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Introduction: Prenatal growth impairment leads to higher preference for palatable foods in comparison to normal prenatal growth subjects, which can contribute to increased body fat mass and a higher risk for developing chronic diseases in small-for-gestational-age (SGA) individuals throughout life. This study aimed to investigate the effect of SGA on feeding behavior in children and adolescents, as well as resting-state connectivity between areas related to reward, self-control, and value determination, such as orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), amygdala and dorsal striatum (DS)., Methods: Caregivers and their offspring were recruited from two independent cohorts in Brazil (PROTAIA) and Canada (MAVAN). Both cohorts included anthropometric measurements, food choice tasks, and resting-state functional magnetic resonance imaging (fMRI) data., Results: In the Brazilian sample (17 ± 0.28 years, n=70), 21.4% of adolescents were classified as SGA. They exhibited lower monetary-related expenditure to buy a snack compared to controls in the food choice test. Decreased functional connectivity (n=40) between left OFC and left DL-PFC; and between right OFC and: left amygdala, right DS, and left DS were observed in the Brazilian SGA participants. Canadian SGA participants (14.9%) had non-significant differences in comparison with controls in a food choice task at 4 years old ( ± 0.01, n=315). At a follow-up brain scan visit (10.21 ± 0.140 years, n=49), SGA participants (28.6%) exhibited higher connectivity between the left OFC and left DL-PFC, also higher connectivity between the left OFC and right DL-PFC. We did not observe significant anthropometric neither nutrients' intake differences between groups in both samples., Conclusions: Resting-state fMRI results showed that SGA individuals had altered connectivity between areas involved in encoding the subjective value for available goods and decision-making in both samples, which can pose them in disadvantage when facing food options daily. Over the years, the cumulative exposure to particular food cues together with the altered behavior towards food, such as food purchasing, as seen in the adolescent cohort, can play a role in the long-term risk for developing chronic non-communicable diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dalle Molle, de Mendonça Filho, Minuzzi, Machado, Reis, Rodrigues, Mucellini, Franco, Buchweitz, Toazza, Bortoluzzi, Salum, Boscenco, Meaney, Levitan, Manfro and Silveira.)

Studies in rodents have shown that early life trauma leads to anxiety, increased stress responses to threatening situations, and modifies food intake in a new environment. However, these associations are still to be tested in humans. This study aimed to verify complex interactions among anxiety diagnosis, maternal care, and baseline cortisol on food intake in a new environment in humans. A community sample of 32 adolescents and young adults was evaluated for: psychiatric diagnosis using standardized interviews, maternal care using the Parental Bonding Inventory (PBI), caloric consumption in a new environment (meal choice at a snack bar), and salivary cortisol. They also performed a brain fMRI task including the visualization of palatable foods vs. neutral items. The study found a three-way interaction between anxiety diagnosis, maternal care, and baseline cortisol levels on the total calories consumed (snacks) in a new environment. This interaction means that for those with high maternal care, there were no significant associations between cortisol levels and food intake in a new environment. However, for those with low maternal care and who have an anxiety disorder (affected), cortisol was associated with higher food intake; whereas for those with low maternal care and who did not have an anxiety disorder (resilient), cortisol was negatively associated with lower food intake. In addition, higher anxiety symptoms were associated with decreased activation in the superior and middle frontal gyrus when visualizing palatable vs. neutral items in those reporting high maternal care. These results in humans mimic experimental research findings and demonstrate that a combination of anxiety diagnosis and maternal care moderate the relationship between the HPA axis functioning, anxiety, and feeding behavior in adolescents and young adults.

The goal of the present study was to investigate whether intrauterine growth restriction (IUGR) affects brain responses to palatable foods and whether docosahexaenoic acid (DHA, an omega-3 fatty acid that is a primary structural component of the human brain) serum levels moderate the association between IUGR and brain and behavioral responses to palatable foods. Brain responses to palatable foods were investigated using a functional magnetic resonance imaging task in which participants were shown palatable foods, neutral foods and non-food items. Serum DHA was quantified in blood samples, and birth weight ratio (BWR) was used as a proxy for IUGR. The Dutch Eating Behavior Questionnaire (DEBQ) was used to evaluate eating behaviors. In the contrast palatable food > neutral items, we found an activation in the right superior frontal gyrus with BWR as the most important predictor; the lower the BWR (indicative of IUGR), the greater the activation of this region involved in impulse control/decision making facing the viewing of palatable food pictures versus neutral items. At the behavioral level, a general linear model predicting external eating using the DEBQ showed a significant interaction between DHA and IUGR status; in IUGR individuals, the higher the serum DHA, the lower is external eating. In conclusion, we suggest that IUGR moderates brain responses when facing stimuli related to palatable foods, activating an area related to impulse control. Moreover, higher intake of n-3 PUFAs can protect IUGR individuals from developing inappropriate eating behaviors, the putative mechanism of protection would involve decreasing intake in response to external food cues in adolescents/young adults.