Nucleus reuniens: Modulating emotional overgeneralization in peri-adolescents with anxiety.

BACKGROUND: Anxiety affects 4.4-million children in the USA with an onset between childhood and adolescence, a period marked by neural changes that impact emotions and memory. Negative overgeneralization - or responding similarly to innocuous events that share features with past aversive experiences - is common in anxiety but remains mechanistically underspecified. The nucleus reuniens (RE) has been considered a crucial candidate in the modulation of memory specificity. Our study investigated its activation and functional connectivity with the medial prefrontal cortex (mPFC) and hippocampus (HPC) as neurobiological mechanisms of negative overgeneralization in anxious youth. METHODS: As part of a secondary data analysis, we examined data from 34 participants between 9 and 14 years of age (mean age ± SD, 11.4 ± 2.0 years; 16 females) with varying degrees of anxiety severity. During the Study session participants rated images as negative, neutral, and positive. After 12 h, participants returned for a Test session, where they performed a memory recognition test with repeated (targets) and similar (lures) images. Labeling negative relative to neutral lures as "old" (false alarms) was our operational definition of negative overgeneralization. RESULTS: Negative relative to neutral false alarmed stimuli displayed elevated RE activation (at Study and Test) and increased functional connectivity with the Cornu Ammonis (CA) 1 (at Test). Elevated anxiety severity was associated with reductions in the RE-mPFC functional coupling for neutral relative to negative stimuli. Exploratory analyses revealed similar patterns in activation and functional connectivity with positive stimuli. CONCLUSIONS: Our findings demonstrate the importance of the RE in negative overgeneralization and anxiety.

Identifying Person-Specific Drivers of Depression in Adolescents: Protocol for a Smartphone-Based Ecological Momentary Assessment and Passive Sensing Study.

BACKGROUND: Adolescence is marked by an increasing risk of depression and is an optimal window for prevention and early intervention. Personalizing interventions may be one way to maximize therapeutic benefit, especially given the marked heterogeneity in depressive presentations. However, empirical evidence that can guide personalized intervention for youth is lacking. Identifying person-specific symptom drivers during adolescence could improve outcomes by accounting for both developmental and individual differences. OBJECTIVE: This study leverages adolescents' everyday smartphone use to investigate person-specific drivers of depression and validate smartphone-based mobile sensing data against established ambulatory methods. We describe the methods of this study and provide an update on its status. After data collection is completed, we will address three specific aims: (1) identify idiographic drivers of dynamic variability in depressive symptoms, (2) test the validity of mobile sensing against ecological momentary assessment (EMA) and actigraphy for identifying these drivers, and (3) explore adolescent baseline characteristics as predictors of these drivers. METHODS: A total of 50 adolescents with elevated symptoms of depression will participate in 28 days of (1) smartphone-based EMA assessing depressive symptoms, processes, affect, and sleep; (2) mobile sensing of mobility, physical activity, sleep, natural language use in typed interpersonal communication, screen-on time, and call frequency and duration using the Effortless Assessment of Risk States smartphone app; and (3) wrist actigraphy of physical activity and sleep. Adolescents and caregivers will complete developmental and clinical measures at baseline, as well as user feedback interviews at follow-up. Idiographic, within-subject networks of EMA symptoms will be modeled to identify each adolescent's person-specific drivers of depression. Correlations among EMA, mobile sensor, and actigraph measures of sleep, physical, and social activity will be used to assess the validity of mobile sensing for identifying person-specific drivers. Data-driven analyses of mobile sensor variables predicting core depressive symptoms (self-reported mood and anhedonia) will also be used to assess the validity of mobile sensing for identifying drivers. Finally, between-subject baseline characteristics will be explored as predictors of person-specific drivers. RESULTS: As of October 2023, 84 families were screened as eligible, of whom 70% (n=59) provided informed consent and 46% (n=39) met all inclusion criteria after completing baseline assessment. Of the 39 included families, 85% (n=33) completed the 28-day smartphone and actigraph data collection period and follow-up study visit. CONCLUSIONS: This study leverages depressed adolescents' everyday smartphone use to identify person-specific drivers of adolescent depression and to assess the validity of mobile sensing for identifying these drivers. The findings are expected to offer novel insights into the structure and dynamics of depressive symptomatology during a sensitive period of development and to inform future development of a scalable, low-burden smartphone-based tool that can guide personalized treatment decisions for depressed adolescents. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43931.

