Single photon emission computed tomography of the brain with Tc-99m HMPAO during sumatriptan challenge in obsessive-compulsive disorder: Investigating the functional role of the serotonin auto-receptor

1. Symptoms of obsessive-compulsive disorder (OCD) may be acutely exacerbat ed by administration of certain serotonin agonists Exacerbation of OCD symp toms by sumatriptan, a 5HT(1D) agonist (Zohar, 1993), is consistent with pr e-clinical data suggesting that the serotonin auto-receptor plays an import ant role in this disorder (El Mansari et al, 1995) 2. In order to investigate the functional role of the serotonin auto-recept or in OCD, the authors undertook single photon emission computed tomography in OCD patients after administration of sumatriptan and placebo. The autho rs hypothesized that, as in the case of m-chlorophenylpiperazine (mCPP) cha llenge (Hollander et al, 1995), exacerbation of OCD symptoms would be accom panied by increased cortical metabolism and thus blood flow, and more speci fically by increased activity in the orbitofrontal-striatal circuit. They a lso expected, that as in the case of mCPP challenge (Hollander et al, 1993) , exacerbation of OCD symptoms would be associated with a relatively poor r esponse to subsequent treatment with serotonin specific reuptake inhibitors . 3. Sumatriptan (100mg orally) and placebo were administered on separate day s to 14 patients who met DSM-IV diagnostic criteria for OCD, using a random ized double-blind design. After 90 minutes, patients were injected with Tc- 99m HMPAO and underwent single photon emission computed tomography (SPECT) of the brain. Activity in regions of interest was calculated, and compared using repeated measures analysis of variance. Patients were subsequently tr eated with a serotonin specific reuptake inhibitor (SSRI) 4. Behavioral response to sumatriptan was heterogenous, with 4 patients sho wing acute exacerbation, and 4 patients demonstrating a decrease in symptom s. On sumatriptan challenge, there was a significant association between sy mptom exacerbation and decreased activity in frontal areas. There was an as sociation between decreased activity in an inferior frontal area with worse response to treatment, and also patients with symptom exacerbation after s umatriptan had poorer response to SSRI treatment. 5. Heterogeneity of behavioral response to sumatriptan in OCD is consistent with previous studies demonstrating conflicting and heterogenous behaviora l responses to serotonergic challenges (Hollander et al, 1992), and with un derlying heterogeneity in the neurobiology of this disorder. 6. It may be hypothesized that increased frontal activity in some patients with OCD is itself a compensatory mechanism. In patients with such compensa tory hyperactivity, administration of a serotonin auto-receptor agonist res ults in decreased frontal activity and exacerbation of OCD symptoms. These patients may also;be less likely to respond to treatment with a SSRI. 7. Further work combining pharmacological challenge paradigms and functiona l imaging techniques in OCD may be helpful in elucidating the neurobiology of this complex disorder.