Feelings of incompleteness : Studies on dopamine in obsessive-compulsive disorder

Although obsessive-compulsive disorders have been subject to intense multimodal research, their pathogeneses are yet to be fully understood. However, increasing evidence from both preclinical and clinical studies support a role for dopamine in OCD. The studies in this thesis provide circumstantial evidence for the involvement of dopamine in OCD. On the one hand, first exacerbation of OCD symptoms by blocking the dopamine transporter (DAT) with bupropion in OCD patients, and second augmentation of the efficacy of citalopram by blocking the D2 receptor with quetiapine, both confirm dopamine abnormalities in OCD. On the other hand, (1) the absence of abnormal striatal D2 receptor binding at baseline in a [11C]raclopride PET study, (2) no differences in change in BP of [11C]raclopride in the striatum after amphetamine in a [11C]raclopride PET study, together with (3) similar distributions of genotypes or allele frequencies of the COMT or DRD2 receptor between responders and nonresponders to citalopram with quetiapine, challenges the evidence for dopamine alterations in OCD. However, conclusions from our PET and pharmacogenetic study are limited by small sample size. Therefore, enlargement of the sample in future studies is warranted. Heterogeneity of OCD symptoms of participants in our PET study could also be a potential confounder, since various neuroimaging studies suggest that different symptoms may be mediated by distinct neural systems. Taken together, results from this thesis show that patients with OCD who have never been treated before, preferentially benefit from a combination of a SSRI and quetiapine, compared to monotherapy with SSRIs. Immediate augmentation increases the number of responders, though psychiatrists need to consider the increased number of dropouts due to side effects with add-on therapy. Genetic research can provide additional information which patients will respond to a combination of SSRIs and quetiapine.