Sex differences in emotion- and reward-related neural responses predicting increases in substance use in adolescence.

Adolescent substance use is a significant public health problem and there is a need for effective substance use preventions. To develop effective preventions, it is important to identify neurobiological risk factors that predict increases in substance use in adolescence and to understand potential sex differences in risk mechanisms. The present study used functional magnetic resonance imaging and hierarchical linear modeling to examine negative emotion- and reward-related neural responses in early adolescence predicting growth in substance use to middle adolescence in 81 youth, by sex. Adolescent neural responses to negative emotional stimuli and monetary reward receipt were assessed at age 12-14. Adolescents reported on substance use at age 12-14 and at 6 month, and 1, 2, and 3 year follow-ups. Adolescent neural responses did not predict initiation of substance use (yes/no), but, among users, neural responses predicted growth in substance use frequency. For girls, heightened right amygdala responses to negative emotional stimuli in early adolescence predicted growth in substance use frequency through middle adolescence. For boys, blunted left nucleus accumbens and bilateral ventromedial prefrontal cortex responses to monetary reward predicted growth in substance use frequency. Findings suggest different emotion and reward-related predictors of the development of substance use for adolescent girls versus boys.

Parent Stress and Trauma, Autonomic Responses, and Negative Child Behaviors.

Cumulative stress and trauma in parents may alter autonomic function. Both may negatively impact child behaviors, however these links have not been well established. We tested hypotheses that parent stress and trauma are associated with and interact with altered autonomic function during the toy wait task, an acute parent-child interaction challenge, to predict greater negative child behaviors. Sixty-eight parents and their 2-5 year old children were enrolled. More parent major and traumatic life events, and more parent recent life events coupled with increased heart rate and decreased heart rate variability (HRV), each related to more child disruptive/aggressive behavior. More major life and traumatic life events coupled with greater HRV predicted more child attention seeking behavior. Our novel approach to assessing parental life stress offers a unique perspective. Interventions mitigating parent stress and regulating physiological coping during parent-child interactions may both promote better parent health and improve child behavioral outcomes.

Behavioral inhibition and approach tendencies are associated with striatal activation to loss: Implications for adolescent substance use.

Behavioral inhibition/avoidance and approach systems (BIS/BAS), which facilitate avoidance of aversive stimuli and approach of enticing stimuli, are thought to underlie engagement in substance use (SU). However, little is known about the neural correlates of these systems, particularly in adolescence. The current study examined associations between BIS/BAS tendencies and neural response to reward and loss and then examined whether there was an indirect effect of BIS/BAS on later SU initiation through these neural responses. 79 12-14 year olds underwent fMRI at baseline during a card guessing task. Adolescents reported on their BIS/BAS at baseline and on their SU at baseline and through a 3-year follow-up period. Results showed that higher BIS was associated with lower striatal activation and higher BAS with higher striatal activation to monetary loss. BIS and BAS were not associated with neural activation to monetary reward. There was no support that BIS or BAS predicted SU initiation through striatal activation to monetary loss. Overall, these results may suggest that adolescents with the tendency to avoid aversive stimuli assign less salience and adolescents with the tendency to approach enticing stimuli assign more salience to monetary loss.

Task-based functional connectivity patterns: Links to adolescent emotion regulation and psychopathology.

Adolescence is a developmental period characterized by heightened emotional reactivity, neurobiological changes, and increased rates of anxiety and depression. Emotion regulation (ER) difficulties-or the inability to effectively regulate one's emotions-have been theoretically and empirically conceptualized as a transdiagnostic factor implicated in virtually all forms of psychopathology among youth. The current fMRI study investigates how young adolescents' ER abilities longitudinally mediate the relationship between their task-based (n=67) limbic-prefrontal functional connectivity values and subsequent levels of internalizing and externalizing symptoms. Findings revealed that adolescents with stronger limbic-prefrontal connectivity when viewing negative emotional images reported more ER difficulties one year later which, in turn, predicted higher levels of adolescent-reported internalizing and externalizing symptoms (with the exception of ADHD) two years later. This is the only study to date that provides compelling-albeit preliminary-evidence that ER problems longitudinally mediate the association between task-based functional connectivity patterns and future psychological symptoms among adolescents. Of note, participants were only scanned at baseline, limiting our ability to assess change in adolescents' task-based functional connectivity patterns as a function of developing ER abilities or burgeoning psychological symptomology. In sum, rather than conferring risk for any particular disorder, our results suggest that functional connectivity and subsequent ER abilities may serve a transdiagnostic risk factor for psychopathology. These findings may inform future emotion-focused prevention and intervention efforts aimed at youth susceptible to future internalizing and externalizing problems.

