Controlled Study of Metabolic Syndrome Among Offspring of Parents With Bipolar Disorder.

Objectives: Bipolar disorder (BD) is highly heritable and associated with increased rates of metabolic syndrome (MetS). However, little is known about MetS in offspring of parents with BD. We therefore examined this topic in the Pittsburgh Bipolar Offspring Study cohort.Methods: Participants included 199 parents (n = 116 BD, diagnosed using DSM-IV; n = 83 non-BD) and 330 offspring (mean age 19.9 ± 5.3 years), including 198 high-risk offspring of parents with BD (n = 80 affected with a mood disorder) and 132 control offspring. We defined MetS and its components using International Diabetes Federation (IDF) guidelines (primary) and National Cholesterol Education Program (NCEP) guidelines (secondary). Multivariable analyses controlled for age and socioeconomic status in offspring. Sensitivity analyses controlled for psychotropic medications.Results: There was higher prevalence of MetS in parents with BD as compared to controls. NCEP-defined MetS was significantly more prevalent among affected high-risk offspring (16.3%) and controls (15.2%) vs unaffected high-risk offspring (6.0%; χ2 = 6.54, P = .04). There was greater mean number of MetS components (IDF: 1.7 ± 1.1; NCEP: 1.4 ± 1.0) among affected high-risk offspring vs unaffected high-risk offspring (IDF: 1.2 ± 1.0; NCEP: 1.0 ± 1.0) and controls (IDF: 1.3 ± 1.2; NCEP: 1.1 ± 1.1; IDF: H[2] = 10.26, P = .006; NCEP: H[2] = 9.18, P = .01). Most findings became nonsignificant in multivariable analyses. Some between-group results became nonsignificant after controlling for second-generation antipsychotics.Conclusions: This preliminary study found increased risk of MetS among affected high-risk offspring, which may be attributable to socioeconomic status. Prospective studies may determine timing of MetS onset in relation to mood disorder onset, and the role of socioeconomic status in moderating this association.

Substance use outcomes from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS).

BACKGROUND: Substance use problems and anxiety disorders are both highly prevalent and frequently cooccur in youth. The present study examined the benefits of successful anxiety treatment at 3-12 years after treatment completion on substance use outcomes (i.e. diagnoses and lifetime expected use). METHODS: The sample was from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS), a naturalistic follow-up study to the Child/Adolescent Anxiety Multimodal Study (CAMS) which randomized youth to cognitive behavioral therapy (CBT; Coping cat), medication (sertraline), their combination, or pill placebo. The first CAMELS visit occurred an average of 6.5 years following CAMS randomization. Participants were 319 youth (65.4% of the CAMS sample), aged 7-17 years at CAMS baseline assessment with a mean age of 17.6 years (range: 11-26 years) at the time of the first CAMELS follow-up. Substance use outcomes included diagnoses as well as lifetime substance use (i.e. alcohol and tobacco use). RESULTS: Eleven of 319 (3.4%) CAMELS participants were diagnosed with a substance use disorder at the initial follow-up visit. When compared to the population lifetime rate of 11.4%, the rate of diagnoses in the posttreated sample was significantly lower. Additionally, rates of lifetime alcohol use were lower than population rates at the initial and final follow-up visits. Rates of lifetime tobacco use were similarly lower than lifetime population rates at the initial visit (driven by significantly lower rates in the CBT treatment condition), but higher by the final visit. Furthermore, treatment remission (but not treatment response) was associated with a lower rate of substance use diagnoses at the initial follow-up visit, although rates of lifetime alcohol and tobacco use did not differ by treatment outcome. CONCLUSIONS: Anxiety treatments confer a beneficial impact on problematic substance use (i.e. diagnoses) as well as on expected substance use (i.e. alcohol and tobacco use) for on average, a period of 6.5 years.

Sleep patterns among preschool offspring of parents with and without psychopathology: Association with the development of psychopathology in childhood.

