Evaluating the effect of birth weight on brain volumes and depression: An observational and genetic study using UK Biobank cohort

Abstract

Background. Birth weight influences not only brain development, but also mental health outcomes, including depression, but the underlying mechanism is unclear. Methods. The phenotypic data of 12,872–91,009 participants (59.18–63.38% women) from UK Biobank were included to test the associations between the birth weight, depression, and brain volumes through the linear and logistic regression models. As birth weight is highly heritable, the polygenic risk scores (PRSs) of birth weight were calculated from the UK Biobank cohort (154,539 participants, 56.90% women) to estimate the effect of birth weight-related genetic variation on the development of depression and brain volumes. Finally, the mediation analyses of step approach and mediation analysis were used to estimate the role of brain volumes in the association between birth weight and depression. All analyses were conducted sex stratified to assess sex-specific role in the associations. Result. We observed associations between birth weight and depression (odds ratio [OR] = 0.968, 95% confidence interval [CI] = 0.957–0.979, p = 2.29 × 10−6). Positive associations were observed between birth weight and brain volumes, such as gray matter (B = 0.131, p = 3.51 × 10−74) and white matter (B = 0.129, p = 1.67 × 10−74). Depression was also associated with brain volume, such as left thalamus (OR = 0.891, 95% CI = 0.850–0.933, p = 4.46 × 10−5) and right thalamus (OR = 0.884, 95% CI = 0.841–0.928, p = 2.67 × 10−5). Additionally, significant mediation effects of brain volume were found for the associations between birth weight and depression through steps approach and mediation analysis, such as gray matter (B = –0.220, p = 0.020) and right thalamus (B = –0.207, p = 0.014). Conclusions. Our results showed the associations among birth weight, depression, and brain volumes, and the mediation effect of brain volumes also provide evidence for the sex-specific of associations.

The Transition From Maternity Blues to Full-Blown Perinatal Depression: Results From a Longitudinal Study

“…Moreover, frequently women with MB tend not to start or discontinue breastfeeding very early and have a significantly reduced interaction with the newborn ( 28 , 29 ). All studies converge on the fact that, if untreated, MB symptoms can have serious consequences on women's and infants' mental health ( 30 , 31 ).…”

Spectral clustering based on structural magnetic resonance imaging and its relationship with major depressive disorder and cognitive ability

“…Some studies also reported lower surface areas in lingual, fusiform, parahippocampal gyrii (Couvy-Duchesne et al, 2018) and subcallosal regions (Wei et al, 2020), as well as cortical volume reduction in prefronal cortex, orbitalfrontal cortex (Grieve et al, 2013), subcallosal regions (Wei et al, 2020), temporal pole, insula lobe (Amidfar et al, 2020) and subgenual anterior cingulate cortex (Niida et al, 2019). Although some research indicated MDD-related reduction in thalamus (Schmaal et al, 2016;Webb et al, 2014;Ye et al, 2020), amygdala (Qi et al, 2018) and hippocampus (Nugent et al, 2013), the MDD case-control volumetric differences in subcortical regions have been found to be insignificant in some other studies (Bos et al, 2018;Shen et al, 2017). Furthermore, white matter microstructure (Chen et al, 2017;Shen et al, 2017;van Velzen et al, 2020), functional connectivity (Qiao et al, 2020;Ran et al, 2020) and abnormalities were also found in MDD patients.…”

Sex-specific effects of Birth Weight on Longitudinal Behavioural Outcomes; a Mendelian Randomisation Approach using Polygenic Scores

“…The neurobiological mechanisms underlying sex-differences in aggression related to BW are not elucidated by this study or to our knowledge any study; however, fetal neurodevelopment differs by offspring sex [48–50] and is in turn affected by BW [51]. A study from the UK biobank suggested that BW-PGS and measured BW affected adult depression through various brain regions, and that these effects differed by offspring sex [52]. Similarly, a recent study found that caudate nucleus volumes in neonates had opposite associations to polygenic scores for adult depression providing evidence for sex-dimorphic relationships between fetal development and mental health [53].…”