Psychology: Science or Religion?

The pathology of depression—the monoamine hypothesis: Antidepressants are believed to exert their therapeutic effects by acting on brain monoamines, which are believed to be important determinants of mood. However, in a circular chain of logic, the monoamine theory of depression was itself formulated primarily in response to observations that early antidepressants increased brain monoamine levels [3]. (EMPHASIS MINE, in other words, "The drugs work, so the depression must be caused by such-and-such in the brain").

Independent evidence has not confirmed that there is a monoamine abnormality in depression. For example, the findings of brain imaging studies of serotonin abnormality are contradictory. Some found reduced serotonin 1A receptor binding in drug-free patients who were depressed, consistent with the hypothesis that selective serotonin reuptake inhibitors (SSRIs) improve depression by correcting a deficiency of serotonin activity [4,5]. Other studies, however, have found no difference between patients who are drug-free and controls [6,7] or increased binding potential in depressed patients [7,8]. Postmortem findings of receptor changes in the brains of people who committed suicide have also been inconsistent [9–11]. In some studies, with patients who had recovered from depression, a tryptophan depletion challenge led to a transient increase in depressive symptoms. However, these results have not been confirmed in volunteer studies [12], and the effect appears to be dependent on previous SSRI use [13]. Research on catecholamines (noradrenaline and adrenalin) is similarly confusing and inconclusive [14]. (EMPHASIS MINE).

1. Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders: A review of supporting evidence. Am J Psychiatry 122:509–522. Find this article online
2. Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, et al. (2000) Brain serotonin 1A receptor binding measured by positron emission tomography with [11C]WAY-100635: Effects of depression and antidepressant treatment. Arch Gen Psychiatry 57:174–180. Find this article online
3. Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, et al. (1999) PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry 46:1375–1387. Find this article online
4. Meyer JH, Houle S, Sagrati S, Carella A, Hussey DF, et al. (2004) Brain serotonin transporter binding potential measured with carbon 11-labeled DASB positron emission tomography: Effects of major depressive episodes and severity of dysfunctional attitudes. Arch Gen Psychiatry 61:1271–1279. Find this article online
5. Parsey RV, Oquendo MA, Ogden RT, Olvet DM, Simpson N, et al. (2006) Altered serotonin 1A binding in major depression: A [carbonyl-C-11]WAY100635 positron emission tomography study. Biol Psychiatry 59:106–113. Find this article online
6. Reivich M, Amsterdam JD, Brunswick DJ, Shiue CY (2004) PET brain imaging with [11C](+)McN5652 shows increased serotonin transporter availability in major depression. J Affect Disord 82:321–327. Find this article online
7. Stockmeier CA, Dilley GE, Shapiro LA, Overholser JC, Thompson PA, et al. (1997) Serotonin receptors in suicide victims with major depression. Neuropsychopharmacology 16:162–173. Find this article online
8. Lowther S, De Paermentier F, Cheetham SC, Crompton MR, Katona CL, et al. (1997) 5-HT1A receptor binding sites in post-mortem brain samples from depressed suicides and controls. J Affect Disord 42:199–207. Find this article online
9. Matsubara S, Arora RC, Meltzer HY (1991) Serotonergic measures in suicide brain: 5-HT1A binding sites in frontal cortex of suicide victims. J Neural Transm Gen Sect 85:181–194. Find this article online
10. Murphy FC, Smith KA, Cowen PJ, Robbins TW, Sahakian BJ (2002) The effects of tryptophan depletion on cognitive and affective processing in healthy volunteers. Psychopharmacology (Berl) 163:42–53. Find this article online
11. Delgado PL, Miller HL, Salomon RM, Licinio J, Krystal JH, et al. (1999) Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: Implications for the role of serotonin in the mechanism of antidepressant action. Biol Psychiatry 46:212–220. Find this article online
12. Healy D (1999) The antidepressant era. New York: Harvard University Press. 336 p.

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