Sleep-sensitive dopamine receptor expression in male mice underlies attention deficits after a critical period of early adversity.

Early life stress (ELS) yields cognitive impairments of unknown molecular and physiological origin. We found that fragmented maternal care of mice during a neonatal critical period from postnatal days P2-9 elevated dopamine receptor D2R and suppressed D4R expression, specifically within the anterior cingulate cortex (ACC) in only the male offspring. This was associated with poor performance on a two-choice visual attention task, which was acutely rescued in adulthood by local or systemic pharmacological rebalancing of D2R/D4R activity. Furthermore, ELS male mice demonstrated heightened hypothalamic orexin and persistently disrupted sleep. Given that acute sleep deprivation in normally reared male mice mimicked the ACC dopamine receptor subtype modulation and disrupted attention of ELS mice, sleep loss likely underlies cognitive deficits in ELS mice. Likewise, sleep impairment mediated the attention deficits associated with early adversity in human children, as demonstrated by path analysis on data collected with multiple questionnaires for a large child cohort. A deeper understanding of the sex-specific cognitive consequences of ELS thus has the potential to reveal therapeutic strategies for overcoming them.

Risk for Suicide Attempts Assessed Using the Patient Health Questionnaire-9 Modified for Teens.

Importance: Suicide is a leading cause of death in US youths. Objective: To assess whether screening with supplemental items 10 to 13 on the Patient Health Questionnaire-9 modified for teens (PHQ-9M) improves prediction of youth suicide attempts beyond the information provided by the first 9 items alone (the PHQ-9). Design, Setting, and Participants: This retrospective cohort study used a retrospective cohort of adolescents aged 12 to 17 years who were screened for depression in outpatient facilities within a pediatric health care system between January 1, 2016, and December 31, 2022, with up to 1 year of follow-up to assess the occurrence of suicidal behavior. Follow-up was completed on December 31, 2023. Exposure: Screening with the PHQ-9M. Main Outcomes and Measures: This study developed and compared prediction using 3 Cox proportional hazards regression models (CR-9, CR-13, and CR-3) of subsequent suicide attempts, determined by the hospital's electronic health records up to 1 year following the last PHQ-9M screening. The CR-9 model used the PHQ-9 and the CR-13 model used all 13 items of PHQ-9M. The CR-3 model used the 3 most impactful variables selected from the 13 PHQ-9M items and PHQ-9 total score. All models were evaluated across 4 prediction horizons (30, 90, 180, and 365 days) following PHQ-9M screenings. Evaluation metrics were the area under the receiver operating characteristic curve (AUROC) and the area under the precision recall curve (AUPRC). Results: Of 130 028 outpatients (65 520 [50.4%] male) with 272 402 PHQ-9M screenings, 549 (0.4%) had subsequent suicide attempts within 1 year following the PHQ-9M screening. The AUROC of the CR-9 model in the 365-day horizon was 0.77 (95% CI, 0.75-0.79); of the CR-13 model, 0.80 (95% CI, 0.78-0.82); and of the CR-3 model, 0.79 (95% CI, 0.76-0.81); the AUPRC of the CR-9 model was 0.02 (95% CI, 0.02-0.03); of the CR-13 model, 0.03 (95% CI, 0.02-0.03); and of the CR-3 model, 0.02 (95% CI, 0.02-0.03). The 3 most impactful items using adjusted hazard ratios were supplemental item 13 (lifetime suicide attempts; 3.06 [95% CI, 2.47-3.80]), supplemental item 10 (depressed mood severity in the past year; 2.99 [95% CI, 2.32-3.86]), and supplemental item 12 (serious suicidal ideation in the past month; 1.63 [95% CI, 1.25-2.12]). All of the models achieved higher AUROCs as prediction horizons shortened. Conclusions and Relevance: In this cohort study of adolescent PHQ-9M screenings, the supplemental items on PHQ-9M screening improved prediction of youth suicide attempts compared with screening using the PHQ-9 across all prediction horizons, suggesting that PHQ-9M screening should be considered during outpatient visits to improve prediction of suicide attempts.

Two-year trajectories of anhedonia in adolescents at transdiagnostic risk for severe mental illness: Association with clinical symptoms and brain-symptom links.

