Decreased risk for substance use disorders in individuals with high-functioning autism spectrum disorder.

The objective of this study was to evaluate the risk for developing a substance use disorder (SUD, alcohol or drug abuse or dependence) in individuals with high-functioning autism spectrum disorder (ASD). Subjects with high-functioning ASD were derived from consecutive referrals to a specialized ambulatory program for ASD at a major academic center from 2007 to 2016. Age-matched controls and attention-deficit hyperactivity disorder (ADHD) comparison subjects were derived from three independent studies of children and adults with and without ADHD using identical assessment methodology. Cox proportional hazard models were used to analyze the prevalence of SUD (alcohol or drug use disorder). Age of onset of SUD was analyzed with linear regression models. Our sample included 230 controls, 219 subjects with ADHD, and 230 subjects with ASD. The mean age for the ASD subjects was 20.0 ± 10.3 years. Among ASD subjects, 69% had a lifetime prevalence of ADHD, and the ASD subjects had significantly higher rates of other psychiatric psychopathology compared to ADHD and control subjects (p < 0.001) ASD subjects were at significantly decreased risk for developing a SUD compared to ADHD (hazard ratio (HR) = 0.22, p < 0.001) and control subjects (HR = 0.62, p = 0.04). The age of onset of a SUD was significantly older in ASD subjects, mean age 21.7 years, when compared to ADHD and control subjects (both p < 0.005). Individuals with ASD are at decreased risk to develop a SUD, and when they do, the onset is significantly later than ADHD and controls.

Treatment Response of Transcranial Magnetic Stimulation in Intellectually Capable Youth and Young Adults with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

To examine current clinical research on the use of transcranial magnetic stimulation (TMS) in the treatment of pediatric and young adult autism spectrum disorder in intellectually capable persons (IC-ASD). We searched peer-reviewed international literature to identify clinical trials investigating TMS as a treatment for behavioral and cognitive symptoms of IC-ASD. We identified sixteen studies and were able to conduct a meta-analysis on twelve of these studies. Seven were open-label or used neurotypical controls for baseline cognitive data, and nine were controlled trials. In the latter, waitlist control groups were often used over sham TMS. Only one study conducted a randomized, parallel, double-blind, and sham controlled trial. Favorable safety data was reported in low frequency repetitive TMS, high frequency repetitive TMS, and intermittent theta burst studies. Compared to TMS research of other neuropsychiatric conditions, significantly lower total TMS pulses were delivered in treatment and neuronavigation was not regularly utilized. Quantitatively, our multivariate meta-analysis results report improvement in cognitive outcomes (pooled Hedges' g = 0.735, 95% CI = 0.242, 1.228; p = 0.009) and primarily Criterion B symptomology of IC-ASD (pooled Hedges' g = 0.435, 95% CI = 0.359, 0.511; p < 0.001) with low frequency repetitive TMS to the dorsolateral prefrontal cortex. The results of our systematic review and meta-analysis data indicate that TMS may offer a promising and safe treatment option for pediatric and young adult patients with IC-ASD. However, future work should include use of neuronavigation software, theta burst protocols, targeting of various brain regions, and robust study design before clinical recommendations can be made.

Findings from a pilot open-label trial of N-acetylcysteine for the treatment of pediatric mania and hypomania.

BACKGROUND: Pediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder. METHODS: We conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5-17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children's Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression. RESULTS: This study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint. CONCLUSIONS: These pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02357290 . First Registration 06/02/2015.

Characterizing autistic traits in treatment-seeking young adults with substance use disorders.

