دانلود کتاب روانپزشکی ماساچوست

It was only a matter of time before a new comprehensive textbook of psychiatry brought together the most up-to-date information (derived from clinicians and researchers) for practitioners, researchers, and life-long learners. Fortunately, our talented faculty was up to the challenge; they collaborated enthusiastically, effectively, and effi ciently to create this comprehensive compendium regarding diagnosis, pathophysiology, and effective treatment.

We are deeply appreciative of the countless hours that went into the creation of these chapters; yeoman’s work (superimposed on full clinical and research schedules) was done by all. This effort would not have been possible without everyone pulling vigorously at the oars. We owe them our heartfelt thanks.

LABORATORY FINDINGS

Laboratory fi ndings are often not useful in establishing the diagnosis or the severity of an eating disorder. The diagnosis may be self-evident with a classic constellation of symptoms, though patients may not always be forthcoming. The clinical history and a directed interview are more useful in establishing the presence of symptoms of an eating disorder; extensive or invasive testing is generally unnecessary and often counterproductive. Laboratory assessment, though sometimes insensitive, is nonetheless essential to exclude other causes of weight loss or complications of the eating disorder.

Normal laboratory fi ndings do not exclude a serious eating disorder; however, even subtle laboratory abnormalities may signal a major physical toll from the illness. Hypokalemia is often a sign of purging behavior, and use of diuretics or laxatives, and hyponatremia is often seen with compulsive waterdrinking. The tests that may be useful are listed in Table 37-10, and abnormalities associated with eating disorders are shown in Table 37-11.

Mechanism of Action of Serotonin Norepinephrine Reuptake Inhibitors

Unlike the TCAs, SNRIs inhibit the reuptake of serotonin more potently than the reuptake of norepinephrine.10 Similar to most SSRIs, the SNRIs have minimal or no affi nity for muscarinic cholinergic, histaminergic, and adrenergic receptors.10 Interestingly enough, administration of these drugs has been shown to prevent a decrease in cell proliferation and BDNF expression in rat hippocampus observed with chronic stress, a study that offers further insights into the “downstream effects” of these agents.12 In parallel, recent data suggest that chronic treatment with the SNRI duloxetine not only produces a marked up-regulation of BDNF mRNA and protein, but may also affect the subcellular redistribution of neurotrophin, potentially improving synaptic plasticity.

Mechanism of Action of Serotonin Receptor Agonist/Antagonists

Both trazodone (Desyrel) and nefazodone (Serzone) are relatively weak inhibitors of serotonin and norepinephrine uptake, and they primarily block serotonin 5-HT2A receptors (in some cases, demonstrating partial agonist properties as well).18-21 They also share a metabolite, m-chlorophenylpiperazine (mCPP), which acts as a serotonin 5-HT2C agonist and appears to be able to release serotonin presynaptically. Trazodone also appears to stimulate the mu1- and mu2-opioid receptors23 and is a potent agonist of the serotonin 5-HT2C receptors, which, when activated,24,25 may inhibit NMDAinduced cyclic GMP elevation. Since trazodone is also a weak inhibitor of serotonin reuptake as well, the overall effect of trazodone appears to be an increase in extracellular levels of serotonin in the brain.26 This effect explains the fact that trazodone treatment has been associated with the occurrence of a serotonin syndrome.27 Both trazodone and (although to a lesser degree) nefazodone are potent blockers of the alpha1- adrenergic receptor.

Agomelatine, a newer agent, is a selective 5-HT2C antagonist and also an agonist at various melatonergic receptors. The 5-HT2C antagonism properties of agomelatine have been thought to be responsible for increases in frontocortical dopaminergic and adrenergic activity in animals during administration of agomelatine.

Buspirone and gepirone act as full agonists at serotonin 5-HT1A autoreceptors and are generally, but not exclusively, partial agonists at postsynaptic serotonin 5-HT1A receptors. Buspirone and gepirone show weak alpha1-adrenoceptor affi nity but signifi cant and selective alpha1-adrenoceptor intrinsic effi cacy, which was expressed in a tissue- and speciesdependent manner.30 They also show weak dopamine D2 antagonism properties.31 The latter effect is thought to lead to excitation of noradrenergic cell fi ring,31 antagonizing primarily presynaptic inhibitory dopamine D2 autoreceptors at dopaminergic neurons.32 Buspirone also has potent alpha2- adrenoceptor antagonist properties via its principal metabolite, 1-(2-pyrimidinyl)-piperazine.