Interaction Effect of D4 Dopamine Receptor Gene and Serotonin Transporter Promoter Polymorphism on the Cortisol Stress Response

Genetic variation of the serotonin transporter (SCL6A4, 5-HTT) has been associated with fear- and anxiety-related behaviors. while a polymorphism in exon III of the D4 dopamine receptor gene (DRD4) has been linked to novelty seeking. The dopaminergic and the serotonergic neurotransmitter system have been found to modulate the amygdala-connected circuitries that are crucial in emotional modulation and response to fearful stimuli Additionally, reactivity of amygdala-innervated effector systems is also essential for our under-standing of anxiety-related behaviors Here, we used the stress-induced activation of the hypothalamic-pituitary-adrenal axis to investigate the impact of 5-HTTLPR and DRD4 on the cortisol stress response in 84 healthy adults. Saliva cortisol was measured during and after the Trier Social Stress Test We found a significant main effect of DRD4 Carriers of the 7R allele exhibited lower cortisol responses. Additionally, a DRD4 by 5-HTTLPR interaction emerged 5-HTTLPR L-A/L-A homozygotes showed a lower cortisol response than did S or L-G allele carriers but only if they possessed at least one copy of the DRD4 7R allele. The results point to independent and joint effects or these polymorphisms on stress responsivity.