BACKGROUND: Disturbed sleep during early childhood predicts social-emotional problems. However, it is not known how various early childhood sleep phenotypes are associated with the development of childhood psychopathology, nor whether these relationships vary as a function of parental psychopathology. We identified sleep phenotypes among preschool youth; examined whether these phenotypes were associated with child and parent factors; and determined if early sleep phenotypes predicted later childhood psychopathology. METHODS: Using data from the Pittsburgh Bipolar Offspring study, parents with bipolar disorder (BD), non-BD psychopathology, and healthy controls reported about themselves and their offspring (n = 218) when their children were ages 2-5. Offspring and parents were interviewed directly approximately every 2 years from ages 6-18. Latent class analysis (LCA) identified latent sleep classes; we compared these classes on offspring demographics, parental sleep variables, and parental diagnoses. Kaplan-Meier survival models estimated hazard of developing any new-onset Axis-I disorders, as well as BD specifically, for each class. RESULTS: The optimal LCA solution featured four sleep classes, which we characterized as (1) good sleep, (2) wake after sleep onset problems, (3) bedtime problems (e.g., trouble falling asleep, resists going to bed), and (4) poor sleep generally. Good sleepers tended to have significantly less parental psychopathology than the other three classes. Risk of developing new-onset Axis-I disorders was highest among the poor sleep class and lowest among the good sleep class. CONCLUSIONS: Preschool sleep phenotypes are an important predictor of the development of psychopathology. Future work is needed to understand the biopsychosocial processes underlying these trajectories.

Dialectical Behavior Therapy for Adolescents With Bipolar Disorder: A Randomized Clinical Trial.

Importance: Early-onset bipolar disorder conveys substantial risk for suicide. No psychosocial intervention for this population expressly targets suicidal behavior. Objective: To determine whether dialectical behavior therapy (DBT) for adolescents with bipolar spectrum disorder is more effective than standard of care (SOC) psychotherapy in decreasing suicide attempts over 1 year. Design, Settings, and Participants: Adolescents aged 12 to 18 years diagnosed with bipolar spectrum disorder were recruited from a specialty outpatient psychiatric clinic between November 2014 and September 2019. Independent evaluators conducted quarterly assessments over 1 year with participants and parents. Data were analyzed from March 2021 to November 2022. Interventions: Participants were randomly assigned to 1 year of DBT (36 sessions; n = 47) or SOC psychotherapy (schedule clinically determined; n = 53). All youth received medication management via a flexible algorithm. Main Outcomes and Measures: Primary outcomes included suicide attempts over 1 year and mood symptoms and states (depression and hypomania/mania). Secondary analyses included moderation of DBT effects by history of suicide attempt and mediation through emotion dysregulation. Results: Of 100 included participants, 85 (85%) were female, and the mean (SD) age was 16.1 (1.6) years. Participants were followed up over a mean (SD) of 47 (14) weeks. Both treatment groups demonstrated significant and similar improvement in mood symptoms and episodes over 1 year (standardized depression rating scale slope, -0.17; 95% CI, -0.31 to -0.03; standardized mania rating scale slope, -0.24; 95% CI, -0.34 to -0.14). DBT and SOC participants reported similar suicide attempt rates at intake as measured on the Adolescent Longitudinal Follow-Up Evaluation (ALIFE; mean [SD] attempts, 2.0 [4.5] vs 1.8 [3.9], respectively; P = .80). DBT participants reported slightly more suicide attempts at intake as measured on the Columbia-Suicide Severity Rating Scale Pediatric Version (C-SSRS; mean [SD] attempts, 1.4 [3.6] vs 0.6 [0.9]; P = .02). DBT participants reported significantly fewer suicide attempts over follow-up compared with SOC participants via the ALIFE (mean [SD] attempts per follow-up period, 0.2 [0.4] vs 1.1 [4.3], controlling for baseline attempts: P = .03) and the C-SSRS (mean [SD] attempts per follow-up period, 0.04 [0.2] vs 0.10 [0.3], controlling for baseline attempts; P = .03). DBT was significantly more effective than SOC psychotherapy at decreasing suicide attempts over 1 year (ALIFE: incidence rate ratio [IRR], 0.32; 95% CI, 0.11-0.96; C-SSRS: IRR, 0.13; 95% CI, 0.02-0.78). Decreased rate of suicide attempts in DBT was moderated by presence of lifetime history of suicide attempt and time (IRR, 0.23; 95% CI, 0.13-0.44) and mediated by improvement in emotion dysregulation (IRR, 0.61; 95% CI, 0.42-0.89), particularly for those with high baseline emotion dysregulation (standardized ß, -0.59; 95% CI, -0.92 to -0.26). Conclusions and Relevance: In this randomized clinical trial, DBT demonstrated efficacy in decreasing suicide attempts among the high-risk population of adolescents with bipolar spectrum disorder. Trial Registration: ClinicalTrials.gov Identifier: NCT02003690.

