L2 Reading - Fetal Origins of Mental Health: The Developmental Origins of Health and Disease Hypothesis

overall findings

• hypothesis

• researchers proposes..

• models + takeaways

• challenges

• developmental origins of health + disease hypothesis suggests that intrauterine signals (fetal programming/developmental signals) affect fetal growth quality + lead to “program” tissue differentiation, leading to specifical health outcomes (increasing risk for later chronic illness + psychopathology)

• researchers propose that antenatal maternal adversity (hardships) affect biological pathways that influence fetal growth + neurodevelopment

• these models have little support because of weak to no associations between maternal anxiety, depression, stress & fetal growth

• compromised fetal development appears to result in a “meta-plastic” state that increases sensitivity to influences after birth

• challenges to the study of fetal origins of metal health: observational studies fail to consider underlying genetic factors + unclear if observed relationship b/w fetal growth and neurodevelopment have meaningful clinical relevance

what catalyzed the interest in fetal origins of chronic/non-communicable diseases?

• relation b/w birth weight + metabolic health

• broadly continuous relationship → as birth weight increases, risk for metabolic disease decreases (up till macrosomia/ normal birth weight)

how is DOHaD seen in psychiatry/psych + studies?

• in psychiatry/psych, early developmental influences are emphasized as determinants of mental health + human capacity

• DOHaD studies can show individual differences in vulnerability to adverse mental health outcomes

fetal origins of brain health

• fetal growth + psychopathology

• antenatal maternal mood + psychopathology

• fetal growth + psychopathology

  • birth weight used as proxy measure for fetal growth → low birth weight (<2.5 kg) + macrosomia (high BW) associated w increased risk of ADHD and other disorders (SZ, alcohol, drug use, anxiety, etc.) and exec function impairments (cognition + emotional difficulties)

  • epidemiological studies good at revealing associations → general conclusion that poor fetal growth = risk factor for various mental health disorders (poor specificity)

• antenatal (= during pregnancy) maternal mood + psychopathology

  • antenatal maternal emotional well-being (including mild symptoms of anxiety + depression) influences neurodevelopmental outcomes + infant temperament of offspring → important public health issue for all pregnant women and not just those diagnosed w mental illnesses

  • rodent models show that offspring of mothers exposed to prenatal stress show increased fearfulness + cognitive & socioemotional impairments → similar results in human children

antenatal “maternal” influences on neurodevelopment

• BW + brain structure

  • BW associated w cortical + moderately associated with HC volume, few studies on neural mechanisms

• antenatal maternal influences + brain structure

  • higher depressive symptoms in mother → greater functional connectivity b/w amygdala and emotion-regulation regions (patterns found in MDD) + also associated w cortical thinning in children

  • antenatal maternal anxiety associated w decrease gray matter volume

issues w fetal neurodevelopment studies

• results collected well after birth → imaging studies on older children may mean that prenatal influences on brain structure are confounded (affected) by postnatal experience

• but imaging right after birth reveals that antenatal maternal anxiety may result in variations in right lateralized clusters important for cognitive-emotional function that predict infant internalizing behaviour

• often based on few cross-sectional studies, need more longitudinal analysis + mechanistic studies

maternal glucocorticoid levels + fetal growth

• research suggests that maternal adversity (incl malnutrition, stressful events, increased anxiety/depression symptoms) may increase glucocorticoids + inflammatory cytokines, which may affect fetal growth → produce changes in neurodevelopment + influence child’s cognitive + MH later in life

challenges for DOHaD models of mental health

• the term “maternal adversity” → cannot always assume that there are common influences or underlying mechanisms (like how depression, anxiety, stress are associated w increased glucocorticoid levels, thus reducing BW + resulting outcomes) - conflicting data

• relation b/w maternal MH + birth outcomes → severe maternal stress + maternal anxiety/depression may be associated w lower BW, but moderate levels of anxiety/depression in nonclinical populations have no consistent effect on birth outcomes, especially in developed countries where there is greater access to resources

• antenatal glucocorticoid effects → antenatal glucocorticoid treatment may impact neurodevelopment of offspring, but these effects are very complex and vary greatly, depending on timing of treatment, unexpected specificity (unexpected brain-region effects) from hormones, and child gender

• genetic influences - links between maternal prenatal stress, BW, and child neurodevelopment may be influenced by genetics rather than just environmental factors - a child’s genotype moderates how prenatal conditions affect their brain (important to consider genetics into developmental models)

• clinical significance - unclear on the independent contribution of low BW or fetal growth on fetal neurodevelopment after controlling for socioeconomic and maternal circumstances, even though maternal MH predicts children’s MH + neurodevelopment

• meta-plasticity → paternal adversity (low BW, maternal stress) may increase a child’s sensitivity to env influences later (meta-plasticity) but does not predetermine a poor outcome → support + early-interventions may greatly improve outcomes