Sexual Identity and its Association with Trajectories of Depressive Symptoms and Emotion Regulation Difficulties from Early to Middle Adolescence.

Few studies have examined how changes in sexual identity impact trajectories of depressive symptoms and emotion regulation difficulties. The current study addresses this gap in the literature by examining these associations over a three-year period in a community sample of adolescents (N = 177; Mage = 12.56; SD = 0.60; nmale = 95). Multilevel modeling revealed that youth who consistently held sexual minority identities from early to middle adolescence-but not youth with inconsistent sexual identity-demonstrated increases in depressive symptoms and emotion regulation difficulties relative to their heterosexual peers. Findings suggest that treatments that bolster emotion regulation abilities and address depressive symptoms may be of particular benefit to youth with consistent sexual minority identities from early to middle adolescence.

Effects of Parenting Environment on Child and Adolescent Social-Emotional Brain Function.

The caregiving environment that children and adolescents experience is critically important for their social-emotional development. Parenting may affect child social-emotional outcomes through its effects in shaping the child's developing brain. Research has begun to investigate effects of parenting on child and adolescent brain function in humans using functional magnetic resonance imaging (fMRI). Here we review these initial studies. These studies find associations between parenting behavior and child and adolescent functional activation in neural networks involved in emotional arousal, emotion regulation (ER), reward processing, cognitive control, and social-emotional information processing. Findings from these studies suggest that higher negative parenting and lower positive parenting are generally associated with heightened activation in emotional arousal networks in response to negative emotional stimuli in youth. Further, findings indicate that lower positive parenting is associated with higher response in reward processing networks to monetary reward in youth. Finally, findings show that lower positive parenting predicts lower activation in cognitive control networks during cognitive control tasks and less adaptive neural responses to parent-specific stimuli. Several studies found these associations to be moderated by child sex or psychopathology risk status and we discuss these moderating factors and discuss implications of findings for children's social-emotional development.

Affect-Related Brain Activity and Adolescent Substance Use: A Systematic Review.

Purpose of review: This review aims to summarize the research on brain activity during affective processing (i.e., reward, negative emotional stimuli, loss) and adolescent substance use (SU). Recent findings: Most research revealed links between altered neural activity in midcingulo-insular, frontoparietal and other network regions and adolescent SU. Increased recruitment of midcingulo-insular regions-particularly the striatum-to positive affective stimuli (e.g., monetary reward) was most often associated with initiation and low-level use of substances, whereas decreased recruitment of these regions was most often associated with SUD and higher risk SU. In regards to negative affective stimuli, most research demonstrated increased recruitment of midcingulo-insular network regions. There is also evidence that these associations may be sex-specific. Summary: Future research should employ longitudinal designs that assess affect-related brain activity prior to and following SU initiation and escalation. Moreover, examining sex as as moderating variable may help clarify if affective neural risk factors are sex-specific.

Neural activation to loss and reward among alcohol naive adolescents who later initiate alcohol use.

Adolescent alcohol use is associated with adverse psychosocial outcomes, including an increased risk of alcohol use disorder in adulthood. It is therefore important to identify risk factors of alcohol initiation in adolescence. Research to date has shown that altered neural activation to reward is associated with alcohol use in adolescence; however, few studies have focused on neural activation to loss and alcohol use. The current study examined neural activation to loss and reward among 64 alcohol naive 12-14 year olds that did (n = 20) and did not initiate alcohol use by a three year follow-up period. Results showed that compared to adolescents that did not initiate alcohol use, adolescents that did initiate alcohol use by the three year follow-up period had increased activation to loss in the left striatum (i.e., putamen), right precuneus, and the brainstem/pons when they were alcohol naive at baseline. By contrast, alcohol initiation was not associated with neural activation to winning a reward. These results suggest that increased activation in brain regions implicated in salience, error detection/self-referential processing, and sensorimotor function, especially to negative outcomes, may represent an initial vulnerability factor for alcohol use in adolescence.