Risk for Suicidal Behavior After Psychiatric Hospitalization Among Sexual and Gender Minority Patients.

Importance: The months following inpatient psychiatric hospitalization are a period of high risk for suicidal behavior. Sexual and gender minority (SGM) individuals have elevated risk for suicidal behavior, but no prior research has examined whether SGM inpatients have disproportionate risk for suicidal behavior following discharge from psychiatric hospitalization. Objectives: To evaluate whether SGM patients have elevated risk for suicidal behavior following discharge from psychiatric hospitalization compared with heterosexual and cisgender patients and to examine whether differences in risk across groups were accounted for by demographic characteristics and clinical factors known to be associated with suicidal behavior. Design, Setting, and Participants: This prospective cohort study was conducted from August 2017 to July 2021 among inpatients aged 18 to 30 years who were voluntarily enrolled during psychiatric hospitalization. The study was conducted at an inpatient psychiatric hospital, with prospective data collected via follow-up visits and electronic health records. Main Outcomes and Measures: Onset and/or recurrence of suicidal behavior following discharge from psychiatric hospitalization, assessed at follow-up visits and through electronic health records. Results: A total of 160 patients were included, with 56 sexual minority (SM) and 15 gender minority (GM) patients. The median (IQR) age of the patients was 23.5 (20.4-27.6) years, 77 (48%) reported male sex assigned at birth, and 114 (71%) identified their race as White. During the follow-up period, 33 suicidal behavior events occurred (among 21% of patients). SM (hazard ratio [HR], 2.02; 95% CI, CI, 1.02-4.00; log-rank P = .04) and GM (HR, 4.27; 95% CI, 1.75-10.40; log-rank P < .001) patients had significantly higher risk for suicidal behavior compared with their heterosexual and cisgender counterparts, respectively, in bivariable analyses. Risk between SM and heterosexual patients was not different after controlling for demographic characteristics and clinical factors associated with suicidal behavior. GM patients exhibited elevated risk during the 100 days following discharge even after controlling for demographic and clinical characteristics (HR, 3.80; 95% CI, 1.18-11.19; P = .03). Conclusions and Relevance: Within this cohort study of psychiatric patients, SGM patients had higher risk for suicidal behavior than non-SGM patients following discharge. While SM patients' risk was accounted for by clinical characteristics, GM patients' risk for suicidal behavior was not accounted for by their acute psychiatric state on admission. Future studies with larger subsamples of GM individuals are needed, and inpatient clinicians must attend to the unique needs of SGM individuals to ensure they receive affirming services.

Anxiety symptom trajectories from treatment to 5- to 12-year follow-up across childhood and adolescence.

OBJECTIVE: The current study examined trajectories of anxiety during (a) acute treatment and (b) extended follow-up to better characterize the long-term symptom trajectories of youth who received evidence-based intervention for anxiety disorders using a person-centered approach. METHOD: Participants were 319 youth (age 7-17 years at enrollment), who participated in a multicenter randomized controlled trial for the treatment of pediatric anxiety disorders, Child/Adolescent Anxiety Multimodal Study, and a 4-year naturalistic follow-up, Child/Adolescent Anxiety Multimodal Extended Long-term Study, an average of 6.5 years later. Using growth mixture modeling, the study identified distinct trajectories of anxiety across acute treatment (Weeks 0-12), posttreatment (Weeks 12-36), and the 4-year-long follow-up, and identified baseline predictors of these trajectories. RESULTS: Three nonlinear anxiety trajectories emerged: "short-term responders" who showed rapid treatment response but had higher levels of anxiety during the extended follow-up; "durable responders" who sustained treatment gains; and "delayed remitters" who did not show an initial response to treatment, but showed low levels of anxiety during the maintenance and extended follow-up periods. Worse anxiety severity and better family functioning at baseline predicted membership in the delayed remitters group. Caregiver strain differentiated short-term responders from durable responders. CONCLUSIONS: Findings suggest that initial response to treatment does not guarantee sustained treatment gains over time for some youth. Future follow-up studies that track treated youth across key developmental transitions and in the context of changing social environments are needed to inform best practices for the long-term management of anxiety.

