Depression biogenic amine hypothesis

Biogenic amine hypothesis. Depression may be caused by decreased brain levels of the neurotransmitters norepinephrine (NE), serotonin (5-HT), and dopamine (DA). 

This phenomenon is one of the pillars of the biogenic amine hypothesis of depression (see Suicide later in this chapter). An intriguing finding with reserpine is that those susceptible to a depressive syndrome while on this agent also have an increased likelihood of a personal or family history of MDD, in comparison with those who are not susceptible. This finding suggests an interaction between a constitutional predisposition and the biochemical effects of this drug. Because depression is a... 

Depression. Depression is our most common mental problem. One in four women and one in ten men will have a major depression during their lifetime.1095 More than 15 million people in the United States are affected by severe depression in any given year and more than 30,000 may commit suicide.1096 1097 Worldwide psychiatric problems, mostly depression, account for 28% of all disabilities.1098 The biogenic amine hypothesis states that depression results from the depletion of neurotransmitters in the areas of the brain involved in sleep, arousal, appetite, sex drive, and psychomotor activity. An excess of transmitters is proposed to give rise to the manic phase of the bipolar (manic-depressive) cycle that is sometimes observed. In support of this hypothesis is the observation that administration of reserpine precipitates depression, which may be serious in 15-20% of hypertensive patients receiving the drug. Similar effects are observed with the dopa decarboxylase inhibitor a-methyldopa... 

Keywords Major depressive disorder Biopolar disorder Schizophrenia Mood disorders Biogenic amine hypothesis Learned helplessness Antidepressant drugs Mood stabilizers Dopamine hypothesis Antipsychotic drugs... 

Most of the evidence supporting the biogenic amine hypothesis is indirect. Specifically, deficits of norepinephrine and/or serotonin have been cUfficult to demonstrate. Considerable research into urinary levels of methoxy-hydroxy-phenylethanolamine glycol (MHPG), a norepinephrine metaboUte, in depressed... 

Another test for the biogenic amine hypothesis w ould involve precursor loading sLategies. In other w ords, compounds w hich could increase brain levels of norepinephrine and/or serotonin should demonsLate antidepressant efficacy. Results of these studies have been mixed. Several positive findings w ere reported wdth Seating depression wdth the serotonin precursors tryptophan and 5-hydroxy tryptophan (5-HT) (Shaw et al., 2001), but these w ere not consistently replicated. Less posidve results w ere reported wdth attempts to increase brain norepinephrine levels wdth precursors. 

This data, coupled with numerous positive outcome studies of the effectiveness of antidepressants, has led to the development of the monoamine (or biogenic amine) hypothesis of depression. The theory holds that depressive symptoms are ushered in by a malfunction of either norepinephrine (NE) or serotonin (5-HT) neurons, which play critical roles in the functioning of the limbic system and the adjacent hypothalamus. The basic neuronal malfunction is felt to be identical for either NE or 5-HT neurons, thus what follows (a description of the pathophysiology of NE neurons) can also be seen to occur in individuals in whom 5-HT neurons are affected. For reasons that are not well understood, patients with major depression (with vegetative symptoms) appear to suffer from either NE or 5-HT dysfunction, but probably not both simultaneously (although some exceptions exist). 

Traditional explanations of the biologic basis of depressive disorders have focused largely on NE and 5-HT however, most of the evidence that coalesced into the biogenic amine hypothesis of depression does not clearly distinguish between NE and DA. ... 

Randrup A, Braestrup C Uptake inhibition of biogenic amines by newer antidepressant drugs relevance to the dopamine hypothesis of depression. Psychopharmacology 53 309-314, 1977... 

So in the hands of Joseph Schildkraut and Seymour Kety, the hypothesis became decreased biogenic amine efficacy = depression. Its corollary was increased biogenic amine efficacy = antidepression. So simple. So clear. So basically correct. But so incomplete. And so unsatisfying because (a) we don t really know how or why biogenic amine deficiencies develop in depression, and (b) we don t really know why the antidepressant effects take so long to kick in. The synaptic deficiencies, if any, must be corrected immediately, but the desired clinical consequences are not. What s going on ... 

Before discussing the cyclics and MAOIs in more detail, we need to present the postulated biochemical hypotheses for depression. It is believed that depression results from a deficiency in biogenic amines, specifically catecholamines and serotonin, which act as central nervous system neurotransmitters (see Chapter 3). According to the catecholamine hypothesis, depression results from a deficiency in catecholamines (particularly norepinephrine) at varied neuron receptor sites in the brain. The cyclics are believed to block the reuptake of norepinephrine from the synaptic cleft. Thus, the result is a greater concentration of norepinephrine in the synaptic cleft, alleviating the hypothesized neurotransmitter deficiency. This cyclic-mediated process is thought to occur in the amygdala and reticular formation areas of the brain. 

Antidepressant-medication treatment of depression follows from the biochemical hypothesis of the disorder. The hypothesis is that depression results from a deficiency in two biogenic amines— catecholamines and serotonin—which act as CNS neurotransmitters. 

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