Prenatal maternal depression and child serotonin transporter linked polymorphic region (5-HTTLPR) and dopamine receptor D4 (DRD4) genotype predict negative emotionality from 3 to 36 months

Abstract

Prenatal maternal depression and a multilocus genetic profile of two susceptibility genes implicated in the stress response were examined in an interaction model predicting negative emotionality (NE) in the first 3 years. In 179 mother-infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment cohort, prenatal depression (CES-D) was assessed at 24 to 36 weeks. The multilocus genetic profile score consisted of the number of susceptibility alleles from 5-HTTLPR (No L A (S/S, S/L G or L G /L G ) vs. any L A ) and Dopamine Receptor D4 (6-8R vs. 2-5R). NE was extracted from the IBQ-R at 3 and 6 months and the ECBQ at 18 and 36 months. Mixed and confirmatory regression analyses indicated that prenatal depression and the multilocus genetic profile interacted to predict NE from 3 to 36 months. Results were characterised by a differential susceptibility model at 3 and 6 months and by a diathesis stress model at 36 months. Negative emotionality (NE) is derived from the temperamental dimensions of sadness, distress towards limitations, fear and excessive reactions to minor changes, and reflects a generally stable tendency to show increased emotional reactivity towards negative situations (Gartstein & Rothbart, 2003;Lemery, Goldsmith, Klinnert, & Mrazek, 1999). NE is associated with the development of later problematic behaviour and psychopathology (Eisenberg et al., 2009;Fox, Henderson, Rubin, Calkins, & Schmidt, 2001;Hyde, Mezulis, & Abramson, 2008). For example, fearful temperament is associated with childhood anxiety disorders (Degnan, Alma, & Fox, 2010;Goldsmith & Lemery, 2000), while NE is associated with depression (Phillips, Lonigan, & Driscoll, 2002) and maladjustment (Eisenberg et al., 2009). Understanding early influences of NE on socio-emotional development (Davis, Glynn, Schetter, Hobel, Chicz-demet, & Sandman, 2007;Davis, Snidman, Glynn, Dunkel Schetter, & Sandman, 2004;Hayden et al., 2010;Hayden et al., 2007) could inform efforts at prevention and early intervention. Recent contradictory findings about the role of genetic and prenatal adversity (Braithwaite et al., 2013;, suggest the need for replication (Duncan, 2013) and modeling of genetic risk with multiple genes (Plomin, 2013). Accordingly, we present the findings from a study of the development of NE from 3 to 36 months of age from the interaction of prenatal maternal depression and a multilocus genetic profile. The Role of Prenatal Maternal StressPrenatal maternal stress, measured in diverse ways is associated with NE (Glover, 2011;O'Connor, Heron, & Glover, 2002a). For example, higher prenatal maternal cortisol is associated with fussier behaviour, more negative facial expressions, crying, as well as higher NE at 7 weeks of age (de Weerth, Hees, & Buitelaar, 2003). Symptoms of prenatal maternal anxiety and depression, loosely associated with the stress response predict behavioural reactivity at 4 months of age (Davis et al., 2004) and behavioural/emotional problems at 4 years of age (O'Connor, et al., 2002a). While most studi...

Alternating optimization for G × E modelling with weighted genetic and environmental scores: Examples from the MAVAN study.

“…In our original study on the prediction of NE (Green et al, 2016), we found that the G×E was consistent with the differential susceptibility model at 3 and 6 months and the diathesisstress model at 36 months (Belsky, 1997a, Belsky, 1997b. In the present study, we were unable to test the specific form of the interaction since our alternating optimization approach has not been yet adapted to work with the confirmatory modelling approach by Belsky et al (2013).…”

Prenatal programming of postnatal plasticity revisited—And extended

“…In turn, these epigenetic changes in placental 11β-HSD2 were themselves related to DNA methylation in the fetal brain as well as increases in fetal corticosterone levels (Peña et al, 2012). Furthermore, in humans, greater maternal anxiety measured 1 day prior to birth predicted lower gene expression of placental 11β-HSD2 (O'Donnell et al, 2012) and decreased activity of placental 11β-HSD2 is associated with early development, including fetal growth restriction (Börzsönyi et al, 2012), prematurity (Demendi et al, 2012), and low birthweight (Green et al, 2017).…”

Prenatal stress and enhanced developmental plasticity

“…Notably, the detected genetic moderation took the form of differential susceptibility -because when children with short alleles were exposed prenatally to high levels of maternal depression, they had the highest levels of dysregulation, but when exposed to lower or little prenatal depression, they had the lowest levels. Finally, a recent inquiry by Green et al (2017) revealed that prenatal depression measured mid-to late-pregnancy interacted with a polygenic profile score that was, in part, based on 5-HTTLPR in predicting infant negative temperament.…”