Do youth anxiety measures assess the same construct consistently throughout treatment? Results are...complicated.

Interventionists interpret changes in symptoms as reflecting response to treatment. However, changes in symptom functioning and the measurement of the underlying constructs may be reflected in reported change. Longitudinal measurement invariance (LMI) is a statistical approach that assesses the degree to which measures consistently capture the same construct over time. We examined LMI in measures of anxiety severity/symptoms [i.e., Pediatric Anxiety Rating Scale (PARS), Multidimensional Anxiety Scale for Children (MASC), Screen for Child Anxiety and Related Disorders (SCARED)] in anxious youth at baseline and posttreatment. Initial fit was inadequate for 27 of 38 baseline and posttreatment models, but model modifications resulted in acceptable fit. Tests of LMI supported scalar invariance for the PARS and many, but not all, MASC and SCARED subscales. Findings suggest that the PARS, and many MASC and SCARED subscales can accurately be used to measure change over time, however, others may reflect changes in measurement properties.

An intensive outpatient program for suicidal college students.

Objective: College counseling centers (CCCs) have limited capacity to accommodate high-risk students who need more intensive care than traditional outpatient treatment. We describe an Intensive Outpatient Program (IOP) to meet the specialized needs of suicidal undergraduates. Participants: Suicidal undergraduates aged 18-24. Methods: Fact-gathering meetings with local universities confirmed high need for prompt access to IOP care for students presenting in crisis at CCCs and emergency rooms, and post-inpatient discharge. We thus iteratively designed and implemented the College Option Services for Teens at Risk (COSTAR) IOP. Results: The 6-week program includes initial diagnostic evaluation and risk assessment followed by weekly skills groups, individual therapy, and medication management. Between September 2017 and January 2020, 148 students (M age = 19.7) attended an average of 5.7 COSTAR group sessions (SD = 4.7). Conclusions: A specialty IOP for suicidal college students holds promise in a stepped care approach for at-risk college students.

Early indicators of bipolar risk in preschool offspring of parents with bipolar disorder.

BACKGROUND: Offspring of parents with bipolar disorder (BD-I/II) are at increased risk to develop the disorder. Previous work indicates that bipolar spectrum disorder (BPSD) is often preceded by mood/anxiety symptoms. In school-age offspring of parents with BD, we previously built a risk calculator to predict BPSD onset, which generates person-level risk scores. Here, we test whether preschool symptoms predict school-age BPSD risk. METHODS: We assessed 113 offspring of parents with BD 1-3 times during preschool years (2-5 years old) and then approximately every 2 years for a mean of 10.6 years. We used penalized (lasso) regression with linear mixed models to assess relationships between preschool mood, anxiety, and behavioral symptoms (parent-reported) and school-age predictors of BPSD onset (i.e., risk score, subthreshold manic symptoms, and mood lability), adjusting for demographics and parental symptomatology. Finally, we conducted survival analyses to assess associations between preschool symptoms and school-age onset of BPSD and mood disorder. RESULTS: Of 113 preschool offspring, 33 developed new-onset mood disorder, including 19 with new-onset BPSD. Preschool irritability, sleep problems, and parental factors were lasso-selected predictors of school-age risk scores. After accounting for demographic and parental factors, preschool symptoms were no longer significant. Lasso regressions to predict mood lability and subthreshold manic symptoms yielded similar predictors (irritability, sleep problems, and parental affective lability), but preschool symptoms remained predictive even after adjusting for parental factors (ps < .005). Exploratory analyses indicated that preschool irritability univariately predicted new-onset BPSD (p = .02) and mood disorder (p = .02). CONCLUSIONS: These results provide initial prospective evidence that, as early as preschool, youth who will develop elevated risk scores, mood lability, and subthreshold manic symptoms are already showing symptomatology; these preschool symptoms also predict new-onset BPSD. While replication of findings in larger samples is warranted, results point to the need for earlier assessment of risk and development of early interventions.

