Introduction: While youth with bipolar disorder (BD) spend the majority of the time experiencing symptoms of depression, there are fewer evidence-based options for the pharmacological treatment of bipolar depression versus mania. Given evidence of increased inflammation and oxidative stress in BD, engaging these treatment targets may address underlying pathophysiological mechanisms. We conducted a pilot trial of curcumin, a widely available, safe nutraceutical with anti-inflammatory and antioxidative properties, for the treatment of bipolar depression in youth. Methods: Six participants with bipolar depression were enrolled and received 8 weeks of open-label curcumin. The starting dose was 500 mg daily, then increased to 500 mg twice daily at week 2, then increased to 1000 mg twice daily at weeks 3–8. Symptoms were evaluated with the Children’s Depression Rating Scale–Revised (CDRS-R), Kiddie Schedule for Affective Disorders and Schizophrenia Depression Rating Scale (DRS), and Clinical Global Impression Scale. Treatment response was defined as greater than or equal to 50% reduction in CDRS-R score. Blood biomarkers of inflammation (interferon‐gamma, interleukin-10 [IL-10], IL-8, tumor necrosis factor alpha) and oxidative stress (8-iso-prostaglandin F2alpha [8-ISO], lipid peroxidation [LPO]) were evaluated at baseline, 4 weeks, and 8 weeks. Analyses examined changes in depressive symptoms in relation to changes in biomarkers over time. Results: There were significant reductions in clinical global impression of depression severity [χ 2 (4) = 10.97, p = 0.03, W = 0.46] and overall illness severity [χ 2 (4) = 10.25, p = 0.04, W = 0.43] from baseline to 8 weeks. The most common side effects were related to the central nervous system and gastrointestinal system. From baseline to 4 weeks, greater reduction in CDRS-R scores was associated with greater reduction in 8-ISO ( r = 0.89, p = 0.02), and a greater reduction in DRS scores was associated with a greater reduction in LPO ( r = 0.82, p = 0.05). Conclusions: This trial provides preliminary evidence that the antidepressant effects of curcumin may be associated with its antioxidative properties. However, larger controlled trials are needed to evaluate the efficacy of curcumin for bipolar depression, and to examine oxidative stress markers as predictors and/or mediators of antidepressant effects.

Background: Risperidone is an atypical antipsychotic commonly used in pediatric psychiatry that may be associated with metabolic and endocrine adverse effects. Prospective data on drug-naive children and adolescents are limited. Objective: To prospectively evaluate anthropometric, metabolic, endocrine, cardiovascular, and clinical changes during the first 6 months of risperidone treatment in drug-naive children and adolescents. Methods: This single-center, prospective observational study included 90 drug-naive patients aged 3–18 years who received risperidone treatment between September 2021 and September 2023. Participants were included if they were aged 3–18 years, planned to start risperidone, accepted treatment, and provided informed consent from parents with verbal or written assent from children. Exclusion criteria included chronic medical or neurological diseases requiring treatment, overweight or obesity, prior child psychiatry referrals, use of psychotropic medications, receipt of chronic medical treatment, and having illiterate parents. Assessments at baseline and visits at three and 6 months included height, weight, body mass index (BMI) percentile, waist circumference, fasting glucose, lipid profile, serum prolactin, blood pressure, pulse, and Clinical Global Impression–Severity (CGI-S) scores. Nonparametric tests were used to compare repeated measures, and correlations between risperidone dose and metabolic/endocrine variables were analyzed. Results: The median age was 10.0 years, and 70% of the participants were male. The participant flow throughout the study is presented in Figures 1 and 2 . The mean risperidone dose was 1.62 ± 1.00 mg/day at 3 months and 1.99 ± 1.12 mg/day at 6 months. Significant increases were observed in height, weight, BMI percentile ( p = 0.000, p = 0.000, p = 0.044, respectively), and waist circumference ( p = 0.014). Serum prolactin levels increased ( p = 0.006), and high-density lipoprotein (HDL) cholesterol levels decreased ( p = 0.018), whereas other metabolic and cardiovascular parameters showed no significant change. CGI-S scores improved ( p < 0.001). A strong positive correlation between risperidone dose and waist circumference was observed at 3 months (r = 0.715, p = 0.000) and 6 months (r = 0.803, p = 0.000). Forty-eight participants did not attend the 3-month evaluation, and 17 did not attend the 6-month evaluation, which was addressed with sensitivity analyses. Conclusions: Within 6 months of initiation, risperidone use in drug-naive pediatric patients was associated with increased weight and abdominal adiposity, early prolactin elevation, HDL reduction, and clinical improvement. Waist circumference showed a strong dose-dependent association and should be routinely monitored along with metabolic and endocrine parameters.

