Pathways to adolescent social anxiety: Testing interactions between neural social reward function and perceived social threat in daily life.

Recent theories suggest that for youth highly sensitive to incentives, perceiving more social threat may contribute to social anxiety (SA) symptoms. In 129 girls (ages 11-13) oversampled for shy/fearful temperament, we thus examined how interactions between neural responses to social reward (vs. neutral) cues (measured during anticipation of peer feedback) and perceived social threat in daily peer interactions (measured using ecological momentary assessment) predict SA symptoms two years later. No significant interactions emerged when neural reward function was modeled as a latent factor. Secondary analyses showed that higher perceived social threat was associated with more severe SA symptoms two years later only for girls with higher basolateral amygdala (BLA) activation to social reward cues at baseline. Interaction effects were specific to BLA activation to social reward (not threat) cues, though a main effect of BLA activation to social threat (vs. neutral) cues on SA emerged. Unexpectedly, interactions between social threat and BLA activation to social reward cues also predicted generalized anxiety and depression symptoms two years later, suggesting possible transdiagnostic risk pathways. Perceiving high social threat may be particularly detrimental for youth highly sensitive to reward incentives, potentially due to mediating reward learning processes, though this remains to be tested.

Continuous theta burst stimulation to dorsomedial prefrontal cortex in young adults with depression: Changes in resting frontostriatal functional connectivity relevant to positive mood.

Depression is associated with diminished positive affect (PA), postulated to reflect frontostriatal reward circuitry disruptions. Depression has consistently been associated with higher dorsomedial prefrontal cortex (dmPFC) activation, a region that regulates PA through ventral striatum (VS) connections. Low PA in depression may reflect dmPFC's aberrant functional connectivity (FC) with the VS. To test this, we applied theta burst stimulation (TBS) to dmPFC in 29 adults with depression (79% female, Mage = 21.4, SD = 2.04). Using a randomized, counterbalanced design, we administered 3 types of TBS at different sessions: intermittent (iTBS; potentiating), continuous (cTBS; depotentiating), and sham TBS (control). We used neuronavigation to target personalized dmPFC targets based on VS-dmPFC FC. PA and negative affect (NA), and resting-state fMRI were collected pre- and post-TBS. We found no changes in PA or NA with time (pre/post), condition (iTBS, cTBS, sham), or their interaction. Functional connectivity (FC) between the nucleus accumbens and dmPFC showed a significant condition (cTBS, iTBS, and sham) by time (pre-vs. post-TBS) interaction, and post-hoc testing showed decreased pre-to post-TBS for cTBS but not iTBS or sham. For cTBS only, reduced FC pre/post stimulation was associated with increased PA (but not NA). Our findings lend support to the proposed mechanistic model of aberrant FC between the dmPFC and VS in depression and suggest a way forward for treating depression in young adults. Future studies need to evaluate multi-session TBS to test clinical effects.

Annual Research Review: Puberty and the development of anhedonia - considering childhood adversity and inflammation.

Anhedonia, or diminished pleasure and motivation, is a symptom of severe mental illness (e.g., depressive disorder, bipolar disorder, schizophrenia) that emerges during adolescence. Anhedonia is a pernicious symptom that is related to social impairments, treatment resistance, and suicide. As the mechanisms of anhedonia are postulated to include the frontostriatal circuitry and the dopamine neuromodulatory system, the development and plasticity of these systems during the vulnerable period of adolescence, as well as their sensitivity to pubertal hormones, suggest that pubertal maturation could play a role in the development of anhedonia. This review takes a developmental perspective, considering the possibility that anhedonia emerges in the context of pubertal maturation and adolescent development, with childhood adversity and chronic inflammation influencing neural reward systems to accelerate anhedonia's progression. Here, we review the relevant extant literature on the components of this model and suggest directions for future research.

Prospective associations between cognitive flexibility and eating disorder symptoms in anorexia nervosa and bulimia nervosa.

