Serotonin, depression and

Cowen, P. J., Serotonin and Depression Pathophysiological Mechanism or Marketing Myth , Trends Pharmacol Sci, no. 9 (2008)... 

Lacasse J, Leo J. Serotonin and depression a disconnect between the advertisements and the scientific literature. PLoS Med 2005 2(12) e392. 

Both suicidal behavior and impulsive aggression have been associated with low levels of brain serotonergic activity [91, 92]. Engelberg suggested that a reduction in serum cholesterol may decrease brain-cell-membrane cholesterol, lower lipid microviscosity, and decrease exposure of protein serotonin receptors on the membrane surface, thus resulting in a poorer uptake of serotonin from the blood and less serotonin entry into brain cells [4]. Other reports have discussed the relationships between cholesterol, serotonin, and depression [6, 93-96]. 

Neumeister A. Tryptophan depletion, serotonin, and depression Where do we stand Psychopharmacol. Bull. 2003 37 99-115. 

Archer JSM. Relationship between estrogen, serotonin, and depression. Menopause 1999 6 71-78. 

Ubiquitous mitochondrial monoamine oxidase [monoamine oxygen oxidoreductase (deaminating) (flavin-containing) EC 1.4.3.4 MAO] exists in two forms, namely type A and type B [ monoamine oxidase (MAO) A and B]. They are responsible for oxidative deamination of primary, secondary, and tertiary amines, including neurotransmitters, adrenaline, noradrenaline, dopamine (DA), and serotonin and vasoactive amines, such as tyramine and phenylethylamine. Their nonselec-tive and selective inhibitors ( selective MAO-A and -B inhibitors) are employed for the treatment of depressive illness and Parkinson s disease (PD). 

Wurtman, RJ and Wurtman, JJ (1995) Brain serotonin, carbohydrate-craving, obesity and depression. Obesity Res. 3 477S-480S. 

SSRIs are theorized to reduce the frequency of hot flashes by increasing serotonin in the central nervous system and by decreasing LH. Of the SSRIs, citalopram, paroxetine, and sertraline all have been studied and have demonstrated a reduction in hot flashes while treating other symptomatic complaints such as depression and anxiety.33 Venlafaxine, which blocks the reuptake of serotonin and norepinephrine, has demonstrated a reduction in hot flashes primarily in the oncology population.34 Overall, these antidepressant medications offer a reasonable option for women who are unwilling or cannot take hormonal therapies, particularly those who suffer from depression or anxiety. These agents should be prescribed at the lowest effective dose to treat symptoms and may be titrated based on individual response. 

Wang, X. X., Mu, J. S. Wang, S. H. (2004). Association study of serotonin transporter gene polymorphism and depression. Chinese Journal of Clinical Psychiatry, 14(4), 195-7. 

After neurotransmitter molecules have influenced the firing of a receiving neuron (more technically called a postsynaptic neuron), some of them are destroyed by enzymes in the synaptic cleft (the synapse), some are reabsorbed by the sending presynaptic neuron in a process that is called reuptake , and the rest remain in the space between the two neurons. The chemical-imbalance hypothesis is that there is not enough serotonin, norepinephrine and/or dopamine in the synapses of the brain. This is more specifically termed the monoamine theory of depression, because both serotonin and norepinephrine belong to the class of neurotransmitters called monoamines. 

Here then is the logic behind the first version of the chemical-imbalance theory. Iproniazid is a monamine oxidase inhibitor - it inhibits the oxidation of norepinephrine and serotonin in the synapses, thereby leaving more of these neurotransmitters available in the brain. When depressed people take iproniazid, they get better. Therefore insufficient norepinephrine and/or serotonin causes depression.12... 

But that was only one half of the logic behind the chemical-imbalance theory. The other half came from studies of reserpine, a drug that was extracted from Rauvolfia serpentina or the Indian snakeroot plant, which had historically been used to treat snakebite, hypertension, insomnia and insanity. In studies of animals, reserpine was reported to induce sedation and to decrease brain levels of norepinephrine, serotonin and dopamine. Clinical reports indicated that some people became severely depressed when taking reserpine.14 Putting these two findings together, it seemed likely that reserpine made people depressed because it decreased neurotransmitter levels. 

When the chemical-imbalance theory was introduced more than 40 years ago, the main evidence in favour of it was the contention that antidepressants, which were thought to increase the availability of serotonin and/or other neurotransmitters in the brain, seemed to be effective in the treatment of depression. As Alec Coppen wrote in 1967, one of the most cogent reasons for believing that there is a biochemical basis for depression or mania is the astonishing success of physical methods of treatment of these conditions. 26 The situation has not changed very much since then. People still cite the supposed effectiveness of antidepressants as fundamental support for the chemical-imbalance hypothesis. This theory, they say, is supported by the indisputable therapeutic efficacy of these drugs .27... 

Different types of antidepressants are supposed to affect different neurotransmitters. Some are supposed to affect only serotonin, others are supposed to affect both serotonin and norepinephrine, and still others are supposed to affect norepinephrine and dopamine. But there is a relatively new antidepressant that has a completely different mode of action. It is a most unlikely medication, and the evidence for its effectiveness puts the last nail in the coffin of the chemical-imbalance theory of depression. 

This type of action is found in kanna, or Sceletium expansum and Sceletium tortuosum (Aizoaceae), which have been used by South African shamans from prehistoric times to enhance animal spirits, sparkle the eyes, and to stimulate gaiety. The active constituent of kanna is a serotonin-like alkaloid called mesembrine, which is a potent serotonin re-uptake inhibitor—hence, some potential for the treatment of anxiety and depression however, careful clinical trials must be performed. 

Reserpine inhibits the synaptic vesicular storage of the monoamines dopamine, serotonin and noradrenaline. As a result they leak out into the cytoplasm where they are inactivated by monoamine oxidase this causes their long-lasting depletion. The resulting low levels of dopamine underlie the antipsychotic actions of reserpine (Chapter 11), whereas the reduced noradrenaline levels underlie its antihypertensive actions. Finally, the resulting low levels of serotonin and noradrenaline mean that reserpine also induces depression. These severe side effects mean that reserpine is no longer used clinically as a treatment for schizophrenia (Chapter 11). 

Stockmeier, C. A. Involvement of serotonin in depression evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. /. Psychiatr. Res. 37 357-373, 2003. 

Duloxetine, a dual inhibitor of serotonin and norepinephrine reuptake indicated for depression and painful diabetic neuropathy, is expected to become first-line therapy for SUI. Duloxetine is thought to facilitate the bladder-to-sympathetic reflex pathway, increasing urethral and external urethral sphincter muscle tone during the storage phase. 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

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