Enhancing post-traumatic stress disorder patient assessment: leveraging natural language processing for research of domain criteria identification using electronic medical records.

BACKGROUND: Extracting research of domain criteria (RDoC) from high-risk populations like those with post-traumatic stress disorder (PTSD) is crucial for positive mental health improvements and policy enhancements. The intricacies of collecting, integrating, and effectively leveraging clinical notes for this purpose introduce complexities. METHODS: In our study, we created a natural language processing (NLP) workflow to analyze electronic medical record (EMR) data and identify and extract research of domain criteria using a pre-trained transformer-based natural language model, all-mpnet-base-v2. We subsequently built dictionaries from 100,000 clinical notes and analyzed 5.67 million clinical notes from 38,807 PTSD patients from the University of Pittsburgh Medical Center. Subsequently, we showcased the significance of our approach by extracting and visualizing RDoC information in two use cases: (i) across multiple patient populations and (ii) throughout various disease trajectories. RESULTS: The sentence transformer model demonstrated high F1 macro scores across all RDoC domains, achieving the highest performance with a cosine similarity threshold value of 0.3. This ensured an F1 score of at least 80% across all RDoC domains. The study revealed consistent reductions in all six RDoC domains among PTSD patients after psychotherapy. We found that 60.6% of PTSD women have at least one abnormal instance of the six RDoC domains as compared to PTSD men (51.3%), with 45.1% of PTSD women with higher levels of sensorimotor disturbances compared to men (41.3%). We also found that 57.3% of PTSD patients have at least one abnormal instance of the six RDoC domains based on our records. Also, veterans had the higher abnormalities of negative and positive valence systems (60% and 51.9% of veterans respectively) compared to non-veterans (59.1% and 49.2% respectively). The domains following first diagnoses of PTSD were associated with heightened cue reactivity to trauma, suicide, alcohol, and substance consumption. CONCLUSIONS: The findings provide initial insights into RDoC functioning in different populations and disease trajectories. Natural language processing proves valuable for capturing real-time, context dependent RDoC instances from extensive clinical notes.

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.

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.

A risk calculator to predict suicide attempts among individuals with early-onset bipolar disorder.

OBJECTIVES: To build a one-year risk calculator (RC) to predict individualized risk for suicide attempt in early-onset bipolar disorder. METHODS: Youth numbering 394 with bipolar disorder who completed ≥2 follow-up assessments (median follow-up length = 13.1 years) in the longitudinal Course and Outcome of Bipolar Youth (COBY) study were included. Suicide attempt over follow-up was assessed via the A-LIFE Self-Injurious/Suicidal Behavior scale. Predictors from the literature on suicidal behavior in bipolar disorder that are readily assessed in clinical practice were selected and trichotomized as appropriate (presence past 6 months/lifetime history only/no lifetime history). The RC was trained via boosted multinomial classification trees; predictions were calibrated via Platt scaling. Half of the sample was used to train, and the other half to independently test the RC. RESULTS: There were 249 suicide attempts among 106 individuals. Ten predictors accounted for >90% of the cross-validated relative influence in the model (AUC = 0.82; in order of relative influence): (1) age of mood disorder onset; (2) non-suicidal self-injurious behavior (trichotomized); (3) current age; (4) psychosis (trichotomized); (5) socioeconomic status; (6) most severe depressive symptoms in past 6 months (trichotomized none/subthreshold/threshold); (7) history of suicide attempt (trichotomized); (8) family history of suicidal behavior; (9) substance use disorder (trichotomized); (10) lifetime history of physical/sexual abuse. For all trichotomized variables, presence in the past 6 months reliably predicted higher risk than lifetime history. CONCLUSIONS: This RC holds promise as a clinical and research tool for prospective identification of individualized high-risk periods for suicide attempt in early-onset bipolar disorder.

Classifying social determinants of health from unstructured electronic health records using deep learning-based natural language processing.

