J Child Adolesc Psychopharmacol [JOURNAL]
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200 papers
Beyond the Wait-and-See: Data-Driven Decision Points for Guiding Selective Serotonin Reuptake Inhibitor Treatment and Cognitive Behavioral Therapy in Pediatric Anxiety Disorders.
Stimpfl JN, Mills JA, Dahlsgaard KK … +4 more , Peris TS, Piacentini JC, Walkup JT, Strawn JR
J Child Adolesc Psychopharmacol · 2026 Jul · PMID 42381504 · Publisher ↗
OBJECTIVES: To identify early markers of acute treatment response among youth with anxiety disorders receiving cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitor (SSRI) monotherapy, or their combi...
OBJECTIVES: To identify early markers of acute treatment response among youth with anxiety disorders receiving cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitor (SSRI) monotherapy, or their combination. BACKGROUND: Although many youth with anxiety disorders benefit from CBT or SSRIs, response trajectories vary. Identifying early indicators of nonresponse may guide sequencing strategies and improve timely treatment delivery. METHODS: Using data from the Child/Adolescent Anxiety Multimodal Study, improvement trajectories were modeled for youth (age 7-17) randomized to sertraline monotherapy ( = 133), CBT monotherapy ( = 139), their combination ( = 140), and placebo ( = 76). Patients were stratified by percent change in Pediatric Anxiety Rating Scale (PARS) scores at multiple time points, and logarithmic and logistic time-trend regression models were used to estimate the probability of response. Receiver operating characteristic (ROC) analyses were used to identify thresholds of improvement for predicting response. RESULTS: In the sertraline group, ≥25% improvement in PARS score at week 4 had a higher probability of response by week 12 (60.8%) than <25% improvement (31.7%, = 0.001). In CBT-treated youth, week 4 PARS improvement was less predictive of response, with ≥25% improvement predicting a 47.9% chance of response compared with 28.6% for <25% improvement ( = 0.025). In the combined treatment, ≥25% improvement predicted a73.3% probability of response, whereas <25% improvement yielded a 51.3% likelihood of response ( < 0.001). ROC analyses similarly suggested that week 4 improvement in PARS scores in the CBT group had near equivocal predictive value, though this improved by week 6 to levels comparable to those of the other treatment groups. At week 6, roughly 25% improvement in PARS score in the combined treatment had the best sensitivity and specificity for predicting response. CONCLUSIONS: Early improvement can predict treatment response in youth with anxiety disorders receiving sertraline monotherapy or combination treatment (sertraline and CBT). Conversely, the absence of early improvement in CBT-treated youth does not reliably predict treatment nonresponse. Treatment-specific thresholds may inform clinical decision making, and support earlier SSRI optimization while allowing more time to observe CBT-related gains.
Efficacy and Safety of Cannabinoid-Based Products in Children and Adolescents with Autism Spectrum Disorder, Fragile X Syndrome and Rett Syndrome: A Systematic Review.
Boeri S, Bosisio L, Prato G … +5 more , Martinez Popple M, De Grandis E, Striano P, Benke TA, Nobili L
J Child Adolesc Psychopharmacol · 2026 Jun · PMID 42339654 · Publisher ↗
INTRODUCTION: Neurodevelopmental disorders (NDDs), including Autism Spectrum Disorder (ASD), Fragile X syndrome (FXS), and Rett Syndrome (RTT), share impairments in cognitive and behavioral functioning and may involve an...
INTRODUCTION: Neurodevelopmental disorders (NDDs), including Autism Spectrum Disorder (ASD), Fragile X syndrome (FXS), and Rett Syndrome (RTT), share impairments in cognitive and behavioral functioning and may involve an altered excitatory/inhibitory balance modulated by the endocannabinoid system. This systematic review evaluated the safety and efficacy of cannabinoid-based products (CBPs) in these pediatric NDDs. METHODS: We conducted a systematic review according to Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) 2020, including randomized and nonrandomized studies of patients under 18 years treated with cannabidiol (CBD), cannabidivarin (CBDV), tetrahydrocannabinol (THC), or their combinations. Outcomes were adverse events (AEs) and treatment discontinuation, seizure reduction, and behavioral and cognitive changes. Study quality and certainty of evidence were assessed using design-specific risk-of-bias tools and the GRADE approach. RESULTS: Seventeen studies (two randomized controlled trials, observational studies, and case series) met the inclusion criteria. Across diagnoses, CBPs were generally associated with mild-to-moderate AEs and low discontinuation rates. Descriptive pooled proportions suggested behavioral improvements in ASD and FXS and seizure reduction in RTT, with exploratory analyses indicating differential effects of CBD versus CBD + THC on behavioral and cognitive outcomes in ASD. CONCLUSION: CBPs may offer potential benefits for selected behavioral symptoms and comorbid epilepsy in pediatric NDDs, but current evidence is insufficient to support routine clinical use. High-quality randomized controlled trials with standardized outcome measures and long-term follow-up are needed to clarify efficacy, safety, and syndrome-specific effects.