Affective Neural Mechanisms of a Parenting-Focused Mindfulness Intervention.

OBJECTIVES: Behavioral evidence suggests that parenting-focused mindfulness interventions can improve parenting practices and enhance family wellbeing, potentially operating through altered emotional processing in parents. However, the mechanisms through which parent mindfulness interventions achieve their positive benefits have not yet been empirically tested, knowledge which is key to refine and maximize intervention effects. Thus, as part of a randomized controlled trial, the present study examined the affective mechanisms of an 8-week parenting-focused mindfulness intervention, the Parenting Mindfully (PM) intervention, versus a minimal-intervention parent education control. METHODS: Twenty highly stressed mothers of adolescents completed pre- and post-intervention behavioral and fMRI sessions, in which mothers completed a parent-adolescent conflict interaction, fMRI emotion task, and fMRI resting state scan. Mothers reported on their mindful parenting, and maternal emotional reactivity to the parent-adolescent conflict task was assessed via observed emotion expression, self-reported negative emotion, and salivary cortisol reactivity. RESULTS: Results indicated that the PM intervention increased brain responsivity in left posterior insula in response to negative affective stimuli, and altered resting state functional connectivity in regions involved in self-reference, behavioral regulation, and social-emotional processing. Changes in mothers' brain function and connectivity were associated with increased mindful parenting and decreased emotional reactivity to the parent-adolescent conflict task. CONCLUSIONS: Findings suggest that mindfulness-based changes in maternal emotional awareness at the neurobiological level are associated with decreased emotional reactivity in parenting interactions, illuminating potential neurobiological targets for future parent-focused intervention.

Effects of A Parenting-Focused Mindfulness Intervention on Adolescent Substance Use and Psychopathology: A Randomized Controlled Trial.

Substance use and psychopathology symptoms increase in adolescence. One key risk factor for these is high parent stress. Mindfulness interventions reduce stress in adults and may be useful to reduce parent stress and prevent substance use (SU) and psychopathology in adolescents. This study tested the feasibility and effects of a mindfulness intervention for parents on adolescent SU and psychopathology symptoms. Ninety-six mothers of 11-17 year olds were randomly assigned to a mindfulness intervention for parents (the Parenting Mindfully [PM] intervention) or a brief parent education [PE] control group. At pre-intervention, post-intervention, 6-month follow-up, and 1-year follow-up, adolescents reported on SU and mothers and adolescents reported on adolescent externalizing and internalizing symptoms. Primary intent to treat analyses found that the PM intervention prevented increases in adolescent SU over time, relative to the PE control group. The PM intervention also prevented increases in mother-reported externalizing symptoms over time relative to the PE control group. However, PM did not have a significant effect on internalizing symptoms. PM had an indirect effect on adolescent-reported externalizing symptoms through greater mother mindfulness levels at post-intervention, suggesting mother mindfulness as a potential intervention mechanism. Notably, while mothers reported high satisfaction with PM, intervention attendance was low (31% of mothers attended zero sessions). Secondary analyses with mothers who attended > = 50% of the interventions (n = 48) found significant PM effects on externalizing symptoms, but not SU. Overall, findings support mindfulness training for parents as a promising intervention and future studies should work to promote accessibility for stressed parents.Clinical Trials Identifier: NCT02038231; Date of Registration: January 13, 2014.

High-Frequency Heart Rate Variability and Emotion-Driven Impulse Control Difficulties During Adolescence: Examining Experienced and Expressed Negative Emotion as Moderators.

