A cholinergic-adrenergic hypothesis of mania and depression

Janowsky, DavidS; Davis, JohnM; El-Yousef, M.Khaled; Sekerke, H.Joseph

doi:10.1016/s0140-6736(72)93021-8

Cited by 1,134Bipolar Disorder and TreatmentTreatment of Major DepressionNeuroscience and Neuropharmacology Research

A cholinergic-adrenergic hypothesis of mania and depression

Janowsky, DavidS, Davis, JohnM, El-Yousef, M.Khaled, Sekerke, H.Joseph·1972·The Lancet

DOI 10.1016/s0140-6736(72)93021-8

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The cholinergic-adrenergic theory of depression postulates that over-activation of the cholinergic component leads to depression.
“The cholinergic-adrenergic theory of depression postulates that a fine balance exists between cholinergic and noradrenergic systems, and that over-activation of the cholinergic component would lead to depression (Janowsky et al., 1972).”
From It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood (2008) · cites this paper as Janowsky et al., 1972
Increasing ACh signaling in humans results in increased symptoms of depression.
“There is strong evidence that increasing ACh signaling in humans results in increased symptoms of depression (Janowsky et al., 1972; Risch et al., 1980).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Janowsky et al., 1972
The lower β2*-nAChR availability in vivo in MDD is likely better explained by increased levels of extracellular ACh rather than by a decrease in the total number of receptors.
“This suggests that, consistent with the cholinergic hypothesis of depression (4), the lower β2*-nAChR availability in vivo is likely better explained by increased levels of extracellular ACh in patients with MDD rather than by a decrease in the total number of receptors.”
From Persistent β 2 *-Nicotinic Acetylcholinergic Receptor Dysfunction in Major Depressive Disorder (2012) · cites this paper as [4]
Cholinergic hyperactivity plays a role in the pathophysiology of depression and can exacerbate depression-like symptoms in patients and controls.
“First, cholinergic hyperactivity plays a role in the pathophysiology of depression (2–4) and can exacerbate depression-like symptoms in patients and controls (4–6).”
From Persistent β 2 *-Nicotinic Acetylcholinergic Receptor Dysfunction in Major Depressive Disorder (2012) · cites this paper as [4]

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Authors: Janowsky, D., Davis, J., El-Yousef, M. K., & Sekerke, H. J.
Affiliations: Vanderbilt University (US)
Venue: The Lancet
Publisher: Elsevier BV
Published: 1972-09
Volume: 300
Issue: 7778
Pages: 632-635
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(72)93021-8
OpenAlex: W2056272943
Cited by: 1,134
References: 41
Citations by year: 2026: 10 · 2025: 14 · 2024: 16 · 2023: 10 · 2022: 20 · 2021: 26 · 2020: 22 · 2019: 20 · 2018: 24 · 2017: 22 · 2016: 16 · 2015: 31 · 2014: 16 · 2013: 22 · 2012: 27
FWCI: 28.53
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: mania, depression, bipolar disorder, acetylcholine, norepinephrine, reserpine, tricyclic antidepressants, physostigmine, cholinomimetic drugs, autonomic nervous system
MeSH terms: Affective Symptoms, Autonomic Nervous System, Bipolar Disorder, Depression, Homeostasis, Humans, Synaptic Transmission, Parasympathetic Nervous System, Parasympathomimetics, Schizophrenia, Sympathetic Nervous System, Sympathomimetics

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A cholinergic-adrenergic hypothesis of mania and depression

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