Abstract:Intracellular signal transduction cascades, particularly those linked to protein kinases A (PKA) and C (PKC), have been implicated in mood disorders. This study examined the activity of PKA and PKC, as well as levels of PKA regulatory (R) and catalytic (C) subunit proteins, in fibroblasts cultured from skin biopsies from patients with major depression, melancholic subtype, in contrast to non-melancholic depressives and controls (n = 12 each group). PKA activity was determined as a function of the transfer of 3… Show more
“…Fibroblasts derived from human skin are used as cellular models to study the pathophysiology of a variety of disorders (28)(29)(30)(31), especially those involved in lipid metabolism (32)(33)(34). For example, fi broblasts from SLOS patients contain elevated levels of 7-DHC and these cells have been used to establish methods for 7-DHC analysis and to determine the biological effects of this lipid ( 32,33 ).…”
“…Fibroblasts derived from human skin are used as cellular models to study the pathophysiology of a variety of disorders (28)(29)(30)(31), especially those involved in lipid metabolism (32)(33)(34). For example, fi broblasts from SLOS patients contain elevated levels of 7-DHC and these cells have been used to establish methods for 7-DHC analysis and to determine the biological effects of this lipid ( 32,33 ).…”
“…251 Moreover, paroxetine and nefazodone may exert their antidepressant effects through regulation of 5-HT 2A receptors, 249,[252][253][254] although controversial findings can also be found. 255 Finally, 5-HT 2A receptors have been reported to mediate some of the antidepressant effects seen in experimental animal models of depression. 256 Three variations within the coding region of 5-HT 2A have been implicated in antidepressant response: 102T>C (rs 6313) 176 and 1438G>A (rs6311) 190,257 and 1420C>T, 153 although results were not unequivocal and some findings not replicated.…”
87Personalized medicine -the adaptation of therapies based on an individual's genetic and molecular profile -is one of the most promising aspects of modern medicine. The identification of the relation between genotype and drug response, including both the therapeutic effect and side effect profile, is expected to deeply affect medical practice. In this paper, we review the current knowledge about the genes related to antidepressant treatment response and provide methodologic proposals for future studies. We have mainly focused on genes associated with pharmacodynamics, for which a list of promising genes has been identified despite some inconsistency across studies. We have also synthesized the main results for pharmacokinetic genes, although so far they seem less relevant than those for pharmaco dynamic genes. We discuss possible reasons for these inconsistent findings and propose new study designs.
“…These data further implicate signal transduction abnormalities in melancholic major depression, particularly PKA and PKC. This suggests an abnormality of factors controlling the expression or degradation of these enzymes (Akin et al 2005). …”
Biological markers for depression are of great interest to aid in elucidating the causes of major depression. We assess currently available biological markers to query their validity for aiding in the diagnosis of major depression. We specifically focus on neurotrophic factors, serotonergic markers, biochemical markers, immunological markers, neuroimaging, neurophysiological findings, and neuropsychological markers. We delineate the most robust biological markers of major depression. These include decreased platelet imipramine binding, decreased 5-HT1A receptor expression, increase of soluble interleukin-2 receptor and interleukin-6 in serum, decreased brain-derived neurotrophic factor in serum, hypocholesterolemia, low blood folate levels, and impaired suppression of the dexamethasone suppression test. To date, however, none of these markers are sufficiently specific to contribute to the diagnosis of major depression. Thus, with regard to new diagnostic manuals such as DSM-V and ICD-11 which are currently assessing whether biological markers may be included in diagnostic criteria, no biological markers for major depression are currently available for inclusion in the diagnostic criteria.
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