Striatal dopamine D(2) receptor availability in OCD with and without comorbid social anxiety disorder: preliminary findings
Schneier FR, Martinez D, Abi-Dargham A, Zea-Ponce Y, Simpson HB, Liebowitz MR, et al.;
Commented by , 29 Feb 2008
Aim
To determine whether Dopamine D2 receptor availability is changed in subjects with obsessive compulsive disorder (OCD) and those with OCD and concurrent social anxiety disorder (SAnD) compared with healthy controls.
Methods
8 subjects with OCD, 7 with OCD + SAnD and 8 age and sex matched controls underwent single-photon emission computerised tomography (SPECT) with the D2 receptor tracer [123 I] iodobenzamide. The tracer binding was correlated with the following rating scales: the Yale-Brown Obsessive Compulsive Scale (YBOCS), the Liebowitz Social Anxiety Scale (LSAS), the Spielberger State-Trait anxiety inventory (STAI), the Hamilton Depression rating Scale (Ham-D) and the detachment subscale of the Karolinska Scale of Personality (DetKSP).
Results
There was significantly lower D2 receptor binding in the striatum of the OCD + SAnD group compared with the control group. There were no significant differences between the OCD and control groups. Lowered binding was correlated with a higher score on the DetKSP, but not any of the other clinical scales.
Dr Christmas', Dr Hood's and Prof Nutt's comments
This study has shown that dopamine D2 receptor binding is reduced in the striatum of sufferers of comorbid SAnD and OCD, but not with OCD alone. This corroborates previous reports of decreased D2 binding in social anxiety disorder alone (ref. 1), but is in contrast to a prior study in OCD (ref. 2).
The study reported here does have some limitations that may go some way to explaining the lack of consistency with previous studies in OCD; viz the relatively small numbers involved and the comorbidity amongst those recruited.
Indeed, there were cases of comorbid depression (previously shown to have increased D2 receptors in the basal ganglia (ref. 3) and panic disorder (sufferers of which behave differently to social anxiety disorder on various challenge studies (ref. 4), which could significantly alter results on such a small sample.
Finding subjects for studies such as this is fraught with difficulty and although heterogeneous samples can sometimes inform fruitful new avenues of research these problems limit our ability to interpret the results alongside existing evidence.
Treatment with D2 receptor antagonists is an established augmentation strategy for OCD - in this context the finding of no difference in striatal D2 receptors between OCD and controls is important. This forum presented a paper in October 2007 [click on this link to see article] showing a decrease in dopamine transporter density following successful treatment of OCD with selective serotonin reuptake inhibitors (SSRIs).
It would be interesting to see a similar study looking at D2 receptor densities before and after treatment.
Dopamine functioning has been implicated for some time in the aetiology of social anxiety; from associations with Parkinson's disease (the archetypal neurological disease involving dopamine deficiency) (ref. 5), through case reports of social phobia in chronic stimulant abusers (who may as a result of the abuse damaged dopaminergic neuronal terminals) (ref. 6), reports of social phobia as a side effect of D2 blocking drugs (ref. 7) and successful treatment with medications which augment the dopamine system (ref. 8).
From this and related (ref. 9) evidence it is tempting to postulate that a striatal dopamine deficiency is important to the disorder. However, this evidence is indirect and must be interpreted with care. Direct imaging studies such as this one have the potential to provide greater clarity on the biological mechanisms of disorders, albeit causality can not be discerned.
A further issue highlighted by this paper relates to defining the syndrome actually being studied. In this study D2 receptor densities did not vary with scales of severity of SAnD, but did vary inversely with trait detachment (or lack of willingness to participate in social situations – more receptors = less detachment) across all three study groups.
Does this finding reflect experimental design and measurement limitations or rather does it point towards subtle dopamine-related phenomenological differences that are yet to be well understood? It still remains to be determined to what degree the current psychiatric classification systems and rating scales reflect underlying brain pathology.
References
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