Serotonin hypothesis

Maes M, Meltzer HY (1995) The serotonin hypothesis of major depression. In Bloom EE, Kupfer DJ (eds) Psychopharmacology the foimth generation of progress, pp 933-944 Mann JJ (1998) The neimobiology of suicide. Nat Med 4 25-30... 

Barr, L.C., Goodman, W.K., Price, L. H., McDougle, C.J. and Char-ney, D.S. (1992) The serotonin hypothesis of obsessive compulsive disorder implications of pharmacologic challenge studies. / Clin Psychiatry 53(4, Suppl) 17-28. 

Some authors (Flament et ah, 1987) found that response to treatment with clomipramine was correlated with a marked decrease in platelet serotonin concentration and monoamine oxidase (MAO) activity. Changes in cerebrospinal fluid (CSF) neuropeptides and monoamine metabolites have also been described with chronic clomipramine administration (Swedo et ah, 1992 Altemus et ah, 1994). Despite these observations, the exact mechanism of action of serotonergic drugs (and the serotonin hypothesis ) remains unproven, although it is thought they mediate their effects via down-regulation of the presynaptic 5-HTlD autoreceptor (Rauch et ah, 1994). 

Barr LC, Goodman WK, Price LH, et al The serotonin hypothesis of OCD implications of pharmacologic challenge studies. J Chn Psychiatry 4 17-28s, 1992 Barr LC, Goodman WK, Price LH The serotonin hypothesis of obsessive compulsive disorder. Int Clin Psychopharmacol 8 (suppl 2 79-82, 1993 Barr LC, Goodman WK, McDougle CJ, et al Tryptophan depletion in patients with OCD who respond to serotonin reuptake inhibitors. Arch Gen Psychiatry 51 309-17, 1994... 

Goodman WK, McDougle CJ, Price LH, et al Beyond the serotonin hypothesis a role for dopamine in some forms of obsessive compulsive disorder J Clin Psychiatry 51 (suppl) 36-43, 1990a... 

It became known in the same year (1954) that the substance reserpine, derived from the Indian plant Rauxcolfia serpentina, had antipsychotic effects similar to those of chlorpromazine This finding was of interest for two reasons the molecular structure of reserpine has some similarity to that of serotonin and LSD and it was found that reserpine liberates serotonin from presynaptic stores in the CNS and thus produces a short-lived excess supply of functionally available serotonin at the synapse. In the context of a serotonin hypothesis of schizophrenia, it could be postulated that the antipsychotic effect of reserpine was due to its ability to liberate serotonin presynaptically and make it functionally available. However, despite its scientific appeal, the serotonin hypothesis of schizophrenia did not last long because it was in conflict with both psychopathological and pharmacological findings ... 

Despite its relatively fast and thorough rebuttal, the serotonin hypothesis of schizophrenia was fruitful in two respects it gave rise to the development of sensitive serotonin assay methods and proof that serotonin does occur in the brain (Carlsson, 1987) and it served as the prototype for other simple and thus readily testable biochemical hypotheses of mental illnesses. Interest in serotonin has been reawakened in recent years in relation to the mechanism of action of some antipsychotics (see below) however, this development had little to do with the serotonin hypothesis of schizophrenia in its original version. 

Although the serotonin hypothesis of schizophrenia was formulated at approximately the same time as the discovery of the first neuroleptics, it had no direct connection with the pharmacological propraties of these drugs. The situation is different in the case of the dopamine hypothesis because all known neuroleptics have some inhibitory action on dopaminergic neurons, even though they vary considerably with regard to other pharmacological effects. 

The catecholamine hypothesis brought several pharmacological findings together in an illuminating relationship but contradicted a number of clinical observations, in particular the delayed onset of action of antidepressant drugs. This also applies to the serotonin hypothesis, which was formulated at about the same time. 

