Biological basis for the co-morbidity between smoking and mood disorders
Open accessAbstract
Nicotine dependence is still the major preventable cause of death in the developed world, and has strong comorbity with mood disorders including major depression. Depressed patients are more likely to smoke cigarettes, and quitting can precipitate an episode of depression in some subjects. Interestingly, antidepressants, particularly the atypical antidepressant buproprion, are therapeutics that can help smokers quit. Despite these observations, the underlying biological factors of the relationship between smoking and depression remain unclear. Results from clinical and pre-clinical studies have seemed somewhat paradoxical because heightened cholinergic activity can induce depression while both nicotine and nicotinic antagonists can be antidepressant-like. These observations can be reconciled by considering that high affinity nicotinic receptors in the brain can be desensitized by chronic nicotine use, leading to blunted cholinergic activity. Based on this hypothesis, nicotinic antagonists have recently been tested as treatments for depression in human subjects, particularly as adjunct therapy along with classical antidepressants. These data suggest that the relationship between smoking and depression may be partially explained by the fact that depressed patients smoke in an effort to self-medicate depressive symptoms by desensitizing their nicotinic receptors. This possibility suggests new avenues for treatment of both nicotine dependence and depressive disorders.
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Smoking may constitute an attempt to self-medicate in people with severe mental disorders including bipolar disorder, in terms of alleviating cognitive deficits, depression and reducing extrapyramidal symptoms associated with antipsychotic treatment.
“Thus, it has been hypothesized that smoking is an effort to self-medicate in people with severe mental disorders (30), including BD, in terms of alleviating cognitive deficits (31), depression (32, 33) and reducing extrapyramidal symptoms associated with antipsychotic treatment.”
From The detrimental effects of smoking on the course and outcome in adults with bipolar disorder—A narrative review (2023) · cites this paper as [33]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredAlcohol use and cigarette smoking during adolescence may procure noxious neurobiological effects.
“Two longitudinal studies indicate that alcohol use and cigarette smoking during adolescence may procure noxious neurobiological effects (33, 34).”
From The detrimental effects of smoking on the course and outcome in adults with bipolar disorder—A narrative review (2023) · cites this paper as [33]
The Smoking and Depression section says chronic nicotine intake through smoking leads to neuroadaptations in brain circuits, including those related to affect. It does not say these effects are noxious or specific to adolescence, and it does not report longitudinal evidence about adolescent alcohol use. (LLM, conf=0.78)
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“Two longitudinal studies indicate that alcohol use and cigarette smoking during adolescence may procure noxious neurobiological effects (33, 34).”
Background
- Authors
- Mineur, Y. S., & Picciotto, M. R.
- Affiliations
- Yale University (US)
- Venue
- Journal of Dual Diagnosis
- Publisher
- Informa UK Limited
- Published
- 2009-05-22
- Volume
- 5
- Issue
- 2
- Pages
- 122-130
- ISSN
- 1550-4263 (ISSN-L)
- 1550-4271
- PMC
- PMC2707026
- OpenAlex
- W1982621267
- Cited by
- 51
- References
- 48
- Citations by year
- 2026: 4 · 2025: 2 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 1 · 2017: 1 · 2016: 3 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 8
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Dual Diagnosis (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH077681)
- National Institute on Drug Abuse (K02DA000436)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- smoking, mood disorders, major depressive disorder, nicotine dependence, nicotinic acetylcholine receptors, receptor desensitization, cholinergic activity, nicotine antagonists, bupropion, antidepressant-like effects, self-medication, smoking cessation, comorbidities
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