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Depression

Description

The causes of clinical depression are likely to be different for different people. Causes can be grouped into different categories, such as biological causes, genetic causes, environmental causes, psychological causes, medical illness, and others.

Who is at Risk?

According to a major 2003 survey, more than 16% of Americans experience major depression disorder over the course of their lifetimes. Depression is an illness that can afflict anyone, regardless of age, race, class, or gender, and it is sometimes referred to as the common cold of mental illness. At any given time, 5% to 9% of women are depressed, compared to 1% to 3% of men. Women who are unhappily married, divorced, or separated, have high rates of major depression. While clinical depression usually occurs for the first time when a person is between the ages of 20 and 50, people over the age of 65 may be especially vulnerable. Being in a low socioeconomic group is a major risk factor for depression, in anyone. Depression in family members increases the risk for depression in other family members. Patients who have had serious bouts of depression usually cite a stressful life event as the precipitating factor for their illness.

Sources: A.D.A.M., Inc., International Society for Mental Health Online

Identifying a Drug Target for Depression

Normal antidepressants take two or three weeks to take effect, and as many as a third of patients do not respond to drugs. One of the longstanding goals of Tamas Bartfai, Ph.D., Professor of Neuropharmacology and Director of TSRI"s Harold L. Dorris Neurological Research Center is to develop a quick-acting compound for the treatment of depression. Electroconvulsive therapy and sleep deprivation are the two known methods of bringing on a rapid antidepressive response, but, while effective, neither method produces longlasting effects.

Recently, Bartfai illuminated the molecular mechanism of a new kind of antidepressant, substance P antagonist, which modifies a previously untapped neurochemical system. This finding may lead to the development of new and more effective drug targets against depression, as well as anxiety disorders and schizophrenia. His work on the design, synthesis and biochemical and pharmacological application of the first galanin antagonists was essential for the elucidation of the biological effects of galanin in depression, cognition and pain, and led to the three galanin receptors becoming the target of more than 20 projects in the pharmaceutical industry.

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Neurobiology of Reward, Motivation, and Emotion in Psychiatric Disorders
TSRI's Athina Markou, Ph.D. and her colleagues have been focusing on the neurobiology of reward, motivation, and emotion in three psychiatric disorders: drug abuse, depression, and schizophrenia. Withdrawal from chronic administration of various drugs of abuse, including withdrawal from tobacco smoking results in a syndrome reminiscent of a major depressive episode and the negative symptoms of schizophrenia. Thus, the researchers working hypothesis is that the same neurological abnormalities mediate the depression seen during a major depressive episode, schizophrenia and drug dependence, and that the study of the neurobiology of drug-induced depression may lead to the discovery of novel therapeutic approaches for the treatment of depression and schizophrenia. In support of this premise, the researchers found that the depression-like aspects of drug withdrawal are reversed by clinically proven antidepressant treatments and partially by atypical antipsychotic drugs which are partially effective against the negative symptoms of schizophrenia. Current work in the laboratory focuses on investigating the role of glutamate and GABA neurotransmission in depression-like symptoms and in nicotine dependence in order to attempt to develop novel treatments for mental illness and tobacco smoking. Glutamate is the major excitatory neurotransmitter in the brain, while GABA is the major inhibitory neurotransmitter.

Recently, the researchers showed that blockade of a subtype of glutamate receptors (metabotropic glutamate receptor 2/3) reversed the depression-like aspects of nicotine withdrawal in rats, suggesting that blockade of these receptors may be a novel strategy to treat depression symptoms in depressed and schizophrenic patients. Other work indicated that blockade of another subtype of glutamate receptor (metabotropic glutamate 5) or of the GABA-B receptor subtype blocks the rewarding effects of nicotine. Nicotine is the main ingredient in tobacco smoking that leads to dependence and thus results in difficulty in quitting smoking. Thus, this data suggests novel pharmacological approaches to assist people in quitting smoking and treating the depression seen in many people after smoking has stopped. In conclusion, there appear to be neurobiological similarities in drug- and non-drug-induced depressions involving decreased glutamate transmission. Therefore, drugs that may positively modulate glutamate transmission may be effective antidepressants. Further, antagonists at specific glutamate and GABA receptors may assist people in quitting smoking and consequently avoiding the harmful health effects of tobacco smoking.

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Scripps Research Scientists Shed Light On How Serotonin Works -- Findings Could Affect Development Of Future Depression, Schizophrenia Treatments
Scripps Research Institute scientists have shown for the first time that the neurotransmitter serotonin uses a specialized signaling pathway to mediate biological functions that are distinct from the signaling pathways used by hallucinogenic substances. The new findings could have a profound effect on the development of new therapies for a number of disorders, including schizophrenia and depression. Serotonin has tremendous influence over several brain functions, including the control of perception, cognition, sleep, appetite, pain, and mood and mediates these effects through interactions with receptors located throughout the central and peripheral nervous systems. The Scripps Research study shows that while both serotonin and hallucinogens act at the serotonin 2A receptor, serotonin utilizes a very specific pathway and its actions are independent of those produced by hallucinogens. Laura Bohn, Ph.D., an associate professor on the Florida campus of The Scripps Research Institute, led the study. Future drug discovery efforts to identify lead compounds for treatment of depression may consider focusing upon those that only engage that pathway. This work may also lend insight into the mechanisms that underlie the hallucinations that occur in schizophrenia.

This may be particularly important for the treatment of depression because traditional therapies, which focus on elevating serotonin levels, can sometimes produce serious side effects such as a serotonin syndrome. This syndrome is often accompanied by hallucinations, and is especially serious when antidepressant treatments such as selective serotonin reuptake inhibitors (SSRIs) are mixed with monoamine oxidase inhibitors (MAOIs). The scientists' current study supports a long-standing hypothesis that hallucinations may arise from the metabolites formed from elevated serotonin levels. Since there is a difference in the way the two neurotransmitters signal, this may represent a means to preserve the effects of serotonin while preventing the adverse side effects caused by the metabolites.

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