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Acetylcholine and affective disorder

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Summary

We reviewed the evidence for involvement of central cholinergic neurons in affective disorder. Cholinomimetics inhibit speech, thought, and activity in most subjects, decrease manic symptoms and, in some affective disorder patients, produce depressive symptoms. Cholinomimetics also cause ACTH and cortisol secretion and decrease latency to REM sleep. It is unclear whether cholinomimetics are specifically “antimanic” or “depressogenic” or whether their fundamental effect is nonspecific behavioral inhibition; whether the observed effects of cholinomimetics are mediated largely through cholinergic pathways, are secondary to changes in other neurotransmitters or are part of a nonspecific stress response. The suggestion that anticholinergic agents have mood elevating properties has not yet been subjected to controlled investigation.

Although the proposal that affective disorders involve cholinergic neurons has received some support from clinical investigation further research is required to substantiate the intriguing observations to date and to clarify the physiologic and psychologic processes mediating them.

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References

  • Berger M, Doerr P, van Zerssen D (1984) Physostigmine's influence on DST results. Am J Psychiatry 141: 469–470

    PubMed  Google Scholar 

  • Bowers MB, Goodman E, Sim VM (1964) Some behavioral changes in man following anticholinesterase administration. J Nerv Ment Dis 138: 383–389

    PubMed  Google Scholar 

  • Brown WA, Krieger DT, van Woert MH, Ambani LM (1974) Dissociation of growth hormone and cortisol release following apomorphine. J Clin Endocrinol Metab 38: 1127–1129

    PubMed  Google Scholar 

  • Carroll BJ, Frazer A, Schless A, Mendels J (1973) Cholinergic reversal of manic symptoms. Lancet 1: 427–428

    Google Scholar 

  • Carroll BJ, Greden JF, Hasket R, Feinberg M, Albala AA, Martin FIR, Rubin RT, Heath B, Sharp PT, McLeod WL, McLeod MF (1980) Neurotransmitter studies of neuroendocrine pathology in depression. Acta Psychiatr Scand [Suppl] 280: 183–200

    Google Scholar 

  • Casey DE (1979) Mood alterations during deanol therapy. Psychopharmacology 62: 187–191

    PubMed  Google Scholar 

  • Cohen BM, Lipinski JF, Altesman RI (1982) Lecithin in the treatment of mania: double-blind, placebo-controlled trials. Am J Psychiatry 139: 1162–1164

    PubMed  Google Scholar 

  • Coid J, Strang J (1982) Mania secondary to procyclidine (‘Kemadrin’) abuse. Br J Psychiatry 141: 81–84

    PubMed  Google Scholar 

  • Corrodi H, Fuxe K, Hammer W, Sjoqvist F, Ungerstedt U (1967) Oxotremorine and central monoamine neurons. Life Sci 6: 2557–2566

    PubMed  Google Scholar 

  • Davis BM, Davis KL (1980) Cholinergic mechanisms and anterior pituitary hormone secretion. Biol Psychiatry 15: 303–310

    PubMed  Google Scholar 

  • Davis KL, Berger PA (1978) Pharmacological investigations of the cholinergic imbalance hypotheses of movement disorders and psychosis. Biol Psychiatry 13: 23–49

    PubMed  Google Scholar 

  • Davis KL, Berger PA, Hollister LE, Defraites E (1978) Physostigmine in mania. Arch Gen Psychiatry 35: 119–122

    PubMed  Google Scholar 

  • Davis KL, Hollister LE, Berger PA (1979) Choline chloride in schizophrenia. Am J Psychiatry 136: 1581–1584

    PubMed  Google Scholar 

  • Davis KL, Hollister LE, Goodwin FK, Gordon EK (1977) Neurotransmitter metabolites in the cerebrospinal fluid of man following physostigmine. Life Sci 21: 933–936

    PubMed  Google Scholar 

  • Davis KL, Hollister LE, Livesey J, Berger PA (1979) Cerebrospinal fluid acetylcholinesterase in neuropsychiatric disorders. Psychopharmacology 63: 155–159

    PubMed  Google Scholar 

  • Davis KL, Hollister LE, Overall J, Johnson A, Train K (1976) Physostigmine: effects on cognition and affect in normal subjects. Psychopharmacology 51: 23–27

    PubMed  Google Scholar 

  • Deutsch SI, Mohs RC, Levy MI, Rothpearl AB, Stockton D, Horvath T, Coco A, Davis KL (1983) Acetylcholinesterase activity in CSF in schizophrenia, depression, Alzheimer's disease, and normals. Biol Psychiatry 18: 1363–1373

    PubMed  Google Scholar 

  • El-Fakahany E, Richelson E (1983) Antagonism by antidepressants of muscarinic acetylcholine receptors of human brain. Br J Pharmacol 78: 97–102

    PubMed  Google Scholar 

  • English DC (1962) Reintegration of affect and psychic emergence with Ditran. J Neuropsychiatry 3: 304–310

