Biochemistry of depression

Green AR and Costain DW (1979). The biochemistry of depression. In ES Paykel and A Coppen (eds), Psychopharmacology of Affective Disorders (pp. 14 40). Oxford University Press, Oxford, UK. 

Another area of clinical interest which has benefited from the use of BCD is the study of tryptophan metabolism. Tryptophan is an essential amino acid which can be metabolized in a number of ways as illustrated in Figure 3. One of the minor pathways leads to the synthesis of the neurotransmitter 5-hydroxytryptamine (5HT), abnormal brain levels of which have been associated with a number of diseases including Down s syndrome[15] and depression [lb] As part of a study into the biochemistry of depressive illnesses, I investigated methods for the determination of tryptophan metabolites in blood and urine. HPLC proved to be a useful technique for separating these compounds, so the possibility of using BCD was examined [17]. 

Direct evidence suggesting that disturbed indolealkylamine or catecholamine metabolism have significant roles in depressive illness is summarized below. A number of important discussions of the biochemistry of depression and of other psychotic states place amine studies within a general context [300-303]. 

So what has gone wrong in the nervous system biochemistry of victims of depression The answer to that question is not completely clear but we have substantial insights. 

Amines in depression. There are grounds for the postulation of at least two biochemically distinct types of endogenous depression and their association with disorders of noradrenergic and serotoninergic functions (see e.g. [480,481]). Attempts to define the biochemistry of human depression include the use of GC-MS methods for the determination in CSF of the principal metabolites of the transmitters in untreated patients and in monitoring their concentration during antidepressant therapy. 

In very similar ways, in numerous studies the biochemistry of people with reactive depressions has been shown to be markedly altered. For example, emotionally healthy individuals without a personal or family history of depression who encounter major psychosocial stressors (especially losses) often become depressed. Presumably such people are not especially at risk (biologically or psychologically) for depression, but nonetheless they become depressed in response to significant stressful events. Further, in the course of their reaction, some patients develop not... 

As glutamic acid is known to be involved in the biochemistry of the central nervous system, various cyclic imides of glutamic acid derivatives have attracted attention as potential central nervous system depressants. " These compounds (150) have been made the subject of a patent claiming central nervous system stimulant and depressant activity in mice." Another 6-oxo compound (132) has been claimed to have antiviral activity. ... 

Serotonin has been found to influence sleeping, the regulation of body temperature, and sensory perception, but its exact role in mental illness is not yet clear. Unusually low levels of 5-hydroxyindoleacetic acid, a product of serotonin utilization, are characteristically found in the spinal fluid of victims of violent suicide. Drugs that mimic serotonin are sometimes used to treat depression, anxiety, and obsessive-compulsive disorder. Serotonin blockers are used to treat migraine headaches and relieve the nausea that accompanies cancer chemotherapy. A better understanding of the biochemistry of the brain may lead to better medications for treating various forms of mental illness. 

The biochemistry of mental depression is not fully understood, but a deficiency of norepinephrine and serotonin (possibly also dopamine see next section) almost certainly plays a role. Evidence is provided by the manner in which three classes of drugs, illustrated by the following three componnds, influence the action of these neurotransmitters. 

A term applied to substances or agents that either depress or elevate the action of a particular catalyst. While often used synonymously with effector, the International Union of Biochemistry has suggested that the term modifier is more appropriate for those substances that are artificially added to in vitro systems. Other investigators restrict the use of the term modifier to those agents that eovalently modify the structure of the catalyst, thereby altering the catalyst s activity. See Effector Activator Inhibitor... 

Hong J-S, Tilson HA, Yoshikawa K Effects of lithium and haloperidol administration on the rat brain levels of Substance P. J Pharmacol Exp Ther 224 590-597, 1983 Honig A, Bartlett JR, Bouras N, et al Amino acid levels in depression a preliminary investigation. J Psychiatr Res 22 159-164, 1989 Honjo H, Ogino Y, Natitoh K, et al In vivo effects by estrone sulphate on the central nervous system on senile dementia [Alzheimer s type). Journal of Steroid Biochemistry 34 521-525, 1989... 

Findings of receptor activity differences in normal young animals, with their own species-specific biochemistry and physiology, which cannot be easily generalized to baseline and posttreatment differences in normai humans or depressed patients... 

Kokkinidis, Larry, and Bryon D. McCarter. 1990. "Postcocaine Depression and Sensitization of Brain Stimulation Reward Analysis of Reinforcement and Performance Effects." Pharmacology Biochemistry and Behavior 36 463-71. 

Kokkinidis, Larry, Robert M. Zacharko, and Patrick A. Predy. 1980. "Post-Amphetamine Depression of Self-Stimulation Responding from the Substantia Nigra Reversal by Tricyclic Antidepressants." Plmmmcotogy Biochemistry and Behavior 13 379-83. 

There is some interesting biochemistry and pharmacology all around the edges of a-MT. The 4-hydroxy analogue of a-MT has been looked at in human subjects. It is reported to be markedly visual in its effects, with some subjects reporting dizziness and a depressed feeling. There... 

The Affective Disorders Manic Depressive Psychoses Lithium in the Affective Disorders A. Side Effects Chemistry Isotopes of Lithium Inorganic Biochemistry Mechanisms of Action Lithium and the Phosphoinositide Signaling System Lithium and the Cell Membrane A. Sodium-Lithium Exchange Anion Exchange Leak... 

Biochemistry—An imbalance of neurotransmitters or neurotransmission may lead to depression. Even though there may be no outward reason to be depressed, a particular biochemistry in someone s brain may predispose him or her to depression. 

Because humans are very complex chemical factories, the positive and negative effects of a drug can be difficult to determine. To some extent, they depend on each persons unique biochemistry, as well as on interactions with other chemicals that may be present in the body. For example, the effects of BD are thought to be enhanced by alcohol and other depressants, so if an individual takes one of the party drugs containing BD (drugs with names like Cherry fX Bombs) and drinks... 

The early pioneering work by Zeller et al. (115) on the potent MAO inhibitory effect of iproniazid—a structural modification of the tuberculostat Isoniazid—and his realization of the physiologic consequences that might arise from such a profound alteration in catecholamine metabolism, the actual confirmation by Brodie, Pletscher, and Shore (27) of the rise in brain monoamine levels following the administration of iproniazid and JB-516 (a-methylphen-ethylhydrazine), and the early euphoric effects noted by Selikoff, Robitzek, and Omstein (96) in tuberculosis patients on iproniazid therapy led Kline and his associates (67) to investigate the possible application of iproniazid in the treatment of mental depression. It was their conclusion that MAO inhibition and antidepressant effect had a causal relationship and that a new approach for the treatment of mental depression had been uncovered. The subject of the MAO inhibitors has been reviewed extensively up to 1960 by Pletscher, Gey, and Zeller (84) and by Biel, Horita, and Drukker (21) to 1963, in comprehensive reviews of the chemistry, biochemistry, pharmacology, clinical application, and structure-activity relationships of the MAO inhibitors. 

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