Low Emotional Awareness and Altered Frontostriatal Functional Connectivity During Reward Processing Prospectively Predict Depressive Symptoms in At-Risk Youth.
Seah THS, Gupta T, Lenniger CJ … +6 more , Eckstrand KL, Rengasamy ML, Horter CM, Lindenmuth MB, Nance M, Forbes EE
J Child Adolesc Psychopharmacol · 2026 Jun · PMID 42334134 · Publisher ↗
OBJECTIVE: To examine how emotional awareness (the ability to understand and identify one's own emotions) and neural reward circuitry, processes that are associated with depression and undergo significant maturation duri...
OBJECTIVE: To examine how emotional awareness (the ability to understand and identify one's own emotions) and neural reward circuitry, processes that are associated with depression and undergo significant maturation during adolescence, prospectively predict depressive symptoms in a community sample of youth at varying risk for affective disorders. METHOD: Youth aged 13-19 years ( = 84), risk-enriched for depression (66% with familial history of affective disorders), completed self-report assessments of emotional awareness and depressive symptoms at baseline. Depressive symptoms were also assessed at 1-year follow-up. Neural reward function, as indexed by functional connectivity of the dorsomedial prefrontal cortex (dmPFC) and nucleus accumbens (NAcc), was assessed via a functional magnetic resonance imaging task of winning versus losing monetary rewards at baseline. Controlling for age, biological sex, familial risk status, and baseline depression, linear regressions examined the interaction of emotional awareness and dmPFC-NAcc functional connectivity to predict changes in depressive symptoms over 1 year. RESULTS: Low emotional awareness at baseline predicted more severe depressive symptoms at 1-year follow-up, particularly among youth demonstrating heightened positive dmPFC-NAcc functional connectivity, a pattern potentially indicating over-regulation of reward responding. DISCUSSION: Low emotional awareness and stronger frontostriatal functional connectivity during processing of reward relative to loss are relevant early-emerging risk factors that could jointly lead to future depression. Interventions targeting emotional regulation skills and reward processing may mitigate the onset and course of adolescent depressive symptoms.
Testing a Developmental Cascade Model from Prenatal Maternal Emotion Dysregulation to Toddler Behavior Dysregulation Through Postnatal Parenting Stress and Infant Physiology.
Zhou AM, Molina NC, Maylott SE … +8 more , Compton AM, Neff D, Gao MM, Denherder S, Bruce M, Raby KL, Conradt E, Crowell SE
J Child Adolesc Psychopharmacol · 2026 Jun · PMID 42332542 · Publisher ↗
OBJECTIVE: Early behavioral dysregulation places children at elevated risk for later psychopathology. Maternal emotion dysregulation during pregnancy is a transdiagnostic vulnerability that may shape child regulatory dev...
OBJECTIVE: Early behavioral dysregulation places children at elevated risk for later psychopathology. Maternal emotion dysregulation during pregnancy is a transdiagnostic vulnerability that may shape child regulatory development through both prenatal biological influences and postnatal caregiving. However, less is known about the specific postnatal mechanisms through which prenatal emotion dysregulation confers risk for toddler behavioral dysregulation. This study examined whether prenatal maternal emotion dysregulation was associated with toddler behavioral dysregulation indirectly through infant parasympathetic regulation (baseline respiratory sinus arrhythmia; RSA) and postnatal parenting stress. METHODS: Participants were 385 mothers and their infants recruited during the third trimester. At the third trimester, maternal emotion dysregulation was assessed using the Difficulties in Emotion Regulation Scale. At 7 months postpartum, parenting stress was measured using the Parenting Stress Index, and infant parasympathetic regulation was assessed using baseline RSA during a neutral resting period. At 18 months, toddler behavioral dysregulation was evaluated using the Infant-Toddler Social Emotional Assessment. We tested direct and indirect pathways among prenatal maternal emotion dysregulation, postnatal parenting stress, infant baseline RSA, and toddler behavioral dysregulation with structural equation models. RESULTS: Higher prenatal maternal emotion dysregulation was associated with greater postnatal parenting stress and lower infant baseline RSA. Postnatal parenting stress was concurrently associated with higher infant baseline RSA and higher toddler behavioral dysregulation. Infant RSA was not directly associated with toddler behavioral dysregulation. Parenting stress partially accounted for associations between prenatal maternal emotion dysregulation and toddler behavioral outcomes. CONCLUSION: This study provides evidence for prospective indirect pathways in which maternal emotion dysregulation during pregnancy contributes to elevated parenting stress in infancy, which is linked to both infant parasympathetic regulation and toddler behavioral dysregulation. Although prenatal maternal emotion dysregulation was associated with infant baseline RSA, infant RSA was not associated with toddler dysregulation, suggesting partly distinct pathways of physiological and behavioral regulation development. These findings highlight pregnancy and infancy as important periods in early child development.