    Google Scholar 

  • Eversmann T, Gottsmann M, Uhlich E, Ulbrecht G, von Werder K, Scriba PC (1978) Increased secretion of growth hormone, prolactin, antidiuretic hormone, and cortisol induced by the stress of motion sickness. Aviat Space Environ Med 49: 53–57

    PubMed  Google Scholar 

  • Gershon S, Shaw FH (1961) Psychiatric sequelae of chronic exposure to organophosphorus insecticides. Lancet 1: 1371–1374

    PubMed  Google Scholar 

  • Gisselmann A, Marin A, Simon P (1975) étude pilote des effets d'un antiparkinsonien anticholinergique au cours d'etats depressifs. L'Encephale 1: 363–366

    PubMed  Google Scholar 

  • Golds PR, Przyslo FR, Strange PG (1980) The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors. Br J Pharmacol 68: 541–549

    PubMed  Google Scholar 

  • Hanin I, Cohen BM, Kopp U, Lipinski JF (1982) Erythrocyte and plasma choline in bipolar psychiatric patients: a follow-up study. Psychopharmacol Bull 18: 186–190

    PubMed  Google Scholar 

  • Hanin I, Kopp U, Spiker DG, Neil JF, Shaw DH, Kupfer DJ (1980) RBC and plasma choline levels in control and depressed individuals: a critical evaluation. Psychiatry Res 3: 345–355

    PubMed  Google Scholar 

  • Hobson JA, McCarley RW, McKenna TM (1976) Cellular evidence bearing on the pontine brain-stem hypothesis of desynchronized sleep control. Prog Neurobiol 6: 279–358

    Google Scholar 

  • Hyslop DK, Taylor DP (1980) The interaction of trazodone with rat brain muscarinic cholinoceptors. BrJ Pharmacol 71: 359–361

    Google Scholar 

  • Janowsky DS, El-Yopusef MK, Davis JM (1974) Acetylcholine and depression. Psychosom Med 36: 248–257

    PubMed  Google Scholar 

  • Janowsky DS, El-Yousef MK, Davis JM, Sekerke HJ (1972) A cholinergicadrenergic hypothesis of mania and depression. Lancet 1: 632–635

    Google Scholar 

  • Janowsky DS, El-Yousef MK, Davis JM, Sekerke HJ (1973) Parasympathetic suppression of manic symptoms by physostigmine. Arch Gen Psychiatry 28: 542–547

    PubMed  Google Scholar 

  • Janowsky DS, Risch SC, Judd LL, Huey LY, Parker DC (1981) Cholinergic supersensitivity in affect disorder patients: behavioral and neuroendocrine observations. Psychopharmacol Bull 17: 129–132

    Google Scholar 

  • Janowsky DS, Risch SC, Kennedy B, Ziegler M, Huey L (1986) Central muscarinic effects of physostigmine on mood, cardiovascular function, pituitary and adrenal neuroendocrine release. Psychopharmacology 89: 150–154

    PubMed  Google Scholar 

  • Janowsky DS, Risch C, Parker D, Huey L, Judd L (1980) Increased vulnerability to cholinergic stimulation in affective-disorder patients. Psychopharmacol Bull 16: 29–31

    Google Scholar 

  • Jimerson DS, Nurnberger JI, Simmons S, Gershon ES (1982) Anticholinergic treatment for depression. Presented at the 1982 American psychiatric association meeting, Toronto, Canada

  • Jope RS, Jenden DJ, Ehrlich BE, Diamond JM, Gosenfeld LF (1980) Erythrocyte choline concentrations are elevated in manic patients. Proc Natl Acad Sci USA 77: 6144–6146

    PubMed  Google Scholar 

  • Kasper S, Moises HW, Bechmann H (1981) The anticholinergic biperiden in depressive disorders. Pharmacopsychiatry 14: 195–198

    Google Scholar 

  • Lavery R, Sharman DF (1965) Modification by drugs of the metabolism of 3,4-dihydroxyphenylethylamine, noradrenaline, and 5-hydroxytryptamine in the brain. Br J Pharmacol 24: 759–772

    PubMed  Google Scholar 

  • Mathew RJ, Ho BT, Khan MM, Perales C, Weinman ML, Claghorn JL (1982) True and pseudo cholinesterases in depression. Am J Psychiatry 139: 125–127

    PubMed  Google Scholar 

  • Meduna LJ, Abood LG (1959) Studies of a new drug (Ditran) in depressive states. J Neuropsychiatry 1: 20–22

    Google Scholar 

  • Milstoc M, Teodoru CV, Fieve RR, Kumbaraci T (1975) Cholinesterase activity and the manic depressive patients. Dis Nerv Sys 36: 197–199

    Google Scholar 

  • Modestin J, Hunger J, Schwartz RB (1973) über die depressogene Wirkung von Physostigmin. Arch Psychiatrie Nervenkr 218: 67–77

    Google Scholar 

  • Morris JB, Beck AT (1974) The efficacy of antidepressant drugs. Arch Gen Psychiatry 30: 667–674

