Monoamine theory of depression

After neurotransmitter molecules have influenced the firing of a receiving neuron (more technically called a postsynaptic neuron), some of them are destroyed by enzymes in the synaptic cleft (the synapse), some are reabsorbed by the sending presynaptic neuron in a process that is called reuptake , and the rest remain in the space between the two neurons. The chemical-imbalance hypothesis is that there is not enough serotonin, norepinephrine and/or dopamine in the synapses of the brain. This is more specifically termed the monoamine theory of depression, because both serotonin and norepinephrine belong to the class of neurotransmitters called monoamines. 

When Schildkraut introduced the monoamine theory of depression, he admitted that there was little direct evidence for it. Instead, it was based on the supposed effectiveness of antidepressant medication and the mistaken belief that reserpine makes people depressed. Schildkraut acknowledged that Most of this evidence is indirect, deriving from pharmacological studies with drugs such as reserpine, amphetamine and the monoamine oxidase inhibitor antidepressants which produce affective changes. 21 A half-century has passed since his chemical-imbalance theory of depression was introduced, and the presumed effectiveness of antidepressants remains the primary evidence in its support. But as we have seen, the therapeutic effects of antidepressants are largely due to the placebo effect, and this pretty much knocks the legs out from under the biochemical theory. 

During the last 50 years researchers have tried to find more direct evidence for the monoamine theory of depression, but by and large they have failed. Instead of finding confirmation, much of the evidence they have found is contradictory or runs counter to the... 

Although there has been a substantial body of pharmacological evidence in support of the monoamine theory of depression, clinical biochemical data have been less convincing (Luchins, 1976) this is where differences in the concentrations of NA and 5-HT and their metabolites or hormones, which are ultimately under the control of brain monoaminergic neurons (neuroendocrine markers), have been compared between depressed patients and normal controls. However, by the early 1970s a major difficulty with the theory was becoming apparent this was the time lag between the immediate... 

What is the evidence for the monoamine theory of depression, and which key observations led to its revision ... 

Heninger GR, Delgado PL, Charney DS. (1996). The revised monoamine theory of depression a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans. Pharmacopsychiatry. 29(1) 2-11. 

The monoamine theory of depression is important because it provides a model for the idea that antidepressant drugs act on the biological basis of depressive symptoms. It forms the basis for the modern idea that depression arises from a chemical imbalance. 

Despite decades of research, there is no evidence to support the monoamine theory of depression (see Chapter 9). Studies of noradrenalin are inconsistent, with as many finding raised levels in people with depression as those finding reduced levels (Dubovsky, Davies, Dubovsky 2002). Evidence on serotonin is similarly inconsistent, and eminent mainstream psychopharmacologists admit that there is no evidence of serotonin dysfunction in depression (Lacasse Leo 2005). Nevertheless, the monoamine hypothesis has survived and remains influential. Contradictory evidence has been overlooked or reframed as supportive. For example, Schildkraut reported research that clearly showed that imipramine decreased noradrenalin levels in the brain, but hypothesised that despite reduced concentrations, the activity of noradrenalin might nevertheless be increased (Schildkraut, Winokur, Applegate 1970). 

Early formulations of the monoamine theory of depression cited two strands of evidence. One was the effects of antidepressant drugs and the other was the effects of reserpine. Skildkraut believed that studies have shown a fairly consistent relationship between drug effects on catechloamines, especially norepinephrine, and affective or behavioural states (Schildkraut 1965, p. 509). He went on to describe how drugs that cause depletion and inactivation of norepinephrine centrally produce sedation or depression, while drugs which increase or potentiate brain norepinephrine are associated with behavioural stimulation or excitement and generally exert an antidepressant effect in man (p. 509). 

Several theories have attempted to explain the pathology of depression. One of these theories is the monoamine theory of depression (Heninger et al., 1996). This theory proposes that impaired monoaminergic function is the central basis behind depression. Serotonin and norepinephrine are the two monoamines that have been primarily implicated in the disease. Pharmacological treatment of depression has focused on increasing synaptic levels of these two neurotransmitters (Table 3). 

Despite evidence for and against, there remains one major problem with the monoamine theory of depression. All antidepressants take weeks to have an effect, which is far longer than it takes to alter brain amines. It has been suggested that effects of antidepressants are due to adaptive changes in the brain, which may involve down regulation of receptors or some other change in their sensitivity. 

Briefly describe the monoamine theory of depression and mania. What is the major problem with this theory ... 

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