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SEROTONIN.
Term Paper ID:22767
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Essay Subject:
Examines possible role of this neurotransmitter in fight against depression.... More...
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6 Pages / 1350 Words
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Paper Abstract:
Examines possible role of this neurotransmitter in fight against depression.
Paper Introduction:
Is Serotonin a Shared Chemical Pathway for Depression?
Serotonin, scientifically termed 5-hydroxytryptamine or
5-HT, was first discovered in research and crystallized 40 years ago. Neuroscientists have determined that 5-HT is a major neurotransmitter involved in a number of physiological processes such as sleep, thermoregulation, appetite control, sexual behavior, cardiovascular function, endocrine regulation and muscle contraction. Additionally, it is implicated in the "mechanism of action of various pharmacological agents (anxiolytic agents, antidepressants, hallucinogenic agents)" (Cannon, 1991, p. 132). After studying 5-HT for over 25 years Page concluded that "no physiological substance has been discovered that has such diverse actions in the body as serotonin" (Cannon, 1991, p. 132). The question which
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Kennett, Guy A., Francis Chaouloff, Margaret Marcou and GeraldCurzon. 1451). Recent research in the field of depression has been dominated by thismodel of the final common pathway. Biological Psychiatry, 28, 443-54. 1451). 177). 416). 215). Serotonin, social behavior and law.Carbondale: Southern Illinois University Press. 1451). (1979).Neurotransmitters and drugs. 215). Holden, Constance. (8 June 1995). Rudge. Rubinow, David R. In a recent letter published in The New England Journal of MedicineRubinow and Schmidt assert that the condition now known as premenstrualsyndrome (PMS) is "a form of atypical depression" which responds positivelyto the "inhibitors of serotonin reuptake" as effective therapy (Rubinow,1995, p. The news isn'tdepressing. 1451).Neuroscientist McEwen indicates that this refocus is shifting from "thelevel of neurotransmitters and second messengers to the level of genes andlong-term structural and chemical changes" in the brain (Holden, 1991, p.1451). The question whichneuroscientists have been asking for over a decade is whether or not "allforms of depression ultimately operate through a shared chemical pathway"and whether that pathway could possibly be identified as serotonin?(Holden, 1991, p. Schmidt. Jimmerson, David C., Michael D. However,"decreased platelet serotonin (5-HT) transport and reduced binding ofimipramine or paroxetine to brain and platelet 5-HT uptakesites/transporters in patients with depression and suicide victims definethe5-HTT as a candidate gene" (Lesch, 1995, p. Neurochemically, 5-HT can be seen operating as if through a cluster effect. Lesem, Walter H. and S. Primary structure of theserotonin transporter in unipolar depression and bipolar depression.Biological Psychiatry, 37, 215-23. 1451). After studying 5-HT for over 25 years Page concluded that "nophysiological substance has been discovered that has such diverse actionsin the body as serotonin" (Cannon, 1991, p. Forward into the past. 145 ). The role of serotonin indepression and anxiety. The majority of theseantidepressants act on one or both of the major neurotransmitter systems,the serotonergic (which uses serotonin as a transmitter) or thenorepinephrine (which uses norepinephrine) systems (Holden, 1991, p. This theory of depression being linked to the deficiency of serotonincollaborates with those who would argue for one common pathway cohesivelycreating depression (Holden, 1992, p. Psychiatrist John Mannrecently confirmed earlier studies that people who commit suicide are"likely to have low levels of a serotonin metabolite, 5HIAA, in theircerebrospinal fluid" (Holden, 1991, p. Although many serotonin receptors (5-HT) have been identified, the knowledge of subtypes remains limited.Currently, 5-HT1A agonists are involved in the "treatment of certainanxiety disorders, 5-HT1C and 5-HT2 may be indicated for generalizedanxiety disorder, and 5-HT1D receptor agonists