This study investigated concurrent and prospective associations between measures of reversal learning and attentional set-shifting and eating disorder symptoms at baseline, 3 months, and 6 months among individuals with anorexia nervosa restricting subtype (AN-R, n = 26), AN binge eating/purging subtype (AN-BP, n = 22), bulimia nervosa (BN, n = 35), and healthy controls (n = 27), and explored whether these associations differed by diagnosis. At baseline, participants completed diagnostic interviews, height/weight measurements, and measures of set-shifting (the Intradimensional/Extradimensional shift task) and reversal learning (a probabilistic reversal learning task). At 3- and 6-month follow-up, participants with eating disorders completed assessments of weight and eating disorder symptoms. A one-way analysis of variance found no evidence that baseline reversal learning and attentional set-shifting differed across diagnostic groups. Multilevel modeling analyses indicated that perseverative errors (an index of reversal learning) predicted an increase in purging over time for individuals with AN-BP and BN. Set-shifting errors differentially predicted frequency of loss of control eating for individuals with AN-BP and BN; however, set-shifting was not related to loss of control eating when examined separately in AN-BP and BN. These findings suggest that disentangling facets of cognitive flexibility may help understand change in eating disorder symptoms.

The association between cortical gyrification and sleep in adolescents and young adults.

STUDY OBJECTIVES: Healthy sleep is important for adolescent neurodevelopment, and relationships between brain structure and sleep can vary in strength over this maturational window. Although cortical gyrification is increasingly considered a useful index for understanding cognitive and emotional outcomes in adolescence, and sleep is also a strong predictor of such outcomes, we know relatively little about associations between cortical gyrification and sleep. We aimed to identify developmentally invariant (stable across age) or developmentally specific (observed only during discrete age intervals) gyrification-sleep relationships in young people. METHODS: A total of 252 Neuroimaging and Pediatric Sleep Databank participants (9-26 years; 58.3% female) completed wrist actigraphy and a structural MRI scan. Local gyrification index (lGI) was estimated for 34 bilateral brain regions. Naturalistic sleep characteristics (duration, timing, continuity, and regularity) were estimated from wrist actigraphy. Regularized regression for feature selection was used to examine gyrification-sleep relationships. RESULTS: For most brain regions, greater lGI was associated with longer sleep duration, earlier sleep timing, lower variability in sleep regularity, and shorter time awake after sleep onset. lGI in frontoparietal network regions showed associations with sleep patterns that were stable across age. However, in default mode network regions, lGI was only associated with sleep patterns from late childhood through early-to-mid adolescence, a period of vulnerability for mental health disorders. CONCLUSIONS: We detected both developmentally invariant and developmentally specific ties between local gyrification and naturalistic sleep patterns. Default mode network regions may be particularly susceptible to interventions promoting more optimal sleep during childhood and adolescence.

Current maternal depression associated with worsened children's social outcomes during middle childhood: Exploring the role of positive affect socialization.

BACKGROUND: Maternal depression negatively predicts aspects of the mother-child relationship and social functioning in offspring. This study evaluated interrelations between mothers' depression history and current severity with dynamic indices of positive affect socialization and indices of offspring' social outcomes. METHODS: N = 66 mother-child dyads in which approximately 50 % of mothers had a history of maternal depression were recruited. Children were 6-8 years old and 47.7 % male. Dyads completed a positive interaction task, which was coded for mother and child positive affect. Mothers and children reported on peer functioning and social problems and children reported on the quality of their best friendships at 1-year follow-up. RESULTS: Current level of maternal depression, but not depression history, was related to more social problems and lower best friend relationship quality. Indices of positive affect socialization were not related to history or current levels of maternal depression, or social outcomes, with the exception of maternal depression history predicting greater likelihood of mothers joining their children in expressing positive affect. Exploratory, supplementary analysis revealed that this may be due to treatment history among these mothers. LIMITATIONS: Conclusions should be tempered by the small sample size, which limited the types of analyses that were conducted. CONCLUSION: Results suggest that the effect of maternal depression on aspects of child social outcomes could be specific to current levels. Our data also did not support previously found associations between maternal depression and positive affect socialization. Results suggest positive implications for the effect of treatment for maternal depression for mother-child dynamics.

Hooked on a thought: Associations between rumination and neural responses to social rejection in adolescent girls.