BACKGROUND AND OBJECTIVES: Recent work highlights an increase in the overlap of autism spectrum disorder (ASD) and substance use disorder (SUD). Little is known about the presence of ASD symptoms in SUD-treatment-seeking populations. METHODS: The informant-rated Social Responsiveness Scale-2 (SRS-2) was completed at intake to an outpatient SUD clinic for youth aged 16-26 (N = 69). Comparisons were made between those with elevated SRS-2 scores on demographic, psychiatric, and substance use variables. RESULTS: Parents of sixty-nine patients with SUD completed the SRS-2. Fourteen (20%) (average age 18.7 ± 2.5) had elevated SRS-2 Total T-scores (≥66) and 55 (average age 18.1 ± 2.8) had non-clinical SRS-2 Total T-scores. There were few differences between groups; however, those with elevated SRS-2 Total T-scores were more likely to have a stimulant use disorder (odds ratio [OR] = 7.59, 95% confidence interval [CI] = 0.77, 101.88; p = 0.05) or an opioid use disorder (OR = 5.02, 95% CI = 0.59, 43.27; p = 0.08) than patients with normal SRS-2 Total T-scores as well as alcohol use in the week prior to intake. DISCUSSION AND CONCLUSIONS: A significant proportion of treatment-seeking SUD outpatients suffer from clinically elevated autistic traits. These findings highlight the importance of assessing for autistic traits in SUD treatment settings yet additional research is needed to determine if these findings are specific to the presence of ASD or secondary to sequelae of specific SUD presentations. SCIENTIFIC SIGNIFICANCE: This study is, to our knowledge, the first to have examined the prevalence, morbidity, or clinical characteristics, associated with ASD symptoms in a SUD-specific population.

How Frequent Is Switching From an Initial Stimulant Family to the Alternative One in the Clinical Setting?: A Pilot Study of 49 Consecutively Referred Medication-Naive Adults With Attention-Deficit/Hyperactivity Disorder.

PURPOSE/BACKGROUND: This study aimed to evaluate the frequency of needing to switch the initial treatment of a stimulant to the alternative family in newly referred, medication-naive adults with attention-deficit/hyperactivity disorder (ADHD) initiating treatment with stimulants. METHODS/PROCEDURES: Subjects were 49 unmedicated adults (18-45 years old) with Diagnostic and Statistical Manual of Disorders (Fifth Edition) ADHD who initiated treatment with a stimulant. Before the clinical assessment with an expert clinician, participants completed the Adult Self-Report, Behavior Rating Inventory of Executive Function-Adult Version, Emotional Dysregulation Subscale of the Barkley Current Behavior Scale-Self-report, and Mind Wandering Questionnaire. The rate of switching was examined using information from the electronic medical record for up to three clinical follow-up visits. Comparisons were made between those who did and did not need to switch on baseline demographic and clinical characteristics. FINDINGS/RESULTS: Sixty-seven percent of ADHD patients were initially prescribed a methylphenidate product, and 33%, an amphetamine product. Forty-one percent of ADHD patients needed to switch from their initially prescribed stimulant family within 90 days of initiating treatment because of poor tolerability. Whereas the rate of switching was significantly higher in those initially prescribed methylphenidate, the rate of patients who required changes in formulation (long- to short-acting and vice versa) or additional antianxiety or antidepressant treatment ("strugglers") was higher in those taking amphetamine. Switchers were more impaired on the Adult Self-Report Intrusive scale, whereas nonswitchers were more impaired on the Behavior Rating Inventory of Executive Function Inhibit and Task Monitor scales. However, these findings were small and of unclear clinical significance. IMPLICATIONS/CONCLUSIONS: Forty-one percent of medication-naive adults with ADHD initiating stimulant treatment required a switch from the initially prescribed stimulant family to the alternative one because of poor tolerability. Switching could not be adequately predicted by baseline demographic or clinical characteristics. These findings call for improved efforts to help identify predictors of response to stimulant treatment in adults with ADHD to avoid unnecessary delays in identifying a safe and effective treatment for these patients.

Rates of switching stimulants in consecutively referred medication naïve adults with ADHD.

