Gilles de La Tourette's syndrome and some forms of obsessive-compulsive disorder may share a common genetic diathesis

Family aggregation and twin studies suggest that Gilles de La Tourette's syndrome (TS) and some forms of obsessive-compulsive disorder (OCD) are etiologically related. Neuroanatomically, the structures of the basal ganglia, thalamus and cortex have also been implicated in both TS and OCD suggesting a common neural substrate for these disorders. Neurochemical and neuropharmacological studies have provided less compelling data concerning this heuristically important association. Clinical studies have largely focused on the role of the nigrostriatal, mesolimbic and mesocortical dopaminergic systems in the pathophysiology of TS. In the case of OCD, serotoninergic systems originating in the raphe nuclei and projecting rostrally, have received considerable attention. Recent neuropathological studies of TS have implicated the endogenous opioid peptide, dynorphin, in the pathophysiology of TS. Animal studies have shown that dynorphin can modulate both dopaminergic and serotonergic systems. We have undertaken a cerebrospinal fluid (CSF) study to determine if abnormalities in dynorphin A concentration can be observed in drug-free TS and OCD patients. Preliminary results from this study suggest: 1) that TS patients have an elevated level of CSF dynorphin A (1-8) compared to normal controls; 2) that their level of CSF dynorphin is correlated with the severity of their OCD symptoms; 3) that some, but not all, OCD patients also have high levels of this neuropeptide in their CSF.