Anhedonia emerges during adolescence and is characteristic of severe mental illness (SMI). To understand how anhedonia emerges, changes with time, and relates with other symptoms, there is a need to understand patterns of this symptom's course reflecting change or stability-and associations with clinical symptoms and neural reward circuitry in adolescents at risk of SMI. In total, 113 adolescents at low or high familial risk of developing SMI completed clinical measures at up to five time points across 2 years and functional magnetic resonance imaging scanning during a guessing reward task at baseline. Growth curve analysis was used to determine the trajectory of anhedonia across 2 years, including different phases (consummatory and anticipatory) and their association with clinical features (risk status, average suicidal ideation, and average depression across time) and neural activation in response to rewards (ventral striatum and dorsal medial prefrontal cortex). The findings revealed anhedonia decreased across 2 years. Furthermore, lower depression severity was associated with decreases in anhedonia across 2 years. There were no interactions between neural reward activation and anhedonia slopes in predicting clinical features. Exploratory analyses examining latent classes revealed three trajectory classes of anhedonia across phases. While preliminary, in the low and decreasing consummatory anhedonia trajectory class, there was a positive association between neural activation of the right ventral striatum in response to rewards and depression. Certain patterns of anhedonia development could confer risk or resilience for specific types of psychopathologies. The results are preliminary but do highlight the complexity and heterogeneity in anhedonia development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Predictive Validity of the K-CAT-SS in High-Risk Adolescents and Young Adults.

OBJECTIVE: Suicide is a leading cause of death in adolescents and young adults and has increased substantially in the past 15 years. Accurate suicide risk stratification based on rapid screening can help reverse these trends. This study aimed to assess the ability of the Kiddie Computerized Adaptive Test Suicide Scale (K-CAT-SS), a brief computerized adaptive test of suicidality, to predict suicide attempts (SAs) in high-risk youth. METHOD: A total of 652 participants (age range, 12-24 years), 78% of whom presented with suicidal ideation or behavior, were recruited within 1 month of mental health care contact. The K-CAT-SS, scaled from 0 to 100, was administered at baseline, and participants were assessed at about 1, 3, and 6 months after intake. Weekly incidence of SAs was assessed using the Adolescent Longitudinal Interval Follow-up Evaluation and Columbia-Suicide Severity Rating Scale. A secondary outcome was suicidal behavior, including aborted, interrupted, and actual SAs. RESULTS: The K-CAT-SS showed a 4.91-fold increase in SAs for every 25-point increase in the baseline score (95% CI 2.83-8.52) and a 3.51-fold increase in suicidal behaviors (95% CI 2.32-5.30). These relations persisted following adjustment for prior attempts; demographic variables including age, sex, gender identity, sexual orientation, and race/ethnicity; and other measures of psychopathology. No moderating effects were identified. At 3 months, area under the receiver operating characteristic curve was 0.83 (95% CI 0.72-0.93) for 1 or more SAs. CONCLUSION: The K-CAT-SS is an excellent tool for suicide risk stratification, particularly in higher-risk populations where other measures have shown lower predictive validity.

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.

Adolescent, Parent, and Provider Perceptions of a Predictive Algorithm to Identify Adolescent Suicide Risk in Primary Care.

OBJECTIVE: To understand adolescent, parent, and provider perceptions of a machine learning algorithm for detecting adolescent suicide risk prior to its implementation primary care. METHODS: We conducted semi-structured, qualitative interviews with adolescents (n = 9), parents (n = 12), and providers (n = 10; mixture of behavioral health and primary care providers) across two major health systems. Interviews were audio recorded and transcribed with analyses supported by use of NVivo. A codebook was developed combining codes derived inductively from interview transcripts and deductively from implementation science frameworks for content analysis. RESULTS: Reactions to the algorithm were mixed. While many participants expressed privacy concerns, they believed the algorithm could be clinically useful for identifying adolescents at risk for suicide and facilitating follow-up. Parents' past experiences with their adolescents' suicidal thoughts and behaviors contributed to their openness to the algorithm. Results also aligned with several key Consolidated Framework for Implementation Research domains. For example, providers mentioned barriers inherent to the primary care setting such as time and resource constraints likely to impact algorithm implementation. Participants also cited a climate of mistrust of science and health care as potential barriers. CONCLUSIONS: Findings shed light on factors that warrant consideration to promote successful implementation of suicide predictive algorithms in pediatric primary care. By attending to perspectives of potential end users prior to the development and testing of the algorithm, we can ensure that the risk prediction methods will be well-suited to the providers who would be interacting with them and the families who could benefit.

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.

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.

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.

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.

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.

Examining Factors Associated With Medication Adherence in Youth With Bipolar Disorder.