Rumination is a significant risk factor for psychopathology in adolescent girls and is associated with heightened and prolonged physiological arousal following social rejection. However, no study has examined how rumination relates to neural responses to social rejection in adolescent girls; thus, the current study aimed to address this gap. Adolescent girls (N = 116; ages 16.95-19.09) self-reported on their rumination tendency and completed a social evaluation fMRI task where they received fictitious feedback (acceptance, rejection) from peers they liked or disliked. Rejection-related neural activity and subgenual anterior cingulate cortex (sgACC) connectivity were regressed on rumination, controlling for rejection sensitivity and depressive symptoms. Rumination was associated with distinctive neural responses following rejection from liked peers including increased neural activity in the precuneus, inferior parietal gyrus, dorsolateral prefrontal cortex, and supplementary motor area (SMA) and reduced sgACC connectivity with multiple regions including medial prefrontal cortex, precuneus and ventrolateral prefrontal cortex. Greater precuneus and SMA activity mediated the effect of rumination on slower response time to report emotional state after receiving rejection from liked peers. These findings provide clues for distinctive cognitive processes (e.g., mentalizing, conflict processing, memory encoding) following the receipt of rejection in girls with high levels of rumination.

Therapeutic Alliance, Attendance, and Outcomes in Youths Receiving CBT or Client-Centered Therapy for Anxiety.

OBJECTIVE: Positive associations between therapeutic alliance and outcome (e.g. youth symptom severity) have been documented in the youth anxiety literature; however, little is known about the conditions under which early alliance contributes to positive outcomes in youth. The present study examined the relations between therapeutic alliance, session attendance, and outcomes in youths (N = 135; 55.6% female) who participated in a randomized clinical trial testing the efficacy of cognitive-behavioral therapy or client-centered therapy for anxiety. METHOD: We evaluated a conceptual model wherein: (1) early alliance indirectly contributes to positive outcomes by improving session attendance; (2) alliance-outcome associations differ by intervention type, with stronger associations in cognitive-behavioral therapy compared to client-centered therapy; and (3) alliance-outcome associations vary across outcome measurement timepoints, with the effect of early alliance on outcomes decaying over time. RESULTS: Contrary to hypotheses, provider ratings of early alliance predicted greater youth-rated anxiety symptom severity post-treatment (i.e. worse treatment outcomes). Session attendance predicted positive youth-rated outcomes, though there was no indirect effect of early alliance on outcomes through session attendance. CONCLUSIONS: Results show that increasing session attendance is important for enhancing outcomes and do not support early alliance as a predictor of outcomes.

Risk-Sensitive Decision-Making and Self-Harm in Youth Bipolar Disorder.

Background: Youth with bipolar disorder (BD) are at high risk for suicide and have high rates of self-harm, which includes both suicide attempts and non-suicidal self-injury. Greater risk-taking has been associated with suicide attempts in youth with major depression, although there are no studies examining the relationship between risk-related decision-making and self-harm in youth with BD. We aimed to examine the association of suicide risk with risk-sensitive decision-making in a controlled sample of youth with BD.Methods: Eighty-one youth with BD (based on DSM-IV criteria; 52 youth with a history of self-harm [BDSH+]; 29 without a history of self-harm [BDSH-]) and 82 age- and sex-matched control youth aged 13-20 years were recruited between 2012 and 2020. Decision-making and risk-taking performance were assessed via the Cambridge Gambling Task within the Cambridge Neuropsychological Test Automated Battery (CANTAB). General linear models were used to examine differences between groups with control for age, sex, and IQ.Results: There was a significant difference in the overall proportion of points bet (F2,157 = 3.87, P = .02, η2 = 0.23) such that BDSH- youth performed better than both BDSH+ (P = .02) and control youth (P = .04). Mean latency was significant (F3,156 = 4.12, P = .017, η2 = 0.03), with BDSH- youth deliberating longer than controls (P = .03). Risk-taking significantly differed between groups (F2,157 = 3.83, P = .02, η2 = 0.23), with BDSH- youth showing greater self-control compared to BDSH+ (P = .01) and control youth (P = .01).Conclusions: BDSH- youth had greater self-control and lower risk-taking. We speculate this finding may be reflective of a compensatory process among BDSH- youth serving a protective role in suicide risk. Future longitudinal studies are needed to examine the temporal association of neurocognition and self-harm among youth with BD.

The association between cortical gyrification and sleep in adolescents and young adults.

