Deep brain stimulation induces striatal dopamine release in obsessive-compulsive disorder.
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.
Department of Psychiatry, Academic Medical Center, Amsterdam; Brain Imaging Center, Academic Medical Center, Amsterdam. Electronic address: m.figee@amc.nl.
Martijn
M
Figee
Department of Psychiatry, Academic Medical Center, Amsterdam.
Pelle
P
de Koning
Department of Psychiatry, Academic Medical Center, Amsterdam.
Sanne
S
Klaassen
Department of Psychiatry, Academic Medical Center, Amsterdam.
Nienke
N
Vulink
Department of Psychiatry, Academic Medical Center, Amsterdam.
Mariska
M
Mantione
Department of Neurosurgery, Academic Medical Center, Amsterdam.
Pepijn
P
van den Munckhof
Department of Neurosurgery, Academic Medical Center, Amsterdam.
Richard
R
Schuurman
Department of Psychiatry, Academic Medical Center, Amsterdam.
Guido
G
van Wingen
Department of Psychiatry, Academic Medical Center, Amsterdam; Department of Psychiatry and Psychology, Maastricht University, Maastricht.
Thérèse
T
van Amelsvoort
Brain Imaging Center, Academic Medical Center, Amsterdam; Department of Nuclear Medicine, Academic Medical Center, Amsterdam.
Jan
J
Booij
Department of Psychiatry, Academic Medical Center, Amsterdam; Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
Damiaan
D
Denys
D000328:Adult; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000503:physiopathology*; D046690:Deep Brain Stimulation / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D007462:Iodobenzenes; D008279:Magnetic Resonance Imaging; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy*; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D012720:Severity of Illness Index; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D007462:Iodobenzenes; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C426805:idobenzamide; D004298:Dopamine; D006719:Homovanillic Acid
Deep brain stimulation; dopamine; homovanillic acid; neuroimaging; nucleus accumbens; obsessive-compulsive disorder