Seasonal effects on human striatal presynaptic dopamine synthesis

Past studies in rodents have demonstrated circannual variation in central dopaminergic activity as well as a host of compelling interactions between melatonin - a scotoperiod-responsive neurohormone closely tied to seasonal adaptation - and dopamine in the striatum and in midbrain neuronal populations with striatal projections. In humans, seasonal effects have been described for dopaminergic markers in CSF and postmortem brain, and there exists a range of affective, psychotic, and substance abuse disorders that have been associated with both seasonal symptomatic fluctuations and dopamine neurotransmission abnormalities. Together, these data indirectly suggest a potentially crucial link between circannual biorhythms and central dopamine systems. However, seasonal effects on dopamine function in the living, healthy human brain have never been tested. For this study, 86 healthy adults underwent ¹⁸F-DOPA positron emission tomography scanning, each at a different time throughout the year. Striatal regions of interest (ROIs) were evaluated for differences in presynaptic dopamine synthesis, measured by the kinetic rate constant, K_i, between fall-winter and spring-summer scans. Analyses comparing ROI average K_i values showed significantly greater putamen ¹⁸F-DOPA K_i in the fall-winter relative to the spring-summer group (p = 0.038). Analyses comparing voxelwise K_i values confirmed this finding and evidenced intrastriatal localization of seasonal effects to the caudal putamen (p < 0.05, false-discovery rate corrected), a region that receives dopaminergic input predominantly from the substantia nigra. These data are the first to directly demonstrate a seasonal effect on striatal presynaptic dopamine synthesis and merit future research aimed at elucidating underlying mechanisms and implications for neuropsychiatric disease and new treatment approaches.