The environment that developing offspring experience during the perinatal period is markedly influenced by maternal health and diet composition. Evidence from both epidemiological studies and animal models indicates that maternal diet and metabolic status play a critical role in programming the neural circuitry that regulates behavior, resulting in long-term consequences for offspring behavior. Maternal diet and metabolic state influence the behavior of offspring directly by impacting the intrauterine environment and indirectly by modulating maternal behavior. The mechanisms by which maternal diet and metabolic profile shape the perinatal environment remain largely unknown, but recent research has found that increases in inflammatory cytokines, nutrients (glucose and fatty acids), and hormones (insulin and leptin) affect the environment of the developing offspring. Offspring exposed to maternal obesity and high fat diet consumption during development are more susceptible to developing mental health and behavioral disorders such as anxiety, depression, attention deficit hyperactivity disorder, and autism spectrum disorders. Recent evidence suggests that this increased risk for behavioral disorders is driven by modifications in the development of neural pathways involved in behavioral regulation. In particular, research indicates that the development of the serotonergic system is impacted by exposure to maternal obesity and high fat diet consumption, and this disruption may underlie many of the behavioral disturbances observed in these offspring. Given the high rates of obesity and high fat diet consumption in pregnant women, it is vital to examine the influence that maternal nutrition and metabolic profile have on the developing offspring.

The increased prevalence and high comorbidity of metabolic syndrome (MetS) and mental health disorders (MHDs) have prompted investigation into the potential contributing mechanisms. There is a bidirectional association between MetS and MHDs including schizophrenia, bipolar disorder, depression, anxiety, attention-deficit/hyperactivity disorder, and autism spectrum disorders. Medication side effects and social repercussions are contributing environmental factors, but there are a number of shared underlying neurological and physiological mechanisms that explain the high comorbidity between these two disorders. Inflammation is a state shared by both disorders, and it contributes to disruptions of neuroregulatory systems (including the serotonergic, dopaminergic, and neuropeptide Y systems) as well as dysregulation of the hypothalamic-pituitary-adrenal axis. MetS in pregnant women also exposes the developing fetal brain to inflammatory factors that predispose the offspring to MetS and psychopathologies. Due to the shared nature of these conditions, treatment should address aspects of both mental health and metabolic disorders. Additionally, interventions that can interrupt the transfer of increased risk of the disorders to the next generation need to be developed.

Affective response at 6 months of age may identify infants with familial history of ADHD, providing an early indicator of ADHD liability. These preliminary results provide a foundation for further studies and will be amplified by enlarging this cohort and following participants longitudinally to evaluate ADHD outcomes.

Maternal depressive symptoms during pregnancy are associated with risk for offspring emotional and behavioral problems, but the mechanisms by which this association occurs are not known. Infant elevated negative affect (increased crying, irritability, fearfulness, etc.) is a key risk factor for future psychopathology, so understanding its determinants has prevention and early intervention potential. An understudied yet promising hypothesis is that maternal mood affects infant mood via maternal prenatal inflammatory mechanisms, but this has not been prospectively examined in humans. Using data from a pilot study of women followed from the second trimester of pregnancy through six months postpartum (N = 68) our goal was to initiate a prospective study as to whether maternal inflammatory cytokines mediate the association between maternal depressive symptoms and infant offspring negative affect. The study sample was designed to examine a broad range of likely self-regulation and mood-regulation problems in offspring; to that end we over-selected women with a family history or their own history of elevated symptoms of attention-deficit/hyperactivity disorder. Results supported the hypothesis: maternal pro-inflammatory cytokines during the third trimester (indexed using a latent variable that included plasma interleukin-6, tumor necrosis factor-alpha and monocyte chemoattractant protein-1 concentrations as indicators) mediated the effect, such that higher maternal depressive symptoms were associated with higher maternal inflammation, and this mediated the effect on maternal report of infant negative affect (controlling for maternal affect during the infant period). This is the first human study to demonstrate that maternal inflammatory cytokines mediate the association between prenatal depression and infant outcomes, and the first to demonstrate a biological mechanism through which depressive symptoms impact infant temperament.

Maternal diet and metabolic state are important factors in determining the environment experienced during perinatal development. Epidemiological studies and evidence from animal models provide evidence that a mother’s diet and metabolic condition are important in programming the neural circuitry that regulates behavior, resulting in a persistent impact on the offspring’s behavior. Potential mechanisms by which maternal diet and metabolic profile influence the perinatal environment include placental dysfunction and increases in circulating factors such as inflammatory cytokines, nutrients (glucose and fatty acids) and hormones (insulin and leptin). Maternal obesity and high-fat diet (HFD) consumption exposure during development have been observed to increase the risk of developing serious mental health and behavioral disorders including anxiety, depression, attention deficit hyperactivity disorder and autism spectrum disorder. The increased risk of developing these behavioral disorders is postulated to be due to perturbations in the development of neural pathways that regulate behavior, including the serotonergic, dopaminergic and melanocortinergic systems. It is critical to examine the influence that a mother’s nutrition and metabolic profile have on the developing offspring considering the current and alarmingly high prevalence of obesity and HFD consumption in pregnant women.