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Serotonin-related, anxiety/aggression-driven, stressor-precipitated depression. A psycho-biological hypothesis

Published online by Cambridge University Press:  16 April 2020

HM van Praag*
Affiliation:
Academic Psychiatric Centre. University of Limburg, PO Box 616, 6200 MD Muastricht, The Netherlands
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Summary

The concept of a 5-HT related, anxiety and/or aggression-driven, stressor-precipitated depression is formulated and discussed. It comprises the following elements. The 5-HT ergic disturbances found in some depressed individuals - and of them particularly lowered CSF 5-HIAA - are linked to the anxiety- and the aggression-components of the depressive sydrome. In this type of depression - called 5-HT related depression - dysregulation of anxiety and/or aggression are primordial and mood lowering is a derivative phenomenon. In other words this is a group of anxiety/aggression-driven depressions. The 5-HT ergic impairment in certain types of depression is a trait-phenomenon, ie, persists during remission. This disturbance makes the individual susceptable for perturbation of anxiety- and aggression-regulation. Anxiety and (overt or suppressed) anger, are core constituents of the stress-syndrome. Thus, the 5-HT ergic disturbance will induce a heightened sensitivity for stressful events, ie, the latter will induce more readily than normal, stress phenomena , among which anxiety and anger. The latter psychological features induce lowering of mood and thus “drive” the patient into a fullblown depression. Furthermore it is predicted that anxiolytics and serenics (ie, anti-aggressive drugs) that act via normalisation of 5-HT ergic circuits, will exert a antidepressant effect in 5-HT related depression, in addition to their therapeutic actions in anxiety disorders and states of increased aggressiveness, respectively. The exact nature of the 5-HT ergic impairment in 5-HT related depression has yet to be elucidated.

Type
Original article
Copyright
Copyright © Elsevier, Paris 1996

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Footnotes

*

Paper read in part at the 7th Congress of the Association of European Psychiatrists, Copenhagen, 1994.