OBJECTIVE: Social determinants of health (SDOH) are non-medical factors that can profoundly impact patient health outcomes. However, SDOH are rarely available in structured electronic health record (EHR) data such as diagnosis codes, and more commonly found in unstructured narrative clinical notes. Hence, identifying social context from unstructured EHR data has become increasingly important. Yet, previous work on using natural language processing to automate extraction of SDOH from text (a) usually focuses on an ad hoc selection of SDOH, and (b) does not use the latest advances in deep learning. Our objective was to advance automatic extraction of SDOH from clinical text by (a) systematically creating a set of SDOH based on standard biomedical and psychiatric ontologies, and (b) training state-of-the-art deep neural networks to extract mentions of these SDOH from clinical notes. DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC-III) database. The corpus comprised 3,504 social related sentences from 2,670 clinical notes. METHODS: We developed a framework for automated classification of multiple SDOH categories. Our dataset comprised narrative clinical notes under the "Social Work" category in the MIMIC-III Clinical Database. Using standard terminologies, SNOMED-CT and DSM-IV, we systematically curated a set of 13 SDOH categories and created annotation guidelines for these. After manually annotating the 3,504 sentences, we developed and tested three deep neural network (DNN) architectures - convolutional neural network (CNN), long short-term memory (LSTM) network, and the Bidirectional Encoder Representations from Transformers (BERT) - for automated detection of eight SDOH categories. We also compared these DNNs to three baselines models: (1) cTAKES, as well as (2) L2-regularized logistic regression and (3) random forests on bags-of-words. Model evaluation metrics included micro- and macro- F1, and area under the receiver operating characteristic curve (AUC). RESULTS: All three DNN models accurately classified all SDOH categories (minimum micro-F1 = 0.632, minimum macro-AUC = 0.854). Compared to the CNN and LSTM, BERT performed best in most key metrics (micro-F1 = 0.690, macro-AUC = 0.907). The BERT model most effectively identified the "occupational" category (F1 = 0.774, AUC = 0.965) and least effectively identified the "non-SDOH" category (F = 0.491, AUC = 0.788). BERT outperformed cTAKES in distinguishing social vs non-social sentences (BERT F1 = 0.87 vs. cTAKES F1 = 0.06), and outperformed logistic regression (micro-F1 = 0.649, macro-AUC = 0.696) and random forest (micro-F1 = 0.502, macro-AUC = 0.523) trained on bag-of-words. CONCLUSIONS: Our study framework with DNN models demonstrated improved performance for efficiently identifying a systematic range of SDOH categories from clinical notes in the EHR. Improved identification of patient SDOH may further improve healthcare outcomes.

Changes in Affective Network Variability Among Youth Treated for Anxiety Disorders.

Cognitive behavioral therapy (CBT) has been shown to be an efficacious treatment for youth anxiety, but we need to know more about the process of change. Affective network variability, or the "spread" of positive and negative emotions activated across a given time period, has been found to be positively associated with anxiety disorder symptomatology, but it is not yet known how this construct changes in response to intervention or its association with anxiety-focused treatment outcomes. The present study used a dynamical systems framework to model ecological momentary assessment (EMA) data collected via a cellular telephone from 114 youth aged 9-14 years (Mage = 10.94, SD = 1.46) who were seeking treatment for a primary anxiety disorder. We examined patterns of affective network variability over time and across (a) CBT and (b) client-centered therapy (CCT) to determine whether affective network changes were specific to CBT or due to nonspecific factors. Associations between treatment outcomes and patterns of affect at pretreatment and over the course of the treatments were also examined. Results revealed significant decreases in affective network variability over the course of treatment for youth who received CBT, but not for youth who received CCT. Changes in affective network variability over the course of treatment did not predict treatment outcomes. Findings provide initial support for the dynamical systems approach to examining changes that occur during treatment. Implications and future research are discussed.

Prospectively ascertained mania and hypomania among young adults with child- and adolescent-onset bipolar disorder.

OBJECTIVES: While adults with bipolar disorder (BD) often report symptoms starting in childhood, continuity of mania and/or hypomania (mania/hypomania) from childhood to adulthood has been questioned. Using longitudinal data from the Course and Outcome of Bipolar Youth (COBY) study, we assessed threshold mania/hypomania in young adults who manifested BD as youth. METHODS: COBY is a naturalistic, longitudinal study of 446 youth with BD (84% recruited from outpatient clinics), 7-17 years old at intake, and over 11 years of follow-up. Focusing on youth with BD-I/II (n = 297), we examined adult mania/hypomania risk (>18 years old; mean 7.9 years of follow-up) according to child (<13 years old) versus adolescent (13-17 years old) onset. We next used penalized regression to test demographic and clinical predictors of young adult mania/hypomania. RESULTS: Most participants (64%) had child-onset mania/hypomania, 57% of whom also experienced mania/hypomania in adolescence. Among those who experienced an episode in adolescence, over 40% also had mania/hypomania during adulthood; the risk did not differ according to child versus adolescent onset. In contrast, 7% with mania/hypomania in childhood, but not adolescence, experienced mania/hypomania in adulthood. Family history (of mania and suicide attempts) predicted mania/hypomania in young adulthood (p-values <0.05); age of onset was not a significant predictor. Among participants with no mania/hypomania during adulthood, 53% (105/198) still experienced subthreshold manic episodes. DISCUSSION: We find substantial continuity across developmental stage indicating that, in this carefully characterized sample, children who experience mania/hypomania-particularly those who also experience mania/hypomania in adolescence-are likely to experience mania/hypomania in young adulthood.

