Deep brain stimulation induces striatal dopamine release in obsessive-compulsive disorder

Biol Psychiatry. 2014 Apr 15;75(8):647-52. doi: 10.1016/j.biopsych.2013.06.021. Epub 2013 Aug 12.

Abstract

Background: Obsessive-compulsive disorder is a chronic psychiatric disorder related to dysfunctional dopaminergic neurotransmission. Deep brain stimulation (DBS) targeted at the nucleus accumbens (NAc) has recently become an effective treatment for therapy-refractory obsessive-compulsive disorder, but its effect on dopaminergic transmission is unknown.

Methods: We measured the effects of NAc DBS in 15 patients on the dopamine D2/3 receptor availability in the striatum with [(123)I]iodobenzamide ([(123)I]IBZM) single photon emission computed tomography. We correlated changes in [(123)I]IBZM binding potential (BP) with plasma levels of homovanillic acid (HVA) and clinical symptoms.

Results: Acute (1-hour) and chronic (1-year) DBS decreased striatal [(123)I]IBZM BP compared with the nonstimulated condition in the putamen. BP decreases were observed after 1 hour of stimulation, and chronic stimulation was related to concurrent HVA plasma elevations, implying DBS-induced dopamine release. BP decreases in the area directly surrounding the electrodes were significantly correlated with changes in clinical symptoms (45% symptom decrease).

Conclusions: NAc DBS induced striatal dopamine release, which was associated with increased HVA plasma levels and improved clinical symptoms, suggesting that DBS may compensate for a defective dopaminergic system.

Keywords: Deep brain stimulation; dopamine; homovanillic acid; neuroimaging; nucleus accumbens; obsessive-compulsive disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / physiopathology*
  • Deep Brain Stimulation* / methods
  • Dopamine / metabolism*
  • Female
  • Homovanillic Acid / blood
  • Humans
  • Iodobenzenes
  • Magnetic Resonance Imaging
  • Male
  • Obsessive-Compulsive Disorder / diagnostic imaging
  • Obsessive-Compulsive Disorder / physiopathology*
  • Obsessive-Compulsive Disorder / therapy*
  • Putamen / diagnostic imaging
  • Putamen / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Dopamine D3 / metabolism
  • Severity of Illness Index
  • Time Factors
  • Tomography, Emission-Computed, Single-Photon
  • Treatment Outcome

Substances

  • Iodobenzenes
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • idobenzamide
  • Dopamine
  • Homovanillic Acid