Bridging Gaps in Care Following Hospitalization for Suicidal Adolescents: As Safe As Possible (ASAP) and BRITE App.

OBJECTIVE: We present results from a 2-site, randomized clinical trial to assess the efficacy of a brief intervention (As Safe As Possible [ASAP]), a safety plan phone application (BRITE), and their combination on suicide attempts, suicidal ideation, non-suicidal self-injury, re-hospitalizations. and suicidal events among adolescents. METHOD: Adolescents (n= 240; 12-17 years of age) who were hospitalized for suicidal ideation with plan and/or intent, and/or suicide attempt, were assigned to 1 of 4 treatment conditions in a 2 by 2 design: ASAP+BRITE app+treatment as usual (TAU); (2) BRITE+TAU; (3) ASAP+TAU; and (4) TAU alone. Independent evaluators assessed suicidal ideation and behavior at 4, 12, and 24 weeks using the Columbia-Suicide Severity Rating Scale (C-SSRS) and re-hospitalization using the Child and Adolescent Services Assessment (CASA). RESULTS: No group differences were found on primary outcomes, except that ASAP participants were less likely to be re-hospitalized over 6 months (15.6%, vs 26.5%, p = .046). Participants hospitalized for an attempt and assigned to BRITE had a lower rate of subsequent attempts (odds ratio [OR] = 0.16, p = .01) and a greater time to attempt (hazard ratio [HR] = 0.20, p = .02). ASAP+BRITE, albeit not statistically significant, was most consistently associated with a reduction (60% reduction) in suicide attempts. CONCLUSION: ASAP, BRITE, and their combination are equally effective at decreasing risk for suicidal events 6 months post hospital discharge among suicidal adolescents; the ASAP intervention (with or without BRITE) was associated with lower rates of re-hospitalization. The BRITE app in youth hospitalized for suicide attempt had promising outcomes in regard to future attempts. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. The research was performed with permission from the University of Pittsburgh Institutional Review Board and the University of Texas Institutional Review Board. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. CLINICAL TRIALS REGISTRATION INFORMATION: Establishing Efficacy of an Inpatient Intervention and Phone App to Reduce Suicidal Risk (ASAP+BRITE); https://clinicaltrials.gov/study/; NCT03825588.

Associations between sleep health, negative reinforcement learning, and alcohol use among South Florida college students with elevated internalizing symptoms.

Negative reinforcement is proposed to mediate associations between sleep and alcohol use, especially among people with depression and/or anxiety symptoms. Worse sleep (e.g., shorter duration, less efficiency, more irregular timing) exacerbates negative emotions, which alcohol may temporarily relieve. Not yet examined, we propose sleep indirectly impacts early stages of alcohol use via differences in negative reinforcement learning (NRL), since sleep impacts emotion, reward response, and learning. The current study aimed to replicate associations between sleep and alcohol use, test associations with NRL, and examine indirect associations between sleep health and alcohol use via NRL among 60 underage college students (ages 18-20 years, 77% female) varying in depression and anxiety symptoms. Participants wore Fitbit smartwatches and completed daily diaries measuring sleep and substance use for ∼14 days before completing two computer tasks assessing social (SNRL) and monetary (MNRL) negative reinforcement learning. Robust generalized linear models tested direct associations within the proposed model. SNRL performance was positively associated with alcohol use, but no other associations were observed. Statistical mediation models failed to indicate indirect effects of sleep on alcohol use via SNRL or MNRL performance. Post-hoc exploratory models examining depression and anxiety symptoms as moderators of direct associations indicated several interactions. Positive associations between sleep timing variability and alcohol use were weakened at higher anxiety symptom severity and stronger at higher depression symptom severity. The positive association between SNRL performance and alcohol use was also stronger at higher depression symptom severity. Among students with elevated depression symptoms, variable sleep timing and stronger SNRL performance were independently associated with more alcohol use, but indirect effects were not supported. Future research should replicate findings, confirm causality of interactions, and examine sleep timing and behavioral responses to negative social stimuli as targets for improving alcohol-related outcomes among underage college students with elevated depressive 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.

