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Outline of Article:

1. Jan Fawcett, M. D., Depression at Biochemical Level. Psychiatric Annals 1980, 10 (9), S9-S15.


 * Overview of History & Criticisms of depression:**
 * Research seems to continually support some kind of genetic link, which makes certain individuals more susceptible to developing depressive disorders.
 * Serotonin and Norepinephrine are the two neurotransmitters thought to play key role in depression.
 * This is based on the observed improvements in patients taking drugs known to affect the levels of these monoamine neurotransmitters available in the brain.

//Catecholamine Theory:// //Serotonin Theory:// //Permissive Theory://
 * Biochemical Theories of Depression:**
 * Depression is related to the depletion of norepinephrine in the brain.
 * This theory was proposed based on the observations of the development of depression in patients taking medications known to deplete the amount of available norepinephrine in the brain.
 * MAOIs & Tricyclic antidepressants proved able to reverse this kind of depression (presumably) by increasing the amount of norepinephrine present in the “synaptic cleft of noradrenergic neurons”.
 * Explains these symptoms of depression: mood; metabolism; circadian rhythms; sex drive.
 * While this theory seems to make sense, it ignores the nervous system’s complexity and adaptability in addition to the effect that serotonin has on the brain.
 * Also considers the depletion of a monoamine in the brain, but suggests that serotonin provides a more accurate portrayal.
 * A serotonin inhibitor can reverse the beneficial effects that MAOIs and tricyclic antidepressants have in treating depression, but this does not occur when a norepinephrine inhibitor is introduced.
 * This theory can be applied to both unipolar and bipolar cases of depression, because it takes into account an individual’s susceptibility to become depressed based on whether they generally have low levels of serotonin.


 * MHPG (3-methoxy-4-hydroxyphenylglycol):**
 * This is a metabolite of norepinephrine degradation.
 * The MHPG levels can be measured by testing the urine of patients.
 * (Although still controversial) By testing MHPG levels in patients suffering from depression, one can estimate whether blocking the reuptake of serotonin or norepinephrine will be more efficient in treating an individual.

//Acetylcholine:// //Dopamine:// //Phenylethylamine (PEA):// //Endorphins://
 * Other neurotransmitters:**
 * This neurotransmitter is suspected to have some effect in the development of the symptoms of depression.
 * Acetylcholine promotes REM sleep, helps sustain attention/concentration, & plays some role in memory.
 * This neurotransmitter tends to take a more prominent role in manic states, associated with bipolar disorder.
 * Although dopamine does seem to play some role in depression since a decrease in dopamine is usually associated with lower activity, energy, concentration, & alertness (echoes symptoms of depression).
 * PEA is not strictly a neurotransmitter; it is more of a neuromodulator since it can penetrate the blood-brain barrier.
 * Elevate PEA levels are linked to mania, while low PEA levels are linked to depression.
 * The role of endorphins in depression is not clearly stated, although their affect on the body is not dissimilar to that of opiates.
 * Endorphins (also called enkephalins) are involved in the neurological process of pleasure or positive reinforcement.


 * “Limbic System-Hypothalamopituitary Adrenal (HPA) Dysfunction”:**
 * Many individuals with clinical depression seem to have an “abnormal activation state of the limbic-HPA system”, in addition to altered responses of the anterior pituitary to the release of hormones from the hypothalamus.


 * Alteration of Sleep:**
 * Alterations in sleep may be observed through EEG recordings.
 * Common effects of depression on sleep include: decreased sleep time, less stage 4 sleep, and alterations in REM sleep.


 * Postsynaptic Hypersensitivity:**
 * The increase in the sensitivity of the postsynaptic monoaminergic receptors may be related to underlying alterations of the monoamines.
 * It is hypothesized that instead of increasing the amount of monoamine available in the brain, antidepressants may actually desensitize the receptors.


 * Lithium & Electrolytes:**
 * There is no detailed hypothesis relating the effects of lithium & electrolytes to depression.
 * The anitmanic and prophylactic effects of lithium make it an effective treatment for bipolar disorder.


 * Q&A:**
 * Amphetamines are used to speed the response time of tricyclic antidepressants.