A Bayesian multilevel analysis of the longitudinal associations between relationship quality and suicidal ideation and attempts among youth with bipolar disorder.

BACKGROUND: Youth with bipolar disorder (BD) are at high risk for suicidal thoughts and behaviors and frequently experience interpersonal impairment, which is a risk factor for suicide. Yet, no study to date has examined the longitudinal associations between relationship quality in family/peer domains and suicidal thoughts and behaviors among youth with BD. Thus, we investigated how between-person differences - reflecting the average relationship quality across time - and within-person changes, reflecting recent fluctuations in relationship quality, act as distal and/or proximal risk factors for suicidal ideation (SI) and suicide attempts. METHODS: We used longitudinal data from the Course and Outcome of Bipolar Youth Study (N = 413). Relationship quality variables were decomposed into stable (i.e., average) and varying (i.e., recent) components and entered, along with major clinical covariates, into separate Bayesian multilevel models predicting SI and suicide attempt. We also examined how the relationship quality effects interacted with age and sex. RESULTS: Poorer average relationship quality with parents (ß = -.33, 95% Bayesian highest density interval (HDI) [-0.54, -0.11]) or friends (ß = -.33, 95% HDI [-0.55, -0.11]) was longitudinally associated with increased risk of SI but not suicide attempt. Worsening recent relationship quality with parents (ß = -.10, 95% HDI [-0.19, -0.03]) and, to a lesser extent, friends (ß = -.06, 95% HDI [-0.15, 0.03]) was longitudinally associated with increased risk of SI, but only worsening recent relationship quality with parents was also associated with increased risk of suicide attempt (ß = -.15, 95% HDI [-0.31, 0.01]). The effects of certain relationship quality variables were moderated by gender but not age. CONCLUSIONS: Among youth with BD, having poorer average relationship quality with peers and/or parents represents a distal risk factor for SI but not suicide attempts. Additionally, worsening recent relationship quality with parents may be a time-sensitive indicator of increased risk for SI or suicide attempt.

Parents still matter! Parental warmth predicts adolescent brain function and anxiety and depressive symptoms 2 years later.

Anxiety is the most prevalent psychological disorder among youth, and even following treatment, it confers risk for anxiety relapse and the development of depression. Anxiety disorders are associated with heightened response to negative affective stimuli in the brain networks that underlie emotion processing. One factor that can attenuate the symptoms of anxiety and depression in high-risk youth is parental warmth. The current study investigates whether parental warmth helps to protect against future anxiety and depressive symptoms in adolescents with histories of anxiety and whether neural functioning in the brain regions that are implicated in emotion processing and regulation can account for this link. Following treatment for anxiety disorder (Time 1), 30 adolescents (M age = 11.58, SD = 1.26) reported on maternal warmth, and 2 years later (Time 2) they participated in a functional neuroimaging task where they listened to prerecorded criticism and neutral statements from a parent. Higher maternal warmth predicted lower neural activation during criticism, compared with the response during neutral statements, in the left amygdala, bilateral insula, subgenual anterior cingulate (sgACC), right ventrolateral prefrontal cortex, and anterior cingulate cortex. Maternal warmth was associated with adolescents' anxiety and depressive symptoms due to the indirect effects of sgACC activation, suggesting that parenting may attenuate risk for internalizing through its effects on brain function.

Longitudinal course and risk factors associated with psychosis in bipolar youths.

