Neuromodulation by acetylcholine: examples from schizophrenia and depression
Open accessAbstract
The contribution of acetylcholine to psychiatric illnesses remains an area of active research. For example, increased understanding of mechanisms underlying cholinergic modulation of cortical function has provided insight into attentional dysfunction in schizophrenia. Acetylcholine normally enhances cortical sensitivity to external stimuli and decreases corticocortical communication, increasing focused attention; however, increases in ACh signaling can lead to symptoms related to anxiety and depression. For example, while stress-induced ACh release can result in adaptive responses to environmental stimuli, chronic elevations in cholinergic signaling may produce maladaptive behaviors. Here, we review several innovations in human imaging, molecular genetics and physiological control of circuits that have begun to identify mechanisms linking altered cholinergic neuromodulation to schizophrenia and depression.
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Impairments to cholinergic signaling in the adult human brain have been linked to psychiatric disorders in adult patients, including schizophrenia, anxiety, and depression.
“Impairments to cholinergic signaling in the adult human brain have been linked to psychiatric disorders in adult patients, including schizophrenia, anxiety, and depression [101–103].”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [102]
The schizophrenia section links aberrant acetylcholine signaling to schizophrenia in patients, and the stress and depression section reports altered signaling in depressed patients and anxiety symptoms induced in human subjects. The copy does not establish a link to a diagnosed anxiety disorder in adult patients, nor does it specify that the human subjects were adults. (LLM, conf=0.82)
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- Authors
- Higley, M. J., & Picciotto, M. R.
- Affiliations
- Yale University (US)
- Corresponding author
- Higley, Michael J
- Picciotto, Marina R
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 29
- Pages
- 88-95
- ISSN
- 0959-4388 (ISSN-L)
- PMC
- PMC4268065
- OpenAlex
- W2074521340
- Cited by
- 184
- References
- 92
- Citations by year
- 2026: 14 · 2025: 17 · 2024: 26 · 2023: 19 · 2022: 20 · 2021: 22 · 2020: 12 · 2019: 15 · 2018: 11 · 2017: 8 · 2016: 12 · 2015: 6 · 2014: 2
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (MH099045, MH077681, DA033945, DA014241)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- acetylcholine, cholinergic modulation, schizophrenia, depression, attention, anxiety, cortical function, molecular genetics, human neuroimaging
- MeSH terms
- Acetylcholine, Anxiety, Attention, Bipolar Disorder, Brain, Humans, Neural Pathways, Schizophrenia, Neuroimaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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