are used for migraines"(Baldwin, 1995, p. Earlier scientists conjectured thatthere existed an indirect causal relationship via such variables aspersonality disorders and developmental deficits (Cannon, 1991, p. (6 December 1991). Pharmaceutical research has overcomethe bewildering heterogeneity of depression to produce antidepressantmedication which have proved to be 7 % effective. (1995, January). In reviewing the history of 5-HT and its own marked path ofreception, the complication of gender also frequently arises. Murphy. The research concluded that "similardifferences could be involved in the higher incidence of depressive illnessin women" (Kennet, 1986, p. Masters, Roger D. Neuroscientists seems to be constructinga theory of the brain which privileges the positioning and impact ofserotonin levels and pathways. 421). and Peter J. Vol. In "Eating disorders and depression: Is there aserotonin connection?" Jimerson indicates that central serotonin pathwaysmodulate eating patterns, and may even impact the regulation of behavioralimpulsivity and mood. 1. and Michael T. Additionally, it isimplicated in the "mechanism of action of various pharmacological agents(anxiolytic agents, antidepressants, hallucinogenic agents)" (Cannon, 1991,p. Brewerton. Depression. The complexity of research surrounding studies of serotonin can be atleast partially explained by its own multi-functioning. Science, 254, 145 -2. Solomon and P.J. 1574). Baltimore: University Park Press. Lesch Peter K., Jorg Gross, Ernst Franzek, Benjamin L. Greenwich, CT: JAI Press Davis, J.M. Attempting to bypass this serotonin-norepinephrine opposition,recent research is now scrutinizing a mechanism likely to be found at amore basic level than synaptic transmission (Holden, 1991, p. Wolozin, PeterRiederer, and Dennis L. Advances in CNS drug-receptorinteractions. (1995). (199 ). References Baldwin, D. 132). da Roza, A.L. 1451). Thetreatment of premenstrual syndrome. It can be triggered bystress, biochemical dysfunction, illness or unknown causes. (1986, September). 132). The tantalizing possibility is that ifscientists can "target the final common pathway" than ideally they couldproduce "a drug that directly affects gene expression", that "fast-actingantidepressant we all have been looking for" (Holden, 1991, p. Sharpley, R.A. Cannon, Joseph G. Whether ornot it will actually emerge as that final common pathway remains yet to beseen. Is Serotonin a Shared Chemical Pathway for Depression? Female rats are more vulnerable than males inan animal model of depression: The possible role of serotonin. When these rats werekilled after 24 hours of stress-experience, the female rats exhibiteddecreased brain regional 5-hydroxyindoleacetic acid concentrations,particularly in the frontal cortex. Sinceserotonin effects not only mood swing but both physical and sexualappetites, researchers have frequently attempted to isolate its impact onwomen. 2, 416-21. 1452). Cowen.(1992). 443). Kruk, Zygmut L. Sleep and 5-HT2 receptor sensitivity in recovered depressedpatients. The multi-functional cluster trait characterizing 5-HT indicates theextremely sophisticated levels of research necessary to advance or defeatany given theory. In presenting thecomplexity of the research preceding his own, Lesch (1995) does concedethat since depressed patients exhibit such vast differences in sensitivityto antidepressant drug treatment, this "nonresponse rate of 3 %-4 %" mustbe taken into consideration (p. Researchconducted over the last 2 years discovered and continues to investigatethe "multiple populations" of a centralized 5-HT operating as a primarybinding site (Cannon, 1991, p. McGuire (Eds.), Theneurotransmitter revolution. In a recent study on "Sleep and 5-HT2 receptorsensitivity in recovered depressed patients" Davis concludes that "there isno underlying abnormality in the 5-HT2 receptor regulation of slow wavesleep in recovered depressives" (Davis, 1992, p. 18 ). Role of serotoninin the pathophysiology of depression: focus on the serotonin transporter.Clinical Chemistry, 4 , 288-95. (Ed.), (1991). Two of the main classes of antidepressants,tricyclic and monoamine oxidase inhibitors act on both the serotonergic andnorepinephrine systems. (1994). 