Opioid use as a proximal risk factor for suicidal behavior in young adults.

INTRODUCTION: There is a concomitant rise in suicide rates with the prevalence of opioids involved in overdose deaths, especially among adolescents and young adults. However, there are limited studies on whether opioid use prospectively predicts suicidal behavior in youth. METHODS: Our sample included 183 psychiatric patients (18-30 years) admitted for a suicide attempt (SA), have current suicidal ideation (SI), and psychiatric controls without ideation or attempt (PC). Suicidal behavior was assessed using the Columbia Suicide Severity Rating Scale. We also recruited a healthy control group (HC; n = 40). Patients and controls were followed over a year. ANOVA, regression, and cox regression were used. RESULTS: Suicide attempt (ß = 0.87, CI [0.1-1.6], p = 0.02) and SI [(ß = 0.75, CI [0.03-1.5], p = 0.04) were significantly more likely than HCs to have used opioids in the past year at baseline. Opioid use was associated with increased anxiety symptoms (ß = 0.75, CI [0.001-1.5], p = 0.05), PTSD symptoms (ß = 3.90, CI [1.1-6.7], p = 0.01), and aggression (ß = 0.02, CI [0.01-0.04], p = 0.02). Opioid use in the month prior to hospitalization predicted SA at 6 months (OR = 1.87, CI [1.06-3.31], p = 0.032). CONCLUSIONS: Opioid use is a proximal predictor for SA. These findings may help clinicians better identify patients at risk for suicidal behavior, allowing for more personalized treatment approaches.

Role of Polygenic Risk Score in the Familial Transmission of Bipolar Disorder in Youth.

Importance: Establishing genetic contributions to the transmission of bipolar disorder (BD) from parents to offspring may inform the risk of developing this disorder and further serve to validate BD in youth. Objective: To evaluate the specific association of BD polygenic risk scores (PRSs) on the familial transmission and validity of pediatric BD. Design, Setting, and Participants: This community-based case-control longitudinal study (Pittsburgh Biological Offspring Study) included parents with BD I/II and their offspring and parents without BD (healthy or non-BD psychopathology) and their offspring. Participants were recruited between March 2001 and May 2007, and analysis took place from December 2020 to September 2021. Exposures: PRSs for BD, major depressive disorder, schizophrenia, and attention-deficit/hyperactivity disorder. Main Outcomes and Measures: Participants were prospectively evaluated using standardized interviews blind to parental diagnosis. DNA was extracted from saliva and genotyped. PRSs were constructed based on independent large-scale genome-wide association studies. Results: A total of 156 parents with BD I/II and 180 parents without BD (mean [SD] age, 39.6 [7.9] years; 241 female [72%]) as well as 251 offspring of parents with BD and 158 offspring of parents without BD (mean [SD] age, 10.4 [4.7] years; 213 female [52%]) of European ancestry were analyzed. Participants were assessed a mean of 6.7 times during a mean (SD) of 13 (3.4) years of follow-up (84% retention). More offspring of parents with BD developed BD (58 [23.1%] vs 8 [5.1%]; P < .001) and depression (126 [50.2%] vs 52 [32.9%]; P < .001) compared with offspring of parents without BD. BD PRS was higher in both parents and offspring with BD than parents and offspring without BD (parents: odds ratio, 1.50; 95% CI, 1.19-1.89; P < .001; explained 4.8% of the phenotypic variance vs offspring: hazard ratio, 1.34; 95% CI, 1.03-1.7; P = .02; explained 5.0% of the phenotypic variance). BD PRS did not differ across BD subtypes. In a model combining parental and offspring BD PRS, the parental BD PRS association with offspring BD was fully mediated by offspring BD PRS (hazard ratio, 1.40; 95% CI, 1.05-1.86; P = .02). Parental BD had a stronger direct association than parental or offspring BD PRS with offspring BD risk (hazard ratio, 5.21; 95% CI, 1.86-14.62; P = .002), explaining 30% of the variance. Parental and offspring BD PRS explained 6% of the BD onset variance beyond parental diagnosis. There were no significant between-group differences in PRSs for major depressive disorder, schizophrenia, and attention-deficit/hyperactivity disorder in parents or offspring and they were not significantly associated with BD onset. Conclusions and Relevance: The findings of this study add to the extant clinical validation of BD in youth. Parental BD and offspring BD PRS independently associated with the risk of BD in offspring. Although this is promising, the association of BD PRS was relatively small and cannot be used alone to determine BD risk until further developments occur.

