Toxicant exposure and the developing brain: A systematic review of the structural and functional MRI literature.

Youth worldwide are regularly exposed to pollutants and chemicals (i.e., toxicants) that may interfere with healthy brain development, and a surge in MRI research has begun to characterize the neurobiological consequences of these exposures. Here, a systematic review following PRISMA guidelines was conducted on developmental MRI studies of toxicants with known or suspected neurobiological impact. Associations were reviewed for 9 toxicant classes, including metals, air pollution, and flame retardants. Of 1264 identified studies, 46 met inclusion criteria. Qualitative synthesis revealed that most studies: (1) investigated air pollutants or metals, (2) assessed exposures prenatally, (3) assessed the brain in late middle childhood, (4) took place in North America or Western Europe, (5) drew samples from existing cohort studies, and (6) have been published since 2017. Given substantial heterogeneity in MRI measures, toxicant measures, and age groups assessed, more research is needed on all toxicants reviewed here. Future studies should also include larger samples, employ personal exposure monitoring, study independent samples in diverse world regions, and assess toxicant mixtures.

Reduced cortical surface area globally and in reward-related cortex is associated with elevated depressive symptoms in preschoolers.

BACKGROUND: Elevated depressive symptoms in early childhood strongly predict depression onset in youth. Nevertheless, little is known about the neural correlates of these symptoms, information that is key for understanding the early development of depression. As a result, the present study conducted a novel investigation of the association between cortical structure and depressive symptoms in preschoolers. METHODS: Forty-six preschool age children (Mage = 5.90, SD = 0.75), some (N = 15) at high risk for depression, participated in the study. Data included parent-report of child depressive symptoms and measures of child whole brain and regional cortical structure acquired via 3T MRI. RESULTS: After adjustment for maternal depression, socio-economic status, child age, child sex, and intracranial volume, reduced total cortical surface area and reduced surface area of the lateral orbitofrontal cortex were associated with elevated depressive symptoms. Cortical thickness was not associated with depressive symptoms. LIMITATIONS: The present data are cross-sectional, limiting any causal interpretations. CONCLUSIONS: Results suggest that reduced cortical surface area, rather than thickness, is a neural correlate of depressive symptoms in preschoolers. Findings highlight the importance of surface area in reward processing regions (i.e., lateral orbitofrontal cortex) in particular. The present results provide novel insight into early emerging associations between brain structure and features of depression in young children and underscore early childhood as an important developmental period for understanding depression.

Stress-induced cortisol response is associated with right amygdala volume in early childhood.

Rodent research suggests that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and the resulting cortisol stress response can alter the structure of the hippocampus and amygdala. Because early-life changes in brain structure can produce later functional impairment and potentially increase risk for psychiatric disorder, it is critical to understand the relationship between the cortisol stress response and brain structure in early childhood. However, no study to date has characterized the concurrent association between cortisol stress response and hippocampal and amygdala volume in young children. In the present study, 42 young children (M age  = 5.97, SD = 0.76), completed a frustration task and cortisol response to stress was measured. Children also underwent magnetic resonance imaging (MRI), providing structural scans from which their hippocampal and amygdala volumes were extracted. Greater cortisol stress response was associated with reduced right amygdala volume, controlling for whole brain volume, age, sex, and number of cortisol samples. There were no significant associations between cortisol stress response and bilateral hippocampus or left amygdala volumes. The association between right amygdala volume and cortisol stress response raises the non-mutually exclusive possibilities that the function of the HPA axis may shape amygdala structure and/or that amygdala structure may shape HPA axis function. As both cortisol stress response and amygdala volume have been associated with risk for psychopathology, it is possible that the relationship between cortisol stress response and amygdala volume is part of a broader pathway contributing to psychiatric risk.

Like me Back: Neural Correlates of Low Perceived Relational Value in Peer Victimized Youth.

Perceived relational value describes the extent to which individuals consider themselves to be liked and valued. Given the salience of peer opinions in adolescence, perceived relational value is an important part of adolescents' developing self-concept. Here, we examined the neural correlates of youth's perceptions of their relational value in two independent samples (N = 33, Mage  = 13.71, SD = 2.71; N = 26, Mage  = 15.43, SD = 0.33). In both studies, peer victimization was associated with lower perceived relational value behaviorally and with altered frontostriatal connectivity when perceiving low relational value during fMRI. Our results suggest that peer victimization may lead youth to become biased about how they will be perceived socially and may disrupt connectivity between brain regions involved in responding to appetitive social stimuli.

The depressogenic potential of added dietary sugars.