OBJECTIVE: To evaluate the frequency and correlates of needing to switch the initial treatment with a stimulant medication to the alternative family in newly referred, untreated adults with ADHD initiating treatment. METHODS: Subjects were consecutively referred unmedicated adults with DSM-5 ADHD who initiated stimulant treatment. Before assessment with an expert clinician, participants completed a battery of self-report measures to assess psychopathology, executive functioning, emotional dysregulation, and mind wandering. The rate of switching was examined using information from electronic medical records for up to three clinical follow-up visits. Those who did and did not need to switch were compared on baseline demographic and clinical characteristics. RESULTS: Twenty-four percent (N = 21/86) of ADHD patients needed to switch from their initially prescribed stimulant family within 60 days of initiating treatment due to poor tolerability. While the rate of switching was significantly higher in those initially prescribed MPH, the rate of patients requiring changes in formulation or additional antianxiety or antidepressant treatment was higher in those taking AMPH. There were some hints about predictive risk factors for switching by the presence of emotional dysregulation and depressive symptoms, depending on age and sex. CONCLUSIONS: These findings call for improved efforts to help identify predictors of response to stimulant treatment in adults with ADHD to avoid unnecessary delays in identifying safe and effective treatments for these patients.

Predictive utility of autistic traits in youth with ADHD: a controlled 10-year longitudinal follow-up study.

The objective of this study was to investigate the stability and predictive utility of autistic traits (ATs) in youth with attention-deficit/hyperactivity disorder (ADHD). Participants were referred youth with and without ADHD, without a diagnosis of autism spectrum disorder, and their siblings, derived from identically designed longitudinal case-control family studies of boys and girls with ADHD. Subjects were assessed with structured diagnostic interviews and measures of social, cognitive, and educational functioning. The presence of ATs at baseline was operationalized using a unique profile of the Child Behavior Checklist (CBCL) consisting of an aggregate T score of ≥ 195 on the Withdrawn, Social, and Thought Problems subscales (CBCL-AT profile). At the follow-up, 83% of the ADHD youth with a positive AT profile at baseline continued to have a positive CBCL-AT profile. The presence of a positive CBCL-AT profile at baseline in youth with ADHD heralded a more compromised course characterized by a greater burden of psychopathology that emerged at an earlier age, along with poorer interpersonal, educational, and neurocognitive outcomes. Findings indicate a high level of persisting ATs in ADHD youth over time, as indexed through the CBCL-AT profile, and the presence of this profile prognosticates a compromised course in adult life in multiple domains of functioning.

High Correspondence Between Child Behavior Checklist Rule Breaking Behavior Scale with Conduct Disorder in Males and Females.

This study investigated the diagnostic utility of the Child Behavior Checklist (CBCL) Rule-Breaking Behavior scale to identify children of both sexes with conduct disorder (CD). Participants were derived from four independent datasets of children with and without attention deficit hyperactivity disorder and bipolar-I disorder of both sexes. Participants had structured diagnostic interviews with raters blinded to subject ascertainment status. Receiver operating characteristic (ROC) curves were used to examine the scale's ability to identify children with and without CD. The sample consisted of 674 participants (mean age of 11.7 ± 3.3 years, 57% male, 94% Caucasian). The interaction to test if CBCL Rule-Breaking Behavior scores identified males and females with CD differently was not significant, thus we performed ROC analysis in the combined group. The ROC analysis of the scale yielded an area under the curve of 0.9. A score of ≥ 60 on the scale correctly classified 82% of participants with CD with 85% sensitivity, 81% specificity, 48% positive predictive value, 96% negative predictive value. The CBCL Rule-Breaking Behavior scale was an efficient tool to identify children with CD.

A Novel Text Message Intervention to Improve Adherence to Stimulants in Adults With Attention Deficit/Hyperactivity Disorder.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a prevalent neurobiological disorder associated with a wide range of adverse outcomes. Although large data sets document that stimulants decrease the risks for many ADHD-associated adverse outcomes, compliance with stimulants remains very poor. The main aim of this study was to assess the effectiveness of a novel text messaging-based intervention aimed at improving the poor rate of adherence to stimulant medications in adults with ADHD. METHODS: Subjects were adults with ages 18 to 55, prescribed a stimulant medication for ADHD treatment. For comparators, we identified at a 5-to-1 ratio (age and sex matched) adult patients from the Partners HealthCare electronic medical record who had been prescribed stimulant medications over a 1-year period. We determined whether patients had timely prescription refills, defined as refilled within 37 days, using prescriptions documented in their electronic medical record. RESULTS: Our results showed that 68% of the SMS intervention group refilled their prescriptions in a timely manner. In contrast, only 34% of patients receiving treatment as usual refilled their prescriptions in a timely fashion (odds ratio, 4.04; 95% confidence interval, 2.49-6.56; P < 0.001). CONCLUSIONS: These data indicate that an innovative ADHD-centric text messaging intervention significantly improved patient engagement to treatment with stimulants in adults with ADHD. Findings provide strong support for the use of a readily accessible, inexpensive, and widely available technology to improve the poor rate of adherence to stimulant treatment in adults with ADHD. To the best of our knowledge, this study is the first digital health intervention aimed at improving adherence to stimulant medication for adults with ADHD.

