Neuroendocrine aspects of Tourette syndrome

There is sparse evidence suggesting the participation of neuroendocrine mechanisms, mainly involving sex and stress steroid hormones, to the pathophysiology of neurodevelopmental disorders such as Tourette syndrome (TS) and obsessive-compulsive disorder (OCD). Patients with TS exhibit a sex-specific variability in gender distribution (male/female ratio=3-4/1) and in its natural history, with a severity peak in the period around puberty. The administration of exogenous androgens may worsen tics in males with TS, whereas drugs counteracting the action of testosterone might show some antitic efficacy. This suggests a higher susceptibility of patients with TS to androgen steroids. There are insufficient data on the regulation of the hypothalamic-pituitary-gonadal (HPG) axis in TS. However, preliminary evidence suggests that a subgroup of women with TS might be more sensitive to the premenstrual trough of estrogen levels. Patients with TS exhibit differences in a number of behavioral, cognitive, and anatomical traits that appear to be sex related. There is a body of evidence supporting, albeit indirectly, the hypothesis of an increased exposure to androgenic steroids during the very early phases of neural development. Animal models in rodents suggest a complex role of gonadal hormones upon the modulation of anxiety-related and stereotyped behaviors during adult life. Patients with TS exhibit an enhanced reactivity of the hypothalamic-pituitary-adrenal axis to external stressors, despite a preserved diurnal cortisol rhythm and a normal restoration of the baseline activity of the axis following the acute stress response. Preliminary evidence suggests the possible implication of oxytocin (OT) in disorders related to the TS spectrum, especially non-tic-related OCD. The injection of OT in the amygdala of rodents was shown to be able to induce hypergrooming, suggesting the possible involvement of this neuropeptide in the pathophysiology of complex, stereotyped behaviors. In contrast, there is anecdotal clinical evidence that tics improve following periods of affectionate touch and sexual intercourse.