Role of dopamine in the pathophysiology and treatment of obsessive–compulsive disorder

Abstract

The differential effects of serotonin-reuptake inhibitors on obsessive-compulsive disorder (OCD) were sufficient to presume that a serotonin regulatory disorder is the most essential part of the pathophysiology of OCD. In patients with OCD, however, a high-dose of serotonin-reuptake inhibitor monotherapy may not be sufficient, and approximately half of patients were noted to be treatment-resistant. As results from previous studies have shown, there have been positive treatment responses to the dopaminergic antagonists. This suggests that other neurotransmitter systems, such as dopamine, are involved in the pathophysiology of OCD. Preclinical, neuroimaging and neurochemical studies have provided evidence demonstrating that the dopaminergic system is involved in inducing or aggravating the symptoms that are indicative of OCD. In this article, we review the dopaminergic system in OCD pathophysiology as well as reviewing the effect of drugs that act on dopaminergic activity in OCD.

Symmetry symptoms in obsessive-compulsive disorder: clinical and genetic correlates

“…12 This is consistent with a range of data pointing to an important role for the dopamine system in OCD. 13 Alterations in the dopaminergic system may reflect the influence of particular environmental factors (e.g., exposure to stress or adversity) 14 or particular genetic factors (e.g., functional variants in the dopamine system). 15 However, although OCD is considered a polygenic disorder, 16 the particular association of symmetryrelated symptomatology, early adversity, and selected polymorphisms in dopaminergic genes has, to our knowledge, not been investigated in this condition.…”

Effect of Gonadal Hormones on Neurotransmitters Implicated in the Pathophysiology of Obsessive-Compulsive Disorder: A Critical Review

“…1 ) [71] . As previously discussed, since OCD patients are thought to have impaired serotonin signaling, it is possible that this deficiency is leading to dopaminergic hyperactivity, characteristic of OCD [65] .…”

“…Although numerous studies have demonstrated the effectiveness of SRIs as a primary treatment option for OCD, there appears to be a subset of OCD patients that are resistant to SRI treatment [65] . Furthermore, pharmacological challenge studies of the serotonin system, as well as studies measuring serotonin metabolite levels in the CSF have not always shown consistent results [66] .…”

“…It was suggested that this modification of D2 receptor availability is a result of fluvoxamine's modulation of the serotonergic system. Serotonergic neurons projecting from the raphe nuclei are thought to modulate the cortico-striato-thalamo-cortical (CSTC) loop that is associated with OCD, in which dopamine is the dominant neurotransmitter [65] . When serotonin is released from a presynaptic neuron, it may bind to 5-HT 2A receptors on the somatodendritic surface of dopamine neurons.…”

“…When research revealed that there is some modulation of the dopaminergic system by serotonin, investigators proposed that concomitant use of SSRIs and dopaminergic antagonists may be an effective option for SSRI treatment-refractory patients [65,71] . Indeed, co-administration of the 2 drugs appeared to be quite efficacious in a number of trials, including an open trial by Metin's group that showed a significant improvement in 95% of the patients treated with an SSRI and amisulpiride [72,73] .…”