors of putamen in unaffected family members at increased genetic risk for schizophrenia

Objective: Dopamine dysregulation has been implicated in the pathophysiology of schizophrenia. The present study was performed to examine whether unaffected relatives at high genetic risk of schizophrenia have dopamine dysregulation in comparison with healthy controls. Method: Eleven unaffected relatives from families with two or more first- or second-degree relatives with schizophrenia (n = 9) or with a monozygotic schizophrenic twin (n = 2) and 11 age- and sex-matched controls were examined using positron emission tomography (PET) with [C-11] raclopride. Subjects also underwent extensive neuropsychological testing. Results: Subjects with high genetic risk showed a loss of asymmetry of D-2 receptors in the putamen in comparison with healthy controls. In addition, they showed significantly poorer performance on neuropsychological tests than controls. Conclusion: Our results suggest that dopamine dysregulation and neuropsychological dysfunction may be present in subjects at high genetic risk of schizophrenia. However, further studies are required to confirm these findings.