Risk Factors for Overdose in Young People Who Received Substance Use Disorder Treatment.

BACKGROUND AND OBJECTIVES: To identify substance and psychiatric predictors of overdose (OD) in young people with substance use disorders (SUDs) who received treatment. METHODS: We conducted a retrospective review of consecutive medical records of young people who were evaluated in a SUD program between 2012 and 2013 and received treatment. An independent group of patients from the same program who received treatment and had a fatal OD were also included in the sample. OD was defined as substance use associated with a significant impairment in level of consciousness without intention of self-harm, or an ingestion of a substance that was reported as a suicide attempt. t Tests, Pearson's χ2 , and Fisher's exact tests were performed to identify predictors of OD after receiving treatment. RESULTS: After initial evaluation, 127 out of 200 patients followed up for treatment and were included in the sample. Ten (8%) of these patients had a nonfatal OD. Nine patients who received treatment and had a fatal OD were also identified. The sample's mean age was 20.2 ± 2.8 years. Compared with those without OD, those with OD were more likely to have a history of intravenous drug use (odds ratio [OR]: 36.5, P < .001) and mood disorder not otherwise specified (OR: 4.51, P = .01). DISCUSSION AND CONCLUSIONS: Intravenous drug use and mood dysregulation increased risk for OD in young people who received SUD treatment. SCIENTIFIC SIGNIFICANCE: It is important to identify clinically relevant risk factors for OD specific to young people in SUD treatment due to the risk for death associated with OD. (Am J Addict 2019;28:382-389).

Stimulant Treatment and Potential Adverse Outcomes in Pediatric Populations With Bipolar Disorder: A Systematic Review of the Literature.

OBJECTIVE: To explore outcomes of stimulant treatment for ADHD in pediatric populations with particular attention to bipolar disorder (BPD). METHOD: We conducted a literature search of PubMed articles published prior to August 25, 2022 that focused on BPD, mania, and psychosis prior to, or as result of, stimulant treatment. We excluded studies: (1) unrelated to stimulants, (2) general stimulant research, (3) articles older than 40 years, (4) study protocols, or (5) case reports. RESULTS: A total of 11 articles met all inclusion/exclusion criteria. Some reports found stimulant treatment safe and well-tolerated in children with comorbid BPD and ADHD. Others found evidence of treatment-emergent mania (TEM), discontinuation, and other adverse events with stimulant treatment. CONCLUSION: Poor outcomes associated with stimulant treatment in pediatric populations with BPD necessitate work to identify patients at risk of serious stimulant-related adverse events. Our results were limited by automated search filters and a pediatric, primarily male sample.

ADHD in Adults: Does Age at Diagnosis Matter?

OBJECTIVE: To provide additional information about clinical features associated with adult ADHD in patients diagnosed in childhood compared to those first diagnosed in adulthood. METHOD: We stratified a sample of adults with ADHD into patients diagnosed in childhood versus adulthood and compared demographic and clinical characteristics. RESULTS: We found similar clinical features in adults diagnosed in childhood and adults diagnosed in adulthood. Among those diagnosed in adulthood, 95% reported symptom onset in youth. Our results do not support the hypothesis that ADHD diagnosed in adulthood is due to misinterpreting symptoms of other disorders as ADHD. They also suggest incorporating behavioral signs of executive dysfunction into diagnostic criteria for ADHD in adults may increase diagnostic sensitivity. CONCLUSION: These results support the validity of ADHD diagnoses in adulthood, as these adults show similar clinical profiles to those diagnosed in youth. Our results also suggest that if adult-onset ADHD exists, it is rare.