Neighborhood Disadvantage as a Moderator of Children's Response to a Dyadic Positive Affect Intervention for Children of Mothers with Depressive Symptoms.
Yerger J, Cárdenas EF, Granros M … +6 more , Feurer C, Patel KR, Moon G, Stibor A, Kujawa A, Burkhouse KL
J Child Adolesc Psychopharmacol · 2026 Jun · PMID 42318623 · Publisher ↗
BACKGROUND: Family promoting positive emotions (FPPE) is a dyadic, positive affect-focused preventive intervention shown to reduce perceived stress and emotional symptoms among children of mothers with elevated depressiv...
BACKGROUND: Family promoting positive emotions (FPPE) is a dyadic, positive affect-focused preventive intervention shown to reduce perceived stress and emotional symptoms among children of mothers with elevated depressive symptoms, a population at heightened risk for psychopathology. Emerging evidence suggests that contextual disadvantages (e.g., socioeconomic, neighborhood) may shape vulnerability for major depressive disorder in children. The present study examined whether family- and neighborhood-level disadvantage moderated children's response to FPPE relative to a psychoeducation comparison condition, with the goal of informing precision prevention efforts for high-risk families. METHODS: Participants included 74 children (ages 8-12 years; 46.3% female) and their biological mothers with elevated depressive symptoms (i.e., Patient Health Questionnaire scores ≥ 8). Following random assignment, 47 dyads were assigned to FPPE, and 27 dyads were assigned to a written information psychoeducation condition. Neighborhood and family-level disadvantage was assessed using the Child Opportunity Index (COI) scores and family-level income-to-needs ratio (INR), respectively. Parent-reported child perceived stress and emotional distress (depressive, anxiety, and anger symptoms) were assessed pre- and post-intervention using the Perceived Stress Scale and Patient-Reported Outcomes Measurement Information System Emotional Distress Scales. RESULTS: Family-level INR did not moderate intervention effects. Results revealed a significant time × group × COI interaction for child-perceived stress, such that greater neighborhood disadvantage was associated with a larger reduction in child-perceived stress pre-to-post intervention in the FPPE but not the written information group. No other significant effects emerged. CONCLUSIONS: FPPE was most effective in reducing perceived stress among children of mothers with elevated depression symptoms exposed to greater neighborhood-level disadvantage, suggesting that a positive valence system (PVS) may be a particularly sensitive and proximal preventive intervention target through which downstream reductions in stress occur. These findings suggest that youth facing both intergenerational and environmental risk may benefit the most from dyadic, positive affect-focused interventions to reduce stress. Research should test downstream effects of FPPE on clinical symptoms emerging over longer periods.
Psychosis Following Hormonal Therapy in NAA15-Related Neurodevelopmental Disorder.
Christ C, Makwana R, Appah FSK … +5 more , Cheng H, Moreno C, Marchi E, Harpell R, Lyon GJ
J Child Adolesc Psychopharmacol · 2026 Jun · PMID 42316871 · Publisher ↗
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Tool for Converting ADHD Rating Scales Scores Based on Individual Participant Data from 53 Randomized Controlled Trials of ADHD Medications.
Christogiannis C, Garcia-Argibay M, Tomlinson A … +11 more , Roy S, Farhat LC, Fusetto Veronesi G, Parlatini V, Bellato A, Gosling CJ, Mavridis D, Efthimiou O, Ostinelli EG, Cipriani A, Cortese S
J Child Adolesc Psychopharmacol · 2026 Jun · PMID 42316867 · Publisher ↗
INTRODUCTION: A variety of rating scales are currently being used to assess symptom severity and quantify symptoms change in attention-deficit/hyperactivity disorder (ADHD) research and clinical practice. This poses diff...
INTRODUCTION: A variety of rating scales are currently being used to assess symptom severity and quantify symptoms change in attention-deficit/hyperactivity disorder (ADHD) research and clinical practice. This poses difficulties in interpreting scores from different scales in clinical practice and synthesizing data from studies using different scales. We aimed to develop algorithms for converting scores across the ADHD scales most often used in randomized controlled trials (RCTs) of ADHD medications in children/adolescents and adults, and to develop an online tool for implementing the algorithms. METHODS: We analyzed individual participant data from RCTs of ADHD medications (32 RCTs in children/adolescents, 21 in adults), with data on at least two scales per participant at the same timepoint. We applied a series of competing models, that is, univariable and multivariable regression, random forests, and an equipercentile linkage approach, to link pairs of scales. To assess the error of the linking procedure and identify the optimal model, we calculated the median absolute error and of all approaches by comparing the values predicted from the models to the observed ones. We subsequently developed a tool to implement the best algorithms. RESULTS: We linked six commonly used ADHD scales, such as the ADHD Rating Scale (ADHD-RS-IV; investigator-rated) and the Conners' Parent Rating Scale (CPRS-R:S). Spline models most frequently yielded the lowest prediction error, outperforming alternative conversion algorithms for absolute scores in 6 out of 12 univariable models and 8 out of 12 multivariable models. The tool for scores conversion is available at ADHD_Scale_Conversion_Tool. CONCLUSIONS: Our linkage algorithms enable the comparison and harmonization of findings across studies using different ADHD rating scales. Translating scores across scales improves the interpretability of research findings, facilitates future evidence synthesis across studies, and may support clinical practice. Our online tool supports the practical uptake of our results.
