Perinatal Nutrition and Programmed Risk for Neuropsychiatric Disorders: A Focus on Animal Models.

Maternal nutrition is critically important for fetal development. Recent human studies demonstrate a strong connection between diet during pregnancy and offspring risk for neuropsychiatric disorders including depression, anxiety, and attention-deficit/hyperactivity disorder. Animal models have emerged as a crucial tool for understanding maternal nutrition's contribution to prenatal programming and the later development of neuropsychiatric disorders. This review highlights preclinical studies examining how maternal consumption of the three macronutrients (protein, fats, and carbohydrates) influence offspring negative-valence behaviors relevant to neuropsychiatric disorders. We highlight the translational aspects of animal models and so examine exposure periods that mirror the neurodevelopmental stages of human gestation. Because of our emphasis on programmed changes in neurobehavioral development, studies that continue diet exposure until assessment in adulthood are not discussed. The presented research provides a strong foundation of preclinical evidence of nutritional programming of neurobehavioral impairments. Alterations in risk assessment and response were observed alongside neurodevelopmental impairments related to neurogenesis, synaptogenesis, and synaptic plasticity. To date, the large majority of studies utilized rodent models, and the field could benefit from additional study of large-animal models. Additional future directions are discussed, including the need for further studies examining how sex as a biological variable affects the contribution of maternal nutrition to prenatal programming.

Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates.

Nutritional status influences brain health and gestational exposure to metabolic disorders (e.g. obesity and diabetes) increases the risk of neuropsychiatric disorders. The aim of the present study was to further investigate the role of maternal Western-style diet (WSD), metabolic state, and inflammatory factors in the programming of Japanese macaque offspring behavior. Utilizing structural equation modeling, we investigated the relationships between maternal diet, prepregnancy adiposity, third trimester insulin response, and plasma cytokine levels on 11-month-old offspring behavior. Maternal WSD was associated with greater reactive and ritualized anxiety in offspring. Maternal adiposity and third trimester macrophage-derived chemokine (MDC) exerted opposing effects on offspring high-energy outbursts. Elevated levels of this behavior were associated with low maternal MDC and increased prepregnancy adiposity. This is the first study to show that maternal MDC levels influence offspring behavior. We found no evidence suggesting maternal peripheral inflammatory response mediated the effect of maternal diet and metabolic state on aberrant offspring behavior. Additionally, the extent of maternal metabolic impairment differentially influenced chemokine response. Elevated prepregnancy adiposity suppressed third trimester chemokines, while obesity-induced insulin resistance augmented peripheral chemokine levels. WSD also directly increased maternal interleukin-12. This is the first non-human primate study to delineate the effects of maternal diet and metabolic state on gestational inflammatory environment and subsequent offspring behavior. Our findings give insight to the complex mechanisms by which diet, metabolic state, and inflammation during pregnancy exert unique influences on offspring behavioral regulation.

Exposure to a High-Fat Diet during Early Development Programs Behavior and Impairs the Central Serotonergic System in Juvenile Non-Human Primates.

Perinatal exposure to maternal obesity and high-fat diet (HFD) consumption not only poses metabolic risks to offspring but also impacts brain development and mental health. Using a non-human primate model, we observed a persistent increase in anxiety in juvenile offspring exposed to a maternal HFD. Postweaning HFD consumption also increased anxiety and independently increased stereotypic behaviors. These behavioral changes were associated with modified cortisol stress response and impairments in the development of the central serotonin synthesis, with altered tryptophan hydroxylase-2 mRNA expression in the dorsal and median raphe. Postweaning HFD consumption decreased serotonergic immunoreactivity in area 10 of the prefrontal cortex. These results suggest that perinatal exposure to HFD consumption programs development of the brain and endocrine system, leading to behavioral impairments associated with mental health and neurodevelopmental disorders. Also, an early nutritional intervention (consumption of the control diet at weaning) was not sufficient to ameliorate many of the behavioral changes, such as increased anxiety, that were induced by maternal HFD consumption. Given the level of dietary fat consumption and maternal obesity in developed nations these findings have important implications for the mental health of future generations.