The Heritability of ADHD in Children of ADHD Parents: A Post-hoc Analysis of Longitudinal Data.

OBJECTIVE: A growing literature suggests attention-deficit/hyperactivity disorder (ADHD) is a heritable disorder. We evaluated children at risk for ADHD by virtue of having parents with ADHD and compared them with children of parents without ADHD to assess the degree of heritability of ADHD. METHOD: The sample for this study was derived from three longitudinal studies that tracked families with various disorders, including ADHD. Children were stratified based on presence of parental ADHD, and clinical assessments were taken to evaluate presence of ADHD and related psychiatric and functional outcomes in children. RESULTS: Children with parental ADHD had significantly more full or subthreshold psychiatric disorders (including ADHD) as well as functional impairments compared to children without parental ADHD. CONCLUSION: Our findings suggest that offspring of parents with ADHD are at significant risk for ADHD and its associated psychiatric, cognitive, and educational impairments. These findings aid in identifying early manifestations of ADHD in young children at risk.

Solriamfetol for Attention-Deficit/Hyperactivity Disorder in Adults: A Double-Blind Placebo-Controlled Pilot Study.

Objective: Some individuals with attention-deficit/hyperactivity disorder (ADHD) may not tolerate or adequately respond to currently available treatments. This study examined whether solriamfetol could have a favorable pattern of effects and tolerability as a treatment for ADHD in adults.Methods: Sixty adults with DSM-5 ADHD participated from August 2021 through January 2023 in a remotely conducted, randomized, double-blind, placebo-controlled, 6-week dose-optimization trial of 75 mg or 150 mg of solriamfetol. Measures included the Adult ADHD Investigator Symptom Rating Scale (AISRS), which was our primary outcome measure, as well as the Clinical Global Impressions scale (CGI), vital signs, the Global Assessment of Functioning (GAF), the Behavior Rating Inventory of Executive Function-Adult Form (BRIEF-A), the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and a modified Adult ADHD Self-Report Scale (MASRS).Results: Solriamfetol was well tolerated, with no significant effect on mean heart rate (+3.7 vs +2.2 bpm, P = .5609), systolic blood pressure (+2.4 vs +1.5 mm Hg, P = .6474), or diastolic blood pressure (+1.1 vs +1.5 mm Hg, P = .8117). There was no statistically significant treatment effect on occurrence of adverse events. Compared to individuals on placebo, individuals on solriamfetol treatment experienced adverse events at a rate of at least 10 percentage points higher in the categories of decreased appetite, headache, gastrointestinal, insomnia, increased energy, cardiovascular, and neurologic. Compared to individuals on placebo, by study endpoint, a greater proportion of individuals in the treatment group met the a priori-defined treatment response (CGI score indicating much or very much improved and AISRS score reduced ≥ 25%: 45% vs 6.9%, P = .0020); those treated with solriamfetol also had greater improvement in total AISRS scores by week 3 through week 6 (P = .0012; week 6 effect size = 1.09). Significantly more solriamfetol-treated adults than placebo-treated adults had 0.5-standard deviation improvement in T-score on the BRIEF-A Global Executive Composite (P = .0173); those treated with solriamfetol also had greater mean change in GAF score (-4.8 vs -0.3, P = .0006) and greater mean MASRS total score change (P = .0047; effect size = 1.23). Mean ESS score improved more with solriamfetol than with placebo (P = .0056), but this difference did not predict AISRS response (P = .3735). There was no significant association between solriamfetol and change in PSQI scores.Conclusions: Solriamfetol may be a novel and effective treatment for the management of ADHD in adults. Further replication in larger trials is indicated.Trial Registration: ClinicalTrials.gov identifier: NCT04839562.

Growth Trajectories in Stimulant-Treated Children Ages 6 to 12: An Electronic Medical Record Analysis.

