Depressive disorders mood regulation

Lithium inhibits inositol monophosphate and decreases brain levels of inositol. Belmaker s group [see Levine et ah. Chapter 9, in this volume) showed a selective therapeutic effect of inositol in patients with either depression or panic disorder. Because of the possible importance of the second-messenger system of the phosphatidylinositol [PI) cycle in mood regulation, and because of its influence by lithium, it would be of future in-... 

Although lithium is not a true antipsychotic drug, it is considered with the antipsychotics because of its use in regulating the severe fluctuations of the manic phase of bipolar disorder (a psychiatric disorder characterized by severe mood swings of extreme hyperactivity to depression). During the manic phase, the person experiences altered thought processes, which can lead to bizarre delusions. The drug diminishes the frequency and intensity of hyperactive (manic) episodes. 

Depression, we are told over and over again, is a brain disease, a chemical imbalance that can be adjusted by antidepressant medication. In an informational brochure issued to inform the public about depression, the US National Institute for Mental Health tells people that depressive illnesses are disorders of the brain and adds that important neurotransmitters - chemicals that brain cells use to communicate - appear to be out of balance . This view is so widespread that it was even proffered by the editors of PLoS [Public Library of Science] Medicine in their summary that accompanied our article. Depression, they wrote, is a serious medical illness caused by imbalances in the brain chemicals that regulate mood , and they went on to say that antidepressants are supposed to work by correcting these imbalances. 

Mood stabilisers are used to regulate the cyclical change in mood characteristic of bipolar disorder, since they can attenuate both manic and depressive phases. Their main use is as a prophylactic for manic depression and unipolar mania. However, they can also be administered concomitantly with antidepressants for refractory (non-responsive) unipolar depression. 

In addition to their proven efficacy in the treatment of all types of depression, the SSRIs have been shown to be the drugs of choice in the treatment of panic disorder, obsessive-compulsive disorder, bulimia nervosa, and as an adjunct to the treatment of alcohol withdrawal and relapse prevention, premenstrual dysphoric disorder and post-traumatic stress disorder. The usefulness of these drugs in treating such a diverse group of disorders reflects the primary role of serotonin in the regulation of sleep, mood, impulsivity and food intake. 

Another approach considers the effects of various ligands on their receptors located in the diencephalic and mesiotemporal areas. Cell clusters in the hypothalamus coordinate the normal regulation of the vegetative functions of sleep, appetite, and sexual drive, which are typically disrupted in severe depression. In addition, the limbic area modulates many aspects of behavior and mood that are characteristically disturbed in affective disorders. 

Mood disorders characterized by elevations of mood above normal as well as depressions below normal are classically treated with lithium, an ion whose mechanism of action is not certain. Candidates for its mechanism of action are sites beyond the receptor in the second messenger system, perhaps either as an inhibitor of an enzyme, called inositol monophosphatase, involved in the phosphatidyl inositol system as a modulator of G proteins, or even as a regulator of gene expression by modulating protein kinase C (Fig. 7—22). 

J. Rosenthal et al. s (1986) dysregulation theory includes (but by definition is not specific to) bipolar disorder. In this model, mood is regulated by several homeostatic mechanisms. The failure of a component part leads to the expression of mood outside of set limits, which are identified as the "symptoms" of mania and depression. R. Post, S. Weiss, and O. Chuang (1992) offer a similar explanahon that overactivity in either of the mediating "circuits" of mania or depression leads to the appearance of associated behavioral manifestations. 

The permissive hypothesis (10) emphasizes the importance of the balance between 5-HT and NE in regulating mood, not the absolute levels of these neurotransmitters or their receptors. If 5-HT levels are too low, the balanced control of the NE system is lost, permitting abnormal levels of NE to cause mania, as seen in bipolar disorders. If the NE levels fall, the balanced control of the 5-HT system is lost, allowing abnormal levels of 5-HT to cause the person to exhibit the symptoms of depression. 

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