Acetylcholine and Depression*

Abstract

Physostigmine, a cholinesterase inhibitor which increases central acetylcholine levels, has been found in man to decrease manic symptoms, antagonize methylphenidate-induced behavioral activation, and induce severe depression and psychomotor retardation in marijuana intoxicated normals. In the current study, physostigmine was found to increase depressed mood in patients with an affective component to their symptoms (manics, depressives, and schizoaffectives). Schizophrenics without an affective component did not become depressed. After physostigmine administration, all subject groups showed a significant increase in symptoms including lethargy, slowed thoughts, withdrawal, apathy, decreased energy, decreased thoughts, motor retardation, and feeling drained, indicating a state of psychomotor retardation; and all became less cheerful, friendly, and talkative. The above information is compatible with the hypothesis that acetylcholine may be involved in the etiology of affective disorders.

A final common pathway for depression? Progress toward a general conceptual framework

“…) has suggested a key role for cholinergic neurotransmission in the PAG in stress responses related to depression confirming the earlier hypothesis of Janowsky et al (1974).…”

Depression and Risk of Incident Asthma in Adults. The CARDIA Study

“…One potential central nervous system pathway involves the insular and anterior cingulated cortices (i.e., brain regions implicated in the regulation of emotion) that influence the development and persistence of symptom expression in asthma via changes in airway efferent neural activity (38). Others have suggested that depression is associated with autonomic dysregulation in the form of cholinergic activation, which, in turn, leads to airway constriction (39)(40)(41). Conversely, happiness affects autonomic patterns that may relieve airway constriction (41).…”

Antidepressant Efficacy of the Antimuscarinic Drug Scopolamine

“…Moreover, our results complement the previously reported findings that cholinergic enhancement using physostigmine induces symptoms of depression in currently manic individuals with BD and worsens symptoms in patients with unipolar depression. 4,6 Determination of the optimal schedule of administration and the potential long-term use of scopolamine as an antidepressant agent requires further study, particularly because potential adverse effects include confusion and delirium. Future studies also may examine the antidepressant efficacy of scopolamine when using routes of administration that are more clinically practical in outpatient settings.…”

“…Increasing cholinergic activity using physostigmine (an anticholinesterase inhibitor) provides a challenge uniquely capable of exacerbating depressive symptoms in currently depressed patients with MDD and inducing depressive symptoms in currently manic patients with BD. [4][5][6][7][8][9] The cholinergic system also is implicated in depression by evidence showing that polysomnographic responses to muscarinic receptor agonists [10][11][12] and neuroendocrine and pupillary responses to cholinomimetics [13][14][15][16] are exaggerated in depressed patients and that some muscarinic receptor gene polymorphisms are associated with an elevated incidence of depression. 17,18 Elevated cholinergic function thus was hypothesized to participate in the pathogenesis of mood disorders.…”