Emotion-driven impulse control difficulties are associated with negative psychological outcomes. Extant research suggests that high frequency heart rate variability (HF-HRV) may be indicative of emotion-driven impulse control difficulties and potentially moderated by negative emotion. In the current study, 248 eleven- to 14-year-olds and their parent engaged in a negatively emotionally arousing conflict task at Time 1. Adolescents' HF-HRV and negative emotional expression and experience were assessed before, during, and/or after the task. Adolescents reported on their levels of emotion-driven impulse control difficulties at Time 1 and one year later. Results revealed that higher levels of HF-HRV reactivity (i.e., higher HF-HRV augmentation) predicted higher levels of emotion-driven impulse control difficulties one year later among adolescents who experienced higher negative emotion. These findings suggest that negative emotional context should be considered when examining HF-HRV reactivity as a risk factor for emotion-driven impulse control difficulties and associated outcomes.

Getting to the heart of food craving with resting heart rate variability in adolescents.

BACKGROUND: There is an epidemic of obesity in children and adolescents. Research into the self-regulatory factors that drive eating behavior is of critical importance. Food craving contributes to overeating and difficulty with weight loss and is strongly correlated with self-regulation. High-frequency heart rate variability (HF HRV) reflects parasympathetic activity and is positively associated with self-regulation. Few studies of HF HRV and food craving have been conducted in adolescents. The current study examined the association between HF HRV and food craving in a large-scale sample of healthy adolescents. METHOD: Electrocardiogram (ECG) was recorded in 134 healthy adolescents aged 10-17 during a 7-min resting state. Participants also completed the Food Craving Questionnaire-Trait (FCQ-T). The relative power of HF HRV was calculated. Association between HF HRV and food craving was examined in the context of sex and age. Next, the relative significance of all food craving subscales was considered in relation to HF HRV. RESULTS: HF HRV was inversely correlated with food craving, taking into account sex and age. Considering all the subscales of FCQ-T in relation to HF HRV, the "lack of control over eating" subscale accounted for the most significant variance. CONCLUSION: This was the first study to evaluate resting HRV and eating behaviors in a large-scale adolescent sample. HF HRV was negatively associated with food craving, with lower HF HRV correlating with higher food craving, especially in the context of diminished control over eating. HF HRV could be a potential biomarker for food craving and food-related self-regulation capacity, and therefore may aid weight management interventions.

Does Alcohol Initiation in Early-To-Middle Adolescence Predict Changes in Reward Motivation? Evidence of Sex Differences.

BACKGROUND: Reward motivation has been cross-sectionally correlated with adolescent alcohol use, but the temporal nature of this relationship remains unclear. This project sought to determine whether adolescent alcohol initiation longitudinally predicted changes in reward motivation and behavioral inhibition from early to middle adolescence, and explored the role of adolescent sex in this prediction. METHODS: A total of 180 11- to 14-year-olds were recruited and then followed for 3 years to age 14 to 17. Participants self-reported their alcohol use at all time points. We selected participants who were alcohol-naïve at Baseline (early adolescence) and then grouped them based on whether or not they reported alcohol initiation by Year 3 (Y3: middle adolescence). Adolescents completed self-report and experimental (delay discounting) measures of reward motivation and self-report measures of behavioral inhibition at Baseline and Y3. RESULTS: Adolescents' alcohol initiation significantly predicted higher Y3 self-reported reward motivation on one measure. Additionally, a significant sex × alcohol initiation interaction was found predicting Y3 task-based reward motivation (delay discounting), with boys' alcohol initiation predicting increased bias toward immediate reward at Y3. There was also a sex × alcohol initiation interaction predicting behavioral inhibition, with girls' alcohol initiation predicting higher behavioral inhibition at Y3. CONCLUSIONS: Results suggest that alcohol initiation among adolescents might precede changes in reward motivation, and the effects of alcohol on reward and behavioral inhibition may differ by adolescent sex.

Properties of the Continuous Assessment of Interpersonal Dynamics Across Sex, Level of Familiarity, and Interpersonal Conflict.