OBJECTIVE: The aim of this study was to evaluate growth trajectories in stimulant-exposed and stimulant-unexposed children using electronic medical record data from a large health care organization attending to moderating effects of the magnitude of exposure to stimulants, sex, and race. METHODS: Weight, height, body mass index (BMI), prescription, and sociodemographic information were extracted from the electronic medical records of a large health care organization. Included were children who were 6 to 12 years at the time they were receiving stimulants with a concurrent growth assessment (index assessment) plus 1 to 4 years of additional growth assessments thereafter. Non-attention-deficit/hyperactivity disorder (ADHD) children who were unexposed to stimulants were age and sex matched to those exposed. Stimulant exposure was examined as the total number of months with stimulant prescriptions, percentage of follow-up time exposed to stimulants, and cumulative stimulant dose. RESULTS: Our sample consisted of 323 children exposed to stimulants with available growth data and 1615 unexposed children. Small but significant decreases in height trajectories were found over time in exposed children compared with those unexposed. Weight and BMI trajectories decreased in the first year of follow-up with stabilization and increased thereafter. Growth trajectory effects were largest in girls (height, weight, and BMI), White children (weight), and children with more total stimulant exposure (weight). CONCLUSION: This comprehensive analysis of an ecologically informative sample attending to key covariates of the magnitude of exposure to stimulants, sex, and race extends previous findings, showing that effects on growth trajectories are small and do not appear to pose a significant clinical concern for most children with ADHD treated with stimulants from childhood onto adolescent years.

Further Evidence of an Association Between a Positive Child Behavior Checklist-Bipolar Profile and a Diagnosis of Pediatric Bipolar Disorder: A Meta-Analysis.

Background: Previous research has found that a unique profile of the Child Behavior Checklist comprising of aggregate elevations of the Attention, Anxiety/Depression and Aggression scales (A-A-A profile, CBCL-Bipolar (BP) profile, CBCL-Dysregulation profile (DP); henceforth CBCL-BP/DP profile) is associated with a clinical diagnosis of pediatric bipolar (BP) disorder. Objective: The main aim of the study is to evaluate the strength of the association between the CBCL-BP/DP profile and the clinical diagnosis of pediatric BP disorder through a meta-analysis. Methods: A literature search was performed to identify studies that examined the association between a positive CBCL-BP/DP profile and a clinical diagnosis of pediatric BP disorder. The meta-analyses first examined studies assessing the rates of a positive CBCL-BP/DP profile in youth with BP disorder versus those with 1) ADHD, anxiety/depression, or disruptive behavior disorders (DBDs), and 2) non-bipolar controls. The second analysis evaluated studies examining the rates of pediatric BP disorder in youth with and without a positive CBCL-BP/DP profile. Results: Eighteen articles met our inclusion and exclusion criteria, and fifteen articles had adequate data for meta-analysis. Results showed that BP youth were at significantly increased odds of having a positive CBCL-BP/DP profile compared to those with other psychiatric disorders (i.e., ADHD, anxiety/depression, or DBDs) (pooled OR=4.34, 95% CI=2.82, 8.27; p<0.001) and healthy control groups (pooled OR=34.77, 95% CI=2.87, 420.95; p=0.005). Further, meta-analysis results showed that youth with a positive CBCL-BP/DP profile were at significantly increased odds of having a BP disorder diagnosis compared to those without (pooled OR=4.25, 95% CI=2.12, 8.52; p<0.001). Conclusion: Our systematic review and meta-analysis of the extant literature provides strong support for the association between the CBCL-BP/DP profile and pediatric BP disorder.

Substance Use Disorders and Psychiatric Illness Among Transitional Age Youth Experiencing Homelessness.