Study objectives: Healthy sleep is important for adolescent neurodevelopment, and relationships between brain structure and sleep can vary in strength over this maturational window. Although cortical gyrification is increasingly considered a useful index for understanding cognitive and emotional outcomes in adolescence, and sleep is also a strong predictor of such outcomes, we know relatively little about associations between cortical gyrification and sleep. Methods: Using Local gyrification index (lGI) of 34 bilateral brain regions and regularized regression for feature selection, we examined gyrification-sleep relationships in the Neuroimaging and Pediatric Sleep databank (252 participants; 9-26 years; 58.3% female) and identified developmentally invariant (stable across age) or developmentally specific (observed only during discrete age intervals) brain-sleep associations. Naturalistic sleep characteristics (duration, timing, continuity, and regularity) were estimated from wrist actigraphy. Results: For most brain regions, greater lGI was associated with longer sleep duration, earlier sleep timing, lower variability in sleep regularity, and shorter time awake after sleep onset. lGI in frontoparietal network regions showed associations with sleep patterns that were stable across age. However, in default mode network regions, lGI was only associated with sleep patterns from late childhood through early-to-mid adolescence, a period of vulnerability for mental health disorders. Conclusions: We detected both developmentally invariant and developmentally specific ties between local gyrification and naturalistic sleep patterns. Default mode network regions may be particularly susceptible to interventions promoting more optimal sleep during childhood and adolescence.

Adolescents' neural reactivity to parental criticism is associated with diminished happiness during daily interpersonal situations.

The goal of this study was to examine the relation between real-world socio-emotional measures and neural activation to parental criticism, a salient form of social threat for adolescents. This work could help us understand why heightened neural reactivity to social threat consistently emerges as a risk factor for internalizing psychopathology in youth. We predicted that youth with higher reactivity to parental criticism (vs neutral comments) in the subgenual anterior cingulate cortex (sgACC), amygdala and anterior insula would experience (i) less happiness in daily positive interpersonal situations and (ii) more sadness and anger in daily negative interpersonal situations. Participants (44 youth aged 11-16 years with a history of anxiety) completed a 10-day ecological momentary assessment protocol and a neuroimaging task in which they listened to audio clips of their parents' criticism and neutral comments. Mixed-effects models tested associations between neural activation to critical (vs neutral) feedback and emotions in interpersonal situations. Youth who exhibited higher activation in the sgACC to parental criticism reported less happiness during daily positive interpersonal situations. No significant neural predictors of negative emotions (e.g. sadness and anger) emerged. These findings provide evidence of real-world correlates of neural reactivity to social threat that may have important clinical implications.

Adolescents' Hormonal Responses to Social Stress and Associations with Adolescent Social Anxiety and Maternal Comfort: A Preliminary Study.

Both social support and social stress can impact adolescent physiology including hormonal responses during the sensitive transition to adolescence. Social support from parents continues to play an important role in socioemotional development during adolescence. Sources of social support and stress may be particularly impactful for adolescents with social anxiety symptoms. The goal of the current study was to examine whether adolescent social anxiety symptoms and maternal comfort moderated adolescents' hormonal response to social stress and support. We evaluated 47 emotionally healthy 11- to 14-year-old adolescents' cortisol and oxytocin reactivity to social stress and support using a modified version of the Trier Social Stress Test for Adolescents that included a maternal comfort paradigm. Findings demonstrated that adolescents showed significant increases in cortisol and significant decreases in oxytocin following the social stress task. Subsequently, we found that adolescents showed significant decreases in cortisol and increases in oxytocin following the maternal comfort paradigm. Adolescents with greater social anxiety symptoms showed higher levels of cortisol at baseline but greater declines in cortisol response following maternal social support. Social anxiety symptoms were unrelated to oxytocin response to social stress or support. Our findings provide further evidence that mothers play a key role in adolescent regulation of physiological response, particularly if the stressor is consistent with adolescents' anxiety. More specifically, our findings suggest that adolescents with higher social anxiety symptoms show greater sensitivity to maternal social support following social stressors. Encouraging parents to continue to serve as a supportive presence during adolescent distress may be helpful for promoting stress recovery during the vulnerable transition to adolescence.

Mother-child neural synchronization is time linked to mother-child positive affective state matching.

