Causes of Affective
|Neurochemical Factors||Neuroendocrine Abnormalities||Genetic Factors||Environmental and Social Factors|
|The causes of mental illness are clearly multifactorial and, like cancer, are at present only particually understood. The various forms of mental illness are due to many different types of brain abnormalities, including the loss of nerve cells and excesses and deficits in chemical thansmisson between neurons. The tendency to develope these abnormalities may run in families and therefore be particually hereditary. Since depression is such a a common illness, affecting between 10 and 25 percent of the population, it has received much attention from researchers.|
Scientists research with drugs led to the formulation of the "catecholamine hypothesis" about the cause of affective disorder. This hypothesis in its simplest form, stated that depression was due to a deficiency of norepinephrine, one of the major catecholamine systems in the brain. The catecholamine theory received some suppport as the mechanisms of the new antidepressant drugs were illuminated. Both types of drugs used to treat depression - the tricyclics and the monoamineoxidase inhibitors (MAOIs) - tend to increase the amount of norepinephrine available in the central nervous system, although they work in somewhat different ways.
The MAOIs block the action of monoamine oxidase, thereby preventing norepinephrine from being destroyed and increasing the amount available for transmission. The tricyclilc antidepressants work by preventing the norepinephrine present in the synaptic cleft from being returned to the transmitter neuron and its synaptic vesicles (see
Communications between neurons), thereby increasing the amount of norepinephrine continually available in the synapse and thus enchancing transmission and excitaion.
MHPG excretion test of depressed patients gives support to this hypothesis.
The catecholamine hypothesis was supplemented by another one, the "serotonin hypothesis". Serotonin is also a major transmitter in the central nervous system. The tricyclics increase the amount of serotonin available at the synapse by preventing reuptaking, just as they do for norepinephrine. 5-HIAA excreation test gives supports to this hypothesis.
These two hypotheses combine to suggest the possibility that there may be two subtypes of depressive illness: one due to norepinephrine deficiency and the other to a serotonin deficiency in the brain. This possibility is supported by the fact that some antidepressants work principally by enhancing norepinephrine transmission, while others, seem to enhance serotonin transmission.
The catecholamine theory of depression was once supplemented by a corolalary hypothesis suggesting that manic patiens had excessive norepinephrine transmission occuring in their brains. This corollary has received very little research support. Manic patients do not produce increased amounts of catecholamine metabolites in their urine or cerebrospinal fluid.
Many depressed patients have neuroendocrine abnormalities. They produce large amounts of cortisol, and they are unable to cut down these excessive cortisol production when given dexamethasone. Investigators have also observed other types of failure in neuroendocrine modulation and secreation. Depressed patients failed "insulin tolerance test", thyrotropin-releasing hormone (TRH) test and others.
The pattern of abnormality suggests that the defects do not lie in target organs, such as the adrenals or thyroid, or even in the pituitary gland itself. Rather, they are probably at the level of the hypothalamus, the command center governing the pituaitary, or at some even higher level. Messages sent from other parts of the brain to the hypothalamus usually use the norepinephrine system. Likewise, dopamine and norepinephrine are the neurotransmitters used by the hypothalamus to talk to the pituitary. It is therefore possible that all the
neuroendocrine abnormalities in depression could be explained
through the catecholamine hypothesis - that is, depressed patients have a defect in norepinephrine transmission that impairs their ability to regulate the secretion of all types of hormones. Of course it is a simplification.
Affective disorders are even more likely to run in families than is schizsophrenia. The rates of illness in relatives are higher than occure in general population. About 20 percent of the parents of patients with affective illness also have affective disorders, the rate in brothers and sisters and children is even higher - possibly as high as 30 percent. The rate tends to be higher in the female relatives. For identical twins the rate is around 50 - 60 percent.
An inherited lack of emotional resilience may be the predisposing factor - the neccessary but not sufficient cause - in the development of affective disorders. The enviromental or social factors that trigger the development of depression may be either physical (illness), or psychological (stresses). The model described concerning the interaction between social and biological factors has not been proved, but it is widely accepted by many physicians.
More about Causes (Etiology) of Mood Disorders