5-HTT and TPH2 variations did not contribute significantly to the prediction of interferon-induced depression by HTR1A (sensitivity, 35.9%; specificity, 84.0%).
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.
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.
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.
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.
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.
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)].
Here, we appraise the genetic and neurobiological evidence to illustrate the critical role of TPH2 in central 5-HT system function and in the pathophysiology of a wide spectrum of disorders of cognitive control and emotion regulation, ranging from depression to attention-deficit/hyperactivity disorder (ADHD), a phenotype commonly associated with difficulties in the control of emotion and with a high co-morbidity of depression.
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 addition, there was a significant correlation between the methylation status of the TPH2 promoter and depression, hopelessness and cognitive impairment in the MDD + suicide group.
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.
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.
Serotonin (5-HT) in the regulation of depression-related emotionality: insight from 5-HT transporter and tryptophan hydroxylase-2 knockout mouse models.
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).
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.
The participation of estradiol in depression may include regulation of the expression of tryptophan hydroxylase-2, monoamine oxidase A and B, serotonin transporter and serotonin-1A receptor.
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.
The results of the present study suggest that TPH2 gene expression in the midbrain part of the DRN is implicated in depression and stress response, as well as in the antidepressant fluoxetine action.