Objective: To assess medication adherence and factors associated with poor adherence in youth with bipolar disorder (BD) followed from adolescence through young adulthood. Method: Participants with BD recruited through the Course and Outcome of Bipolar Youth (COBY) study were included in this study if they were prescribed psychotropic medications and had at least 3 follow-up assessments of medication adherence (N= 179, ages 12-36). Medication adherence had been evaluated for a median of 8 years using a questionnaire derived from the Coronary Artery Risk Development in Young Adults (CARDIA) study. For the longitudinal evaluation, adherence was measured as the percentage of follow-up assessments in which the participants did not endorse any of the nonadherence items included in the questionnaire. Concurrent and future predictors of poor adherence were assessed using both univariate and multivariate longitudinal analyses. Results: Among the participants, 51% reported poor adherence in more than 50% of their follow-up assessments. Younger age, family conflicts, polypharmacy, lower functioning, greater severity of mood symptoms, and comorbid disorders were associated with poor adherence in the univariate analyses. In the multivariate analyses, comorbid ADHD was the single most influential factor associated with concurrent and future poor adherence in all age groups. Participants' most reported reasons for poor adherence were forgetfulness (56%), negative attitudes toward medication treatment (10.5%), and disturbed daily routine (7%). Conclusions: Poor medication adherence is a significant problem in youth with BD with the most influential factor being the presence of comorbid ADHD. Thus, it is important to identify and appropriately treat comorbid ADHD to improve medication adherence and patients' prognosis. Providers should also recommend tools to enhance consistent medication intake and address patients' concerns and negative beliefs about their illness and treatment.

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.

Neural indices of performance monitoring are associated with daily emotional functioning in youth with anxiety disorders: An ERP and EMA study.

Excessive monitoring of one's performance is a characteristic of anxiety disorders that has been linked to alterations in implicit emotion regulation (ER), including elevations in neural measures of performance monitoring (i.e., error- and correct-related negativity; ERN and CRN). Elevations in ERN and CRN amplitudes have been reported consistently in anxiety disorders, suggesting that an overactive performance monitoring system is linked to ER difficulties in anxiety. Yet, the relevance of these lab-based neural measures for day-to-day emotional functioning remains poorly understood. This study examined the degree to which ERN and CRN amplitudes are associated with measures of daily ER difficulties in youth with anxiety disorders. Youth (N = 100, Mage = 11.14, SDage = 1.46) completed a computerized flanker task assessing the ERN and CRN. They then completed a 5-day ecological momentary assessment (EMA) protocol assessing their daily ER (i.e., intensity of momentary and peak negative affect, intensity of worry, reliance on maladaptive ER strategies). Results showed that more negative mean CRN amplitudes were associated with higher levels of negative emotional reactivity and more intense worries. There were no significant associations between ERN amplitude and EMA measures. Furthermore, elevations in CRN were linked to more frequent use of maladaptive ER strategies (i.e., rumination, physiological reactivity, avoidance). Together, results indicate that among youth with anxiety, individual differences in CRN, but not ERN, amplitudes are related to daily ER difficulties. Findings highlight the clinical utility of a lab-based neural measure of ER, suggesting that the CRN, rather than the ERN, reflects individual ER differences in the context of daily life among youth with pediatric anxiety disorders. As such, the CRN might serve as an important dimensional index of a treatment target that can be tracked with a validated, multi-method measure.

Risk factors preceding new onset abuse among youth with bipolar disorder: A longitudinal prospective analysis.

BACKGROUND: Childhood abuse negatively impacts the course of Bipolar Disorder (BD). Yet, no study has examined risk factors associated with prospectively evaluated physical/sexual abuse, specifically, those preceding first abuse among BD youth. We investigate past/intake/follow-up factors preceding first physical/sexual abuse among BD youth. METHODS: Childhood-onset BD participants (n = 279 youth, mean age at intake = 12, mean length of follow-up = 12 years) enrolled in the Course and Outcome of Bipolar Youth (COBY) study. Demographic, clinical and family history variables were assessed every 7 months on average using Longitudinal Interval Follow-up Evaluation and Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL). Abuse was evaluated at intake using the K-SADS-PL, over follow-up with a Traumatic Events Screen. Family psychopathology was assessed using Family History Screen/Structured Clinical Interview for Diagnostic Statistical Manual-IV. RESULTS: Fifteen-percent of youth reported new-onset abuse during follow-up (62% physical, 26% sexual; 12% both). Intake predictors included more severe depressive symptoms (HR = 1.29), low socioeconomic-status (SES) in families with substance abuse (HR = 0.84) (physical abuse), and female sex (HR = 2.41) (sexual abuse). Follow-up predictors preceding physical abuse included: older age (HR = 1.42), disruptive disorders (HR = 1.39), and the interaction between low SES and family substance abuse (HR = 0.86). For sexual abuse, female sex (HR = 4.33) and a non-biologically related father presence in the household (HR = 2.76). Good relationships with friends (prospectively evaluated) protected against physical/sexual abuse (HR = 0.72/0.70, respectively). LIMITATIONS: Prospective data was gathered longitudinally but assessed retrospectively at every follow-up; perpetrator information and abuse severity were not available. CONCLUSIONS: Identifying factors temporally preceding new onset physical/sexual abuse may hold promise for identifying high-risk youth with BD.