Validation of the Temper Outbursts/Irritability-2: A Two-Item Screener for Temper Outbursts and Irritability in Youth.
Waschbusch DA, Babinski DE, Saunders EFH … +2 more , Waxmonsky JG, Baweja R
J Child Adolesc Psychopharmacol · 2026 Jun · PMID 42298975 · Publisher ↗
OBJECTIVE: Irritability and temper outbursts are common presenting concerns in pediatric mental health settings, but systematic monitoring can be difficult to sustain with broad, repeated assessment batteries. This study...
OBJECTIVE: Irritability and temper outbursts are common presenting concerns in pediatric mental health settings, but systematic monitoring can be difficult to sustain with broad, repeated assessment batteries. This study evaluated the temper outbursts/irritability-2 (TOI-2), an ultra-brief, two-item screener assessing temper outbursts and frequently irritable mood in youth. METHODS: Participants were 1515 youth aged 5-17 years ( = 11.80, SD = 3.60) referred to an outpatient child psychiatry clinic. Female caregivers (90.4% biological mothers) completed the TOI-2 and criterion measures at intake. Convergent and discriminant validity were assessed via correlations with the Affective Reactivity Index (ARI), administered with a current-state timeframe, oppositional defiant disorder (ODD) symptom dimensions, attention-deficit/hyperactivity disorder, conduct disorder (CD), depression, and anxiety. Screening accuracy was evaluated using receiver operating characteristic analysis, with elevated irritability defined as ARI ≥ 4. Clinical utility was examined using screen-positive and screen-negative comparisons and known-group analyses. RESULTS: The TOI-2 showed strong convergence with the ARI and ODD-Irritability symptoms (s = 0.82). Its association with ODD-Irritability was significantly stronger than with ODD-Behavioral symptoms ( = 0.70; < 0.001), supporting relative specificity to irritability within the broader disruptive behavior spectrum. ROC analysis indicated excellent classification accuracy, area under the curve = 0.91. Cut scores of ≥2.5 and ≥3.0 both optimized overall performance, Youden's J = 0.66. A threshold of ≥3.0 is recommended for specialty-clinic triage, whereas ≥2.5 may be preferable when maximizing case detection is the priority. Youth who screened positive showed greater symptom severity and poorer adjustment across clinical domains. Known-groups analyses showed the largest TOI-2 elevations among youth meeting symptom-count thresholds for ODD and CD. CONCLUSIONS: The TOI-2 is a psychometrically sound, ultra-brief screener for clinically significant irritability in youth. Positive screens should prompt more comprehensive clinical assessment of irritability, impairment, disruptive behavior, mood symptoms, and treatment needs.
Polygenic Risk for Insomnia in Relation to Sleep Disturbance and Psychiatric Characteristics in Youth with Mood Disorders.
Puchiele AA, Mio M, Dimick MK … +4 more , Zai CC, Boulos MI, Rabin JS, Goldstein BI
J Child Adolesc Psychopharmacol · 2026 Jun · PMID 42267832 · Publisher ↗
BACKGROUND: Sleep disturbance is common in youth with mood disorders and correlates with mood symptom burden. Insomnia polygenic risk scores (PRS), computed from adult genome-wide association study (GWAS) data, are assoc...
BACKGROUND: Sleep disturbance is common in youth with mood disorders and correlates with mood symptom burden. Insomnia polygenic risk scores (PRS), computed from adult genome-wide association study (GWAS) data, are associated with sleep disturbance among youth within the general population. However, no studies have examined insomnia-PRS in a clinical sample of youth with mood disorders. METHODS: Participants included 374 youth aged 13-20 years, 247 with mood disorders (135 bipolar disorder [BD] and 112 major depressive disorder) and 127 controls. Insomnia-PRS was constructed using an adult insomnia GWAS ( = 360,738). Sleep disturbance was computed using the most severe lifetime insomnia and hypersomnia (i.e., excessive sleep) items from the Kiddie Schedule for Affective Disorders and Schizophrenia Depression Rating Scale. General linear models or logistic regressions examined main effects of insomnia-PRS on sleep disturbance and psychiatric characteristics (mood symptom severity, anxiety comorbidity, suicide risk, global functioning), controlling for age, sex, and genetic principal components. RESULTS: Insomnia-PRS was higher in youth with mood disorders versus controls ( = 0.03, = 0.24). Insomnia-PRS was associated with insomnia severity in youth with mood disorders ( = 0.03, = 0.02), and with mania severity in youth with BD ( = 0.03, = 0.03), although the insomnia severity finding did not survive Bonferroni correction. In sex-stratified analyses, insomnia-PRS was significantly associated with insomnia ( = 0.02, = 0.03), depression ( 0.02, 0.03), and mania ( 0.02, = 0.05) severity in females but not males. There were no significant findings for excessive sleep. CONCLUSIONS: This study extends prior findings linking adult-derived insomnia-PRS with insomnia in youth with mood disorders, with evidence of differences related to sex and BD. These preliminary findings suggest that sleep and mood in youth may be sensitive to adult-derived insomnia-PRS.
