Under typical conditions, medial prefrontal cortex (mPFC) connections with the amygdala are immature during childhood and become adult-like during adolescence. Rodent models show that maternal deprivation accelerates this development, prompting examination of human amygdala-mPFC phenotypes following maternal deprivation. Previously institutionalized youths, who experienced early maternal deprivation, exhibited atypical amygdalamPFC connectivity. Specifically, unlike the immature connectivity (positive amygdala-mPFC coupling) of comparison children, children with a history of early adversity evidenced mature connectivity (negative amygdala-mPFC coupling) and thus, resembled the adolescent phenotype. This connectivity pattern was mediated by the hormone cortisol, suggesting that stress-induced modifications of the hypothalamic-pituitary-adrenal axis shape amygdala-mPFC circuitry. Despite being age-atypical, negative amygdala-mPFC coupling conferred some degree of reduced anxiety, although anxiety was still significantly higher in the previously institutionalized group. These findings suggest that accelerated amygdala-mPFC development is an ontogenetic adaptation in response to early adversity.fMRI | emotion regulation | stress | neurodevelopment

Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. While tracing studies have suggested changes in amygdala-cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala-prefrontal circuitry across the ages of 4 to 22 years using task-based functional magnetic resonance imaging (fMRI). Results suggest positive amygdala-prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala-mPFC functional connectivity was significantly positive (greater than zero) among participants younger than ten, whereas functional connectivity was significantly negative (less than zero) among participants ten years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections.

Given the clinical and public health significance of substance disorders and the need to identify their early risk factors, we examined the association of childhood attention-deficit/hyperactivity disorder (ADHD) with substance use (e.g., nicotine, alcohol) and abuse/dependence outcomes (nicotine, alcohol, marijuana, cocaine, other). To strengthen a potential causal inference, we meta-analyzed longitudinal studies that prospectively followed children with and without ADHD into adolescence or adulthood. Children with ADHD were significantly more likely to have ever used nicotine and other substances, but not alcohol. Children with ADHD were also more likely to develop disorders of abuse/dependence for nicotine, alcohol, marijuana, cocaine, and other substances (i.e., unspecified). Sex, age, race, publication year, sample source, and version of the Diagnostic and Statistical Manual of Mental Disorders (DSM) used to diagnose ADHD did not significantly moderate the associations with substance outcomes that yielded heterogeneous effect sizes. These findings suggest that children with ADHD are significantly more likely to develop substance use disorders than children without ADHD and that this increased risk is robust to demographic and methodological differences that varied across the studies. Finally, few studies addressed ADHD and comorbid disruptive behavior disorders (DBD), thus preventing a formal meta-analytic review. However, we qualitatively summarize the results of these studies and conclude that comorbid DBD complicates inferences about the specificity of ADHD effects on substance use outcomes.

Functional connections (FC) between the amygdala and cortical and subcortical regions underlie a range of affective and cognitive processes. Despite the central role amygdala networks have in these functions, the normative developmental emergence of FC between the amygdala and the rest of the brain is still largely undefined. This study employed amygdala subregion maps and resting-state functional magnetic resonance imaging to characterize the typical development of human amygdala FC from age 4 to 23 years old (n = 58). Amygdala FC with subcortical and limbic regions was largely stable across this developmental period. However, three cortical regions exhibited age-dependent changes in FC: amygdala FC with the medial prefrontal cortex (mPFC) increased with age, while amygdala FC with a region including the insula and superior temporal sulcus decreased with age, and amygdala FC with a region encompassing the parahippocampal gyrus and posterior cingulate also decreased with age. The transition from childhood to adolescence (around age 10 years) marked an important change-point in the nature of amygdala-cortical FC. We distinguished unique developmental patterns of coupling for three amygdala subregions and found particularly robust convergence of FC for all subregions with the mPFC. These findings suggest that there are extensive changes in amygdala-cortical functional connectivity that emerge between childhood and adolescence.

Mature amygdala-prefrontal circuitry regulates affect in adulthood, but shows protracted development. In (semi-)altricial species, caregivers provide potent affect regulation when mature neurocircuitry is absent. This investigation examined a potential mechanism through which caregivers provide regulatory influences in childhood. Children, but not adolescents, showed evidence of maternal buffering, such that maternal stimuli suppressed amygdala reactivity. In the absence of maternal stimuli, children exhibited immature amygdala-prefrontal connectivity. However, in the presence of maternal stimuli, children displayed mature-like connectivity that resembled adolescents’ connectivity. Children showed improved affect-related regulation in the presence of their mother. Individual differences emerged, with maternal influence on amygdalaprefrontal circuitry associated with stronger mother-child relationships and maternal modulation of behavioral regulation. These findings suggest a neural mechanism through which caregivers modulate children's regulatory behavior by inducing mature-like connectivity and buffering against heightened reactivity. Maternal buffering in childhood, but not adolescence, suggests that childhood may be a sensitive period for amygdala-prefrontal development.

The misuse of stimulant medication among college students is a prevalent and growing problem. The purpose of this review and meta-analysis is to summarize the current research on rates and demographic and psychosocial correlates of stimulant medication misuse among college students, to provide methodological guidance and other ideas for future research, and to provide some preliminary suggestions for preventing and reducing misuse on college campuses. Random-effects meta-analysis found that the rate of stimulant medication misuse among college students was estimated at 17 % (95 % CI [0.13, 0.23], p < .001) and identified several psychological variables that differentiated misusers and nonusers, including symptoms of attention-deficit/hyperactivity disorder, problems associated with alcohol use, and marijuana use. A qualitative review of the literature also revealed that Greek organization membership, academic performance, and other substance use were associated with misuse. Students are misusing primarily for academic reasons, and the most common source for obtaining stimulant medication is peers with prescriptions. Interpretation of findings is complicated by the lack of a standard misuse definition as well as validated tools for measuring stimulant misuse. The relation between stimulant medication misuse and extra curricular participation, academic outcomes, depression, and eating disorders requires further investigation, as do the reasons why students divert or misuse and whether policies on college campuses contribute to the high rates of misuse among students. Future research should also work to develop and implement effective prevention strategies for reducing the diversion and misuse of stimulant medication on college campuses.

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