The role of maternal obesity in the risk of neuropsychiatric disorders

Abstract

Recent evidence indicates that perinatal exposure to maternal obesity, metabolic disease, including diabetes and hypertension, and unhealthy maternal diet has a long-term impact on offspring behavior and physiology. During the past three decades, the prevalence of both obesity and neuropsychiatric disorders has rapidly increased. Epidemiologic studies provide evidence that maternal obesity and metabolic complications increase the risk of attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, anxiety, depression, schizophrenia, eating disorders (food addiction, anorexia nervosa, and bulimia nervosa), and impairments in cognition in offspring. Animal models of maternal high-fat diet (HFD) induced obesity also document persistent changes in offspring behavior and impairments in critical neural circuitry. Animals exposed to maternal obesity and HFD consumption display hyperactivity, impairments in social behavior, increased anxiety-like and depressive-like behaviors, substance addiction, food addiction, and diminished cognition. During development, these offspring are exposed to elevated levels of nutrients (fatty acids, glucose), hormones (leptin, insulin), and inflammatory factors (C-reactive protein, interleukin, and tumor necrosis factor). Such factors appear to permanently change neuroendocrine regulation and brain development in offspring. In addition, inflammation of the offspring brain during gestation impairs the development of neural pathways critical in the regulation of behavior, such as serotoninergic, dopaminergic, and melanocortinergic systems. Dysregulation of these circuits increases the risk of mental health disorders. Given the high rates of obesity in most developed nations, it is critical that the mechanisms by which maternal obesity programs offspring behavior are thoroughly characterized. Such knowledge will be critical in the development of preventative strategies and therapeutic interventions.

Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the Pregnancy and Childhood Epigenetics (PACE) consortium

“…Before adjustment for cell-counts, lambdas (k), a measure of Pvalue inflation, were generally high and QQ plots showed inflation of P-values in most cohorts (Table 2, Supplementary Material, Table S2 and Supplementary Figures pages [2][3][4][5].…”

“…The criteria for evidence of an intrauterine effect were, in the mutually adjusted models, 1) maternal BMI and paternal BMI show the same direction of association with offspring methylation (i.e. paternal BMI is not having an independent effect in the opposite direction to the effect of maternal BMI), 2) the magnitude of association with offspring methylation is larger for maternal BMI than for paternal BMI, 3) there is evidence of heterogeneity (an I 2 value >40) in a metaanalysis of the maternal and paternal mutually-adjusted estimates. We also calculated heterogeneity P-values between the mutually adjusted maternal and paternal BMI estimates using the metafor R package (91).…”

“…Maternal obesity in pregnancy is also associated with other offspring outcomes, including neurodevelopmental and respiratory outcomes (2)(3)(4)(5). These associations might be explained by shared mother-child genetic or postnatal environmental influences, or they could also reflect a causal intrauterine mechanism leading to early programming of adverse health in the offspring (6).…”

Parental Obesity and Early Childhood Development

“…1 Concerns have risen that prepregnancy obesity may be adversely associated with childhood neurodevelopment. 2,3 Potential mechanisms include exposure to inflammation during prenatal brain development, adipokine dysregulation, micronutrient insufficiency, hyperglycemia, and abnormal development of the serotonin system. 2,4 Evidence regarding the role of maternal obesity on childhood neurodevelopment was recently reviewed.…”

Long-term Cognitive Implications of Intrauterine Hyperglycemia in Adolescent Offspring of Women With Type 1 Diabetes (the EPICOM Study)

“…These processes are known to be vulnerable to a large number of adverse environmental factors associated with an increased risk of neurological and psychiatric disorders in later life (11)(12)(13)(14)(15)(16).…”