Monoamine hypothesis of depression

The original monoamine hypothesis of depression states that depressions are associated with a deficiency of catecholamines, particularly norepinephrine, at functionally important adrenergic receptor sites in the brain. Elation conversely may be associated with an excess of such amines. The hypothesis was articulated in 1966 only after the mechanism of action of the tricyclic antidepressant desipramine and of the psychostimulants... 

Reserpine and iproniazid research led to the monoamine hypothesis of depression. This hypothesis proposed that a reduction in the monoamine neurotransmitters caused depression. As described in the sidebar on pages 82-83, only a small number of neurons use serotonin as a neurotransmitter, but these cells project to widespread regions of the brain. The same holds true for norepinephrine and dopamine. Although not widely used in the nervous system, these neurotransmitters are apparently involved in networks of neurons that greatly influence a person s mood. Synaptic transmission between neurons in other areas of the brain—such as neurons that process visual information, for instance—often carry specific messages, such as the presence of an object at a certain point in the person s visual field. In contrast, the monoamine neurotransmitters underlie information processing of a more general nature, some of which correlates with mood. 

Like the monoamine hypothesis of depression, such a simple hypothesis was appeaUng but, perhaps predictably, a Uttle too simple to be true. Further research using a technique known as positron emission tomography (PET) showed the relationship between dopamine and schizophrenia is more complex. PET detects radioactive emissions of certain isotopes these isotopes are incorporated into a molecule and injected into a patient. The machine measures the radioactivity with detectors positioned aroimd the body. PET lets researchers study the distribution of certain molecules in Uving tissue since, imUke autoradiography, the tissue is not sliced and treated chemically. The amoimt of radioactivity must be small, however, to avoid harming the human subjects. 

The monoamine hypothesis of depression develops from the finding that drugs reducing monoamine neurotransmission cause depression. Monoamines include serotonin, norepinephrine, and dopamine. 

The monoamine hypothesis of depression (Figure 30-2) suggests that depression is related to a deficiency in the amount or function of cortical and limbic serotonin (5-HT), norepinephrine (NE), and dopamine (DA). 

Hirschfeld RM History and evolution of the monoamine hypothesis of depression. J Clin Psychiatry 2000 61(Suppl 6) 4. 

Owens, M.J. (2004). Selectivity of antidepressants from the monoamine hypothesis of depression to the SSRI revolution and beyond. J Clin Psychiatry, 65, 5-10. 

Depletion of monoamine neurotransmitters (cf. Fig. 5—60 and Fig. 5—61) has already been discussed as the central theme of the monoamine hypothesis of depression (see Figs. 5—13 and 5—14). The neurotransmitter receptor hypothesis of depression takes this theme one step further—namely, that the depletion of neurotransmitter causes compensatory up regulation of postsynaptic neurotransmitter receptors (Fig. 5—62). 

The monoamine hypothesis of depression suggests that depression is predominantly caused by deficiency of serotonin. 

In the 1960s researchers formulated, and later refined, the so-called monoamine hypothesis of depression. This hypothesis states that symptoms of depression are due to alterations in the functioning of certain neurotransmitters known as monoamines, notably norepinephrine, serotonin, and to a lesser degree, dopamine. Roles for other neurotransmitters have been identified in recent years. The foundation of this hypothesis rests on the finding that all antidepressant medications known at the time had, to some extent, the ability to increase the availability of these neurotransmitters at the synaptic level. Patients and the general public often refer to this hypothesis as chemical imbalance. ... 

While the monoamine hypothesis of depression is conceptually straightforward, it is in reality it is an oversimplification of a complicated picture. Other systems that are implicated in the aetiology of depression (and which provide potential targets for drug therapy) include the hypothalamopituitary-thyroid axis and the hypothalamopituitary-adrenal axis (HEA). The finding that 50% of depressed patients have elevated plasma cortisol concentrations constitutes evidence that depression may be associated with increased HPA drive. 

Depressive symptoms often accompany neurodegenerative disorders, especially in PD and HD. Although the monoamine hypothesis of depression has long been proposed, the pathologies and mechanisms for depressive disorders remain only partially understood. A number of proposed mechanisms for depression such as diminishing neurotrophic factors and neuroinflammation appear to be similar to those implicated in neurodegenerative diseases [330, 331]. Many patients suffering from these disorders are treated with conventional antidepressants. 

The monoamine hypothesis of depression was proposed in 1965 to describe the biochemical basis of depression. Basically, it proposes that depression is caused by a depletion of monoamines (e.g. noradrenaline and/or serotonin) from the synapses. This reduces synaptic activity in the brain causing depression. Conversely, it suggests that mania is caused by an excess of monoamines in synapses, with excessive synaptic activity in the brain resulting in excessive euphoria. In bipolar disorder, patients have mood changes that cycle between depression and mania (Fig. 49.2). 

Antidepressants cover a wide range of indications and include depression, obsessive-compulsive disorders, anxiety, pain, panic, eating disorders or social phobia. The monoamine hypothesis of depression is an often-used term that describes a concept that arose over 50 years ago when a direct link was observed between major depression and imbalance/deficiency of available monoamines such as serotonin and catecholamines. 

Originally, the monoamine hypothesis of depression has gained support from the fact that increased serotonergic neurotransmission led to symptom alleviation in humans after exposure to MAO inhibitors (MAOls). Over... 

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