    PubMed  Google Scholar 

  • Nurnberger JI, Jimerson DC, Simmons-Alling S, Tamminga C, Nadi NS, Lawrence D, Sitaram N, Gillin JC, Gershon ES (1983) Behavioral, physiological, and neuroendocrine responses to arecoline in normal twins and “well state” bipolar patients. Psychiatry Res 9: 191–200

    PubMed  Google Scholar 

  • Oppenheim G, Ebstein RP, Belmaker RH (1979) Effect of lithium on the physostigmine induced behavioral syndrome and plasma cyclic GMP. J Psychiatr Res 15: 133

    PubMed  Google Scholar 

  • Risch SC (1982) Beta-endorphin hypersecretion in depression: possible cholinergic mechanisms. Biol Psychiatry 17: 1071–1079

    PubMed  Google Scholar 

  • Risch SC, Cohen RM, Janowsky DS, Kalin NH, Murphy DL (1980) Mood and behavioral effects of physostigmine on humans are accompanied by elevations in plasma beta-endorphin and cortisol. Science 209: 1545–1546

    PubMed  Google Scholar 

  • Risch SC, Cohen RM, Janowsky DS, Kalin NH, Sitaram N, Gillin JC, Murphy DL (1981) Physostigmine induction of depressive symptomatology in normal human subjects. Psychiatry Res 4: 89–94

    PubMed  Google Scholar 

  • Robinson RA (1961) L'utilisation de l'orphenadrine chez les patients psychiatriques ages. Ann Med Psychol 1: 792

    Google Scholar 

  • Rowntree DW, Nevin S, Wilson A (1950) The effects of diisopropylfluorophosphonate in schizophrenia and manic depressive psychosis. J Neurol Neurosurg Psychiatry 13: 47–59

    Google Scholar 

  • Sagales T, Erill S, Domino EF (1969) Differential effects of scopolamine and chlorpromazine on REM and NREM sleep in normal male subjects. Clin Pharmacol Ther 10: 522–529

    PubMed  Google Scholar 

  • Sagales T, Erill S, Domino EF (1975) Effects of repeated doses of scopolamine on the electroencephalographic stages of sleep in normal volunteers. Clin Pharmacol Ther 18: 727–732

    PubMed  Google Scholar 

  • Schwartz RD, Lehmann J, Kellar KJ (1984) Presynaptic nicotinic cholinergic receptors labeled by [3H]acetylcholine on catecholamine and serotonin axons in brain. J Neurochem 42: 1495–1498

    PubMed  Google Scholar 

  • Sitaram N, Gillin JC (1980) Development and use of pharmacological probes of the CNS in man: evidence of cholinergic abnormality in primary affective illness. Biol Psychiatry 15: 925–955

    PubMed  Google Scholar 

  • Sitaram N, Nurnberger JI, Gershon ES, Gillin JC (1980) Faster cholinergic REM sleep induction in euthymic patients with primary affective illness. Science 208: 200–202

    PubMed  Google Scholar 

  • Sitaram N, Wyatt RJ, Dawson S, Gillin JC (1976) REM sleep induction by physostigmine infusion during sleep. Science 191: 1281–1283

    PubMed  Google Scholar 

  • Smith JM (1980) Abuse of the antiparkinson drugs: a review of the literature. J Clin Psychiatry 41: 351–354

    PubMed  Google Scholar 

  • Snyder SH, Yamamura HI (1977) Antidepressants and the muscarinic acetylcholine receptor. Arch Gen Psychiatry 34: 236–239

    PubMed  Google Scholar 

  • Tamminga C, Smith RC, Chang S, Haraszti JS, Davis JM (1976) Depression associated with oral choline. Lancet 2: 905

    Google Scholar 

  • Taylor DP, Hyslop DK, Becker JA (1981) Trazodone does not competitively inhibit binding at muscarinic cholinoceptors. Gen Pharmacol 12: 391–392

    PubMed  Google Scholar 

  • Ungvari G, Karczag I, Gerevich J (1981) Petho: clinical notes on the possible anticholinergic reversal of depressive syndromes. Pharmacopsychiatry 14: 71–73

    Google Scholar 

  • Vaillant GE (1969) Clinical significance of anticholinergic effects of imipramine-like drugs. Am J Psychiatry 125: 154–156

    Google Scholar 

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  1. W. A. Brown

    Present address: Department of Psychiatry, Providence Veterans Administration Medical Center, Providence, Rhode Island, USA

Authors and Affiliations

  1. Department of Psychiatry, Providence Veterans Administration Medical Center, Providence, Rhode Island, USA

    Sandra S. Leong

  2. Brown University, Providence, Rhode Island, USA

    Sandra S. Leong & W. A. Brown

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  1. Sandra S. Leong
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Leong, S.S., Brown, W.A. Acetylcholine and affective disorder. J. Neural Transmission 70, 295–312 (1987). https://doi.org/10.1007/BF01253604

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