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Cited by 88Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorStress Responses and Cortisol

Psychiatric symptoms of noradrenergic dysfunction: A pathophysiological view

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Yamamoto, Ken‐ichi, Shinba, Toshikazu, Yoshii, Mitsunobu·2014·Psychiatry and Clinical Neurosciences
DOI 10.1111/pcn.12126
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Abstract

What psychiatric symptoms are caused by central noradrenergic dysfunction? The hypothesis considered in this review is that noradrenergic dysfunction causes the abnormalities in arousal level observed in functional psychoses. In this review, the psychiatric symptoms of noradrenergic dysfunction were inferred pathophysiologically from the neuroscience literature. This inference was examined based on the literature on the biology of psychiatric disorders and psychotropics. Additionally, hypotheses were generated as to the cause of the noradrenergic dysfunction. The central noradrenaline system, like the peripheral system, mediates the alarm reaction during stress. Overactivity of the system increases the arousal level and amplifies the emotional reaction to stress, which could manifest as a cluster of symptoms, such as insomnia, anxiety, irritability, emotional instability and exaggerated fear or aggressiveness (hyperarousal symptoms). Underactivity of the system lowers the arousal level and attenuates the alarm reaction, which could result in hypersomnia and insensitivity to stress (hypoarousal symptoms). Clinical data support the hypothesis that, in functional psychoses, the noradrenergic dysfunction is in fact associated with the arousal symptoms described above. The anti‐noradrenergic action of anxiolytics and antipsychotics can explain their sedative effects on the hyperarousal symptoms of these disorders. The results of animal experiments suggest that excessive stress can be a cause of long‐term noradrenergic dysfunction.

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  • NE is an important NT in behaviour control, playing a key role in high-level cognitive processes such as working memory and inhibitory response, which appear to be disrupted in ADHD, producing irritability and anxiety.

    “NE, also known as noradrenaline (NA), is an important NT in behaviour control, playing a key role in high-level cognitive processes such as working memory and inhibitory response, which appear to be disrupted in ADHD [79], producing irritability and anxiety [85].”

    From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [85]

    The Discussion (page not provided) says overactivity of the noradrenergic system could manifest as anxiety and irritability. That supports the symptoms linked to citation [85], but the paper does not establish that disrupted working memory or inhibitory responses in ADHD produce them; it also presents the symptom link as a possibility, not a certainty. (LLM, conf=0.83)

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Cited by

Sorted by citations

Authors
Yamamoto, K., Shinba, T., & Yoshii, M.
Affiliations
  • Stress Disorder Research Project Team Tokyo Metropolitan Institute of Medical Science (the former Tokyo Institute of Psychiatry) Tokyo Japan
  • Tokyo Institute of Psychiatry (JP)
ORCID
Shinba, Toshikazu
Venue
Psychiatry and Clinical Neurosciences
Publisher
Wiley
Published
2013-12-29
Volume
68
Issue
1
Pages
1-20
ISSN
  • 1323-1316 (ISSN-L)
  • 1440-1819
DOI
10.1111/pcn.12126
OpenAlex
W1604468358
Cited by
88
References
11
Citations by year
2026: 8 · 2025: 10 · 2024: 11 · 2023: 4 · 2022: 11 · 2021: 8 · 2020: 9 · 2019: 6 · 2018: 4 · 2017: 1 · 2016: 8 · 2015: 7 · 2014: 1
FWCI
0.73
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Psychiatry and Clinical Neurosciences (publishedVersion)
  • PubMed (publishedVersion)
Funders
Japan Society for the Promotion of Science (22591308)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
noradrenergic dysfunction, arousal level, functional psychoses, hyperarousal symptoms, insomnia, anxiety, irritability, neuroticism, hypersomnia, anxiolytics, antipsychotic drugs, sedative effects, psychotropic drugs
MeSH terms
Animals, Arousal, Mental Disorders, Behavioral Symptoms, Humans, Stress, Psychological, Antipsychotic Agents, Anti-Anxiety Agents, Adrenergic Neurons

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