Development by environment interactions controlling tryptophan hydroxylase expression

Tryptophan hydroxylase is the rate-limiting enzyme in the biosynthesis of serotonin (5-hydroxytryptamine; 5-HT). Two isoforms of tryptophan hydroxylase, derived from different genes, tph1 and tph2, have been identified. The tph1 isoform is expressed in peripheral tissues, whereas tph2 is brain and neuron-specific. Recent studies suggest that tph2 expression and brain serotonin turnover are upregulated in depressed suicide patients, and drug-free depressed patients, respectively. Increased tph2 expression could result from genetic influences, early life developmental influences, adverse experience during adulthood, or interactions among these factors. Studies in rodents support the hypothesis that interactions between early life developmental influences and adverse experience during adulthood play an important role in determining tph2 expression. In this review, we highlight the evidence for the effects of adverse early life experience and stressful experience during adulthood on both tph1 and tph2 expression.

► Tryptophan hydroxylase is the rate-limiting enzyme in the biosynthesis of serotonin
► The tph1 isoform is believed to be expressed in peripheral tissues, whereas the tph2 isoform is believed to be brain and neuron-specific.
► tph2 expression is upregulated in the dorsal raphe nucleus of depressed suicide victims.
► Adverse early life experience increases vulnerability to stress-induced increases in tph2 expression.
► Neonatal handling decreases tph2 expression during adulthood.