What you carry at this position in your DNA and what research says about it.
Anxiety and Mood Regulation: 5/10 evidence, 30 publications.
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Sample genotype (not yours): G/G
Higher Risk of Anxiety and Neuroticism
Carrying two copies of the G allele is associated with higher scores on anxiety-related personality traits and neuroticism. However, this genotype also correlates with a significantly stronger response to placebo treatments.
What this genotype means: Higher scores on anxiety-related personality traits; Increased risk of ADHD and OCD transmission; Stronger clinical placebo response.
Sample genotype (not yours): G/T
Typical Emotional and Cognitive Profile
Carrying one G and one T allele generally results in typical levels of anxiety, emotional regulation, and cognitive control. This heterozygous profile represents the baseline response pattern in most populations.
What this genotype means: Typical baseline anxiety and neuroticism levels; Standard cognitive control and working memory; Typical response to SSRI antidepressants.
Sample genotype (not yours): T/T
Lower Anxiety Risk and Better Antidepressant Response
Carrying two copies of the T allele is linked to lower levels of anxiety, neuroticism, and aggressiveness. It also predicts a more favorable response to the antidepressant fluoxetine, though specific medications may pose unique risks.
What this genotype means: Lower levels of anxiety and neuroticism; Better therapeutic response to fluoxetine; Increased depression risk under specific HIV medications.
Gene function and biological role
Gene Function: The TPH2 gene encodes tryptophan hydroxylase 2, the rate-limiting enzyme responsible for synthesizing serotonin in the central nervous system. Serotonin is a critical neurotransmitter that regulates mood, emotional processing, and cognitive control. Because TPH2 is primarily expressed in the brainstem raphe nuclei, its activity directly shapes serotonin availability in key emotional centers like the amygdala. Variations in this gene can alter enzyme expression, leading to differences in emotional resilience, susceptibility to psychiatric conditions, and response to medications.
Variant Impact: The rs4570625 variant, also known as G-703T, is located in the promoter regulatory region of the TPH2 gene. This genetic change alters transcription factor binding sites, which can influence how efficiently the gene is transcribed into the serotonin-synthesizing enzyme. Studies indicate that the G and T alleles modulate brain serotonin levels and amygdala reactivity to emotional stimuli. Consequently, this variant is widely studied for its impact on anxiety, attention-deficit/hyperactivity disorder (ADHD), and antidepressant treatment outcomes.
Key Insight: The same genetic variant that influences anxiety levels also predicts how strongly a person responds to inactive placebo treatments.
Location: TPH2. Chromosome 12 · 12q21.1 · 71.9 Mb
Estimated prevalence by population
Global 53.0%; European 61.4%; African 40.3%; East Asian 20.9%; South Asian 51.0%; Americas 51.4%; Ashkenazi 59.2%; Finnish 65.7%; Middle Eastern 59.6%; Amish 54.8%.
Estimated GG genotype frequency.
Global 38.7%; European 33.9%; African 46.4%; East Asian 49.6%; South Asian 40.8%; Americas 40.6%; Ashkenazi 35.5%; Finnish 30.7%; Middle Eastern 35.2%; Amish 38.5%.
Estimated GT genotype frequency.
Global 8.3%; European 4.7%; African 13.3%; East Asian 29.4%; South Asian 8.2%; Americas 8.0%; Ashkenazi 5.3%; Finnish 3.6%; Middle Eastern 5.2%; Amish 6.8%.
Estimated TT genotype frequency.
Showing effects for G/G genotype
Neurology & Mental Health
Anxiety & Stress Disorders
Anxiety and Neuroticism. Evidence: 4/10. Source: PMID 17176492. Increased Risk.
Neurodevelopmental Traits
ADHD Susceptibility. Evidence: 4/10. Source: PMID 16116490. Increased Risk.
Behavioral & Personality Traits
Placebo Response. Evidence: 3/10. Source: PMID 17176492. Greater Response.
Pharmacogenomics
Antidepressant & Psychiatric Drug Response
Fluoxetine Response. Evidence: 5/10. Source: PMID 27660918. Typical Response.
Adverse Drug Reactions
Drug-Induced Depression. Evidence: 5/10. Source: PMID 39768746. Typical Severity.
Showing effects for G/T genotype
Anxiety and Neuroticism. Evidence: 4/10. Source: PMID 17176492. Typical Risk.
ADHD Susceptibility. Evidence: 4/10. Source: PMID 16116490. Typical Risk.
Placebo Response. Evidence: 3/10. Source: PMID 17176492. Typical Response.
Showing effects for T/T genotype
Anxiety and Neuroticism. Evidence: 4/10. Source: PMID 17176492. Lower Risk.
ADHD Susceptibility. Evidence: 4/10. Source: PMID 16116490. Lower Risk.
Fluoxetine Response. Evidence: 5/10. Source: PMID 27660918. Stronger Response.
Drug-Induced Depression. Evidence: 5/10. Source: PMID 39768746. Increased Severity.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Emotional processing in the brain is highly sensitive to serotonin levels, which are regulated by the TPH2 gene. Having two copies of the G allele is linked to higher levels of harm avoidance and neuroticism. Research suggests this genetic profile may increase susceptibility to panic disorder and post-stroke anxiety. Children carrying this genotype also show a higher rate of transmission in attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Interestingly, clinical trials have identified this group as having a significantly higher placebo response, showing greater anxiety symptom improvement even when given inactive treatments. This heightened sensitivity to expectation highlights the complex role of serotonin in shaping both emotional vulnerability and therapeutic response.
Higher scores on anxiety-related personality traits; Increased risk of ADHD and OCD transmission; Stronger clinical placebo response.
Sample genotype: GT (Heterozygous)
Balanced serotonin synthesis supports stable communication between the brainstem and emotional processing centers. Individuals with the G/T genotype exhibit typical levels of neuroticism, harm avoidance, and general anxiety. Cognitive control processes, such as response inhibition and working memory, also function at a standard baseline level. While some studies suggest intermediate emotional reactivity, the overall psychiatric risk remains comparable to the general population. Response to selective serotonin reuptake inhibitors (SSRIs) like fluoxetine is typical, without the heightened sensitivity seen in other genotypes. This genetic profile provides a stable, average foundation for emotional and cognitive processing.
Typical baseline anxiety and neuroticism levels; Standard cognitive control and working memory; Typical response to SSRI antidepressants.
Sample genotype: TT (Homozygous)
Serotonin synthesis pathways are optimized for emotional resilience in individuals with this genotype. Carrying two T alleles is associated with significantly lower levels of neuroticism, anxiety, and impulsivity. Clinical studies show that pediatric patients with this profile experience a significantly better response to the SSRI fluoxetine. However, this genotype may also carry unique vulnerabilities under specific environmental or chemical stressors. For instance, individuals taking certain HIV medications, such as efavirenz or atazanavir, have shown an increased severity of depressive symptoms. Additionally, some research suggests a higher risk of depressive symptoms following severe, stressful life events. Overall, this profile offers strong natural protection against everyday anxiety and standard psychiatric conditions.
Lower levels of anxiety and neuroticism; Better therapeutic response to fluoxetine; Increased depression risk under specific HIV medications.
Variants with shared genetic architecture
rs1843809 · TPH2 Gene · Chr 12 · ADHD and Mood Regulation
rs4290270 · TPH2 Gene · Chr 12 · Mood and Addiction Risk
rs7305115 · TPH2 Gene · Chr 12 · Suicidal Behavior Risk
Content updated August 2026.
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