Social media use and prospective suicidal thoughts and behaviors among adolescents at high risk for suicide.

OBJECTIVE: To examine the relationship between social media use and suicidal thoughts and behaviors among adolescents in the first 30 days of an intensive outpatient program (IOP) for depression and suicidality. METHOD: Participants included 100 adolescents who enrolled in an IOP for depression and suicidality and completed baseline measures of social media and weekly measures of depression and suicidal thoughts and behaviors at clinical visits over the next month. RESULTS: Lower levels of social media use (overall and messaging) were associated with a greater likelihood of having suicidal ideation with plan over the next 30 days. There was no effect on suicidal behavior. Multilevel modeling indicated no main effects of social media use on depression or average days of suicidal thoughts. However, individuals with lower levels of social media use maintained more depression symptoms and days with passive death wish across the first month of treatment. CONCLUSIONS: Among adolescents at high risk for suicide, less engagement in social media may reflect social anhedonia or withdrawal, which may heighten risk for more severe suicidal ideation or impede initial treatment. Findings highlight the importance of considering social media as an additional context when assessing social dysfunction in treatment for depression and suicidality.

Differentiating white matter measures that protect against vs. predispose to bipolar disorder and other psychopathology in at-risk youth.

Bipolar disorder (BD) is highly heritable. Identifying objective biomarkers reflecting pathophysiological processes predisposing to, versus protecting against BD, can help identify BD risk in offspring of BD parents. We recruited 21 BD participants with a first-degree relative with BD, 25 offspring of BD parents, 27 offspring of comparison parents with non-BD psychiatric disorders, and 32 healthy offspring of healthy parents. In at-risk groups, 23 had non-BD diagnoses and 29, no Axis-I diagnoses(healthy). Five at-risk offspring who developed BD post scan(Converters) were included. Diffusion imaging(dMRI) analysis with tract segmentation identified between-group differences in the microstructure of prefrontal tracts supporting emotional regulation relevant to BD: forceps minor, anterior thalamic radiation(ATR), cingulum bundle(CB), and uncinate fasciculus(UF). BD participants showed lower fractional anisotropy (FA) in the right CB (anterior portion) than other groups (q < 0.05); and in bilateral ATR (posterior portion) versus at-risk groups (q < 0.001). Healthy, but not non-BD, at-risk participants showed significantly higher FA in bilateral ATR clusters than healthy controls (qs < 0.05). At-risk groups showed higher FA in these clusters than BD participants (qs < 0.05). Non-BD versus healthy at-risk participants, and Converters versus offspring of BD parents, showed lower FA in the right ATR cluster (qs < 0.05). Low anterior right CB FA in BD participants versus other groups might result from having BD. High bilateral ATR FA in at-risk groups, and in healthy at-risk participants, versus healthy controls might protect against BD/other psychiatric disorders. Absence of elevated right ATR FA in non-BD versus healthy at-risk participants, and in Converters versus non-converter offspring of BD parents, might lower protection against BD in at-risk groups.

An Emulation of Randomized Trials of Administrating Antipsychotics in PTSD Patients for Outcomes of Suicide-Related Events.

