High pregnancy anxiety during mid-gestation is associated with decreased gray matter density in 6–9-year-old children

Abstract

Summary Because the brain undergoes dramatic changes during fetal development it is vulnerable to environmental insults. There is evidence that maternal stress and anxiety during pregnancy influences birth outcome but there are no studies that have evaluated the influence of stress during human pregnancy on brain morphology. In the current prospective longitudinal study we included 35 women for whom serial data on pregnancy anxiety was available at 19 (±0.83), 25 (±0.9) and 31 (±0.9) weeks gestation. When the offspring from the target pregnancy were between six to nine years of age, their neurodevelopmental stage was assessed by a structural MRI scan. With the application of voxel based morphometry, we found regional reductions in gray matter density in association with pregnancy anxiety after controlling for total gray matter volume, age, gestational age at birth, handedness and postpartum perceived stress. Specifically, independent of postnatal stress, pregnancy anxiety at 19 weeks gestation was associated with gray matter volume reductions in the prefrontal cortex, the premotor cortex, the medial temporal lobe, the lateral temporal cortex, the postcentral gyrus as well as the cerebellum extending to the middle occipital gyrus and the fusiform gyrus. High pregnancy anxiety at 25 and 31 weeks gestation was not significantly associated with local reductions in gray matter volume. This is the first prospective study to show that a specific temporal pattern of pregnancy anxiety is related to specific changes in brain morphology. Altered gray matter volume in brain regions affected by prenatal maternal anxiety may render the developing individual more vulnerable to neurodevelopmental and psychiatric disorders as well as cognitive and intellectual impairment.

Intergenerational Transmission of Stress in Humans

“…Neuroimaging studies have primarily focused on changes in limbic structures responsive to stress and critical for emotion, including the prefrontal cortex and hippocampus. For instance, prenatal anxiety was reported to associate with offsprings' gray matter volume reductions in the prefrontal cortex at 6-9 years of age (Buss et al, 2010). A separate study similarly observed an effect of prenatal maternal anxiety on neonatal frontal cortical thickness that was moderated by functional variants of the catechol-O-methyltransferase (COMT) gene, which regulates catecholamine signaling and is implicated in anxiety, pain, and stress responsivity (Qiu et al, 2014).…”

Stress and the social brain: behavioural effects and neurobiological mechanisms

“…Developmental trajectories in the brain are strongly altered by prenatal stress or high pregnancy anxiety, which leads to grey matter volume reductions in several brain areas (prefrontal cortex (PFC), hippocampus and hypothalamus) in humans 90,91 and rodents [92][93][94] . Rodent studies suggest an important role for glucocorticoid-induced apoptosis in some of these effects 95 .…”

Determinants of cortisol during pregnancy – The ABCD cohort

“…A wealth of studies have shown that offspring of mothers with high levels of psychosocial stress, depression or anxiety are at increased risk for adverse neurodevelopmental outcomes, showing more internalizing and externalizing behavior problems (O'Connor et al 2002;O'Connor et al 2003;O'Donnell et al 2014) higher symptoms of depression (Pawlby et al 2009;Pearson et at 2013;Plant et al 2013) and alterations in biological systems such as brain morphology (Buss et al 2010) and epigenetic profiles (Oberlander et al 2016). Higher levels of cortisol during pregnancy have also been related to offspring IQ (LeWinn et al 2009), behavior and temperament (de Weerth et al 2013).…”