Context Matters: Variation in Pharmacologic Management of Pediatric Agitation Across Emergency and Inpatient Psychiatric Settings.
Lynch ST, Chaia AI, Burns R … +3 more , Noureddine C, Rice TR, Sterchele AN
J Child Adolesc Psychopharmacol · 2026 Jun · PMID 42261239 · Publisher ↗
BACKGROUND: Management of acute agitation in youth frequently involves intramuscular (IM) antipsychotics; however, little is known about how treatment strategies vary across care settings. Differences between emergency a...
BACKGROUND: Management of acute agitation in youth frequently involves intramuscular (IM) antipsychotics; however, little is known about how treatment strategies vary across care settings. Differences between emergency and inpatient psychiatric environments may influence medication selection and dosing. METHODS: This retrospective secondary analysis included youth (<18 years) who received IM antipsychotics for agitation across multiple emergency departments and inpatient psychiatric units within a large urban health system (2019-2023). Comparisons between settings examined antipsychotic selection, coadministration of adjunctive medications, and dosing. To account for differences in medication selection, dosing comparisons were conducted within each antipsychotic agent. Secondary outcomes included repeat IM administration and restraint or seclusion within 24 hours. RESULTS: The sample included 158 youth (86 emergency, 72 inpatient). Antipsychotic selection differed significantly by setting, with greater use of haloperidol in emergency settings and chlorpromazine in inpatient settings ( < 0.001). Midazolam coadministration was more common in emergency settings (10.5% vs. 1.4%, = 0.020). When examined within agents, chlorpromazine doses were higher in inpatient settings (36.7 mg vs. 30.4 mg, = 0.035), while haloperidol and olanzapine dosing did not differ. Rates of additional IM administration were similar across settings ( = 0.295), although restraint or seclusion was more common in inpatient settings ( < 0.001). CONCLUSIONS: Pharmacologic management of pediatric agitation varies by care setting, particularly in antipsychotic selection and adjunctive medication use. Differences in dosing were limited to chlorpromazine, suggesting that variation reflects agent-specific prescribing patterns rather than overall treatment intensity. These findings highlight the influence of clinical context and provider practice patterns in shaping management strategies for pediatric agitation.
Effects of Fluoxetine on Cognitive Functioning in Children with Down Syndrome: A Prospective Open-Label Exploratory Study of Safety and Efficacy.
Scala I, Bravaccio C, Marino M … +8 more , Scicolone O, Maffettone V, Riccio MP, Terrone G, Cattaneo D, Clementi E, Bartesaghi R, Strisciuglio P
J Child Adolesc Psychopharmacol · 2026 Jun · PMID 42261237 · Publisher ↗
BACKGROUND: Down syndrome (DS) is a major genetic cause of intellectual disability. In an animal model of DS, fluoxetine was shown to restore brain architecture and cognitive performance, acting primarily on the hippocam...
BACKGROUND: Down syndrome (DS) is a major genetic cause of intellectual disability. In an animal model of DS, fluoxetine was shown to restore brain architecture and cognitive performance, acting primarily on the hippocampus, with effects persisting after treatment discontinuation. In this translational study, we assessed the safety and tolerability of fluoxetine at the standard labeled dose and explored selected efficacy endpoints to inform future clinical trials. METHODS: The study was approved as a phase I, open-label study. Participants with full trisomy 21 received fluoxetine (10 mg/day) for 6 months, followed by a 6-month observation period. The primary endpoint, safety and tolerability, was evaluated through clinical examinations, biochemistry, plasma fluoxetine and norfluoxetine levels, electroencephalography, and electrocardiography at multiple time-points. As a secondary efficacy endpoint, we selected a set of cognitive tests to explore hippocampus-dependent functions and adaptive behavior. RESULTS: Fourteen children with DS (8.1 ± 1.24 years; range 6-10) were enrolled, and 12 completed the 12-month study. No serious or severe adverse events (AEs) occurred. All AEs resolved without sequelae. Short-term terminal insomnia was observed in two patients. Neuropsychological assessments revealed improvements in visuospatial processing tasks during the study. Analysis of adaptive behavior suggested enhanced expression skills. CONCLUSIONS: These findings indicate that fluoxetine is safe in children with DS. The association with terminal insomnia warrants specific investigation in future trials and strategies to optimize tolerability are discussed. Efficacy analyses highlight the visuospatial processing domain as potentially responsive to treatment, supporting further research.
