Changes in the Cholinergic System between Bipolar Depression and Euthymia as Measured with [123I]5IA Single Photon Emission Computed Tomography
Open accessAbstract
Background The cholinergic system is substantially altered in individuals with major depression and is partially restored when depression remits. We quantified the availability of β2-subunit-containing nicotinic acetylcholine receptors (β2*-nAChR) in subjects with bipolar disorder.Methods Twenty-five subjects with bipolar disorder (15 depressed, 10 euthymic) and 25 sex- and age-matched control subjects had a [(123)I]5IA-85380 single photon emission computed tomography scan to quantify β2*-nAChR VT/fP (total volume of distribution, corrected for individual differences in metabolism and protein binding of the radiotracer). Average VT/fP was compared between groups and correlated with clinical characteristics. Postmortem analysis of β2*-nAChRs was conducted using equilibrium binding with [(125)I]5IA in subjects with bipolar disorder and matched control subjects.Results We showed significantly lower β2*-nAChR availability (20%-38%) in subjects with bipolar depression compared with euthymic and control subjects across all brain regions assessed (frontal, parietal, temporal, and anterior cingulate cortex, hippocampus, amygdala, thalamus, striatum). The postmortem binding study in which endogenous acetylcholine was washed out did not show a statistically significant difference in β2*-nAChR number in temporal cortex of the bipolar depressed and control groups (15% difference; p = .2).Conclusions We show that the alteration in the cholinergic system observed during a depressive episode appears to resolve during euthymia. We suggest that lower VT/fP observed in vivo may be due to a combination of higher endogenous acetylcholine levels during depression, which could compete with radiotracer binding to the receptor in vivo, and lower receptor number in bipolar depression. Identification of differences in cholinergic signaling in subjects with bipolar depression may improve our understanding of its etiology and reveal new treatment targets.
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Elevated ACh levels observed in human subjects who are actively depressed contribute to the disorder.
“supports the idea that the elevated ACh levels observed in human subjects who are actively depressed contributes to the disorder (Saricicek et al. 2012;Hannestad et al. 2013).”
From Mechanisms of Nicotine Addiction (2021) · cites this paper as Hannestad et al. 2013
The Results report lower receptor availability in actively depressed subjects, not a direct measurement of elevated ACh. The Discussion suggests that higher extracellular ACh may explain the finding and could be associated with depression, but it does not establish that elevated ACh was observed or that it contributes causally to the disorder. No page numbers are available in our copy. (LLM, conf=0.88)
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References 42 · Cited by 63
Research works printed but not linked: 3
- [24]First MB Spitzer RL Gibbon M Williams JBW Structured Clinical Interview for DSM-IV Axis I disorders—Clinician Version (SCID-CV) 1997 Washington, DC American Psychiatric Press
- [28]Saricicek A Esterlis I Maloney K Mineur Y Ruf B Muralidharan A Persistent β2*-nicotinic acetylcholinergic receptor dysfunction in major depressive disorder Am J Psychiatry 2012 169 851 859 22772158 PMC3494404
- [29]Staley JK Krishnan-Sarin S Cosgrove KP Krantzler E Frohlich E Perry E Human tobacco smokers in early abstinence have higher levels of beta2* nicotinic acetylcholine receptors than non-smokers J Neurosci 2006 26 8707 8714 16928859 PMC6674379
- Authors
- Hannestad, J. O., Cosgrove, K. P., DellaGioia, N. F., Perkins, E., Bois, F., Bhagwagar, Z., Seibyl, J. P., McClure-Begley, T. D., Picciotto, M. R., & Esterlis, I.
- Affiliations
- Yale University (US)
- Institute for Neurodegenerative Disorders (US)
- Corresponding author
- Esterlis, Irina
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 74
- Issue
- 10
- Pages
- 768-776
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC3805761
- OpenAlex
- W1995481789
- Cited by
- 63
- References
- 42
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 10 · 2019: 5 · 2018: 3 · 2017: 6 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 2
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (K12DA00167, K02DA031750, R01DA015577, K01MH092681, MH077681)
- National Institute of Mental Health (R21MH085198-02)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- bipolar depression, cholinergic system, nicotinic acetylcholine receptors, beta2 nAChR, receptor availability, euthymia, endogenous acetylcholine, receptor density, depression remission
- MeSH terms
- Adult, Azetidines, Bipolar Disorder, Brain Chemistry, Female, Humans, Male, Pyridines, Receptors, Nicotinic, Smoking, Tomography, Emission-Computed, Single-Photon
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