What are the etiologies of obsessive-compulsive disorder (OCD)?

Updated: May 17, 2018
  • Author: William M Greenberg, MD; Chief Editor: David Bienenfeld, MD  more...
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Answer

The exact process that underlies the development OCD has not been established. Research and treatment trials suggest that abnormalities in serotonin (5-HT) neurotransmission in the brain are meaningfully involved in this disorder. This is strongly supported by the efficacy of serotonin reuptake inhibitors (SRIs) in the treatment of OCD. [16, 17]

Evidence also suggests abnormalities in dopaminergic transmission in at least some cases of OCD. In some cohorts, Tourette disorder (also known as Tourette syndrome) and multiple chronic tics genetically co-vary with OCD in an autosomal dominant pattern. OCD symptoms in this group of patients show a preferential response to a combination of serotonin specific reuptake inhibitors (SSRIs) and antipsychotics. [18]

Functional imaging studies in OCD have demonstrated some reproducible patterns of abnormality. Specifically, magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning have shown increases in blood flow and metabolic activity in the orbitofrontal cortex, limbic structures, caudate, and thalamus, with a trend toward right-sided predominance. In some studies, these areas of overactivity have been shown to normalize following successful treatment with either SSRIs or cognitive-behavioral therapy (CBT). [19]

These findings suggest the hypothesis that the symptoms of OCD are driven by impaired intracortical inhibition of specific orbitofrontal-subcortical circuitry that mediates strong emotions and the autonomic responses to those emotions. Cingulotomy, a neurosurgical intervention sometimes used for severe and treatment-resistant OCD, interrupts this circuit (see Treatment and Management).

Similar abnormalities of inhibition are observed in Tourette disorder, with a postulated abnormal modulation of basal ganglia activation.

Attention has also been focused on glutamatergic abnormalities and possible glutamatergic treatments for OCD. [20, 21] Although modulated by serotonin and other neurotransmitters, the synapses in the cortico-striato-thalamo-cortical circuits thought to be centrally involved in the pathology of OCD principally employ the neurotransmitters glutamate and gamma-aminobutyric acid (GABA).


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