Diminished insulin sensitivity is associated with altered brain activation to food cues and with risk for obesity - Implications for individuals born small for gestational age.

While classically linked to memory, the hippocampus is also a feeding behavior modulator due to its multiple interconnected pathways with other brain regions and expression of receptors for metabolic hormones. Here we tested whether variations in insulin sensitivity would be correlated with differential brain activation following exposure to palatable food cues, as well as with variations in implicit food memory in a cohort of healthy adolescents, some of whom were born small for gestational age (SGA). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was positively correlated with activation in the cuneus, and negatively correlated with activation in the middle frontal lobe, superior frontal gyrus and precuneus when presented with palatable food images versus non-food images in healthy adolescents. Additionally, HOMA-IR and insulinemia were higher in participants with impaired food memory. SGA individuals had higher snack caloric density and greater chance for impaired food memory. There was also an interaction between the HOMA-IR and birth weight ratio influencing external eating behavior. We suggest that diminished insulin sensitivity correlates with activation in visual attention areas and inactivation in inhibitory control areas in healthy adolescents. Insulin resistance also associated with less consistency in implicit memory for a consumed meal, which may suggest lower ability to establish a dietary pattern, and can contribute to obesity. Differences in feeding behavior in SGA individuals were associated with insulin sensitivity and hippocampal alterations, suggesting that cognition and hormonal regulation are important components involved in their food intake modifications throughout life.

Early environmental influences on the development of children's brain structure and function.

The developing brain in utero and during the first years of life is highly vulnerable to environmental influences. Experiences occurring during this period permanently modify brain structure and function through epigenetic modifications (alterations of the DNA structure and chromatin function) and consequently affect the susceptibility to mental disorders. In this review, we describe evidence linking adverse environmental variation during early life (from the fetal period to childhood) and long-term changes in brain volume, microstructure, and connectivity, especially in amygdala and hippocampal regions. We also describe genetic variations that moderate the impact of adverse environmental conditions on child neurodevelopment, such as polymorphisms in brain-derived neurotrophic factor and catechol-O-methyltransferase genes, as well as genetic pathways related to glutamate and monoaminergic signaling. Lastly, we have depicted positive early life experiences that could benefit childhood neurodevelopment and reverse some detrimental effects of adversity in the offspring. WHAT THIS PAPER ADDS: Prenatal, peripartum, and postnatal adversities influence child behavior and neurodevelopment. Exposure to environmental enrichment and positive influences may revert these effects. Putative mechanisms involve alterations in neurotrophic factors and neurotransmitter systems. New tools/big data improved the understanding on how early adversity alters neurodevelopment. This permits better translation/application of the findings from animal models to humans.

INFLUENCIAS AMBIENTALES TEMPRANAS EN EL DESARROLLO DE LA ESTRUCTURA Y FUNCIÓN DEL CEREBRO DE LOS NIÑOS: El cerebro en desarrollo en el útero y durante los primeros años de vida es altamente vulnerable a las influencias ambientales. Las experiencias que se producen durante este período modifican permanentemente la estructura y función del cerebro a través de modificaciones epigenéticas (alteraciones de la estructura del ADN y la función de la cromatina) y, por consiguiente, afectan la susceptibilidad a los trastornos mentales. En esta revisión, describimos la evidencia que vincula la variación ambiental adversa durante la vida temprana (desde el período fetal hasta la infancia) y los cambios a largo plazo en el volumen cerebral, la microestructura y la conectividad, especialmente en las regiones de la amígdala y el hipocampo. También describimos variaciones genéticas que moderan el impacto de las condiciones ambientales adversas en el desarrollo neurológico infantil, como los polimorfismos en los genes del factor neurotrófico derivado del cerebro y de la catecol-O-metiltransferasa, así como las vías genéticas relacionadas con el glutamato y la señalización monoaminérgica. Por último, hemos descrito experiencias positivas de la vida temprana que podrían beneficiar el desarrollo neurológico infantil y revertir algunos efectos perjudiciales de la adversidad en la descendencia.

INFLUÊNCIAS AMBIENTAIS PRECOCES NO DESENVOLVIMENTO DA ESTRUTURA E FUNÇÃO CEREBRAL EM CRIANÇAS: O cérebro em desenvolvimento no útero e durante os primeiros anos devida é altamente vulnerável a influências ambientais. Experiências que ocorrem durante este período modificam permanentemente a estrutura e função cerebrais por meio de modificações epigenéticas (alterações da estrutura do DNA e função da cromatina). Consequentemente, afetam a suscetibilidade a desordens mentais. Nesta revisão, nós descrevemos a evidência relacionando variação ambiental adversa durante o início da vida (do período fetal à infância) e mudanças de longo prazo no volume, microestrutura e conectividade cerebral, especialmente nas regiões da amídala e hipocampo. Também descrevemos variações genéticas que moderam o impacto de condições ambientais adversas no neurodesenvolvimento infantil, tais como polimorfismos em fatores neurotróficos derivados do cérebro, e genes catechol-O-metiltransferases, assim como vias genéticas ligadas à sinalização por glutamato e momonoaminérgica. Por fim, descrevemos experiências precoces positivas que podem beneficiar o neurodesenvolvimento infantil e reverter alguns efeitos detrimentais da adversidade na prole.