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Balancing act: Neural correlates of affect dysregulation in youth depression and substance use - A systematic review of functional neuroimaging studies.

ABSTRACT: Both depression and substance use problems have their highest incidence during youth (i.e., adolescence and emerging adulthood), and are characterized by emotion regulation deficits. Influential neurodevelopmental theories suggest that alterations in the function of limbic and frontal regions render youth susceptible to these deficits. However, whether depression and substance use in youth are associated with similar alterations in emotion regulation neural circuitry is unknown. In this systematic review we synthesized the results of functional magnetic resonance imaging (fMRI) studies investigating the neural correlates of emotion regulation in youth depression and substance use. Resting-state fMRI studies focusing on limbic connectivity were also reviewed. While findings were largely inconsistent within and between studies of depression and substance use, some patterns emerged. First, youth depression appears to be associated with exaggerated amygdala activity in response to negative stimuli; second, both depression and substance use appear to be associated with lower functional connectivity between the amygdala and prefrontal cortex during rest. Findings are discussed in relation to support for existing neurodevelopmental models, and avenues for future work are suggested, including studying neurodevelopmental trajectories from a network perspective.

SUBMITTER: Rakesh D

PROVIDER: S-EPMC7139159 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Balancing act: Neural correlates of affect dysregulation in youth depression and substance use - A systematic review of functional neuroimaging studies.

Rakesh Divyangana D Allen Nicholas B NB Whittle Sarah S

Developmental cognitive neuroscience 20200313

Both depression and substance use problems have their highest incidence during youth (i.e., adolescence and emerging adulthood), and are characterized by emotion regulation deficits. Influential neurodevelopmental theories suggest that alterations in the function of limbic and frontal regions render youth susceptible to these deficits. However, whether depression and substance use in youth are associated with similar alterations in emotion regulation neural circuitry is unknown. In this systemat ...[more]

PMID: 32452461

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Project description:Depression and insulin resistance are becoming increasingly prevalent in younger populations. The origin and consequence of insulin resistance in depressed youth may, in part, be rooted in exposure to environmental stressors, such as early life abuse, that may lead to aberrant brain motivational networks mediating maladaptive food-seeking behaviors and insipient insulin resistance. In this paper, we aimed to investigate the impact of early life abuse on the development of insulin resistance in depressed and overweight youth aged 9 to 17 years. We hypothesized that youth with the greatest burden of early life abuse would have the highest levels of insulin resistance and corresponding aberrant reward network connectivities. To test this hypothesis, we evaluated sixty-nine depressed and overweight youth aged 9 to 17, using multimodal assessments of early life abuse, food-seeking behavior, and insulin resistance. Based on results of the Childhood Trauma Questionnaire (CTQ), we separated our study participants into two groups: 35 youth who reported high levels of the sum of emotional, physical, or sexual abuse and 34 youth who reported insignificant or no levels of any abuse. Results of an oral glucose tolerance test (OGTT) and resting state functional connectivity (RSFC), using the amygdala, insula, and nucleus accumbens (NAcc) as seed-based reward network regions of interest, were analyzed for group differences between high abuse and low abuse groups. High abuse youth exhibited differences from low abuse youth in amygdala-precuneus, NAcc-paracingulate gyrus, and NAcc-prefrontal cortex connectivities, that correlated with levels of abuse experienced. The more different their connectivity from of that of low abuse youth, the higher were their fasting glucose and glucose at OGTT endpoint. Importantly, level of abuse moderated the relation between reward network connectivity and OGTT glucose response. In contrast, low abuse youth showed hyperinsulinemia and more insulin resistance than high abuse youth, and their higher OGTT insulin areas under the curve correlated with more negative insula-precuneus connectivity. Our findings suggest distinct neural and endocrine profiles of youth with depression and obesity based on their histories of early life abuse.

Project description:IntroductionHigh comorbidity among pediatric disorders characterized by behavioral and emotional dysregulation poses problems for diagnosis and treatment, and suggests that these disorders may be better conceptualized as dimensions of abnormal behaviors. Furthermore, identifying neuroimaging biomarkers related to dimensional measures of behavior may provide targets to guide individualized treatment. We aimed to use functional neuroimaging and pattern regression techniques to determine whether patterns of brain activity could accurately decode individual-level severity on a dimensional scale measuring behavioural and emotional dysregulation at two different time points.MethodsA sample of fifty-seven youth (mean age: 14.5 years; 32 males) was selected from a multi-site study of youth with parent-reported behavioral and emotional dysregulation. Participants performed a block-design reward paradigm during functional Magnetic Resonance Imaging (fMRI). Pattern regression analyses consisted of Relevance Vector Regression (RVR) and two cross-validation strategies implemented in the Pattern Recognition for Neuroimaging toolbox (PRoNTo). Medication was treated as a binary confounding variable. Decoded and actual clinical scores were compared using Pearson's correlation coefficient (r) and mean squared error (MSE) to evaluate the models. Permutation test was applied to estimate significance levels.ResultsRelevance Vector Regression identified patterns of neural activity associated with symptoms of behavioral and emotional dysregulation at the initial study screen and close to the fMRI scanning session. The correlation and the mean squared error between actual and decoded symptoms were significant at the initial study screen and close to the fMRI scanning session. However, after controlling for potential medication effects, results remained significant only for decoding symptoms at the initial study screen. Neural regions with the highest contribution to the pattern regression model included cerebellum, sensory-motor and fronto-limbic areas.ConclusionsThe combination of pattern regression models and neuroimaging can help to determine the severity of behavioral and emotional dysregulation in youth at different time points.

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Balancing act: Neural correlates of affect dysregulation in youth depression and substance use - A systematic review of functional neuroimaging studies.

Publications

Balancing act: Neural correlates of affect dysregulation in youth depression and substance use - A systematic review of functional neuroimaging studies.

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