3.3. Obsessive compulsive disorder

OCD is characterized by recurrent, intrusive thoughts (obsessions) that cause marked distress and/or by repetitive behaviors (compulsions) which are aimed at preventing or reducing anxiety. Importantly, the obsessions and compulsions are time consuming, or significantly interfere with the person s normal routine, occupational functioning, or social activities (American Psychiatric Association, 1994). The OCD category is heterogeneous in terms of symptoms, because the obsessions and compulsions can be related to many different dimensions (e.g., contamination/cleaning, hoarding/collecting, checking) as listed in the Yale-Brown Obsessive Compulsive Scale (Goodman et al., 1989). The most frequent comorbid diagnoses are other anxiety disorders (e.g., social phobia), mood disorders, tic disorders, and substance abuse (Abramowitz et al., 2009). According to an American survey, the lifetime prevalence of OCD is 1.6%, and the median age of onset is 19, with 25% of the cases starting in adolescence (Kessler et al., 2005). Twin studies indicate the importance of separating childhood-onset OCD, because the observed genetic influence on OCD symptoms is much higher in children (ranging from 45% to 65%) compared to adults (ranging from 27% to 47%) (van Grootheest et al., 2005).

Based on the efficiency of serotonin reuptake inhibitors in the pharmacotherapy of OCD, most candidate gene studies focused on the serotonin transporter linked polymorphic region (5-HTTLPR) and serotonin receptor polymorphisms (see review papers by Grados, 2010 and by Walitza et al., 2010). A meta-analysis of the serotonin transporter gene studies reported that the long 5-HTTLPR allele was associated with childhood-onset OCD (Bloch et al., 2008). In terms of dopaminergic polymorphisms, there are fewer candidate gene studies in the OCD literature, although the high comorbidity with tic disorders and the usefulness of additive antipsychotic treatment in serotonin reuptake inhibitor resistant cases point to the involvement of the dopamine system (Abramowitz et al., 2009). A meta-analysis of the COMT Val158Met polymorphism indicated an association of the Met-allele with OCD in men (OR = 1.88, 95% CI 1.45 – 2.44) but not in women (Pooley et al., 2007). Recent studies started to utilize dimensional symptom scales or factors in the COMT candidate gene analyses (Lochner et al., 2008; Katerberg et al., 2010), but these results have not been confirmed by independent workgroups. Of the dopamine receptor polymorphisms, only the DRD4 VNTR showed positive associations: The protective effect of the DRD4 4-repeat allele in OCD was indicated by a case-control study (Camarena et al., 2007) and by a family-based study (Walitza et al., 2008); whereas the increased frequency of the DRD4 7-repeat allele was shown in late-onset OCD group (Hemmings et al., 2004), and in a subgroup of OCD patients with comorbid tics (Cruz et al., 1997). The MAOA genetic findings are less consistent (Grados, 2010). Interestingly, both linkage studies and family-based association analyses indicated the glutamate transporter gene (SLC1A1) on chromosome 9p24 in the development of OCD (Grados, 2010), which started pharmacological trials of glutamate antagonist riluzole augmentation in treatment-resistant cases (Abramowitz et al., 2009), showing the possible usefulness of genetic study findings.