Added sugars are ubiquitous in contemporary Western diets. Although excessive sugar consumption is now robustly associated with an array of adverse health consequences, comparatively little research has thus far addressed its impact on the risk of mental illness. But ample evidence suggests that high-dose sugar intake can perturb numerous metabolic, inflammatory, and neurobiological processes. Many such effects are of particular relevance to the onset and maintenance of depressive illness, among them: systemic inflammation, gut microbiota disruption, perturbed dopaminergic reward signaling, insulin resistance, oxidative stress, and the generation of toxic advanced glycation end-products (AGEs). Accordingly, we hypothesize that added dietary sugars carry the potential to increase vulnerability to major depressive disorder, particularly at high levels of consumption. The present paper: (a) summarizes the existing experimental and epidemiological research regarding sugar consumption and depression vulnerability; (b) examines the impact of sugar ingestion on known depressogenic physiological processes; and (c) outlines the clinical and theoretical implications of the apparent sugar-depression link. We conclude that the extant literature supports the hypothesized depressogenic impact of added dietary sugars, and propose that an improved understanding of the effects of sugar on body and mind may aid in the development of novel therapeutic and preventative measures for depression.

Hungry for inclusion: Exposure to peer victimization and heightened social monitoring in adolescent girls.

Belonging to a social group is one of the most important factors contributing to well-being. The Belonging Regulation model proposes that humans possess a social monitoring system (SMS) that evaluates social inclusion and monitors belonging needs. Here, we used a prospective longitudinal design to examine links between peer victimization experienced across 7 years and social monitoring at the behavioral and neural level in adolescent girls (n = 38, Mage = 15.43 years, SD = .33). Participants completed a social evaluation task during a functional magnetic resonance imaging (fMRI) scan. More severe peer victimization was associated with increased activation to in-group versus out-group peers in the amygdala, ventral striatum, fusiform gyrus, and temporoparietal junction. Moreover, participants who displayed increased activation in these regions reported lower social self esteem and higher levels of internalizing and externalizing symptoms. These results suggest that exposure to peer victimization across the school years is associated with heightened social monitoring at the neural level during adolescence, which has potential adverse implications for girls' adjustment and well-being.

Adolescents' behavioral and neural responses to e-cigarette advertising.

Although adolescents are a group heavily targeted by the e-cigarette industry, research in cue-reactivity has not previously examined adolescents' behavioral and neural responses to e-cigarette advertising. This study addressed this gap through two experiments. In Experiment One, adult traditional cigarette smokers (n = 41) and non-smokers (n = 41) answered questions about e-cigarette and neutral advertising images. The 40 e-cigarette advertising images that most increased desire to use the product were matched to 40 neutral advertising images with similar content. In Experiment Two, the 80 advertising images selected in Experiment One were presented to adolescents (n = 30) during an functional magnetic resonance imaging brain scan. There was a range of traditional cigarette smoking across the sample with some adolescents engaging in daily smoking and others who had never smoked. Adolescents self-reported that viewing the e-cigarette advertising images increased their desire to smoke. Additionally, all participants regardless of smoking statuses showed significantly greater brain activation to e-cigarette advertisements in areas associated with cognitive control (left middle frontal gyrus), reward (right medial frontal gyrus), visual processing/attention (left lingual gyrus/fusiform gyrus, right inferior parietal lobule, left posterior cingulate, left angular gyrus) and memory (right parahippocampus, left insula). Further, an exploratory analysis showed that compared with age-matched non-smokers (n = 7), adolescent smokers (n = 7) displayed significantly greater neural activation to e-cigarette advertising images in the left inferior temporal gyrus/fusiform gyrus, compared with their responses to neutral advertising images. Overall, participants' brain responses to e-cigarette advertisements suggest a need to further investigate the long-run impact of e-cigarette advertising on adolescents.

Disrupted amygdala-prefrontal connectivity during emotion regulation links stress-reactive rumination and adolescent depressive symptoms.

Rumination in response to stress (stress-reactive rumination) has been linked to higher levels of depressive symptoms in adolescents. However, no work to date has examined the neural mechanisms connecting stress-reactive rumination and adolescent depressive symptoms. The present work attempted to bridge this gap through an fMRI study of 41 adolescent girls (Mage=15.42, SD=0.33) - a population in whom elevated levels of depressive symptoms, rumination, and social stress sensitivity are displayed. During the scan, participants completed two tasks: an emotion regulation task and a social stress task. Using psychophysiological interaction (PPI) analyses, we found that positive functional connectivity between the amygdala and ventrolateral prefrontal cortex (VLPFC) during the emotion regulation task mediated the association between stress-reactive rumination and depressive symptoms. These results suggest that stress-reactive rumination may interfere with the expression and development of neural connectivity patterns associated with effective emotion regulation, which may contribute, in turn, to heightened depressive symptoms.