Dopaminergic Projection Abnormalities in Schizophrenia Subjects and Unaffected First Degree Relatives

ALBA FERRARA, L.

San Pablo

Congreso; Sao Paulo school of advances science for prevention of mental disorders; 2013

UNIFESP

IMAGING DOPAMINERGIC PROJECTION ABNORMALITIES IN UNTREATED SCHIZOPHRENIA SUBJECTS AND UNAFFECTED FIRST DEGREE RELATIVES: TOWARDS CONSTRUCTING AN ENDOPHENOTYPE. Objective: Parkinsonism is present in ~30% of patients with never-treated schizophrenia and it predicts greater susceptibility to neuroleptic side effects. Parkinsonism in schizophrenia is a heritable trait independent of clinical state. The pathogenesis of parkinsonism is related to neuronal loss in dopaminergic circuits of the substantia nigra and ventral tegmental area. We have identified a population of patients with schizophrenia that are neuroleptic naive and have shown that parkinsonism and its associated deficits have characteristics of an endophenotype in first degree relatives. We investigated white matter tracts of dopaminergic networks in schizophrenia patients and their unaffected relatives by using DTI. Design:3 medication naive schizophrenia patients (SZ),5 first degree relatives and 3 healthy matched controls underwent a diffusion weighted MRI scan. Left and right substantia nigra pars compacta and ventral tegmental area were traced manually and selected as ROIs. Fractional anisotropy (FA) and number of fibers for each ROI were calculated. Results: A discriminant analysis revealed that FA and number of fibers were able to classify 52% of the cases accurately. Moreover, there was a numerical difference by which schizophrenia subjects had increased FA and decreased fiber density in all ROIs in comparison to controls. First degree relatives FA and number of fiber values were in between patients and controls. Conclusion: This preliminary data illustrates the neural bases of motor dysfunction in schizophrenia, suggesting an endophenotype. Further data is currently being collected.