Numerous antidepressants were synthesized, developed and marketed on the basis of the serotonin hypothesis. The selective serotonin reuptake inhibitors (SSRIs) are similarly effective as the older tricyclic antidepressants, but have the advantage of being less toxic and not inducing anticholinergically mediated side effects (Chapter 1). From the scientific point of view1 they represent an example of mechanistic, hypothesis-driven research and development in psychopharmacology (Chapter 2). 

Meltzer, H.Y. Clinical studies on the mechanism of action of clozapine the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 99, 518-527, 1989. 

It is important to point out that basic sleep researchers make mistakes that are every bit as egregious and every bit as persistent as those of our clinical colleagues. From 1969 to 1975, it was widely held that serotonin promoted sleep. If that were true, then the SSRIs would be sedatives, not sleep saboteurs In fact, there is paradoxical sedation in a very high percentage of users, but this effect is not easily attributable to the enhancement of serotonergic efficacy. So strong was the serotonin hypothesis that it worked its way into textbooks, where it lived for fifteen years after it had been clearly shown that serotonin was actually a sleep inhibitor and, reciprocally, a wake-state enhancer. 

The serotonin hypothesis. Although it is unlikely that one neurotransmitter system can explain all the complexities of OCD, recent efforts to elucidate the pathophysiology of OCD have centered largely around the role of the neurotransmitter serotonin... 

HT). The serotonin hypothesis of OCD, which states that OCD is linked to 5HT dysfunction, stems largely from pharmacological treatment studies. 

Feverfew is most often used as a prophylactic remedy for migraine headache. This action has been related to the serotonin hypothesis for migraine causation (see also Chapter 16 Histamine, Serotonin, the Ergot Alkaloids). In vitro, feverfew and parthenolide inhibit platelet aggregation and serotonin release from platelets. 

The role of cADP-ribose and NAADP in regulating cytosolic calcium may provide an alternative explanation to the serotonin hypothesis for the psychiatric and neurological signs of the niacin deficiency disease pellagra (Section 8.5 Petersen and Cancela, 1999). 

The serotonin hypothesis, the other central theory of antidepressant action, postulates that depression is the result of a deficiency of the ncurotransmitter serotonin in the brain stem (Galenbcrg Schoonover, 1991 Kalus, Asnis, van Praag, 1989). Persons who are depressed have reduced levels of serotonin and chemicals involved in... 

Meltzer HY, Lowey MT. The serotonin hypothesis of depression. In Meltzer HY,ed. Psychopharmacology The Third Generation of Progress. Raven, New York, 1987, pp. 233-248. 

The permissive serotonin hypothesis proposes that serotonin (5-hydroxytryptamine or 5-HT) plays a critical role in modulating brain activity (e.g., stabilization of the catecholamine system and inhibition of dopamine [DA] release), and is low in both mania and depression. L-tryptophan or 5-HT deficiency and changes in the light-dark cycle may result in reduced melatonin secretion from the pineal gland that disrupts the sleep-wake cycle, alters circadian rhythms, and causes seasonal affective changes. ... 

Woolley, D. W., The Biochemical Basis of Psychoses or the Serotonin Hypothesis about Mental Disease, John Wiley Sons, New York, 1962. 

Mayeux, R. (1990) The serotonin hypothesis for depression in Parkinson s disease. In M.B. Streifler, A.D. Korczyn, E. Melamed M.B.H. and Youdim (Eds.), Advances in Neurology Parkinson s Disease Anatomy, Pathology and Therapy, Vol. 53, Raven Press, New York, pp. 163-165. 

Among the above-listed abnormalities in schizophrenia, neurotransmitter abnormalities (especially the dopamine/serotonin hypothesis of schizophrenia) are widely accepted as directly inducing or at least mediating certain symptoms of the disorder. The major empirical observations concerning the role of abnormal neurotransmitter functioning in schizophrenia are as follows. 

Selective 5-HT Reuptake Inhibitors (SSRIs) Serotonin Hypothesis of Depression... 

Cowen PJ. Serotonin hypothesis. In Feighner JP, Boyer WR, eds. Selective Serotonin Reuptake Inhibitors, 2nd Ed. 1996 63-86. 

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