Attentional Control Accounts for the Association Between Anxiety Sensitivity and Sleep Efficiency in Clinic-Referred Youth.

Youth with anxiety disorders report difficulty falling asleep and returning to sleep after sleep onset (i.e., poor sleep efficiency). Anxiety sensitivity, the excessive attention to physical symptoms of anxiety and their threatening interpretations, has been linked to poor sleep efficiency. We tested a conceptual model wherein attentional control, attentional focusing and attentional shifting would account for the relationship between anxiety sensitivity and poor sleep efficiency. 255 youths (6-17 years old, 78% Hispanic/Latino) who presented to a university-based research clinic completed measures on anxiety sensitivity, sleep, and attentional control. Poorer sleep efficiency was significantly correlated with higher anxiety sensitivity and lower attentional control, attentional focusing, and attentional shifting. Higher anxiety sensitivity was significantly correlated with lower attentional control and attentional focusing. Attentional control and attentional focusing, not attentional shifting, accounted for the relationship between anxiety sensitivity and poor sleep efficiency. These findings identify attentional control and attentional focusing as variables that may explain the association between anxiety sensitivity and sleep efficiency in youth.

Nucleus Reuniens: Modulating Negative Overgeneralization in Periadolescents with Anxiety.

Background: Anxiety affects 4.4-million children in the United States with an onset between childhood and adolescence, a period marked by neural changes that impact emotions and memory. Negative overgeneralization - or responding similarly to innocuous events that share features with past aversive experiences - is common in anxiety but remains mechanistically underspecified. The nucleus reuniens (RE) has been considered a crucial candidate in the modulation of memory specificity. Our study investigated its activation and functional connectivity with the medial prefrontal cortex (mPFC) and hippocampus (HPC) as neurobiological mechanisms of negative overgeneralization in anxious youth. Methods: As part of a secondary data analysis, we examined data from 34 participants between 9-14 years (mean age ± SD, 11.4 ± 2.0 years, 16 females) with varying degrees of anxiety severity. During the Study session participants rated images as negative, neutral, and positive. After 12-hours, participants returned for a Test session, where they performed a memory recognition test with repeated (targets) and similar (lures) images. Labeling negative relative to neutral lures as "old" (false alarms) was our operational definition of negative overgeneralization. Results: Negative relative to neutral false alarmed stimuli displayed elevated RE activation (at Study and Test) and increased functional connectivity with the CA1 (at Test only). Elevated anxiety severity was associated with reductions in the RE-mPFC functional coupling for neutral relative to negative stimuli. Exploratory analyses revealed similar patterns in activation and functional connectivity with positive stimuli. Conclusions: Our findings demonstrate the importance of the RE in the overgeneralization of memories in anxious youth.

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.

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.

Subjective and neural reactivity during savoring and rumination.

Repetitive thinking about negative emotions or events is strongly associated with worse mental health, whereas repetitive positive thought is generally believed to be beneficial. This observation is at odds with the idea that all forms of repetitive thinking share underlying neural mechanisms. To resolve this apparent discrepancy, the present study examined relationships between subjective affect and neural mechanisms during periods of sustained processing of positive (savoring) and negative (rumination) emotion. We also examined potential common moderators of savoring and rumination including memory specificity and sleep quality. Results indicated that individuals who experience high positive affect during savoring also are likely to experience more intense negative affect during rumination. fMRI-derived brain activity revealed common mechanisms of rumination and savoring. Memory specificity had common effects on neural correlates of rumination and savoring; sleep quality was not associated with mechanisms of savoring or rumination. These results suggest that repetitive engagement with positive and negative affect is similar both subjectively and mechanistically. Clinical interventions for rumination may benefit from capitalizing on preserved capacity for savoring.

Development of the Nighttime Parenting Scale: Differentiating nighttime versus general parenting practices and their impact on youth sleep health.