1451). Journal of Affective Disorders, 24, 177-81. However, hisconjecture that the abnormalities in the measure previously reported mayhave been caused by the use of concomitant tricylic antidepressantmedication suggests the difficulty researchers have in distinguishingbetween 5-HT's effect as determined by nature as opposed to clinicalintervention (Davis, 1992, p. A comparative study of stress effects upon male and femalerats concluded that female rats exhibit greater sensitivity to stress whichcannot be as easily allievated by 5MD, a serotonin agonist, which workedeffectively for the male rats (Kennet, 1986, p. 1451). Newer drugs, especially the lauded fluoxetine orProzac act exclusively on serotonin. 443). 145 ) First, researchers agree that depression must be recognized as a"heterogeneous disorder" (Holden, 1991, p. 216). Henninger asserts that eventually pharmaceutical companies willbegin producing drugs that "can bypass all these transmitter and receptorsystems" (Holden, 1991, p. and C.B. "Recent studies lend support to the hypothesis thatimpaired prostingestive satiety in bulimia nervosa is associated withreduced hypothalamic serotonergic responsiveness" (Jimerson, 199 , p. 41). Owens, M.J. 132). Serotonin, scientifically termed 5-hydroxytryptamine or5-HT, was first discovered in research and crystallized 4 years ago.Neuroscientists have determined that 5-HT is a major neurotransmitterinvolved in a number of physiological processes such as sleep,thermoregulation, appetite control, sexual behavior, cardiovascularfunction, endocrine regulation and muscle contraction. Research conducted by Delgado concluded that serotonin may not be thecommon pathway since experiments conducted using only "desipramine, atricyclic that primarily affects norepinephrine" did not cause depressedpatients to relapse but allowed their conditions to improve (Holden, 1991,p. Similarly, recent research which has focused on eating disorderswhich are proportionately more pronounced among the female population hasseen the lack of serotonin as a prominent potential cause for binge eating,behavioral impulsivity, and depression in patients with eating disorders(Jimerson, 199 , p. The complex inheritance patterns of affective disorders(inclusive of depression) has made it difficult to isolate those geneticfactors most likely to be disruptive to its inheritors. The NewEngland Journal of Medicine, 32, 1574-5.----------------------- 1 135).What has repeatedly emerged in recent research is that serotonin can serveas a key player in the neurochemical fight against depression. Mann also noted that therewas a significant change in the numbers of 5HT receptors in a particulararea of the prefrontal cortex, a condition which would be consistent withdecreased transmission (Holden, 1991, p. These drugs block the "re-uptake of these neurotransmitters by the cellsthat send them" eventually leading to the regulation of mood, arousal,appetite and sleep (Holden, 1991, p. Pycock. 1452). Again this research on women and potential eating disorders highlights thecentrality of serotonin pathways. Yale psychiatrist George Henninger borrowing an analogyfrom the manner in which anemia operates asserts that there may be a"[final] pathway where both the primary and secondary abnormalitiesinteract to produce the symptom of depression" (Holden, 1991, p. International Clinical Psychopharmacology, 9, 41-5. Current research focuses on 5-HT transporter identified as 5-HTT as apotential genetic factor in the etiology of affective disorders (Lesch,1995, p. (1994, February). Not only must 5-HT be evaluated but allof its cluster sites must be also scrutinized. Scientists have asked how can therebe a common pathway if drugs operating on different brain systems achievethe same effect? Kaye, Ariene P.Hegg, and Timothy D. Yet the debate over whether or not there exists a shared commonpathway for depression is complicated by the variety of drugs which can beeffectively used as treatment. Nemeroff. Yet clinicallabels of description such as endogenous or reactive depression carryalmost no relevance for treatment. BrainResearch, 382, No. and Christopher J. Eating disorders and depression:Is there a serotonin connection?
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