OBJECTIVES: To compare the longitudinal clinical course of youths with bipolar disorder (BD) spectrum with lifetime (past, intake, and/or follow-up) psychosis (BDP+) to youths with BD without lifetime psychosis (BDP-). Also, to identify risk factors associated with increased risk of first onset of psychosis during prospective follow-up. METHOD: Bipolar disorder youths (BDP+ = 137, BDP- = 233), aged 7-17 years old, were followed on average every 7 months for 11.7 years and were evaluated using standardized instruments. Data were analyzed using linear and generalized linear models for the full sample, as well as for youths who developed first period of psychosis (n = 55). RESULTS: After adjusting for confounders, BDP+ youths with one, and in particular ≥2 lifetime psychotic episodes, had higher rates and more severe mood and anxiety symptoms, higher rates of suicidality, psychiatric hospitalizations, and sexual/physical abuse, and poorer psychosocial functioning than BDP- youths. Even before the first onset of psychosis during follow-up, BDP+ youths showed more psychopathology and had more family history of psychiatric illness than those who never developed psychosis. First-onset psychosis was associated with low socioeconomic status (SES), living with one parent, bipolar disorder type one and type two, comorbid anxiety, history of hospitalizations, and family history of mania and suicidality. CONCLUSION: BDP+ is associated with poor prognosis and worse clinical picture, even before the onset of psychosis, indicating the need for prompt identification and treatment of these youths. Studies aimed to treat acute symptoms of psychosis, as well as prevent the onset of psychosis, including risk factors amenable to change, are warranted.

Suicidal Ideation Among Anxious Youth: A Preliminary Investigation of the Role of Neural Processing of Social Rejection in Interaction with Real World Negative Social Experiences.

Suicidal ideation increases in adolescence, especially for anxious youth, and is a frequent precursor to suicide. This study examined whether neural processing of social rejection interacted with negative social experiences to predict suicidal ideation. Thus, to our knowledge this is the first study to examine how brain function may interact with the environment to contribute to suicidal ideation in youth, consistent with a developmental psychopathology perspective. Thirty-six anxious youth (ages 11 to 16) completed diagnostic interviews and questionnaires, an ecological momentary assessment (EMA) protocol, and a functional magnetic resonance imaging paradigm. Results showed that youth experienced greater severity of suicidal ideation when they exhibited heightened activation to social rejection in the right anterior insula and also experienced high levels of peer victimization or EMA-measured daily negative social experiences. Findings provide preliminary evidence that alterations in neural processing of social rejection interacts with exposure to negative social experiences to contribute to suicidal ideation.

Parental coping socialization is associated with healthy and anxious early-adolescents' neural and real-world response to threat.

The ways parents socialize their adolescents to cope with anxiety (i.e., coping socialization) may be instrumental in the development of threat processing and coping responses. Coping socialization may be important for anxious adolescents, as they show altered neural threat processing and over reliance on disengaged coping (e.g., avoidance and distraction), which can maintain anxiety. We investigated whether coping socialization was associated with anxious and healthy adolescents' neural response to threat, and whether neural activation was associated with disengaged coping. Healthy and clinically anxious early adolescents (N = 120; M = 11.46 years; 71 girls) and a parent engaged in interactions designed to elicit adolescents' anxiety and parents' response to adolescents' anxiety. Parents' use of reframing and problem solving statements was coded to measure coping socialization. In a subsequent visit, we assessed adolescents' neural response to threat words during a neuroimaging task. Adolescents' disengaged coping was measured using ecological momentary assessment. Greater coping socialization was associated with lower anterior insula and perigenual cingulate activation in healthy adolescents and higher activation in anxious adolescents. Coping socialization was indirectly associated with less disengaged coping for anxious adolescents through neural activation. Findings suggest that associations between coping socialization and early adolescents' neural response to threat differ depending on clinical status and have implications for anxious adolescents' coping.

Anxiety Treatment and Targeted Sleep Enhancement to Address Sleep Disturbance in Pre/Early Adolescents with Anxiety.

Sleep disturbance is prevalent in anxious youth and prospectively predicts poor emotional adjustment in adolescence. Study 1 examined whether anxiety treatment improves subjective and objective sleep disturbance in anxious youth. Study 2 examined whether a sleep intervention called Sleeping TIGERS can further improve sleep following anxiety treatment. Study 1 examined 133 youth (ages 9-14; 56% female; 11% ethnic/racial minority) with generalized, social, or separation anxiety over the course of anxiety treatment (cognitive behavioral treatment or client-centered treatment). Sleep-related problems (parent-, child-report) and subjective (diary) and objective (actigraphy) sleep patterns were assessed across treatment in an open trial design. Study 2 included 50 youth (ages 9-14; 68% female; 10% ethnic/racial minority) who continued to report sleep-related problems after anxiety treatment and enrolled in an open trial of Sleeping TIGERS. Pre- and postassessments duplicated Study 1 and included the Focal Interview of Sleep to assess sleep disturbance. Study 1 demonstrated small reductions in sleep problems and improvements in subjective sleep patterns (diary) across anxiety treatment, but outcomes were not deemed clinically significant, and 75% of youth stayed above clinical cutoff. Study 2 showed clinically significant, large reductions in sleep problems and small changes in some subjective sleep patterns (diary). Anxiety treatment improves, but does not resolve, sleep disturbance in peri-pubertal youth, which may portend risk for poor emotional adjustment and mental health. The open trial provides preliminary support that Sleeping TIGERS can improve sleep in anxious youth to a clinically significant degree.