A Phase-2 Open-Label Trial of Cannabidiol to Treat Core and Associated Symptoms of Autism in Children and Adolescents Without Intellectual Disability.
Lawson J, Robinson L, Conlon GR … +8 more , Shalev RA, Cervantes PE, Yoncheva Y, Hirsch GS, Troxel AB, Friedman D, Devinsky O, Castellanos FX
J Child Adolesc Psychopharmacol · 2026 Aug · PMID 42204954 · Publisher ↗
OBJECTIVE: To evaluate cannabidiol (CBD) in pediatric patients with autism spectrum disorder (ASD), fluent verbal language and an estimated full-scale IQ of 80 or above. BACKGROUND: Preliminary evidence suggests CBD may...
OBJECTIVE: To evaluate cannabidiol (CBD) in pediatric patients with autism spectrum disorder (ASD), fluent verbal language and an estimated full-scale IQ of 80 or above. BACKGROUND: Preliminary evidence suggests CBD may ameliorate challenges associated with ASD. Whether CBD benefits pediatric ASD without accompanying intellectual or language impairment remains unknown. METHODS: We enrolled 23 participants, ages 7.8-17.8 (Mean [M] = 11.3 ± 2.8) with ASD and IQ ≥ 80 in a 6-week Phase-2 open-label trial of ≥98% CBD (Epidiolex, 100 mg/mL) at 3, 6, or 9 mg/kg/day using a Bayesian optimal interval dosing design. The primary endpoint was the CBD dose associated with the highest response rate (i.e., Clinical Global Impression Scale-Improvement [CGI-I] score = 1 or 2) on a target symptom domain designated individually based on informant report, standardized scales, and clinical observation. Secondary endpoints were effect sizes of changes from baseline in measures assessing ASD core and associated symptoms, and global functioning. Adverse events (AEs) were assessed weekly. Plasma CBD levels and clinical labs were obtained at the final visit. RESULTS: All 23 enrolled participants completed the trial. The highest response (62%) was observed at 9 mg/kg/day ( = 8). Overall, 10 of 23 patients (44%) were responders. Response varied across domains: Irritability/Tantrums ( = 5, 60%), Social ( = 8, 50%), Anxiety ( = 5, 40%), Restricted, Repetitive Behaviors ( = 4, 25%), and Sleep Problems ( = 1, 0%). Dose correlated with individualized CGI-I (r = -0.42, = 23, = 0.04).Individualized domain CGI-Severity scores improved from pre-(M = 4.6 ± 0.5) to post-(M = 3.9 ± 0.8) treatment, t = -4.36, ≤ 0.001; = 0.91; 95%CI [0.37,1.03]. Social Responsiveness Scale-2 Total-Score (SRS2-T) had the largest effect size ( ≤ 0.001; = 1.36, 95% CI [0.78-1.93]).Of 222 reported AEs, 27 unique AEs were considered treatment-related. Most AEs (93%) were mild and expected (82%); none was severe. The most frequent related AEs were increased salivation (30%), increased sleep duration (39%), sleepiness/sedation (26%), increased dream activity (35%), and polyuria (22%). Vital signs, physical exams, weight, liver function tests, and complete blood counts were unaffected. CBD plasma levels did not correlate with response. CONCLUSIONS: In this preliminary study, CBD was well tolerated; AEs were mild-moderate. Mean SRS2-T and subscores decreased significantly with large effect sizes, shifting from the severe to the moderate range. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03900923.
Symptoms Improve for Inpatient Adolescents According to Measurement-Based Care.
Tebbett-Mock AA, Gasparro S, Chaplin W … +1 more , Saito E
J Child Adolesc Psychopharmacol · 2026 Aug · PMID 42198952 · Publisher ↗
OBJECTIVE: Use measurement-based care to assess symptom change across diagnostic categories for adolescents receiving acute-care psychiatric inpatient treatment including both psychopharmacology and dialectical behavior...
OBJECTIVE: Use measurement-based care to assess symptom change across diagnostic categories for adolescents receiving acute-care psychiatric inpatient treatment including both psychopharmacology and dialectical behavior therapy. METHODS: Adolescents were aged 12-17 and hospitalized on a coeducational, acute-care inpatient unit within a psychiatric hospital in New York City. We conducted a retrospective chart review to analyze symptoms across two or more timepoints from the first 15 days of admission using mixed effects regression models to estimate linear change on five outcome measures including Generalized Anxiety Disorder-7 (GAD-7), General Behavior Inventory-Mania subscale (GBI-10M), Patient Health Questionnaire-9 (PHQ-9), Prodromal Questionnaire Brief-21 (PQB-21), and Schwartz Outcome Scale-10 (SOS-10). RESULTS: There were improvements on all five measures. For the GAD-7, GBI-10M, PHQ-9, and PQB-21, the change is negative, indicating a decrease in symptoms. For the SOS-10, the change is positive, suggesting an increase in well-being. The covariance parameters indicate that there is generally significant individual variation around the adolescent's initial assessment as well as significant individual variation around the slope, suggesting that patients change at different rates. The Days Intercept covariance parameter is generally negative, indicating that adolescents who started with higher symptom severity showed greater symptom reduction. For well-being, the negative change indicates that adolescents with higher well-being on the first assessment showed smaller increases in well-being over time. CONCLUSION: Adolescents experienced improvements in their symptoms of anxiety, mania, depression, psychosis, and well-being during acute psychiatric inpatient treatment. These are notable findings, particularly for demonstrating the impact of psychiatric inpatient treatment on improving symptoms/diagnoses.
