Priming with Ucn1 increased tph2 mRNA expression selectively within the anxiety-related dorsal part of the DR (DRD) and decreased social interaction (SI) time, a measure of anxiety-related defensive behavioral responses in rodents.
In the full cohort of mice, TPH2 activity in the mid-rostrocaudal DR was correlated with anxious behaviour in the EPM, however these correlations were not statistically significant within each strain, suggesting that TPH2 activity was not directly associated with either anxiety or sociability.
We conclude that BH<sub>4</sub> treatment of HPA toward systemic L-Phe lowering reverses elevated brain L-Phe content but the recovery of TPH2 protein and activity as well as serotonin levels is suboptimal, indicating that patients with mild HPA and mood problems (depression or anxiety) treated with the current diet may benefit from supplementation with BH<sub>4</sub> and 5-OH-tryptophan.
Specifically, the correlation between amygdala-hippocampus connectivity and Gray's trait anxiety scores is positive in individuals homozygous for the TPH2 G-allele, while carriers of at least one T-allele show a negative association.
Based on genetic variation, there is accumulating evidence that altered function of tryptophan hydroxylase-2 (TPH2), the enzyme critical for synthesis of serotonin (5-HT) in the brain, plays a role in anxiety-, aggression- and depression-related personality traits and in the pathogenesis of disorders featuring deficits in cognitive control and emotion regulation.
Population-specific functional variant of the TPH2 gene 2755C>A polymorphism contributes risk association to major depression and anxiety in Chinese peripartum women.
A gene x glycemic control interaction (p=0.032) was observed on the anxiety scale at the TPH2 promoter polymorphism: the -703T-allele decreased anxiety scores only in the GC group (p=0.008).