OBJECTIVES: The current study provides a novel method of assessing the impact of nighttime parenting practices on youth sleep health during the sensitive transition from childhood to adolescence (ie., peri-puberty). Specifically, we aimed to advance the measurement of nighttime parenting by developing a conceptually driven questionnaire for use in research and clinical settings. METHOD: A total of 625 parents (67.9% mothers) of peripubertal youth (age M=11.6, SD=1.31) were recruited online and completed self-report questionnaires. The sample was primarily White (67.4%), followed by 16.5% Black, 13.1% Latinx, and 9.6% Asian. Factor structure was examined through four empirically-driven stages (ie, exploratory factor analyses, confirmatory factor analyses, examining internal and test-retest reliability, and indices of validity). Furthermore, the current study sought to validate nighttime parenting as a unique construct by exploring associations with peripubertal youth sleep health. RESULTS: A factor structure consisting of six dimensions of nighttime parenting was established (ie, nighttime supportiveness, hostility, physical control, limit-setting, media monitoring, and co-sleeping behaviors). Furthermore, the current measure demonstrated strong psychometric properties. Finally, the established dimensions were cross-sectionally associated with youth sleep health indices. CONCLUSIONS: This study extends previous research by examining the influence of distinct domains of parenting practices that specifically occur at nighttime and how these differentially relate to youth sleep health. Results suggest that intervention and/or prevention programs targeting sleep should place emphasis on fostering positive parenting at nighttime as a strategy for creating an evening environment that is conducive to optimizing youth sleep health.

Differential effects of emotional valence on mnemonic performance with greater hippocampal maturity.

The hippocampal formation (HF) facilitates declarative memory, with subfields providing unique contributions to memory performance. Maturational differences across subfields facilitate a shift toward increased memory specificity, with peripuberty sitting at the inflection point. Peripuberty is also a sensitive period in the development of anxiety disorders. We believe HF development during puberty is critical to negative overgeneralization, a common feature of anxiety disorders. To investigate this claim, we examined the relationship between mnemonic generalization and a cross-sectional pubertal maturity index (PMI) derived from partial least squares correlation (PLSC) analyses of subfield volumes and structural connectivity from T1-weighted and diffusion-weighted scans, respectively. Participants aged 9-14 yr, from clinical and community sources, performed a recognition task with emotionally valent (positive, negative, and neutral) images. HF volumetric PMI was positively associated with generalization for negative images. Hippocampal-medial prefrontal cortex connectivity PMI evidenced a behavioral relationship similar to that of the HF volumetric approach. These findings reflect a novel developmentally related balance between generalization behavior supported by the hippocampus and its connections with other regions, with maturational differences in this balance potentially contributing to negative overgeneralization during peripuberty.

Sleep fails to depotentiate amygdala-reactivity to negative emotional stimuli in youth with elevated symptoms of anxiety.

Sleep-related problems often precede escalating anxiety in early adolescence. Pushing beyond broad sleep-mental health associations and toward mechanistic theories of their interplay can inform etiological models of psychopathology. Recent studies suggest that sleep depotentiates neural (e.g., amygdala) reactivity during reexposure to negative emotional stimuli in adults. Persistent amygdala reactivity to negative experiences and poor sleep characterize anxiety, particularly at the transition to adolescence. We propose that sleep depotentiates amygdala reactivity in youth but fails to do so among youth with anxiety. Participants (n = 34; 18 males; age, mean [M] = 11.35, standard deviation [SD] = 2.00) recruited from the community and specialty anxiety clinics viewed valenced images (positive, negative, and neutral) across two fMRI sessions (Study, Test), separated by a 10-12-hour retention period of sleep or wake (randomized). Mixed linear models regressed basolateral amygdala (BLA) activation and BLA-medial prefrontal cortex (mPFC) functional connectivity to negative images on Time, Condition, and Anxiety Severity. There were greater reductions in BLA activations to negative target images from Study to Test in the Sleep Condition, which was blunted with higher anxiety (b = -0.065, z = -2.355, p = 0.019). No such sleep- or anxiety-related effects were observed for BLA-mPFC functional connectivity (ps > 0.05). Sleep supports depotentiation of amygdala reactivity to negative stimuli in youth, but this effect is blunted at higher levels of anxiety. Disruptions in sleep-related affective habituation may be a critical, modifiable driver of anxiety.

The Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric and parent-proxy short forms for anxiety: Psychometric properties in the Kids FACE FEARS sample.

