A strong link between estradiol and dopamine (DA) neurotransmission, which is regulating cognitive and affective pathways, has been provided by animal studies.

Catechol-O-methyltransferase (COMT) enzyme activity, which degrades DA and Noradrenaline, is influenced by a single nucleotide polymorphism (COMTVal158Met). This variation has been reported to be related to both executive and emotional functions.

To investigate whether the physiologically high estradiol levels during pregnancy affect emotional processing in relation to COMTVal158Met genotype.

To test the hypothesis that the Val/Val genotype, associated with high COMT enzyme activity and therefore decreased DA signalling, shows a different startle response compared to the other COMTVal158Met genotypes, in the presence of an enhancer of DAergic neurotransmission, such as estradiol.

Seventy-eight pregnant women were assessed at gestational week 38 for startle response, measured by eye blink, during control condition, positive and negative anticipation stimuli and pleasant and unpleasant image stimuli. A blood sample was used for measurement of hormonal levels and genetic analyses. Personality traits (SSP), depression (MADRS) and anxiety (STAI) symptoms were also investigated.

COMTVal158Met heterozygote women (N = 29) scored the lowest in overall startle response magnitude (p < 0.05). No difference was observed between homozygous women with regard to the Met (N = 23) and Val alleles (N = 22). No significant difference by genotype was found in affective modulation, depression or anxiety scores.

Enhancement of DA signalling by estradiol might result in a U-shaped response curve, as has been shown with regard to administration of amphetamine, in relation the COMTVal158Met polymorphism.