Importance: Psychotropic classes concomitant with stimulants (PCCWS) in children and adolescents have shown an inconsistent impact on the risk of diabetes mellitus. PCCWS with 2-5 classes is common but the risk of diabetes subsequent to stimulant initiation is unknown. Objective: To assess the risk of diabetes in youth with PCCWS regimens with 2-5 additional psychotropic classes. Design: A retrospective cohort study was conducted using Medicaid claims data from 2007-2014. Youth aged 2-17 years with 1-7.5 years of continuous enrollment who were new stimulant users with clinician-reported psychiatric diagnosis were followed. Setting: Outpatient clinic and inpatient records for statewide Medicaid-insured youth in a mid-Atlantic state. Participants: The study cohort comprised 30,112 youth with an average follow-up of 6.4 years. Exposures: Among stimulant users, five groups were defined according to concomitant use. Main Outcomes and Measures: The major outcome is diabetes risk and was assessed using discrete-time failure models, after adjustment for disease risk score which was categorized using more than 120 baseline and time-dependent covariates. Results: Among 30,112 new stimulant users, 43 were new diabetes patients and 30,069 were nondiabetes patients. The absolute risk of diabetes in youth had an eight-fold increase from 3 to 5 class PCCWS regimens that included antipsychotics, antidepressants, or anticonvulsant-mood stabilizers (0.5; 1.13; 4.20 per 10,000 person-months, respectively). Compared with stimulant monotherapy, PCCWS with any of these 3 classes were significantly more likely to develop diabetes (adjusted relative risk [ARR], 2.58, (95% CI 1.05-6.82); 5.81, (2.29-14.75); 18.91, (6.07-58.90) for 3, 4 and 5 class PCCWS, respectively). Similarly, there was a significantly greater risk of diabetes for those with 120-779 days of cumulative duration than for shorter exposures, and in 4 and 5 class combined PCCWS including antipsychotics, antidepressants, or anticonvulsant-mood stabilizers [ARR, 3.78, (1.16-12.40)]. Conclusions: In a large Medicaid-insured, long-enrolled youth cohort, the use of PCCWS, particularly concomitant use with antipsychotic, antidepressant, and/or antipsychotic-mood stabilizers, and with long duration of these combinations were associated with an increased risk of diabetes. Relevance: The findings support a call for corroboration in a large national cohort of continuously enrolled Medicaid-insured pediatric youth with long follow-up.

Objective: Evidence for medical cannabis use and effectiveness in autism has begun to accumulate but remains limited, even as clinical interest has rapidly increased. In Israel, medical cannabis may be prescribed for autism with severe behavioral disturbances under strict Ministry of Health criteria requiring prior trials of two Food and Drug Administration (FDA)-approved antipsychotics. Using a large real-world dataset, this study aimed to characterize autistic individuals prescribed medical cannabis and evaluate adherence to national guidelines. Methods: A retrospective cohort study was conducted using electronic medical records from Clalit Health Services, Israel's largest Health Maintenance Organization. All individuals with a documented autism diagnosis between 1990 and 2025 were identified (N = 36,610) and classified as cannabis-prescribed (N = 462) or not-prescribed (N = 36,148). Demographic and clinical characteristics were compared, including prior use of FDA-approved antipsychotics. Results: Only 1.2% of individuals with autism were prescribed medical cannabis. Of these, 4.3% of prescriptions were issued for children under 5 years of age. The cannabis-prescribed group was diagnosed earlier (median 3 vs. 5 years, p < 0.001) and had higher rates of ADHD (42% vs. 30%), intellectual disability (12% vs. 5%), and epilepsy (14% vs. 6%) (all p < 0.001). While 69% had used at least one FDA-approved antipsychotic medication prior to cannabis initiation, only 28% had documented trials of both, as required by national guidelines. Marked sociodemographic disparities were also observed: the cannabis-prescribed group had a higher socioeconomic status (median SES 7 vs. 6, p < 0.001) and lower representation of Arab individuals (2.7% vs. 11%, p < 0.001). Conclusions: Medical cannabis use among autistic individuals was rare and mainly observed among those with more complex clinical profiles and higher socioeconomic backgrounds. Most prescriptions did not fully comply with guidelines requiring prior antipsychotic trials. These findings underscore the need for enhanced regulatory oversight, equitable access, and longitudinal research to evaluate real-world outcomes and guide evidence-based clinical practice.

Objective: Children who experience prolonged separation anxiety may develop "avoidance" patterns of emotional regulation that manifest in stressful behavioral responses. This study tests whether maladaptive habits and adjustment disorders mediate the link between separation anxiety and depression in primary school students. Methods: In November 2022, we conducted a cross-sectional survey of 4474 students from elementary schools in Qionghai and Dongfang cities, Hainan Province, China, using stratified cluster sampling. Parents completed the Mental Health Rate Scale for Pupils. Data were analyzed with SPSS 22.0 (descriptive statistics, analysis of variance, correlations), AMOS 26.0 (structural equation modeling [SEM]), and Mplus 8.3 (latent class analysis). Results: SEM revealed that 12.2% of participants met criteria for depression. Students with separation anxiety had 4.5-5.0 times higher odds of depression compared to those without separation anxiety (95% confidence interval [CI]: 3.8-6.2). Mediation analysis indicated that maladaptive habits and adjustment difficulties partially mediated this association, with stronger indirect effects observed in older grades (Grades 5 and 6: β = 0.32, 95% CI: 0.24-0.41 vs. Grades 3 and 4: β = 0.21, 95% CI: 0.15-0.28). Conclusions: These findings suggest that early identification of maladaptive coping patterns in children with separation anxiety could improve mental health outcomes. We recommend integrating "secure separation" education strategies into teacher training programs and school counseling services, including structured transition activities and separation rituals, to support children's emotional adjustment during school transitions.