Post-traumatic stress disorder (PTSD) is a prevalent mental disorder marked by psychological and behavioral changes. Currently, there is no consensus of preferred antipsychotics to be used for the treatment of PTSD. We aim to discover whether certain antipsychotics have decreased suicide risk in the PTSD population, as these patients may be at higher risk. A total of 38,807 patients were identified with a diagnosis of PTSD through the ICD9 or ICD10 codes from January 2004 to October 2019. An emulation of randomized clinical trials was conducted to compare the outcomes of suicide-related events (SREs) among PTSD patients who ever used one of eight individual antipsychotics after the diagnosis of PTSD. Exclusion criteria included patients with a history of SREs and a previous history of antipsychotic use within one year before enrollment. Eligible individuals were assigned to a treatment group according to the antipsychotic initiated and followed until stopping current treatment, switching to another same class of drugs, death, or loss to follow up. The primary outcome was to identify the frequency of SREs associated with each antipsychotic. SREs were defined as ideation, attempts, and death by suicide. Pooled logistic regression methods with the Firth option were conducted to compare two drugs for their outcomes using SAS version 9.4 (SAS Institute, Cary, NC, USA). The results were adjusted for baseline characteristics and post-baseline, time-varying confounders. A total of 5294 patients were eligible for enrollment with an average follow up of 7.86 months. A total of 157 SREs were recorded throughout this study. Lurasidone showed a statistically significant decrease in SREs when compared head to head to almost all the other antipsychotics: aripiprazole, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (p < 0.0001 and false discovery rate-adjusted p value < 0.0004). In addition, olanzapine was associated with higher SREs than quetiapine and risperidone, and ziprasidone was associated with higher SREs than risperidone. The results of this study suggest that certain antipsychotics may put individuals within the PTSD population at an increased risk of SREs, and that careful consideration may need to be taken when prescribed.

A Longitudinal Study of Psychiatric Disorders in Offspring of Parents With Bipolar Disorder From Preschool to Adolescence.

OBJECTIVE: To compare the prevalence of psychopathology, particularly bipolar disorder (BD), between preschool offspring of parents with BD and community controls. METHOD: A total of 116 offspring of BD-I/II parents and 98 controls (53 parents with non-BD psychopathology and 45 healthy parents) were recruited at ages 2 to 5 years and followed on average 9.6 years (on average: 2-5: 1.6 times; after age 5: 4 times) (average ages at intake/last follow-up: 3.8/13.4, retention: 98%). Participants were evaluated with standardized instruments blinded to parental diagnoses. RESULTS: After adjusting for confounders, offspring of BD parents only showed more attention-deficit/hyperactivity disorder (ADHD) during ages 2 to 5 years than the other 2 groups. After age 5, offspring of BD parents did not differ from offspring of parents with non-BD psychopathology, but they had more anxiety, ADHD, and behavior problems than offspring of healthy parents. Only offspring of BD parents developed BD-I/II: 3.4% (n = 4) and BD-not-otherwise-specified (BD-NOS): 11.2% (n = 13), with mean onset ages 11.4 and 7.4, respectively. About 70% of offspring with BD had non-BD disorders before BD. Only ADHD, diagnosed before age 6 years, and early-onset parental BD were significantly associated with BD risk. CONCLUSION: Most offspring of BD parents did not develop BD, but they were at specific high risk for developing BD, particularly those with preschool ADHD and early-onset parental BD. BD symptoms were scarce during the preschool years and increased throughout the school age, mainly in the form of BD-NOS, a disorder that conveys poor prognosis and high risk to develop BD-I/II. Developing early interventions to delay or, ideally, to prevent its onset are warranted.

Impact of treatment improvement on long-term anxiety: Results from CAMS and CAMELS.

OBJECTIVE: This article examined associations between change in youth and family characteristics during youth anxiety treatment and long-term anxiety severity and overall functioning. METHOD: Participants (N = 488; age 7-17 years; 45% male; 82% white) were randomized to 12 weeks of cognitive behavioral therapy (Coping Cat), medication (sertraline), their combination, or pill placebo in the Child/Adolescent Anxiety Multimodal Study (CAMS). A subset participated in the naturalistic follow-up Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS; n = 319; 3.70-11.83 years post-treatment). The current secondary analyses examined how change in anxiety severity (Child Global Impression-Severity), overall functioning (Children's Global Assessment Scale), caregiver psychopathology (Brief Symptom Inventory), caregiver strain (Family Burden Assessment Scale), and family dysfunction (Brief Family Assessment Measure) during CAMS was associated with anxiety severity and overall functioning years later (M = 7.72 years). CAMS procedures were registered on clinialtrials.gov. RESULTS: Improvements in factors related to functioning (i.e., overall functioning, family dysfunction, caregiver strain) were associated with improvements in anxiety severity in CAMELS (|ßys| ≥ .04, ps ≤ .04). Improvements in factors related to psychopathology (i.e., anxiety severity, caregiver psychopathology) were associated with improvements in overall functioning in CAMELS (|ßys| ≥ .23, ps ≤ .04). It was changes in each of the variables examined (rather than baseline values) that predicted anxiety severity and overall functioning. CONCLUSIONS: Both youth and family factors play a significant role in long-term treatment outcomes. Therapists would be wise to monitor how these factors change throughout treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The p Factor Consistently Predicts Long-Term Psychiatric and Functional Outcomes in Anxiety-Disordered Youth.