In the first years of life, in which self-regulation occurs via external means, mother-child synchronization of positive affect (PA) facilitates regulation of child homeostatic systems. Mother-child affective synchrony may contribute to mother-child synchronization of neural systems, but limited research has explored this possibility. Participants were 41 healthy mother-child dyads (56% girls; Mage = 24.76 months; s.d. = 8.77 months, Range = 10-42 months). Mothers' and children's brain activities were assessed simultaneously using near-infrared spectroscopy while engaging in dyadic play. Mother and child PA during play were coded separately to characterize periods in which mothers and children (i) matched on high PA, (ii) matched on low/no PA or (iii) showed a mismatch in PA. Models evaluated moment-to-moment correlations between affective matching and neural synchrony in mother-child dyads. Greater positive affective synchrony, in which mother and child showed similarly high levels of PA but not similarly low levels of PA, was related to greater synchrony in medial and lateral frontal and temporoparietal regions. Age moderated associations between mother and child neural activities but only during moments of high PA state matching. Positive, synchronous mother-child interactions may foster greater neural responding in affective and social regions important for self-regulation and interpersonal bonds.

Reward-related predictors of symptom change in behavioral activation therapy for anhedonic adolescents: a multimodal approach.

Anhedonia is a cardinal characteristic of depression which predicts worse treatment outcome and is among the most common residual symptoms following treatment. Behavioral Activation (BA) has been shown to be an effective treatment for depressed adults, and more recently, depressed adolescents. Given its emphasis on systematically and gradually increasing exposure to and engagement with rewarding activities and experiences, BA may be a particularly effective intervention for adolescents experiencing anhedonia and associated reward system dysfunction. In the present study, anhedonic adolescents (AA; n = 39) received 12 weekly sessions of BA and completed a multimodal (i.e., neural, behavioral, and self-report [ecological momentary assessment]) assessment of reward function at pre-treatment and post-treatment (as well as weekly self-report assessments of anhedonia). Typically developing adolescents (TDA; n = 41) completed the same measures at corresponding timepoints. Multilevel models tested pre-treatment reward-related predictors of anhedonia improvement, as well as change in reward measures over the course of BA. Analyses revealed significant reductions in anhedonia following BA treatment. Enhanced pre-treatment neural (striatal) reward responsiveness predicted greater anhedonia improvement. In contrast, baseline self-report and behavioral reward measures did not predict treatment outcome. A group x time interaction revealed greater increases in both reward- and loss-related neural responsiveness among AA relative to TDA adolescents. Consistent with a capitalization (rather than compensatory) model, pre-treatment neural - but not self-report or behavioral - measures of relatively enhanced reward responsiveness predicted better BA outcome. In addition to alleviating anhedonia, successful BA may also increase neural sensitivity to affectively salient (e.g., reward- and loss-related) stimuli among anhedonic youth.

More time awake after sleep onset is linked to reduced ventral striatum response to rewards in youth with anxiety.

BACKGROUND: Poor sleep and anxiety disorders are highly comorbid in youth, and each predicts altered ventral striatum (VS) response to rewards, which may impact mental health risk. Contrasting evidence suggests previously reported negative associations between sleep health and VS response may be stronger or weaker in youth with anxiety, indicating sensitivity to win/loss information or blunted reward processing, respectively. We cross-sectionally examined the role of sleep in VS response to rewards among youth with anxiety versus a no-psychiatric-diagnosis comparison (ND) group. We expected a group*sleep interaction on VS response to rewards but did not hypothesize directionality. METHODS: As part of the pretreatment battery for a randomized clinical trial, 74 youth with anxiety and 31 ND youth (ages 9-14 years; n = 55 female) completed a monetary reward task during fMRI. During the same pretreatment window, actigraphy and diary-estimated sleep were collected over 5 days, and participants and their parents each reported participants' total sleep problems. We examined group*sleep interactions on VS response to monetary rewards versus losses via three mixed linear models corresponding to actigraphy, diary, and questionnaires, respectively. RESULTS: Each model indicated group*sleep interactions on VS response to rewards. Actigraphy and diary-estimated time awake after sleep onset predicted reduced VS response in youth with anxiety but not ND youth. Parent-reported sleep problems similarly interacted with group, but simple slopes were nonsignificant. CONCLUSIONS: Wake after sleep onset was associated with blunted reward response in youth with anxiety. These data suggest a potential pathway through which sleep could contribute to perturbed reward function and reward-related psychopathology (e.g., depression) in youth with anxiety.