Objective: To construct a network model depicting non-suicidal self-injury (NSSI) and its influencing factors in adolescents diagnosed with depression, identify the core symptoms within this network, explore the potential causal pathways, and generate hypotheses for future research. Methods: A sample of 705 adolescent patients with depressive disorders was recruited and assessed using three standardized questionnaires, namely the Childhood Trauma Questionnaire, the Aggression Questionnaire, and the Adolescent Self-Injury Questionnaire. Undirected network analysis, coupled with directed Bayesian network analysis, was employed to elucidate the interrelationships among symptoms. Results: In the network of NSSI-related influencing factors in adolescents with depression, emotional abuse, hostility, sexual abuse, and emotional neglect are important influencing factors. Hostility and anger serve as bridges that connect NSSI to other influencing factors. In the Bayesian network, emotional abuse is shown to precede other symptoms, such as hostility and anger; conversely, NSSI and physical aggression were positioned at the periphery of the network, indicating a greater reliance on other symptoms for their occurrence. Emotional abuse demonstrated the strongest associations with the greatest number of other problems in the network, indicating that emotional abuse plays a crucial role. Conclusion: Emotional abuse plays an important role in the network model of NSSI of adolescent depression patients and its influencing factors.

Purpose: There has been recent concern for the rising rates of catatonia diagnosis in pediatric populations. We set out to determine if the rates of catatonia diagnosis have risen at an academic pediatric medical center. Methods: The clinical records of 131 patients were obtained from encounters during 2018-2023 in which a diagnosis of catatonia was made in the pediatric emergency department or inpatient medical hospital. Ordinary least squares regression and linear regression analyses were used to determine if the prevalence of catatonia diagnoses, underlying diagnostic category, and Bush-Francis Catatonia Rating Scale scores changed over time. Results: A 10-fold increase was observed in catatonia diagnoses between 2018 and 2023. A statistically significant relationship between the year of pediatric catatonia diagnoses was discovered (p = 0.01), with an R2 value of 0.83 suggesting that approximately 83% of the variance can be attributed to the passage of time. Both medical and psychiatric causes of catatonia showed an upward trend over the course of the study period. The average Bush-Francis Catatonia Rating Scale scores showed a slight upward trend but were not statistically significant. Conclusion: In this sample of pediatric patients hospitalized at a large academic medical center, the rate of catatonia diagnoses related to both medical and psychiatric causes rose between 2018 and 2023. These data are consistent with previous evidence highlighting an increase in catatonia diagnoses during this period. The COVID-19 pandemic and increasing awareness of catatonia in children may have contributed to this trend. These data support the importance of investigation into this trend and improving education on catatonia for clinicians and the public.

Objective: The current study aimed to investigate the efficacy of probiotics in alleviating anxiety in children and adolescents. Methods: Randomized placebo-controlled trials (RCTs) recruiting children and adolescents were identified through searching major databases using the main keywords "Probiotics" and "Anxiety." Outcomes included improvement in anxiety and treatment acceptability. Continuous and categorical data were expressed as effect size based on standardized mean difference (SMD) and odds ratios (ORs), respectively, with 95% confidence intervals. Results: Meta-analysis of seven RCTs involving 912 participants (mean age = 8.21) showed no significant improvement in anxiety (SMD = -0.09, p = 0.54) between the probiotics and placebo groups. However, subgroup analysis revealed probiotics-associated anxiety improvement (SMD = -0.55, p = 0.02) in studies enrolling individuals with neurodevelopmental disorders but not in those without (SMD = 0.12, p = 0.48). A significant difference was noted between studies recruiting participants with such diagnoses and those without (SMD = -0.55 vs. 0.12, p = 0.05). Moreover, probiotics-related improvement in anxiety was found in individuals diagnosed with autism spectrum disorder (ASD) (SMD = -0.35, p = 0.03) but not attention deficit hyperactivity disorder (ADHD) (SMD = -0.21, p = 0.38). Overall dropouts exhibited no difference between the probiotics and placebo groups (OR = 0.90, p = 0.36). Conclusion: Our results showed efficacy of probiotics against anxiety compared with placebos only in participants diagnosed with neurodevelopmental disorders, especially ASD. Nevertheless, insufficient evidence derived from limited studies (i.e., three trials for ASD and two for ADHD) requires further investigations for verification.