Attention to Peer Feedback Through the Eyes of Adolescents with a History of Anxiety and Healthy Adolescents.

During adolescence, youth may experience heightened attention bias to socially relevant stimuli; however, it is unclear if attention bias toward social threat may be exacerbated for adolescents with a history of anxiety. This study evaluated attentional bias during the Chatroom-Interact task with 25 adolescents with a history of anxiety (18F, Mage = 13.6) and 22 healthy adolescents (13F, Mage = 13.8). In this task, participants received feedback from fictional, virtual peers who either chose them (acceptance) or rejected them (rejection). Overall, participants were faster to orient toward and spent longer time dwelling on their own picture after both rejection and acceptance compared to non-feedback cues. Social feedback was associated with greater pupillary reactivity, an index of cognitive and emotional neural processing, compared to non-feedback cues. During acceptance feedback (but not during rejection feedback), anxious youth displayed greater pupil response compared to healthy youth, suggesting that positive feedback from peers may differentially influence youth with a history of an anxiety disorder.

Vigilant attention to threat, sleep patterns, and anxiety in peripubertal youth.

BACKGROUND: Vigilant attention to threat is commonly observed in anxiety, undergoes developmental changes in early adolescence, and has been proposed to interfere with sleep initiation and maintenance. We present one of the first studies to use objective measures to examine associations between vigilant attention to threat and difficulties initiating and maintaining sleep in an early adolescent anxious sample. We also explore the moderating role of development (age, puberty) and sex. METHODS: Participants were 66 peripubertal youth (ages 9-14) with a primary anxiety disorder and 24 healthy control subjects. A dot-probe task was used to assess attentional bias to fearful relative to neutral face stimuli. Eye-tracking indexed selective attentional bias to threat, and reaction time bias indexed action readiness to threat. Sleep was assessed via actigraphy (e.g. sleep onset delay, wake after sleep onset, etc.), parent report (Children's Sleep Habits Questionnaire), and child report (Sleep Self-Report). The Pediatric Anxiety Rating Scale assessed anxiety severity. RESULTS: Eye-tracking initial threat fixation bias (ß = .33, p = .001) and threat dwell time bias (ß = .22, p = .041) were positively associated with sleep onset latency. Reaction time bias was positively associated with wake after sleep onset (ß = .24, p = .026) and parent-reported sleep disturbance (ß = .25, p = .019). Anxiety (severity, diagnosis) was not associated with these outcomes. Sex (ß = -.32, p = .036) moderated the relation between initial threat fixation bias and sleep onset latency, with a positive association for males (p = .005), but not for females (p = .289). Age and pubertal status did not moderate effects. CONCLUSIONS: Vigilant attention to threat is related to longer sleep onset and reduced sleep maintenance. These associations are not stronger in early adolescents with anxiety. Implications for early intervention or prevention that targets vigilant attention to threat to impact sleep disturbance, and vice versa, are discussed.

Error-related brain activity in pediatric anxiety disorders remains elevated following individual therapy: a randomized clinical trial.

BACKGROUND: Anxiety disorders are associated with an overactive action monitoring system as indexed by a larger error-related negativity (ERN). This study tests whether ERN magnitude changes following treatment, predicts response to treatment, and varies by treatment type. METHODS: The sample included 130 youth (9-14 years): youth with an anxiety disorder (ANX; n = 100) and healthy control (HC; n = 30) youth with no lifetime DSM-IV disorders. ANX youth were randomized to either a manualized cognitive-behavior therapy (CBT) or a comparison child-centered therapy (CCT). The ERN was assessed before and after 16 sessions of treatment and within a comparable interval for HC. Subjective ratings about making errors on the task were obtained following each testing session. The ClinicalTrials.gov identifier is NCT00774150. RESULTS: The ERN was larger in ANX than HC youth but ERN magnitude did not significantly change following treatment in the ANX youth, regardless of treatment type, and baseline ERN did not predict treatment response. Post-task ratings revealed that ANX youth worried more about task performance feedback than HC. Like the ERN, mean ratings did not significantly change following treatment. However, these ratings were not correlated with ERN amplitude. CONCLUSIONS: Findings of greater ERN in pediatric anxiety disorders are replicated in a larger sample. More importantly, findings from this randomized control trial show that a larger ERN and feeling worried about performance feedback remain unchanged following treatment and are unrelated to treatment response. Such findings suggest that action monitoring systems remain overactive in anxious youth treated with psychotherapy, suggesting the need for future investigation of whether novel complimentary cognitive and emotional training programs can modify these systems would be warranted.

