Search tips
Search criteria 


Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
J Addict Med. Author manuscript; available in PMC 2013 March 1.
Published in final edited form as:
PMCID: PMC3478892

Reversible Increase in Smoking after Withdrawal of Ventral Capsule/Ventral Striatum Deep Brain Stimulation in a Depressed Smoker


How smoking affects reward systems in mood disorders remains unclear. Functional neuroimaging suggests more dysfunction among depressed than nondepressed smokers (Brody, 2009). Abnormal reward mechanisms could increase smoking’s hedonic value, thus sustaining dependence (Koob & LaMoal, 1997). Deep brain stimulation (DBS) of the ventral striatum and adjacent ventral capsule (VC/VS) enhances positive affect in OCD or major depression (Greenberg et al., 2008; Malone et al, 2009). DBS might compensate for reward deficits and reduce smoking. Conversely, smoking might increase if DBS stops.

Case Report

A 43-year-old woman enrolled in an FDA- and IRB-approved trial of DBS for otherwise intractable depression (Malone et al, 2009). Before surgery, lifetime cigarette consumption (average <10/day) and tobacco dependence was low (Fagerstrom Test for Nicotine Dependence=3). Bilateral DBS leads (Model 3391, Medtronic Inc.) were implanted following the trajectory of the anterior limb of the internal capsule at the level of the anterior commissure, extending into VS (on right: 0.2mm anterior to the anterior commissure, 7.5mm lateral, and -1.8mm below the AC-PC plane; on left: 0.1, 8.9, and -1.9mm, respectively). Before DBS, depression remained severe despite aggressive conventional treatments (Montgomery-Åsberg Depression Rating Scale (MADRS=33). After left unilateral VC/VS DBS she sustained remission (MADRS≤7) for four years, except when stimulator batteries were depleted. Stimulation parameters: contacts 0+1-2-3+, 130Hz, pw 120 µSec, 6.0V. Concomitant medications including Valproate 1500 mg; Clonezapam 3 mg; Eszopiclone 3 mg; Oxcarbazepine 600 mg.

Smoking before and after DBS interruption

During chronic DBS, smoking remained stable. However, on three separate occasions when DBS was interrupted (e.g. battery depletion), smoking increased dramatically (50–200%). Figure 1 displays her reported smoking during two recent DBS interruption episodes recalled with confidence, including when stimulation restarted. Off DBS, she noticed mood changes and markedly increased urges to smoke, simultaneously experiencing smoking as ‘intensely’ unpleasant. Depressive symptoms increased to near a MADRS remission threshold (<10) on both occasions (MADRS=7 and 10 during episodes 1 and 2, respectively). When DBS resumed, smoking rate and pattern returned to baseline, and depressive symptoms declined (MADRS=5 and 2 during episodes 1 and 2, respectively). No increases in appetite were observed with DBS off; her substance use remained limited to tobacco.

Figure 1
Changes in smoking rate during two episodes of DBS disruption. Therapeutic effects routinely decrease during the final 2 weeks of battery life, when DBS currents diminish markedly. Changes in smoking thus were associated temporally with DBS withdrawal. ...


DBS to the same network modulated reportedly affected reward in depressed patients (Schlapfer et al., 2008) and was associated with smoking cessation in an OCD patient (Mantione et al., 2010). Nicotine and cues for nicotine delivery activate the VS and regions functionally connected to the VC/VS (Brody, et al. 2009; David et al. 2007). Withdrawal of chronic smoking may raise reward thresholds by compromising dopaminergic inputs to the VS (Koob & Lamoal, 1997; Balfour, 2004; Epping-Jordan, et al., 1998). Though reliant upon retrospection, like acute smoking cessation, DBS withdrawal in this case led to reproducible acute increases in craving and increased smoking and mild increases in depressive symptoms. These findings suggest significant potential for exploring the neurobiology of tobacco dependence, which may involve MAO-inhibitors as well as nicotine, in DBS patients. Such patients include those with intractable OCD, depression, and chronic pain.


With support from the National Institutes of Health: NIMH P50MH086400 and NIDA R01MH073111 (Haber)


Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.


  • Balfour DJ. The neurobiology of tobacco dependence: a preclinical perspective on the role of the dopamine projections to the nucleus accumbens [corrected] Nicotine Tob Res. 2004;6(6):899–912. [PubMed]
  • Brody AL, Olmstead RE, Abrams AL, Costello MR, Khan A, Kozman D, et al. Effect of a history of major depressive disorder on smoking-induced dopamine release. Biol Psychiatry. 2009;66(9):898–901. [PMC free article] [PubMed]
  • David SP, Munafo MR, et al. Effects of Acute Nicotine Abstinence on Cue-elicited Ventral Striatum/Nucleus Accumbens Activation in Female Cigarette Smokers: A Functional Magnetic Resonance Imaging Study. Brain Imaging Behav. 2007;1(3–4):43–57. [PMC free article] [PubMed]
  • Epping-Jordan MP, Watkins SS, et al. Dramatic decreases in brain reward function during nicotine withdrawal. Nature. 1998;393(6680):76–79. [PubMed]
  • Epstein J, Pan H, Kocsis JH, Yang Y, Butler T, Chusid J, et al. Lack of ventral striatal response to positive stimuli in depressed versus normal subjects. The American Journal of Psychiatry. 2006;163(10):1784–1790. [PubMed]
  • Greenberg BD, Gabriels LA, et al. Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Mol Psychiatry. 2008;15(1):64–79. [PMC free article] [PubMed]
  • Koob GF, Le Moal M. Drug abuse: hedonic homeostatic dysregulation. Science. 1997;278(5335):52–58. [PubMed]
  • Malone DA, Jr, Dougherty DD, et al. Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol Psychiatry. 2009;65(4):267–275. [PMC free article] [PubMed]
  • Mantione M, van de Brink W, et al. Smoking cessation and weight loss after chronic deep brain stimulation of the nucleus accumbens: therapeutic and research implications: case report. Neurosurgery. 66(1):E218. ; discussion E218. [PubMed]
  • Schlaepfer TE, Cohen MX, Frick C, Kosel M, Brodesser D, Axmacher N, et al. Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. Neuropsychopharmacology. 2008;33(2):368–377. [PubMed]