5-HT_1D Function and Repetitive Behaviors

To the Editor: In a recent article, Emanuela Mundo, M.D., et al. (1) reported a significant linkage disequilibrium between the G861C variant of the serotonin 5-HT_1Dβ receptor gene and obsessive-compulsive disorder (OCD). This is of interest given reports that the 5-HT_1D agonist sumatriptan may improve the symptoms of OCD (2). However, although the effect of the presence of the G variant of the 5-HT_1Dβ receptor gene increases the risk of developing OCD by 5.26-fold, the authors acknowledged that OCD is complex and more than one gene is expected to contribute to its etiology. Each gene has only a relatively small effect in increasing the risk for the disorder.

The OCD phenotype is heterogeneous, and it is possible that transmission disequilibrium of the 5-HT_1D receptor gene may be more closely related to certain behavioral patterns, such as repetitive or compulsive behaviors per se, rather than to a categorical disorder, such as DSM-IV OCD. A neuroscientifically based psychopathology attempted to transcend the boundaries of convenience that permit reliable categorizations because these categories may not have any inherent biological meaning (3). For this reason, it is of interest to explore whether 5-HT_1D function is related to the severity of repetitive behaviors across other neuropsychiatric disorders that cross categorical boundaries.

There is a higher rate of OCD in first-degree family members of autistic probands (4), and parents with high levels of repetitive behaviors have higher whole-blood 5-HT levels (5). Recently, we reported that in autistic patients, a high level of severe repetitive behaviors correlated with higher 5-HT_1D sensitivity, as manifested by the response of growth hormone to sumatriptan (6). Thus, one component of 5-HT function, 5-HT_1D sensitivity, may play a role in mediating one specific behavioral domain within autism—repetitive behaviors—thus influencing heterogeneity in autism.

Future studies might examine the role of 5-HT_1D receptor gene function and the repetitive behavior domain, not only within OCD but across other disorders in which this clinical symptom is a key symptom component.