Dopamine Transporter Density in the Basal Ganglia in Obsessive-Compulsive Disorder, Measured with [123I]IPT SPECT before and after Treatment with Serotonin Reuptake Inhibitors
Kim CH; Cheon KA; Koo MS; Ryu YH; Lee JD; Chang JW; et al.;
Commented by , 31 Oct 2007
Aim of the study
Does successful treatment with a serotonin reuptake inhibitor alter basal ganglia dopamine function in people with obsessive compulsive disorder (OCD)?
Method
Ten right handed patients (9 men) with OCD (DSM-IV) participated in the study. Participants were treated with fluoxetine (n=6), paroxetine (n=3) or chlomipramine (n= 1) for 16 weeks. Patients had been treatment-free for at least 4 weeks prior to entering the study.
Dopamine transporter density in the basal ganglia was measured using [123I]IPT SPECT and OCD symptomatology was measured using the Y-BOCS prior to treatment initiation and after 16 weeks of treatment.
Results
OCD symptoms improved following 16 weeks of treatment according to the Y-BOCS (Total score baseline: 33.1±6.4; total score post-treatment: 8.8±1.9; p<.005).
Specific: non-specific dopamine transporter binding ratios also decreased significantly with treatment in the right, but not the left, basal ganglia (Baseline: 7.6±1.5; post-treatment: 4.8±1.8; p<.05). The improvement in the Y-BOCS (total score) showed a significant, positive association with right basal ganglia specific: non-specific dopamine transporter binding ratios (p<.05; this association was not significant once the Bonferonni correction was applied).
Dr Hood's and Prof Nutt's comments
Although the number of participants in this study is small, the results clearly demonstrate a decrease in dopamine transporter density following successful treatment with a serotonin reuptake inhibitor in people with OCD.
At first glance this may be an unexpected finding to some readers – however there are a number of possible explanations. For example, SRIs are not necessarily entirely 5-HT selective though at clinical doses it is unlikely that direct competition for the DAT would be seen.
Although the correlation between reduction in dopamine transporter (DAT) density (which has previously been shown by this group to be greater in OCD compared with controls (ref. 1) and improvement in symptoms provides some evidence for the therapeutic role of the DA system, whether this is causally related, associated with a third variable or a concurrent but not related change is not clear.
It would be interesting to see whether people with OCD who do not show an improvement following SRI treatment also show this reduction in dopamine transporter binding. Also, it would be informative to know whether SRI treatment reduces DAT density in people without OCD: is this a general effect of increased 5-HT neurotransmission?
The finding that dopamine systems may be involved in OCD outcome may help explain the widley recognised utility of dopamine blockers (neuroleptics) as adjunctive treatments to SSRIs for this disorder (ref. 2).
There is still a tendency in psychopharmacology to attribute successful treatment of mental illness to the neurotransmitter system on which the drug primarily acts. Although this often seems sufficient to placate our junior doctors and inquisitive patients, there is a growing body of evidence implying that multiple, overlapping neurotransmitter systems that are being altered, either directly or indirectly, associated with clinical improvement (for example: (ref. 3).
Our group has reported on 5-HT – Dopamine interplay in social anxiety disorder (ref. 4, ref. 5, ref. 6), and others have looked similarly at patients with major depression (ref. 7), for instance. We need to resist the temptation of an explantatory neurotransmitter reductionism lest our credibility suffer (ref. 8, ref. 9). Studies such as this by Kim et al. remind us of the potential importance of multiple neurotransmitter systems in the treatment of complex psychiatric disorders.
References
1. Kim CH, Koo MS, Cheon KA, Ryu YH, Lee JD, Lee HS. Dopamine transporter density of basal ganglia assessed with [123I]IPT SPET in obsessive-compulsive disorder. European Journal of Nuclear Medicine and Molecular Imaging 2003; 30 (12); 1637-1643
2. Hood SD, Alderton D, Castle DJ. Obsessive-compulsive disorder: treatment and treatment resistance. Australasian Psychiatry 2001; 19; 118-127
3. Hood SD, Argyropoulos SV, Nutt DJ. New directions in the treatment of anxiety disorders. Expert Opinion on Therapeutic Patents 2003; 13(4); 401-424
4. Argyropoulos SV, Hood SD, Davies SJ, Hince DA, Morris K, Nutt DJ et al. Dopaminergic challenges in social anxiety disorder. European Neuropsychopharmacology 2006; 16 (4); S186
5. Williams K, Argyropoulos S, Nutt DJ. Amphetamine misuse and social phobia. American Journal of Psychiatry 2000; 157 (5); 834-835
6. Robinson H, Bell C, Hood S, Nutt D. Dopamine and social anxiety disorder (Editorial). Revista Brasileira de Psiquiatria 2006; 28 (4);263-264
7. Willner P, Hale AS, Argyropoulos S. Dopaminergic mechanism of antidepressant action in depressed patients. Journal of Affective Disorders 2005; 86 (1); 37-45
8. Argyropoulos SV, Hood SD, Nutt DJ. Social phobia: illness or illusion? Acta Psychiatrica Scandinavica 2001; 103 (4); 241-243
9. Dewar KM, Stravynski A. The quest for biological correlates of social phobia: an interim assessment. Acta Psychiatrica Scandinavica 2001; 103 (4); 244-251