References

Ansseau, MPitchot, WGonzalez Moreno, AWauthy, JPapart, PPilot study of flesinoxan, a 5-HT1a agonist, in major depression: effects on sleep REM latency and body temperature Human Psychopharmacol 1993 8 279283CrossRefGoogle Scholar
Apter, APraag, HMPlutchik, RSevy, SKorn, MBrown, SLInterrelationships among anxiety, aggression, impulsivity, and mood: a serotoninergically linked cluster Psych Res 1990 32 191199CrossRefGoogle Scholar
Arango, VErnsberger, PMarzuk, PMet al.Autoradiographic demonstration of increased serotonin 5-HT2 and ß-adrenergic receptor binding sites in the brain of suicide victims Arch Gen Psychiatry 1990 47 10381047CrossRefGoogle Scholar
Arora, RCMeltzer, HYIncrease Serotonin2(5-HT2)receptor binding as measured by 3H-lysergic acid diethylamide (3HLSD) in the blood platelets of depressed patients Life Sci 1989 44 725734CrossRefGoogle Scholar
Asberg, MNorstrom, PTraskman-Bendz, LBiological factors in suicideRoy, ASuicide Baltimore MDWilliams & Wilkins 1986Google ScholarPubMed
Asberg, MSchalling, DTraskman-Bendz, LWagner, APsychobiology of suicide, impulsivity, and related phenomenaMeltzer, HJPsychopharmacology: the Third Generation of Progress New YorkRaven Press 1987 655668Google Scholar
Benkelfat, CEllenbogen, MADean, PPalmour, RMYoung, SNMood-lowering effect of tryptophan depletion. Enhanced susceptibility in young men at genetic risk for major effective disorders Arch Gen Psychiatry 1994 51 687697CrossRefGoogle Scholar
Benkert, OWetzel, HSzegedi, ASerotonin dysfunctions syndromes; a functional common denominator for classification of depression, anxiety, and obsessive-compulsive disorder Int Clin Psychopharmacol 1993 8suppl 1314CrossRefGoogle Scholar
Blier, Pde Montigny, CCurrent advances and trends in the treatment of depresssion TIPS 1994 15 220226Google Scholar
Brain, PFHaug, MHormonal and neurochemical correlates of various forms of animal “aggression” Psychoneuroendocrinology 1992 17 537551CrossRefGoogle ScholarPubMed
Caldecott-Hazard, SGuze, BHKling, MAKling, ABaxter, LRClinical and biochemical aspects of depressive disorders: 1. introduction, classification, and research techniques Synapse 1991 8 185211CrossRefGoogle Scholar
Ceulemans, DLSWestenberg, HGMVan Praag, HMThe effect of stress on dexamethasone suppression test Psych Res 1985 14 189195CrossRefGoogle ScholarPubMed
Chaput, YDe Montigny, CBlier, PEffects of a selective 5-HT reuptake blocker, citalopram, on the sensitivity of 5-HT autoreceptors: Electrophysiological studies in the rat brain Naunyn-Schmied Arch Pharmacol 1986 333 342348CrossRefGoogle ScholarPubMed
Checkley, SNeuroendocrine mechanisms and the precipitation of depression by life events Br J Psychiatry 1992 160 717CrossRefGoogle Scholar
Coccaro, EFImpulsive aggression and central serotonergic system function in humans; an example of a dimensional brain-behavior relationship Int Clinic Psychopharmacol 1992 7 312CrossRefGoogle ScholarPubMed
Coryell, WEndicott, JWinokur, GAnxiety syndromes as epiphenomena of primary major depression: outcome and familial psychopathology Am J Psychiatry 1992 149 100ߝ107Google ScholarPubMed
Cowen, PJThe Effect of Tryptophan on Brain 5-HT function: A review Hum Psychopharmacol 1994 9 371376CrossRefGoogle Scholar
Cowen, PJSerotonin receptor subtypes in depression: evidence from studies in neuroendocrine regulation Clin Neuropharm 1993 16suppl 3S6S18Google ScholarPubMed
Cowen, PJWood, DJBiological markers of depression Psychol Med 1991 21 831836CrossRefGoogle ScholarPubMed
Cowen, PJPower, ACWare, CJAnderson, IM5-HT1a receptor sensitivity in major depression. A neuroendocrine study with buspirone Br J Psychiatry 1994 164 372379CrossRefGoogle ScholarPubMed
Deakin, JFSerotonin subtypes and affective disordersIdzikowski, CCowen, PJSerotonin, sleep and mental disorder 1991 PetersfieldWrightson Biomedical Publishing 161178Google Scholar
Deakin, JFA review of clinical efficacy of 5-HT1a agonists in anxiety and depression J Psychopharmacol 1993 7 283289CrossRefGoogle Scholar
