The association of two tryptophan hydroxylase 2 (TPH2) polymorphisms and treatment response in electroconvulsive therapy (ECT) and the risk of depression was studied.
The major findings were associations of TPH2 (rs12229394) with depression accompanied by fatigue in women and CREB1 (rs11904814) with depression alone in men.
Additive effects of 5-HTTLPR (serotonin transporter) and tryptophan hydroxylase 2G-703T gene polymorphisms on the clinical response to citalopram among children and adolescents with depression and anxiety disorders.
Variations in tryptophan hydroxylase 2 linked to decreased serotonergic activity are associated with elevated risk for metabolic syndrome in depression.
Common polymorphisms involved in the tryptophan hydroxylase 1 (TPH1) and 2 (TPH2), serotonin transporter, monoamine oxidase A (MAOA) and brain-derived neurotrophic factor (BDNF) were investigated in a naturalistic inpatient study of the German research network on depression.
Here we use chronic multicircuit neurophysiological recordings to characterize functional interactions across cortical and limbic circuits in mice engineered to express a human loss-of-function depression allele Tph2-(R441H) [Tph2 knockin (Tph2KI)].
Six functional SNPs in genes related to the serotonergic system were examined: serotonin transporter (5HTTLPR including rs25531), 5HT1A C-(1019)G and 5HT2A T-(102)C, methylene tetrahydrofolate reductase (MTHFR) C-(677)T, brain-derived neurotrophic factor (BDNF) val66met and tryptophan hydroxylase-2 (TPH2) G-(703)T. Regression analyses were performed using the six SNPs as independent variables: Model 1 with response (percentage Hamilton Depression (HAMD) change from baseline to endpoint) as the dependent variable and Model 2 with adverse event index as the dependent variable (Bonferroni corrected p-value < 0.025).
We chose several genetic variants within candidate genes (SLC6A4, TPH2, HTR1A) that have been previously found to provide some evidence of association with depression outcomes.
However, the T/T homozygote of c.-1668T>A-TPH1, the G/T heterozygote and T allele of c.-844G>T-TPH2, and the C/C homozygote and C allele of c.-1449C>A-TPH2 decreased the risk of development of depressive disorders.
In this review, we will critically assess the evidence for 5-HT deficiency in depression and the possible role of polymorphisms in the Tph2 gene as a causal factor in 5-HT deficiency, the latter investigated from a clinical as well as preclinical angle.
We hypothesize that functional polymorphisms (TPH2: rs7305115, 5-HTTLPR and rs25531) within both genes contribute to the risk of depressive disorders after childhood abuse in adult life.
Previous studies found that mutations on the TPH2 locus in humans were associated with depression and studies of mice and studies of rhesus macaques have shown that the TPH2 locus was involved with aggressive behavior.
We studied mice with an analogous mutation (TPH2-R439H), which results in a 60%-80% decrease in levels of 5-HT in the central nervous system and behaviors associated with depression in humans.
Furthermore, the TPH2(-/-) mouse may serve as a useful model in the search for new medications that have therapeutic targets for depression that are outside of the 5HT neuronal system.
The results of our analysis indicated no significant differences in the frequencies of the single alleles and genotypes of two polymorphisms in TPH2 gene between LOD patients and normal controls.
Common polymorphisms involved in the tryptophan hydroxylase 1 (TPH1) and 2 (TPH2), serotonin transporter, monoamine oxidase A (MAOA) and brain-derived neurotrophic factor (BDNF) were investigated in a naturalistic inpatient study of the German research network on depression.
We tested these mice along with C57BL/6 mice (Tph2C/C), congenic C57BL/6 mice homozygous for the Tph21473G-allele (Tph2G/G), and heterozygous Tph2-deficient mice (Tph2C/-) for anxiety- and depression-like behavior, and evaluated brain serotonin metabolism and 5-HT1AR signaling by high-performance liquid chromatography and quantitative autoradiography, respectively.
We hypothesize that functional polymorphisms (TPH2: rs7305115, 5-HTTLPR and rs25531) within both genes contribute to the risk of depressive disorders after childhood abuse in adult life.
5-HTT and TPH2 variations did not contribute significantly to the prediction of interferon-induced depression by HTR1A (sensitivity, 35.9%; specificity, 84.0%).
Although TPH-2 is often implicated in the pathophysiology of depression, few studies have applied a genetic and imaging technique to investigate the mechanism of early wakening symptom in MDD.