Introduction: Fibromyalgia Syndrome (FMS) is considered a ‘stress-related' disorder whose hallmarks include chronic widespread pain, fatigue and cognitive dysfunction. Exposure to chronic stress is known to cause deleterious changes to the brain, and we have previously reported focal loss of gray matter in the limbic system in subjects with FMS. The neurobiological basis for this atrophic change is not well understood; however, we recently reported a reduction of presynaptic dopamine (DA) within the mesencephalon and regions of limbic cortex in FMS. Since DA may act as a neurotrophic agent, we hypothesized that changes in presynaptic DA would correlate with focal gray matter changes in FMS. Methods: 6 female FMS patients and 8 matched controls underwent structural MRI and resting-state FDOPA PET. We used SPM2 to perform a VBM analysis between study groups. A ROI analysis was used to extract regional measures of presynaptic DA activity, and entered as covariates of interest in the VBM analysis. Results: Regional presynaptic DA measure from the ventral tegmental area correlated positively with gray matter density in bilateral parahippocampal gyrus and right anterior cingulate gyrus. Conclusions: There is a positive correlation between measures of dopaminergic metabolism and gray matter density detectable by VBM. DA receptors trigger activation of the mitogen-activated protein kinase signaling cascades via G-couple proteins, and activation of the phosphoionositide 3-kinase by D2 receptors appears to preserve cellular integrity in DA cell lines in vitro. Clinical studies in Parkinson's disease have demonstrated that DA agonists may be protective of DA neurons. Our results offer in vivo evidence to support a role for DA in promoting neuronal integrity. Thus, a disruption of DA metabolism may contribute to the cortical atrophy associated with FMS