Multi-modal assessment of reward functioning in adolescent anhedonia.

BACKGROUND: Anhedonia is a core symptom of depression that predicts worse treatment outcomes. Dysfunction in neural reward circuits is thought to contribute to anhedonia. However, whether laboratory-based assessments of anhedonia and reward-related neural function translate to adolescents' subjective affective experiences in real-world contexts remains unclear. METHODS: We recruited a sample of adolescents (n = 82; ages 12-18; mean = 15.83) who varied in anhedonia and measured the relationships among clinician-rated and self-reported anhedonia, behaviorally assessed reward learning ability, neural response to monetary reward and loss (as assessed with functional magnetic resonance imaging), and repeated ecological momentary assessment (EMA) of positive affect (PA) and negative affect (NA) in daily life. RESULTS: Anhedonia was associated with lower mean PA and higher mean NA across the 5-day EMA period. Anhedonia was not related to impaired behavioral reward learning, but low PA was associated with reduced nucleus accumbens response during reward anticipation and reduced medial prefrontal cortex (mPFC) response during reward outcome. Greater mean NA was associated with increased mPFC response to loss outcome. CONCLUSIONS: Traditional laboratory-based measures of anhedonia were associated with lower subjective PA and higher subjective NA in youths' daily lives. Lower subjective PA and higher subjective NA were associated with decreased reward-related striatal functioning. Higher NA was also related to increased mPFC activity to loss. Collectively, these findings demonstrate that laboratory-based measures of anhedonia translate to real-world contexts and that subjective ratings of PA and NA may be associated with neural response to reward and loss.

Subgenual Anterior Cingulate Cortex Reactivity to Rejection Vs. Acceptance Predicts Depressive Symptoms among Adolescents with an Anxiety History.

OBJECTIVE: The goal of this study was to examine whether neural sensitivity to negative peer evaluation conveys risk for depression among youth with a history of anxiety. We hypothesized that brain activation in regions that process affective salience in response to rejection, relative to acceptance, from virtual peers would predict depressive symptoms 1 year later and would be associated with ecological momentary assessment (EMA) reports of peer connectedness. METHOD: Participants were 38 adolescents ages 11-16 (50% female) with a history of anxiety, recruited from a previous clinical trial. The study was a prospective naturalistic follow-up of depressive symptoms assessed 2 years (Wave 2) and 3 years (Wave 3) following treatment. At Wave 2, participants completed the Chatroom Interact Task during neuroimaging and 16 days of EMA. RESULTS: Controlling for depressive and anxiety symptoms at Wave 2, subgenual anterior cingulate (sgACC; ß = .39, p = .010) activation to peer rejection (vs. acceptance) predicted depressive symptoms at Wave 3. SgACC activation to rejection (vs. acceptance) was highly negatively correlated with EMA reports of connectedness with peers in daily life (r = - .71, p < .001). CONCLUSION: Findings suggest that elevated sgACC activation to negative, relative to positive, peer evaluation may serve as a risk factor for depressive symptoms among youth with a history of anxiety, perhaps by promoting vigilance or reactivity to social evaluative threats. SgACC activation to simulated peer evaluation appears to have implications for understanding how adolescents experience their daily social environments in ways that could contribute to depressive symptoms.

Naturalistic Sleep Patterns are Linked to Global Structural Brain Aging in Adolescence.

