Overview of the Genetics of Major Depressive Disorder
Serotonin Transporter (5HTT/SLC6A4) and Serotonin Receptor 2A (HTR2A)
The serotonin transporter gene and genes involved in the serotonergic system are candidate genes for susceptibility to depression given that many antidepressant medications act on these systems. Several studies have implicated the serotonin transporter gene (SLC6A4) in MDD [17–19]. A 44-bp repeat polymorphism in the promoter region of the gene (5-HTTLPR) has been shown to influence expression levels of the serotonin transporter in vitro ...
Growing evidence suggests an important role for brain-derived neurotrophic factor (BDNF) in affective disorder ...
Tryptophan hydroxylase is the rate-limiting enzyme in brain serotonin synthesis. The discovery of a new brain-specific isoform of the tryptophan hydroxylase (TPH2) has generated new interest in the connection between serotonergic systems and depression [39]. The TPH2 gene is located on chromosome 12q, a region previously implicated in linkage studies of BPD.
Zill et al. [40] reported the first evidence of an association of variants in the THP2 gene and major depression. Zhang et al. [41] identified a functional polymorphism (Arg441His) that results in about 80% loss of function in serotonin production when expressed in a cell system. The authors also reported that this rare mutation was not seen in 219 healthy controls but was seen in 9 of 87 individuals with major depression
Depression: a case of neuronal life and death?
stress or depression can lead to atrophy and cell loss in limbic brain structures that are critically involved in depression, including the hippocampus. Studies in experimental animals demonstrate that decreased birth of new neurons in adult hippocampus could contribute to this atrophy. In contrast, antidepressant treatment increases neurogenesis in the hippocampus of adult animals and blocks the effects of stress. Moreover, blockade of hippocampal neurogenesis blocks the actions of antidepressants in behavioral models of depression, demonstrating a direct link between behavior and new cell birth. This perspective reviews the literature in support of the hypothesis that altered birth of new neurons in the adult brain contributes to the etiology and treatment of depression and considers research strategies to test this hypothesis.
St. John's wort, green tea, ginkgo, ginseng, ash, magensium/zinc/chromium, omega-3s (flax and salmon/sardines),
and still from dietary source: melatonin/PQQ/CoQ10 and various polyphenols, which adapt the mitochondria[1] and endoplasmic reticulum[2] to oxidative stress, which both play roles in depression.
And obviously improving diet, activity levels [mental & physical], or overall lifestyle could help.
Anything which boosts striatal BDNF, increases dopamine/serotonin/GABA activity, or reduces acetylcholine/glutamate/histamine activity.
Mitochondrial dysfunction, oxidative stress, and major depressive disorder
Evaluation of mitochondrial dysfunction in specific tissues may broaden the perspective of depression beyond theories about neurotransmitters or receptor sites, and may explain the persistent signs and symptoms of depression.
Pathological parainflammation and endoplasmic reticulum stress in depression: potential translational targets through the CNS insulin, klotho and PPAR-γ systems
ER stress refers to a complex program set into motion when the ER is challenged by the production or persistence of more proteins than it can effectively fold. If the ER response is overwhelmed, substantial amounts of calcium are released into the cytoplasm, leading to apoptosis. Parainflammation and ER stress generally occur simultaneously. We discuss three highly interrelated mediators that can effectively decrease parainflammation and ER stress .. novel therapeutic targets for the amelioration of the affective, cognitive and systemic manifestations of major depressive disorder.
Bacopa monniera leaf extract up-regulates tryptophan hydroxylase (TPH2) and serotonin transporter (SERT) expression: implications in memory formation</a>
RESULTS:
Oral administration of Bacopa improved learning and retention of memory. Following Bacopa treatment, the level of serotonin (5-HT) increased while dopamine decreased. We also found variation in the level of acetylcholine (ACh). The level of serotonin (5-HT) was significantly elevated up to 30 days after treatment, but was restored to normal on day 60. Interestingly, concomitant up-regulation was recorded in the mRNA expression of serotonin synthesizing enzyme tryptophan hydroxylase-2 (TPH2) and serotonin transporter (SERT) on day 30 and day 39, which was restored on day 60.
Saffron (Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials
Based on our pre-specified criteria, five randomized controlled trials (n = 2 placebo controlled trials, n = 3 antidepressant controlled trials) were included in our review. A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms (M ES = 1.62, P < 0.001), revealing that saffron supplementation significantly reduced depression symptoms compared to the placebo control.
Regulatory effects of Wuzhuyutang (Evodiae) and its consisting herbs on TPH2 promoter
TPH2 promoter drove Red Fluorescent Protein expressing cell line can be used as system screening components targeting TPH2 promoter activity. The possible mechanism of WZYT on migraine may due to its stimulating effects on TPH2 promoter, and promote the synthesis and release of 5-HT in cerebral.
Rhizoma Coptidis and Fructus Evodiae is explained by modulating the monoaminergic neurotransmitter system in mice [courtesy of Flex]
the alkaloids from the two herbs may provide a protective effect for depression in individuals with a low expressing 5-HTT allele by increasing receptor concentration in serotonergic neurons
Edited by gamesguru, 31 August 2015 - 02:41 PM.