Deakin, JFGraeff, FGCritique, 5-HT and mechanisms of defence J Psychopharmacol 1991 5 305315CrossRefGoogle Scholar
Deakin, JWFPennell, I, Upadhyaya, AJ, Lofthouse, RA neuroendocrine study of 5-HT function in depression: evidence for biological mechanisms of endogenous and psychosocial causation Psychopharmacol 1990 101 8592CrossRefGoogle ScholarPubMed
Delgado, PLCharney, DSPrice, LHAghajanian, GKLandis, HHeninger, GRSerotonin function and the mechanism of antidepressant action Arch Gen Psychiatry 1990 47 411418CrossRefGoogle ScholarPubMed
D'Haenen, HBossuyt, AMertens, JBossuyt-Piron, CGijsemans, MKaufman, LSPECT imaging of serotonin 2 receptors in depression Psychiatry Res 1992 45 227237CrossRefGoogle Scholar
Dinan, TGGlucocorticoids the genesis of depressive illness. A psychobiological model Br J Psychiatry 1994 164 365371CrossRefGoogle ScholarPubMed
Eison, ASEison, MSSerotonergic mechanisms in anxiety Prog Neuro-Psychopharmacol & Biol Psychiatry 18 47 199462CrossRefGoogle ScholarPubMed
Fava, GAKellner, RProdromal symptoms in affective disorders Am J Psychiatry 1991 148 823830Google ScholarPubMed
Gotham, ABrown, RG, Marsen, CDDepression in parkinson's disease: a quantitative analysis J Neurol Neurosurg Psychiatry 1986 49 381389CrossRefGoogle Scholar
Handley, SL5HT drugs in animal models of anxiety Psychopharmacol 1993 112 1320CrossRefGoogle ScholarPubMed
Heller, AHBeneke, MKuemmel, BSpencer, DKurtz, NMIpsapirone: evidence for efficacy in depression Psychopharmacol Bull 1990 26 219222Google ScholarPubMed
Henderson, RJurlan, RKersun, JMComo, PPreliminary examination of the comborbidity of anxiety and depression in Parkinson's disease J Neuropsychiatry 1992 4 257264Google Scholar
Hirschfeld, RKlerman, GLClayton, PJKeller, MBMcDonaldScott, P, Larkin, BHAssessing personality: effects of the depressive state on trait measurement Am J Psychiatry 1983 140 695699Google ScholarPubMed
Hjorth, SAuerbach, SFuther evidence for the importance of 5-HT1a autoreceptors in the action of selective serotonin reuptake inhibitors Eur J Pharmacol 1994 260 251255CrossRefGoogle Scholar
Invernizzi, RBramante, MSamanin, RChronic treatment with citalopram facilitates the effect of a challenge dose on cortical serotonin output: role of presynaptic 5-HT1a receptors Eur J Pharmacol 1994 260 243246CrossRefGoogle ScholarPubMed
Jaspers, KAllgemeine Psychopathologie Berlin/HeidelbergSpringer 1948Google Scholar
Kahn, RSWetzler, SVan Praag, HMAsnis, GMBehavioral indications for serotonin receptor hypersensitivity in panic disorder Psych Res 1988 25 101104CrossRefGoogle ScholarPubMed
Kahn, RSWetzler, SVan Praag, HMAsnis, GMNeuroendocrine evidence for 5-HT receptor hypersensitivity in patients with panic disorder Psychopharmacol 1988 96 360364CrossRefGoogle ScholarPubMed
Katon, WRoy-Byrne, PPMixed anxiety and depression J Abnorm Psychology 1991 100 337345CrossRefGoogle ScholarPubMed
Katz, MMKoslow, SMaas, JFrazer, AKocsis, JSecuna, SBoden, CCasper, RIdentifying the specific clinical actions of amitriptyline: irrelationships of behavior, affect and plasma levels in depression Psychol Med 1991 21 599611CrossRefGoogle ScholarPubMed
Kenneth, GA, Curzon, GEvidence that mCPP may have behavioural effects mediated by central 5-HT1a receptors Br J Pharmacol 1988 94 137147CrossRefGoogle Scholar
Kenneth, GAPittaway, KBlackburn, TPEvidence that 5-HT2c receptor antagonists are anxiolytic in the rat Geller-Seifter model of anxiety Psychopharmacol 1994 114 9096CrossRefGoogle Scholar
Kuroda, Y, Mikuni, MOgawa, MTTakahashi, KEffect of ACTH, adrenalectomy and the combination treatment on the density of 5-HT2 receptor binding sites in neocortex of rat forebrain and 5-HT2 receptor-mediated wet-dog shake behaviors Psychopharmacol 1992 108 2732CrossRefGoogle ScholarPubMed
Lesch, KP, Mayer, SDisselkamp-Tietze, JHoh, AWiesmann, MOsterheider, MSchulte, HM5-HT1a Receptor Responsivity in Unipolar Depression Evaluation of Ipsapirone-Induced ACTH and Cortisol Secretion in Patients and Controls Biol Psychiatry 1990 28 620628CrossRefGoogle ScholarPubMed