Outcome Measure Selection as a Source of Null Results in Autism Pharmacotherapy: The Case of Brexpiprazole and the ABC-I.
Şahin B
J Child Adolesc Psychopharmacol · 2026 Aug · PMID 42163535 · Publisher ↗
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Clonidine Hydrochloride Extended-Release Oral Suspension for Pediatric Attention-Deficit/Hyperactivity Disorder: A Meaningful Addition to Clinical Practice?
Tariq M, Genovese A
J Child Adolesc Psychopharmacol · 2026 Aug · PMID 42163533 · Publisher ↗
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Manganese Exposure and Attention-Deficit/Hyperactivity Disorder-Related Neurobehavioral Outcomes in Children: A Systematic Review of Human Studies.
Ogut E, Ilgin S, Atli Eklioglu O
J Child Adolesc Psychopharmacol · 2026 Aug · PMID 42130043 · Publisher ↗
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition with multifactorial etiology involving genetic, neurobiological, and environmental determinants. Emerging evidence sugg...
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition with multifactorial etiology involving genetic, neurobiological, and environmental determinants. Emerging evidence suggests that environmental exposures may influence neurodevelopmental pathways relevant to ADHD pathophysiology. Manganese is an essential trace element required for normal brain development; however, excessive or dysregulated exposure has been associated with neurotoxic effects. This systematic review aimed to synthesize human evidence on the association between manganese exposure and ADHD or ADHD-related neurobehavioral outcomes in children. METHODS: Four electronic databases were systematically searched according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Observational studies meeting predefined Population, Exposure, Comparison, Outcomes, and Study Design criteria were included. Methodological quality was assessed using Joanna Briggs Institute appraisal tools, and certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation framework. RESULTS: Thirty studies met the inclusion criteria. Elevated manganese exposure was more frequently associated with increased risk or severity of ADHD or ADHD-related neurobehavioral symptoms, although inverse and nonlinear (U-shaped) associations were also reported. CONCLUSIONS: The available evidence indicates a complex and potentially nonlinear relationship between manganese exposure and child neurobehavioral outcomes. These findings identify manganese exposure as a potentially modifiable environmental factor influencing neurodevelopmental mechanisms relevant to ADHD and highlight the need for longitudinal studies integrating exposure biomarkers with neurobiological and clinical outcomes to clarify causal pathways and therapeutic implications.
Effectiveness and Safety of Selective Serotonin Reuptake Inhibitors in Individuals with Williams Syndrome.
Snapir L, Elazar M, Cohen T … +4 more , Weinberger R, Schwartz-Lifshitz M, Taler M, Gothelf D
J Child Adolesc Psychopharmacol · 2026 Aug · PMID 42130028 · Publisher ↗
OBJECTIVE: Anxiety and depressive disorders are common in individuals with Williams syndrome (WS), yet data regarding pharmacologic treatment in this population are limited. This study aimed to evaluate the effectiveness...
OBJECTIVE: Anxiety and depressive disorders are common in individuals with Williams syndrome (WS), yet data regarding pharmacologic treatment in this population are limited. This study aimed to evaluate the effectiveness and safety of selective serotonin reuptake inhibitors (SSRIs) in individuals with WS treated for anxiety and/or depressive disorders. METHODS: We conducted a retrospective chart review of patients with a genetically confirmed diagnosis of WS treated with SSRIs between 2010 and 2025 at a clinic for individuals with WS. Fourteen children and adults (5 males and 9 females; mean age: 23.2 ± 11.9 years) met inclusion criteria, contributing 16 distinct SSRI treatment trials. Illness severity was assessed using the Clinical Global Impressions-Severity (CGI-S) scale at baseline and last follow-up and the Clinical Global Impressions-Improvement (CGI-I) scale. RESULTS: The CGI-S score decreased significantly from 4.62 ± 0.81 at baseline to 3.06 ± 1.12 at last follow-up ((15) = 3.83, = 0.002). Nine of 16 trials (56.2%) were rated as much or very much improved (CGI-I = 1 or 2). The mean duration of SSRI treatment was 3.95 ± 3.91 years (range: 0.75-16). Adverse events were documented in two trials (12.5%), and no treatment discontinuations due to adverse events occurred. CONCLUSIONS: SSRI treatment was effective and well tolerated in individuals with WS. Prospective controlled studies are required.