The Continuous Assessment of Interpersonal Dynamics (CAID) is a method in which trained observers continuously code the dominance and warmth of individuals who interact with one another in dyads. This method has significant promise for assessing dynamic interpersonal processes. The purpose of this study was to examine the impact of individual sex, dyadic familiarity, and situational conflict on patterns of interpersonal warmth, dominance, and complementarity as assessed via CAID. We used six samples with 603 dyads, including two samples of unacquainted mixed-sex undergraduates interacting in a collaborative task, two samples of couples interacting in both collaborative and conflict tasks, and two samples of mothers and children interacting in both collaborative and conflict tasks. Complementarity effects were robust across all samples, and individuals tended to be relatively warm and dominant. Results from multilevel models indicated that women were slightly warmer than men, whereas there were no sex differences in dominance. Unfamiliar dyads and dyads interacting in more collaborative tasks were relatively warmer, more submissive, and more complementary on warmth but less complementary on dominance. These findings speak to the utility of the CAID method for assessing interpersonal dynamics and provide norms for researchers who use the method for different types of samples and applications.

Maternal Neurobiological Processing of Negative Adolescent Stimuli: Relations With Positive Parenting and Relationship Quality.

We examined associations between maternal affective neurobiology and positive parenting in a study of 20 mothers of adolescents. Mothers underwent functional magnetic resonance imaging during an emotion image task, rated parent-adolescent relationship quality, and completed an adolescent interaction task in which positive parenting behaviors were observed. Maternal structure was associated with lower responsivity in emotional processing regions in the general negative image contrast and was related to greater dorsolateral prefrontal cortex activation to negative adolescent images. Parent-adolescent relationship quality was associated with lower precuneus activation to negative adolescent images. Findings are among the first to connect functional brain processing with observed parenting behaviors for parents of adolescent children, and underscore the relative importance of affective processing in parenting older children.

Maternal Emotional and Physiological Reactivity: Implications for Parenting and the Parenting-Adolescent Relationship.

OBJECTIVE: Parent physiology and emotion may play an important role in parenting and parent-child relationship quality, yet little research has examined these associations in parents of adolescents. This study employed a naturalistic laboratory-based approach to observe maternal reactivity (mothers' cardiovascular and negative emotional responses) during a parent-adolescent interaction task (PAIT) and associations with parenting behavior and parent-adolescent relationship quality. We also examined possible indirect effect of maternal reactivity on parent-adolescent relationship quality through parenting variables. METHODS: Mothers (n = 196) of 12-14 year olds completed the PAIT, a 10-minute laboratory task in which mothers and adolescents discussed a family conflict topic. Mother-rated negative emotional experience, mother heart rate (HR), and systolic and diastolic blood pressure (BP) responses to PAIT were collected. Additionally, observed maladaptive and positive parenting during PAIT and reported parent-adolescent relationship quality were collected. RESULTS: We found that mothers' heightened negative emotional experience in PAIT was associated with heightened observed and reported maladaptive parenting and lower parent-adolescent relationship quality (p<.001). Additionally, blunted HR reactivity was related to higher positive parenting in PAIT (p<.05). Lastly, we found an indirect effect of HR on parent-adolescent relationship through positive parenting and an indirect effect of maternal negative emotional experience on parent-adolescent relationship quality through maladaptive and positive parenting. In sum, high emotional reactivity and blunted HR predicted poorer parenting, and directly and indirectly affected parent-adolescent relationship quality. CONCLUSIONS: Parent reactivity may be important to consider in interventions.

Sex-Differentiated Associations among Negative Parenting, Emotion-Related Brain Function, and Adolescent Substance Use and Psychopathology Symptoms.

Parenting is a critical factor in adolescent social-emotional development, with maladaptive parenting leading to risk for the development of psychopathology. However, the emotion-related brain mechanisms underlying the influence of parenting on psychopathology symptoms are unknown. The present study utilized functional magnetic resonance imaging and laboratory measures to examine sex-differentiated associations among parenting, adolescent emotion-related brain function, and substance use and psychopathology symptoms in 66 12-14 year olds. Maternal parenting behaviors (warmth, negative parenting) were observed in a laboratory task. Adolescent brain responses to negative emotional stimuli were assessed in emotion processing regions of interest (left [L] and right [R] amygdala, anterior insula, anterior cingulate cortex [ACC]). Adolescents reported on substance use and depressive, anxiety, and externalizing symptoms. Maternal negative parenting predicted adolescent brain activation differently by sex. For girls, negative parenting predicted heightened R ACC activation to negative emotional stimuli. For boys, negative parenting predicted blunted L and R anterior insula and L ACC activation. Furthermore, for girls, but not boys, heightened L anterior insula and heightened L and R ACC activation were associated with substance use and depressive symptoms, respectively. Findings suggest neural response to negative emotion as a possible sex-specific pathway from negative parenting to psychopathology.