Lopez-Ibor, JJThe involvement of serotonin in psychiaric disorders and behavior Br J Psychiatry 1988 153 2639CrossRefGoogle Scholar
Maes, MMeltzer, HThe serotonin hypothesis of major depression Bloom, FEKupfer, DJPsychopharmacology: The Fourth Generation of Progress New York:Raven Press, 1995 111Google ScholarPubMed
Maes, MDe Ruyter, MSuy, EThe renal excretion of xanthurenic acid following 1-tryptophan loading in depressed patients Human Psychopharmacol 1987 2 231235CrossRefGoogle Scholar
Mayeux, RStern, YSano, MWilliams, JEWCôté, LJThe relationship of serotonin to depression in parkinson's disease Movem Disord 1988 3 237244CrossRefGoogle ScholarPubMed
McDougle, CJNaylor, STGoodman, WKVolkmar, FRCohen, DJPrice, LHAcute Tryptophan Depletion in Autistic Disorder: A Controlled Case Study Biol Psychiatry 1993 33 547550CrossRefGoogle ScholarPubMed
Meltzer, HJLowy, MTThe serotonin hypothesis of depression Meltzer, HJPsychopharmacology. The Third Generation of Progress New YorkRaven Press 1987 513526Google Scholar
Menkes, DBCoates, DCFawcett, JPAcute tryptophan depletion aggravates premenstrual syndrome J Affec Disord 1994 32 3744CrossRefGoogle ScholarPubMed
Meijer, OCDe Kloet, ERCorticosterone suppresses the expression of 5-HT1a receptor mRNA in rat dentate gyrus Eur J Pharmacology 1994 266 255261CrossRefGoogle ScholarPubMed
Morgan, CJBadaway, AABEffects of a suppression test dose of dexamethasone on tryptophan metabolism and disposition in the rat Biol Psychiatry 1989 25 359362CrossRefGoogle ScholarPubMed
Nutt, DLawson, CPanic Attacks; a neurochemical overview of models and mechanisms Br J Psychiatry 1992 160 165178CrossRefGoogle ScholarPubMed
O'Keane, VDinan, TGProlactin and Cortisol Responses to d-Fenfluramine in Major Depression: Evidence for Diminished Responsivity of Central Serotonergic Function Am J Psychiatry 1991 148 10091015Google ScholarPubMed
Pandey, GNPandey, SCJanicak, PGMarks, RCDavis, JMPlatelet serotonin-2 receptor binding sites in depression and suicide Biol Psychiatry 1990 28 215222CrossRefGoogle ScholarPubMed
Paykel, EGPrusoff, BAUhlenhuth, EHScaling of life events Arch Gen Psychiatry 1971 24 340347CrossRefGoogle Scholar
Pratt, JAThe neuroanatomical basis of anxiety Pharmacol Ther 1992 55 149181CrossRefGoogle ScholarPubMed
Preskorn, SHFast, GABeyond Signs and Symptoms: The Case Against a Mixed Anxiety and Depression Category J Clin Psychiatry 1993 54suppl2432Google ScholarPubMed
Przegalinski, EChojnacka-Wojcik, E, Flip, MStimulation of Postsynaptic 5-HT1a receptors is responsible for the anticonflict effect of ipsapirone in rats J Pharm Pharmacol 1992 44 780782CrossRefGoogle ScholarPubMed
Rickels, KAmsterdam, JClary, CHassman, JLondon, JPurruoli, GSchweizer, EBuspirone in depressed outpatients: A controlled study Psychopharmacol Bull 1990 26 163167Google ScholarPubMed
Selye, HSelye's Guide to stress research vol.1 New YorkVan Nostrand Reinhold 1980Google Scholar
Siever, LJKahn, RSLawlor, BATrestman, RLLawrence, TLLCoccaro, EFII. Critical issues in defining the role of serotonin in psychiatric disorders Pharmacol Rev 1991 43 509525Google Scholar
Simeon, DStanley, BFrances, AMann, JJWinchel, RStanley, MSelf-mutilation in personality disorders; psychological and biological correlates Am J Psychiatry 1992 149 221226Google ScholarPubMed
Stahl, SMGastpar, MKeppel Hesselink, JMTraber, JSerotonin 1A receptors New YorkRaven Press 1992Google Scholar
Taracha, ESzukalsi, BSerum tryptophan levels in patients with endogenous depression. I. Differences between unipolar and bipolar forms of affective disorder New Trends Exp Clin Psychiatry 1994 10 913Google Scholar
Traskman, LAsberg, MBertilsson, LSjostrand, LMonoamine metabolites in CSF and suicidal behavior Arch Gen Psychiatry 1981 38 633636CrossRefGoogle ScholarPubMed
Traskman-Bendz, LAlling, CAlsén, MRegnéll, GSimonsson, POhman, RThe role of monoamines in suicidal behavior Acta Psychiat Scand 1993 371 4547CrossRefGoogle ScholarPubMed
Van Eck, MMNicolson, NAPerceived stress and salyvary cortisol in daily life Annals Behav Med 1994 16 221226Google Scholar