Prediction Gone Awry: A Computational Framework for Emotion Dysregulation Across Autism and Attention-Deficit/Hyperactivity Disorder.
Srinivasan H, Cascio CJ, Wallace MT
J Child Adolesc Psychopharmacol · 2026 May · PMID 42116687 · Publisher ↗
Emotion dysregulation is a common issue across childhood and adolescence, including in autism and attention-deficit/hyperactivity disorder (ADHD). Yet most accounts remain descriptive-focusing on irritability, rapid esca...
Emotion dysregulation is a common issue across childhood and adolescence, including in autism and attention-deficit/hyperactivity disorder (ADHD). Yet most accounts remain descriptive-focusing on irritability, rapid escalation, slow return to baseline-without specifying the computational processes that stabilize emotions in context. We propose a predictive-coding account in which emotion regulation depends on how the brain predicts bodily and environmental signals, detects mismatches, between expectation and sensation, and determines how much confidence to assign those mismatches. Within this framework, dysregulation can arise when prediction errors are assigned excessive precision (i.e., incoming signals are overweighted relative to prior expectations, making them feel "too loud"), amplifying emotional reactivity or when prior expectations update too slowly (feelings get "stuck"), prolonging emotional states beyond contextual demands. We hypothesize that autism may involve heightened confidence assigned to surprising inputs together with sluggish updating of expectations, a combination that can produce both reactivity and emotional inertia. ADHD, by contrast, may be characterized by weaker expectations and unstable gain control, meaning the system's amplification of incoming signals fluctuates from moment to moment, contributing to rapid, reactive swings in affect. We outline candidate physiological correlates-including heart-rate variability dynamics, pupillary variability, mismatch negativity, and neural indices of interoceptive precision-that could evaluate these hypotheses. Framing intervention around restoring flexible inference rather than suppressing emotion offers a mechanistic direction for developmental research. These predictions await empirical validation in developmental samples.
Without a Broader Understanding of the Variables Involved in the Brain-Gut Axis, Probiotics Use Is still an Open Question.
Pereira Fernandes ME, Sampaio de Lima E, Cruz Rodrigues EH … +4 more , Macedo Alencar G, Louro Filomeno M, Arruda Cavalcante Souza I, Weber Bisol L
J Child Adolesc Psychopharmacol · 2026 Jun · PMID 42104579 · Publisher ↗
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Antipsychotic Prescribing Practice Patterns for Management of Delirium in a Tertiary Care Children's Hospital Intensive Care Units.
Zaim N, Procaccini DE, Adeagbo T … +2 more , Barnes S, Kudchadkar SR
J Child Adolesc Psychopharmacol · 2026 May · PMID 42101111 · Publisher ↗
OBJECTIVE: Delirium in the setting of critical illness occurs in 15%-60% of pediatric patients and is associated with increased duration of hospital admission. Strategies for symptom management include minimizing exposur...
OBJECTIVE: Delirium in the setting of critical illness occurs in 15%-60% of pediatric patients and is associated with increased duration of hospital admission. Strategies for symptom management include minimizing exposure to deliriogenic medications, optimizing day-night cycles, and in some cases prescribing antipsychotic medications. Symptom management occurs while simultaneously identifying and treating the underlying etiology. Over a 5-year period, our pediatric intensive care units implemented several unit-based initiatives to prevent and minimize the severity of delirium in critically ill children. The objective of this study is to retrospectively characterize antipsychotic prescribing practices over the study period. METHODS: Over a 5-year timeframe in our children's hospital, we extracted dispensing data for risperidone, olanzapine, quetiapine, and haloperidol. We used descriptive statistics to characterize patients initiated on an antipsychotic in an ICU area, dosing information, and quantitative change in annual orders over the study period. RESULTS: During the study period, 533 antipsychotic orders were placed for 165 patients. Most of the identified patients were male (60.6%) and Black (44.2%). Ninety (16.9%) of the medication orders remained active after patient transfer to a general care floor. Risperidone was the most prescribed antipsychotic (54%), with a 413% increase observed between 2016 and 2018, followed by a decline of 89% between 2018 and 2021. Use of other antipsychotics was less than risperidone but consistent during the study period. Risperidone was more commonly prescribed for younger children, and prescribing patterns suggest a preference for nighttime administration. CONCLUSIONS: Implementation of unit-based initiatives to promote delirium screening and awareness led to an initial increase in antipsychotic medication prescribing for critically ill children with delirium. This was followed by a significant decline in antipsychotic prescribing with the inclusion of the child and adolescent psychiatry team in our delirium management and prevention algorithm. This study highlights the importance of collaboration with the child and adolescent psychiatry team in the management of pediatric delirium across the hospital system. Additional research on antipsychotic prescribing practices and the associated impact of nonpharmacologic interventions and multidisciplinary collaboration for delirium treatment is warranted.
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