Adolescent Brain Response to Reward Is Associated with a Bias toward Immediate Reward.

The current study examines associations between neural activation to the receipt of monetary reward in a rewarding game task and bias toward immediate reward measured in a behavioral delay discounting task among early adolescents (N = 58, 12-14 years). As expected, heightened brain activation in reward-related regions were correlated with higher bias toward immediate reward. This suggests that bias toward immediate reward in delay discounting tasks may be linked to heightened activation to reward in reward processing regions. This interplay between neural reward processing and bias toward immediate reward might explain the sharp increases in bias toward immediate reward that occur in early adolescence.

Maternal stress and adolescent brain structure and function.

INTRODUCTION: Adolescence is a time of heightened sensitivity in biological stress systems and the emergence of stress-related psychopathology. Thus, understanding environmental factors in adolescence that might be associated with adolescents'' stress systems is important. Maternal stress levels may be involved. However, the relationship between maternal stress and the adolescent brain is unknown. METHOD: The present study examined the association between mothers' self-reported stress levels and mothers' cortisol stress reactivity and their early adolescents' brain structure and functional activation to stressful negative emotional images. Participants included 66 mothers and their 12- to 14-year old adolescents. Mother's perceived stress and salivary cortisol reactivity to a stressful task were collected. Then, adolescents' brain structure and function were assessed in a magnetic resonance imaging session. RESULTS: Functional whole-brain analyses revealed that mothers' higher reported perceived stress, but not cortisol reactivity, predicted adolescents' higher responses in the medial prefrontal cortex (mPFC) to stressful negative emotional stimuli. There were no statistically significant associations for structural analyses. CONCLUSIONS: Given the finding of maternal stress reactivity related to adolescent mPFC function-an integral structure related to stress responses-parent stress may play a role in the development of neural stress systems in adolescence, with potential implications for development of psychopathology.

An inactive control of the 'Trier Social Stress Test' for Youth 10-17 years: Neuroendocrine, cardiac, and subjective responses.

The Trier Social Stress Test for children (TSST-C) adapted from TSST is one of the most commonly used laboratory paradigms for investigating the effects of stress on cognitive, affective and physiological responses in children and adolescents. Considering that laboratory procedures generate a significant amount of stress to children and adolescents, even in the absence of a stress paradigm, it is important to validate TSST-C against an inactive control condition in which the stress components were absent. Using a randomized design, we tested an inactive control condition, which replaced the TSST-C with a benign video clip (nature scenes viewed while standing), thus removing the stress associated components of the TSST-C. Eighty-eight youth between the ages of 10 and 17 years were randomly assigned to complete the TSST-C or the Inactive Control (IC). Subjective anxiety rating, salivary cortisol, systolic and diastolic blood pressure, and heart rate were collected at eight time points. Subjects in the Inactive Control condition showed no significant changes in blood pressure and heart rate, and decreased anxiety rating and salivary cortisol level throughout the study. Subjects in the stress condition (TSST-C) showed increased anxiety ratings, salivary cortisol, systolic and diastolic blood pressure, and heart rate immediately following TSST-C stress induction. Our findings validated that the TSST-C induced a systemic stress response, and that the Inactive Control can be a promising standardized control condition for the TSST-C and a tool for future psychobiological research. Our results also showed that anxiety reactivity decreased with age while HR reactivity increased with age. Cortisol reactivity did not fall in a linear relationship with age but rather via a quadratic curve, suggesting the mid-age adolescents had the highest cortisol responses to stress compared to their younger and older peers, potentially due to a dual factor of pubertal development and self-control and emotion regulation capacity.