A Randomized Clinical Trial Comparing Individual Cognitive Behavioral Therapy and Child-Centered Therapy for Child Anxiety Disorders.

This study compared individual cognitive behavioral therapy (CBT) and a supportive child-centered therapy (CCT) for child anxiety disorders on rates of treatment response and recovery at posttreatment and 1-year follow-up, as well as on real-world measures of emotional functioning. Youth (N = 133; ages 9-14) with anxiety disorders (generalized, separation, and/or social anxiety) were randomized using a 2:1 ratio to CBT (n = 90) or CCT (n = 43), which served as an active comparison. Treatment response and recovery at posttreatment and 1-year follow-up were assessed by Independent Evaluators, and youth completed ecological momentary assessment of daily emotions throughout treatment. The majority of youth in both CBT and CCT were classified as treatment responders (71.1% for CBT, 55.8% for CCT), but youth treated with CBT were significantly more likely to fully recover, no longer meeting diagnostic criteria for any of the targeted anxiety disorders and no longer showing residual symptoms (66.7% for CBT vs. 46.5% for CCT). Youth treated with CBT also reported significantly lower negative emotions associated with recent negative events experienced in daily life during the latter stages of treatment relative to youth treated with CCT. Furthermore, a significantly higher percentage of youth treated with CBT compared to CCT were in recovery at 1-year follow-up (82.2% for CBT vs. 65.1% for CCT). These findings indicate potential benefits of CBT above and beyond supportive therapy on the breadth, generalizability, and durability of treatment-related gains.

Longitudinal cognitive trajectories and associated clinical variables in youth with bipolar disorder.

OBJECTIVE: There is substantial interest in delineating the course of cognitive functioning in bipolar (BP) youth. However, there are no longitudinal studies aimed at defining subgroups of BP youth based on their distinctive cognitive trajectories and their associated clinical variables. METHOD: Cognitive functioning was measured in 135 participants from the Course and Outcome of BP Youth (COBY) study using several subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Youth were prospectively evaluated three times on average every 13.75 months over 2.5 years. Clinical and functional outcomes were assessed using the Longitudinal Interval Follow-Up Evaluation (LIFE). RESULTS: Latent class growth analysis identified three longitudinal patterns of cognitive functioning based on a general cognitive index: class 1, "persistently high" (N=21; 15.6%); class 2, "persistently moderate" (N=82; 60.74%); and class 3, "persistently low" (N=32; 23.7%). All classes showed normal cognitive functioning when compared with the CANTAB normative data. After adjustment for confounders, youth from class 3 had a significantly greater percentage of time with overall, manic, and depressive syndromal symptoms than youth in the other two classes. Also, after adjustment for confounders, youth from class 3 had significantly poorer global, academic, and social functioning than youth from class 1. CONCLUSIONS: BP youth showed normal overall cognitive functioning that remained stable during the follow-up within each class. However, 24% of BP youth showed poorer cognitive functioning than the other BP youth. This subgroup had poorer mood course and functioning, and may benefit from cognitive remediation and early management with evidence-based pharmacological treatments.

Predictive modeling for classification of positive valence system symptom severity from initial psychiatric evaluation records.

In response to the challenges set forth by the CEGS N-GRID 2016 Shared Task in Clinical Natural Language Processing, we describe a framework to automatically classify initial psychiatric evaluation records to one of four positive valence system severities: absent, mild, moderate, or severe. We used a dataset provided by the event organizers to develop a framework comprised of natural language processing (NLP) modules and 3 predictive models (two decision tree models and one Bayesian network model) used in the competition. We also developed two additional predictive models for comparison purpose. To evaluate our framework, we employed a blind test dataset provided by the 2016 CEGS N-GRID. The predictive scores, measured by the macro averaged-inverse normalized mean absolute error score, from the two decision trees and Naïve Bayes models were 82.56%, 82.18%, and 80.56%, respectively. The proposed framework in this paper can potentially be applied to other predictive tasks for processing initial psychiatric evaluation records, such as predicting 30-day psychiatric readmissions.