Van Praag, HMSignificance of biochemical parameters in the diagnosis, treatment and prevention of depressive disorders Biol Psychiatry 1977 12 101131Google Scholar
Van Praag, HMDepression, suicide and the metabolism of serotonin in the brain J. Affec Disord 1982 4 275290CrossRefGoogle Scholar
Van Praag, HMSerotonergic mechanisms and suicidal behavior Psychiat Psychobiol 1988 3 335346CrossRefGoogle Scholar
Van Praag, HMDiagnosing depression-looking backward into the future Psychiat. Developm 1989 7 375394Google ScholarPubMed
Van Praag, HMTwo-tier diagnosing in psychiatry Psych Res 1990 34 111CrossRefGoogle Scholar
Van Praag, HMMake Believes in Psychiatry or the Perils of Progress New YorkBrunner Mazel 1992Google Scholar
Van Praag, HMReconquest of the subjective. Against the waning of psychiatric diagnosing Br J Psychiatry 1992 160 266271CrossRefGoogle ScholarPubMed
Van Praag, HMAbout the centrality of mood lowering in mood disorders Eur Neuropsychopharmacol 1992 2 393404CrossRefGoogle ScholarPubMed
Van Praag, HMDiagnosis, the rate limiting factor of biological depression research Neuropsychobiology 1993 28 197206CrossRefGoogle ScholarPubMed
Van Praag, HMSerotonin and affective psychopathology in Parkinson's disease. A psychobiological hypothesis with therapeutic consequencesWolters, ECScheltens, PMental Dysfunction in Parkinson's Disease AmsterdamVrije Universiteit 1993 325348Google Scholar
Van Praag, HMKorf, JEndogenous depressions with and without disturbances in the 5-hydroxytryptamine metabolism: a biochemical classification? Psychopharmacol 1971 19 148152CrossRefGoogle Scholar
Van Praag, HMDe Haan, SCentral serotonin metabolism and frequency of depression Psych Res 1979 l 219224CrossRefGoogle Scholar
Van Praag, HMDe Haan, SDepression vulnerability and 5-hydroxytryptophan prophylaxis Psych Res 1980 3 7583CrossRefGoogle ScholarPubMed
Van Praag, HMDe Haan, SCentral serotonin deficiency. A factor which increases depression vulnerability? Acta Psychiat Scand 1980 61 8995CrossRefGoogle ScholarPubMed
Van Praag, HMKorf, JPuite, J5-Hydroxyindoleacetic acid levels in the cerosbrospinal fluid of depressive patients treated with probenecid Nature 1970 225 12591260CrossRefGoogle ScholarPubMed
Van Praag, HMKahn, RAsnis, GMLemus, CZBrown, SLTherapeutic indications for serotonin potentiating compounds. A hypothesis Biol Psychiatry 1987 22 205212CrossRefGoogle ScholarPubMed
Van Praag, HMKahn, RSAsnis, GMet al.Denosologization of biological psychiatry or the specifity of 5-HT disturbances in psychiatric disorders J Affec Disord 1987 13 1138CrossRefGoogle ScholarPubMed
Van Praag, HMAsnis, GMKahn, RSBrown, SLKorn, MHarkavy Friedman, JMWetzler, SMonoamines abnormal behavior. A multi-aminergic perspective Brit J Psychiatry 1990 157 723734CrossRefGoogle Scholar
Verhoeven, WMATuinier, SSijben, NASVan den Berg, YWHMDe, WitteEPPM Pepplinkhuizen, LVan Nieuwenhuizen, OEltoprazine in mentally retarded self-injuring patients Lancet 1992 340 10371038CrossRefGoogle ScholarPubMed
Watanabe, YSakai, RRMcEwen, BSMendelson, SStress and antidepressant effects on hippocampal and cortical 5-HT1a and 5-HT2 receptors and transport sites for serotonin Brain Research 1993 615 8794CrossRefGoogle ScholarPubMed
Westenberg, HGMVerhoeven, WMACSF monoamine metabolites in patients and controls: support for a bimodal distribution in major affective disorders Acta Psychiatr Scand 478 1988 541749CrossRefGoogle Scholar
Winchel, RMStanley, MSelf-injurious behavior; a review of the behavior and biology of self-mutilation Am J Psychiatry 1991 148 306317Google ScholarPubMed
Young, SNSmith, SEPihl, ROErving, FRTryptophan depletion causes a rapid lowering of mood in normal males Psychopharmacol 1985 87 173177CrossRefGoogle ScholarPubMed
Young, AHMacDonald, LMJohn, HSTDick, HGoodwin, GMThe effects of corticosterone on 5-HT receptor function in rodents Neuropharmacol 1992 31 433438CrossRefGoogle ScholarPubMed
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