Depression 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... 

The amine hypothesis of major depression. Depression appears to be associated with changes in serotonin or norepinephrine signaling in the brain (or both) with significant downstream effects. Most antidepressants cause changes in amine signaling. AC,... 

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... 

The depletion of the neurotransmitters—as observed with reserpine—came under study as the possible cause of depression and became known as the amine hypothesis of depression. The drug iproniazid reversed some of these negative side effects, confirming the usefulness of drugs in the treatment of depression. 

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. ... 

Major depressive disorders have been postulated to arise from a functional deficiency in brain NE and/or 5HT (amine hypothesis of depression). This notion is largely based on the acute actions of antidepressant drugs (which may t NE and/or 5HT actions) and the fact that reser-pine (which depletes brain amines) causes depression. However, no antidepressant takes effect rapidly, and some drugs do not appear to have significant effects on brain amines. 

The amine hypothesis of depression postulates that symptoms are caused by a functional deficiency of CNS NE and/or 5HT. This is based on the observation that most antidepressants affect the metabolism 1 of these amines. Again, there are exceptions. 

Amine hypothesis of mood The hypothesis that major depressive disorders result from a functional deficiency of norepinephrine or serotonin at synapses in the central nervous system... 

The amine hypothesis of mood postulates that brain amines, particularly norepinephrine (NE) and serotonin (5-HT), are neurotransmitters in pathways that function in the expression of mood. According to the amine hypothesis, a functional decrease in the activity of such amines would result in depression a functional increase of activity would result in mood elevation. Difficulties with this hypothesis include the facts that (1) antidepressant drugs cause changes in amine activity within hours, but weeks may be required for them to achieve clinical effects (2) most antidepressants ultimately cause a down-regulation of amine receptors and (3) at least one antidepressant, bupropion, has minimal effects on brain NE or 5-HT. 

The data presented here lend further support to the idea that PAD patients are a heterogeneous group, and that the catechol amine hypothesis" is a useful but over-simplified model for a very complex pathometabolic picture, in which all the factors are closely interconnected. Depression is the final common phenomenological expression of all these factors. 

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