PURPOSE: We examined whether interindividual differences in naturalistic sleep patterns correlate with any deviations from typical brain aging. METHODS: Our sample consisted of 251 participants without current psychiatric diagnoses (9-25 years; mean [standard deviation] = 17.4 ± 4.52 yr; 58% female) drawn from the Neuroimaging and Pediatric Sleep Databank. Participants completed a T1-weighted structural magnetic resonance imaging scan and 5-7 days of wrist actigraphy to assess naturalistic sleep patterns (duration, timing, continuity, and regularity). We estimated brain age from extracted structural magnetic resonance imaging indices and calculated brain age gap (estimated brain age-chronological age). Robust regressions tested cross-sectional associations between brain age gap and sleep patterns. Exploratory models investigated moderating effects of age and biological gender and, in a subset of the sample, links between sleep, brain age gap, and depression severity (Patient-Reported Outcomes Measurement Information System Depression). RESULTS: Later sleep timing (midsleep) was associated with more advanced brain aging (larger brain age gap), ß = 0.1575, puncorr = .0042, pfdr = .0167. Exploratory models suggested that this effect may be driven by males, although the interaction of gender and brain age gap did not survive multiple comparison correction (ß = 0.2459, puncorr = .0336, pfdr = .1061). Sleep duration, continuity, and regularity were not significantly associated with brain age gap. Age did not moderate any brain age gap-sleep relationships. In this psychiatrically healthy sample, depression severity was also not associated with brain age gap or sleep. DISCUSSION: Later midsleep may be one behavioral cause or correlate of more advanced brain aging, particularly among males. Future studies should examine whether advanced brain aging and individual differences in sleep precede the onset of suboptimal cognitive-emotional outcomes in adolescents.

Cannabis, connectivity, and coming of age: Associations between cannabis use and anterior cingulate cortex connectivity during the transition to adulthood.

Cannabis use is common among adolescents and emerging adults and is associated with significant adverse consequences for a subset of users. Rates of use peak between the ages of 18-25, yet the neurobiological consequences for neural systems that are actively developing during this time remain poorly understood. In particular, cannabis exposure may interfere with adaptive development of white matter pathways underlying connectivity of the anterior cingulate cortex, including the cingulum and anterior thalamic radiations (ATR). The current study examined the association between cannabis use during adolescence and emerging adulthood and white matter microstructure of the cingulum and ATR among 158 male subjects enrolled in the Pitt Mother and Child Project, a prospective, longitudinal study of risk and resilience among men of low socioeconomic status. Participants were recruited in infancy, completed follow-up assessments throughout childhood and adolescence, and underwent diffusion imaging at ages 20 and 22. At age 20, moderate cannabis use across adolescence (age 12-19) was associated with higher fractional anisotropy (FA) of the cingulum and ATR, relative to both minimal and heavy adolescent use. Longitudinally, moderate and heavy extended cannabis use (age 12-21) was associated with reduced positive change in FA in the cingulum from age 20 to 22, relative to minimal use. These longitudinal results suggest that cannabis exposure may delay cingulum maturation during the transition to adulthood and potentially impact individuals' functioning later in development.

Medial Prefrontal Cortex Activity to Reward Outcome Moderates the Association Between Victimization Due to Sexual Orientation and Depression in Youth.

BACKGROUND: Sexual minority youth (SMY) are 3 times more likely to experience depression than heterosexual peers. Minority stress theory posits that this association is explained by sexual orientation victimization, which acts as a stressor to impact depression. For those vulnerable to the effects of stress, victimization may worsen depression by altering activity in neural reward systems. This study examines whether neural reward systems moderate the influence of sexual orientation victimization, a common and distressing experience in SMY, on depression. METHODS: A total of 81 participants ages 15 to 22 years (41% SMY, 52% marginalized race) reported sexual orientation victimization, depression severity, and anhedonia severity, and underwent a monetary reward functional magnetic resonance imaging task. Significant activation to reward > neutral outcome (pfamilywise error < .05) was determined within a meta-analytically derived Neurosynth reward mask. A univariate linear model examined the impact of reward activation and identity on victimization-depression relationships. RESULTS: SMY reported higher depression (p < .001), anhedonia (p = .03), and orientation victimization (p < .001) than heterosexual youth. The bilateral ventral striatum, medial prefrontal cortex (mPFC), anterior cingulate cortex, and right orbitofrontal cortex were significantly active to reward. mPFC activation moderated associations between sexual orientation victimization and depression (p = .03), with higher depression severity observed in those with a combination of higher mPFC activation and greater orientation victimization. CONCLUSIONS: Sexual orientation victimization was related to depression but only in the context of higher mPFC activation, a pattern observed in depressed youth. These novel results provide evidence for neural reward sensitivity as a vulnerability factor for depression in SMY, suggesting mechanisms for disparities, and are a first step toward a clinical neuroscience understanding of minority stress in SMY.