OBJECTIVE: Pediatric anxiety disorders can have a chronic course and are considered gateway disorders to adult psychopathology, but no consistent predictors of long-term outcome have been identified. A single latent symptom dimension that reflects features shared by all mental health disorders, the p factor, is thought to reflect mechanisms that cut across mental disorders. Whether p predicts outcome in youth with psychiatric disorders has not been examined. We tested whether the p factor predicted long-term psychiatric and functional outcomes in a large, naturalistically followed-up cohort of anxiety-disordered youth. METHOD: Children and adolescents enrolled in a randomized controlled treatment trial of pediatric anxiety were followed-up on average 6 years posttreatment and then annually for 4 years. Structural equation modeling was used to estimate p at baseline. Both p and previously established predictors were modeled as predictors of long-term outcome. RESULTS: Higher levels of p at baseline were related to more mental health disorders, poorer functioning, and greater impairment across all measures at all follow-up time points. p Predicted outcome above and beyond previously identified predictors, including diagnostic comorbidity at baseline. Post hoc analyses showed that p predicted long-term anxiety outcome, but not acute treatment outcome, suggesting that p may be uniquely associated with long-term outcome. CONCLUSION: Children and adolescents with anxiety disorders who present with a liability toward broad mental health problems may be at a higher risk for poor long-term outcome across mental health and functional domains. Efforts to assess and to address this broad liability may enhance long-term outcome.

Antidepressant Use in a 3- to 12-Year Follow-up of Anxious Youth: Results from the CAMELS Trial.

The current study explored whether patient characteristics predicted patterns of antidepressant use (i.e., never used, single episode of use, or two or more episodes) in a naturalistic follow-up. Participants in the child/adolescent multimodal (CAMS) extended long-term study. (n = 318) indicated medication use over the course of eight follow-up visits, 3-12 years after receiving treatment in CAMS. 40.6% of participants reported never using an antidepressant during follow-up, 41.4% reported a single episode of antidepressant use, and 18.0% reported multiple episodes of antidepressant use. Greater baseline anxiety severity marginally predicted a single episode of antidepressant use; baseline depression severity predicted multiple episodes of use. Reasons for discontinuing antidepressants included perceived ineffectiveness (31.8%), side effects (25.5%), and improvement in symptoms (18.5%). Exploratory analyses examined predictors of medication use. Findings suggest that antidepressant use is common among anxious youth, as is discontinuation of antidepressant use. Clinical implications and future directions are discussed.

Long-term Service Use Among Youths Previously Treated for Anxiety Disorder.

OBJECTIVE: (1) To describe rates of long-term service use among subjects previously enrolled in a landmark study of youth anxiety disorder treatment and followed into early adulthood; (2) to examine predictors of long-term service use; and (3) to examine the relationship between anxiety diagnosis and service use over time. METHOD: The Child/Adolescent Anxiety Multimodal Extended Long-term Study prospectively assessed youths treated through the Child/Adolescent Anxiety Multimodal Study at ages 7-17 years into early adulthood. A total of 319 youths (mean age 17.7, 55.2% female) previously randomized to cognitive-behavioral therapy, sertraline, combination, or placebo for the treatment of anxiety participated; 318 had service use data. Four annual clinic assessments were conducted along with telephone check-ins every 6 months. RESULTS: Overall, 65.1% of participants endorsed receiving some form of anxiety treatment over the course of the follow-up period, with more subjects reporting medication use than psychotherapy; 35.2% reported consistent use of services over the course of the study. Overall, service use declined over time in subjects with less severe anxiety but remained more steady in those with recurrent/chronic symptoms. Levels of life stress and depressive symptoms were associated with amount of service use over time whereas treatment-related variables (type of initial intervention, acute response, remission) were not. A subset of youths remained chronically anxious despite consistent service use. CONCLUSION: These findings point to the need to develop models of care that approach anxiety disorders as chronic health conditions in need of active long-term management.