Adolescent depression screening in primary care: Who is screened and who is at risk?

BACKGROUND: Limited research has simultaneously focused on sociodemographic differences in who receives recommended adolescent depression screening in primary care and who endorses elevated depression and suicide risk on these screeners. We describe screening and risk rates in a large pediatric primary care network in the United States after the network expanded its universal depression screening guideline to cover all well-visits (i.e., annual medical checkups) for adolescents ages 12 and older. METHODS: Between November 15, 2017 and February 1, 2020, there were 122,682 well-visits for adolescents ages 12-17 (82,531 unique patients). The Patient Health Questionnaire - Modified for Teens (PHQ-9-M) was administered to screen for depression. RESULTS: A total of 99,961 PHQ-9-Ms were administered (screening rate=81.48%). The likelihood of screening was higher among adolescents who were female, 12-14 years of age at their first well-visit during the study, White, Hispanic/Latino, or publicly-insured (i.e., Medicaid-insured). Additionally, 5.92% of adolescents scored in the threshold range for depression symptoms and 7.19% endorsed suicidality. Heightened depression and suicide risk were observed among adolescents who were female, 15-17 years of age at their first well-visit during the study, Black, Hispanic/Latino, attending urban primary care practices, or Medicaid-insured. Odds of endorsing suicidality were also higher among teens who identified as other races. LIMITATIONS: Limitations related to data available in the electronic health record and reliance on data from a single hospital system are noted. CONCLUSIONS: Findings highlight misalignments in screening and risk status that are important to address to ensure more equitable screening implementation and health outcomes.

Inter-class Concomitant Pharmacotherapy in Medicaid-Insured Youth Receiving Psychiatric Residential Treatment.

Background: Concomitant pharmacotherapy has become increasingly common in the treatment of youth, including in psychiatric residential treatment facilities (PRTF) despite limited efficacy and safety data. Research is reported on the prevalence of any class and interclass concomitant pharmacotherapy, specific class combinations of psychotropics, and changes in number of medications from admission to discharge for Medicaid insured youth treated in PRTFs in one mid-Atlantic state. Methods: Medicaid administrative claims data were examined for youth under age 18 years who were discharged from one of 21 PRTFs during calendar year 2019. Descriptive statistics were calculated to examine patterns of service utilization 90 days prior to admission. The rates of concomitant psychotropic use at admission were compared to the rates at discharge. Logistic regression models were used to examine covariates associated with discharging on 4 or more medications. Results: Fifty-four % of youth were admitted on either two or three psychotropics, while 25% were admitted on four or more psychotropics. The proportion of youth admitting and discharging on 2 or 3 medications was stable. There was a 27% increase in number of youth discharging on 4 medications with a 24% decrease in those on a 5- drug regimen. Only the number of medications prescribed at admission was found to be significant (p < 0.001), with more medications at admission contributing to probability of discharging on 4 or more medications. Conclusions: Concomitant pharmacotherapy is common in PRTFs. These findings support the practice of deprescribing and underscore the need for further research.

Associations between brain structure and sleep patterns across adolescent development.

STUDY OBJECTIVES: Structural brain maturation and sleep are complex processes that exhibit significant changes over adolescence and are linked to many physical and mental health outcomes. We investigated whether sleep-gray matter relationships are developmentally invariant (i.e. stable across age) or developmentally specific (i.e. only present during discrete time windows) from late childhood through young adulthood. METHODS: We constructed the Neuroimaging and Pediatric Sleep Databank from eight research studies conducted at the University of Pittsburgh (2009-2020). Participants completed a T1-weighted structural MRI scan (sMRI) and 5-7 days of wrist actigraphy to assess naturalistic sleep. The final analytic sample consisted of 225 participants without current psychiatric diagnoses (9-25 years). We extracted cortical thickness and subcortical volumes from sMRI. Sleep patterns (duration, timing, continuity, regularity) were estimated from wrist actigraphy. Using regularized regression, we examined cross-sectional associations between sMRI measures and sleep patterns, as well as the effects of age, sex, and their interaction with sMRI measures on sleep. RESULTS: Shorter sleep duration, later sleep timing, and poorer sleep continuity were associated with thinner cortex and altered subcortical volumes in diverse brain regions across adolescence. In a discrete subset of regions (e.g. posterior cingulate), thinner cortex was associated with these sleep patterns from late childhood through early-to-mid adolescence but not in late adolescence and young adulthood. CONCLUSIONS: In childhood and adolescence, developmentally invariant and developmentally specific associations exist between sleep patterns and gray matter structure, across brain regions linked to sensory, cognitive, and emotional processes. Sleep intervention during specific developmental periods could potentially promote healthier neurodevelopmental outcomes.