The major psychiatric disorders, including affective disorders and schizophrenia, are disabling diseases with a genetic predisposition and no known cure. The biological basis for these disorders remains obscure, particularly the role of environmental influences on individuals with a genetic predisposition to developing a disorder. Altered states of the brain's monoaminergic systems have been a major focus as possible underlying factors, based on extensive human studies in which neurochemical imbalances in catecholamines, acetylcholine, and serotonin have been observed. Another reason for focusing on the monoamin-ergic systems is that the most effective drugs used in treating psychiatric disorders are agents that alter monoamin-ergic transmission.
Affective Disorders. The affective disorders include major depression, which can be so profound as to provoke suicide, and bipolar disorder (or manic-depressive disorder), in which periods of profound depression are followed by periods of mania, in a cyclic pattern. Biochemical studies indicate that depressed patients show decreased use of brain NE. In manic periods, NE transmission increases. Whether in depression or in mania, all patients seem to have decreased brain serotonergic transmission, suggesting that serotonin may exert an underlying permissive role in abnormal mood swings, in contrast with norepinephrine, whose transmission, in a sense, titrates the mood from highest to lowest extremes.
The most effective treatments for depression, including antidepressant drugs such as MAOIs and selective serotonin reuptake inhibitors (SSRIs) and electroconvulsive therapy, have in common the ability to stimulate both noradrenergic and serotonergic neurons serving the limbic system. A therapeutic response to these treatments ensues only after treatment is repeated over time. Similarly, when treatment stops, symptoms may not reappear for several weeks. This time lag in treatment response is presumably due to alterations in the long-term regulation of receptor and second messenger systems in relevant regions of the brain.
The most effective long-term treatment for mania is lithium, although antipsychotic (neuroleptic) drugs, which block dopamine receptors, are effective in the acute treatment of mania. The therapeutic actions of lithium remain unknown, but the drug has an important action on a receptor-mediated second messenger system. Lithium interferes with regeneration of phosphatidylinositol in neuronal membranes by blocking the hydrolysis of inositol-1-phos-phate. Depletion of phosphatidylinositol in the membrane renders it incapable of responding to receptors that use this second messenger system.
Schizophrenia. Schizophrenia is the collective name for a group of psychotic disorders that vary greatly in symptoms among individuals. The features most commonly observed are thought disorder, inappropriate emotional response, and auditory hallucinations. While the biochemical imbalance resulting in schizophrenia is poorly understood, the most troubling symptoms of schizophrenia are ameliorated by neuroleptic drugs, which block dopamine receptors in the limbic system.
Current research is focused on finding the subtype of dopamine receptor that mediates mesocortical/mesolimbic dopaminergic transmission but does not affect the nigrostri-atal system, which controls motor function (see Fig. 7.12). So far, neuroleptic drugs that block one pathway almost always block the other as well, leading to unwanted neurological side effects, including abnormal involuntary movements (tardive dyskinesia) after long-term treatment or parkinsonism in the short term. Similarly, some patients with Parkinson's disease who receive l-DOPA to augment dopaminergic transmission in the nigrostriatal pathway must be taken off the medication because they develop psychosis.
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Are You Depressed? Heard the horror stories about anti-depressants and how they can just make things worse? Are you sick of being over medicated, glazed over and too fat from taking too many happy pills? Do you hate the dry mouth, the mania and mood swings and sleep disturbances that can come with taking a prescribed mood elevator?