Maternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD

Abstract

Maternal prenatal anxiety is an important risk factor for altered child neurodevelopment but there is uncertainty concerning the biological mechanisms involved and sources of individual differences in children’s responses. We sought to determine the role of functional genetic variation in COMT, which encodes catechol-O-methyltransferase, in the association between maternal prenatal anxiety and child symptoms of ADHD and working memory. We used the prospectively-designed ALSPAC cohort (n = 6,969) for our primary data analyses followed by replication analyses in the PREDO cohort (n = 425). Maternal prenatal anxiety was based on self-report measures; child symptoms of ADHD were collected from 4–15 years of age; working memory was assessed from in-person testing at age 8 years; and genetic variation in COMT at rs4680 was determined in both mothers and children. The association between maternal prenatal anxiety and child attention/hyperactivity symptoms and working memory was moderated by the child’s rs4680 genotype, with stronger effects obtained for the val/val (G:G) genotype relative to val/met (A:G) (all p<0.01) and met/met (A:A) groups (all p<0.05). Similar findings were observed in the PREDO cohort where maternal prenatal anxiety interacted with child rs4680 to predict symptoms of ADHD at 3.5 years of age. The findings, from two cohorts, show a robust gene-environment interaction, which may contribute to inter-individual differences in the effects of maternal prenatal anxiety on developmental outcomes from childhood to mid-adolescence.

Sex Differences in Vulnerability to Prenatal Stress: a Review of the Recent Literature

“…Davis et al ( N  = 91) found no evidence of a sex-dependent association between maternal prenatal plasma cortisol concentrations and child (ages 6–9) cognitive functioning [33]. Finally, data from two independent cohorts ( N = 6969 and N  = 425) provided no evidence of sex dependence in an association between prenatal maternal anxiety and offspring working memory [23]. …”

“…Zhu et al ( N  = 1765) found a sex-specific association: Severe PNLEs were associated with increased odds of clinical ADHD symptoms in preschool boys but not girls [54]. In the ALSPAC data ( N  = 6969), there was a significant interaction of maternal anxiety and a COMT genetic variation in predicting child ADHD symptoms at age 4, but no evidence of sex dependence [23]. Finally, in the Rhea Study ( N  = 288), maternal psychopathology symptoms were associated with child ADHD symptoms, but there was no evidence of sex dependence [27].…”

Maternal depressive symptoms during and after pregnancy and child developmental milestones

“…Nevertheless, the prevalence of maternal antenatal antidepressant use in our sample corresponded to the general Finnish population (Malm et al., ), supporting the representativeness of our sample. On the other hand, while we focused on the effects of maternal depressive symptoms on child neurodevelopment, depression is highly comorbid with anxiety also in the perinatal period (Falah‐Hassani, Shiri, & Dennis, ), and maternal antenatal anxiety has also been shown to affect child neurodevelopment (Buss, Davis, Hobel, & Sandman, ; O'Donnell et al., ; Van den Bergh et al., ). Hence, further studies disentangling the unique effects of maternal depression and anxiety on child neurodevelopment are warranted.…”

Do mothers who are anxious during pregnancy have inattentive children?

“…Genetic variations in the coding of the enzyme catechol-Omethyltransferase (COMT), have been showed to influence the association between maternal prenatal anxiety, child ADHD symptoms and infant's working memory. COMT is involved in the breakdown of catecholamine neurotransmitters including dopamine, noradrenaline and adrenaline (O'Donnell et al, 2017).…”