There is tremendous need for brief and supported, non-commercial youth- and caregiver-report questionnaires of youth anxiety. The pediatric and parent proxy short forms of the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety scale (8a v2.0) are free, brief, publicly accessible measures of youth- and caregiver-reported anxiety in children and adolescents. Despite increased use of the PROMIS, no study has evaluated performance of its anxiety scales in a sample of treatment-engaged anxious youth. Analyses were conducted on baseline data from the first 265 families (child MAge=11.14 years, 70% racial/ethnic minoritized youth) to enroll in the Kids FACE FEARS trial, a multisite comparative effectiveness trial of therapist-led vs. self-administered treatment for elevated youth anxiety. Confirmatory factor analysis (CFA) examined factor structure; omega coefficients and regression models examined internal consistency, convergent validity, and cross-informant reliability. CFA supported adjusted single-factor solutions across youth and caregiver reports, and internal consistency was high. Convergent validity was supported by medium-to-large associations with anxiety-related impairment and severity. Moderate cross-informant reliability between reports was found. Results showcase the first psychometric study of the PROMIS Anxiety scale short forms among treatment-engaged youth with elevated anxiety. Findings highlight the PROMIS Anxiety scale's utility in typical care settings for youth anxiety.

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.

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.

The late positive potential during affective picture processing: Associations with daily life emotional functioning among adolescents with anxiety disorders.

Pediatric anxiety disorders are characterized by potentiated threat responses and maladaptive emotion regulation (ER). The Late Positive Potential (LPP) is a neural index of heightened attention to emotional stimuli. Anxious individuals typically exhibit a larger LPP to unpleasant stimuli, but the LPP may also be blunted to unpleasant and pleasant stimuli for those with co-morbid depression. While a larger LPP is thought to reflect greater emotional reactivity, it is unknown to what extent variation in the LPP to laboratory stimuli corresponds to daily emotional functioning. We assessed the LPP in the laboratory in response to unpleasant, pleasant, and neutral images in combination with ecological momentary assessment of emotional reactivity and regulation in daily life among youth (9-14 years old; 55 % female) with anxiety disorders (ANX, N = 130) and no psychiatric diagnoses (ND, N = 47). We tested whether LPP amplitudes to unpleasant and pleasant stimuli (vs. neutral) are greater in ANX (vs. ND) youth and whether LPP amplitudes inversely correlate with co-morbid depression symptoms. We also examined associations between the LPP and daily life emotional functioning among ANX and ND youth. We found no group-by-valence effects on LPP amplitudes. Within ANX youth, higher depression symptoms were associated with smaller LPP amplitudes to unpleasant, but not pleasant, stimuli relative to neutral stimuli. Larger LPP amplitudes to emotional (relative to neutral) stimuli were correlated with use of specific ER strategies among ANX and ND youth but not emotional reactivity. While the LPP may reflect initial emotional reactivity to laboratory stimuli, it is associated with ER behaviors, and not emotional reactivity, in daily life.

Sleep to Internalizing Pathway in Young Adolescents (SIPYA): A proposed neurodevelopmental model.

The prevalence of internalizing disorders, i.e., anxiety and depressive disorders, spikes in adolescence and has been increasing amongst adolescents despite the existence of evidence-based treatments, highlighting the need for advancing theories on how internalizing disorders emerge. The current review presents a theoretical model, called the Sleep to Internalizing Pathway in Young Adolescents (SIPYA) Model, to explain how risk factors, namely sleep-related problems (SRPs), are prospectively associated with internalizing disorders in adolescence. Specifically, SRPs during late childhood and early adolescence, around the initiation of pubertal development, contribute to the interruption of intrinsic brain networks dynamics, both within the default mode network and between the default mode network and other networks in the brain. This interruption leaves adolescents vulnerable to repetitive negative thought, such as worry or rumination, which then increases vulnerability to internalizing symptoms and disorders later in adolescence. Sleep-related behaviors are observable, modifiable, low-stigma, and beneficial beyond treating internalizing psychopathology, highlighting the intervention potential associated with understanding the neurodevelopmental impact of SRPs around the transition to adolescence. This review details support for the SIPYA Model, as well as gaps in the literature and future directions.