Objective: Transitional age youth experiencing homelessness (TAY-EH) bear a high burden of substance use disorders (SUDs) and psychopathology. However, limited data exist on the co-occurrence and interactions between these diagnoses in this marginalized group. This study sought to identify rates of single and co-occurring SUDs and psychiatric diagnoses among a sample of TAY-EH and to investigate associations between psychopathology and prevalence and severity of SUDs in this group. Method: TAY-EH accessing a low-threshold social service agency in a large metropolitan area completed psychosocial and diagnostic interviews to assess for SUDs and psychopathology. Analyses examined rates of single and co-occurring disorders and associations between burden of psychopathology and presence and severity of SUDs. Results: The assessment was completed by 140 TAY-EH; the majority were youth of color (54% Black/African American, 16% Latinx), and 57% identified as male. Rates of single and co-occurring psychiatric disorders and specific SUDs (cannabis use disorder [CUD] and alcohol use disorder [AUD]) were notably high. An increasing number of psychiatric diagnoses was significantly associated with elevated CUD/AUD prevalence and severity. Mood, anxiety, attention-deficit/hyperactivity, and antisocial personality disorders were significantly associated with elevated CUD/AUD prevalence and severity, as was suicidality (all p < .05). Conclusion: This study reveals a complex overlay of SUDs and psychopathology facing TAY-EH, with a significant association between co-occurring psychopathology and severity of CUD/AUD. To the authors' knowledge, this is the first study to examine associations between specific psychopathology and severity of SUDs among TAY-EH. Further research into the mechanistic and temporal links between these conditions is needed to inform tailored treatment interventions.

Growth Trajectories in Stimulant Treated Children and Adolescents: A Qualitative Review of the Literature from Comprehensive Datasets and Registries.

Objective: Attention-deficit/hyperactivity disorder (ADHD) treatment with stimulant products has been shown to be safe and effective; however, there are remaining concerns about their possible adverse effects on growth trajectories. We conducted a systematic review of the extant literature derived from ecologically valid databases and registries to assess the body of knowledge about the effects of stimulants on growth trajectories in naturalistic samples. Methods: Using PubMed and PsycINFO, we searched for articles published before February 8, 2023 that focused on growth findings associated with stimulant treatment in pediatric ADHD from comprehensive datasets derived from naturalistic population studies. Results: Of the 1070 articles initially identified, 12 met all inclusion criteria. Sample sizes ranged from 157 to 163,820 youths. Seven of 10 articles examining height found significant decreases in height associated with chronic stimulant treatment that normalized over time in 2 studies. Three articles found no significant association between stimulant treatment and height. No clear associations were identified between cumulative duration and dose of stimulant treatment and adult height. All articles examining weight and six of eight articles examining body mass index (BMI) found significant initial decreases that tended to normalize then increase over time. Longer duration of stimulant medication use was predominantly associated with significant weight and BMI reductions. The effects of stimulant dose on weight and BMI were mostly weak and clinically insignificant. Most studies found no significant association between age at start of stimulant treatment and change in height, weight, or BMI. Most studies did not find significant sex effects in relation to growth parameters. Conclusions: This review of ecologically informative samples revealed that the effects of stimulant treatment on growth trajectories are mainly small and transient. These effects seem to be clinically insignificant for most youth with ADHD who receive stimulant treatment from childhood onto adolescence and adulthood.

Diagnosing major depressive disorder and substance use disorder using the electronic health record: A preliminary validation study.

Background: One mechanism to examine if major depressive disorder (MDD) is related to the development of substance use disorder (SUD) is by leveraging naturalistic data available in the electronic health record (EHR). Rules for data extraction and variable construction linked to psychometrics validating their use are needed to extract data accurately. Objective: We propose and validate a methodologic framework for using EHR variables to identify patients with MDD and non-nicotine SUD. Methods: Proxy diagnoses and index dates of MDD and/or SUD were established using billing codes, problem lists, patient-reported outcome measures, and prescriptions. Manual chart reviews were conducted for the 1-year period surrounding each index date to determine (1) if proxy diagnoses were supported by chart notes and (2) if the index dates accurately captured disorder onset. Results: The results demonstrated 100% positive predictive value for proxy diagnoses of MDD. The proxy diagnoses for SUD exhibited strong agreement (Cohen's kappa of 0.84) compared to manual chart review and 92% sensitivity, specificity, positive predictive value, and negative predictive value. Sixteen percent of patients showed inaccurate SUD index dates generated by EHR extraction with discrepancies of over 6 months compared to SUD onset identified through chart review. Conclusions: Our methodology was very effective in identifying patients with MDD with or without SUD and moderately effective in identifying SUD onset date. These findings support the use of EHR data to make proxy diagnoses of MDD with or without SUD.

Examining the clinical correlates of conduct disorder in youth with bipolar disorder.

BACKGROUND: Conduct Disorder (CD) is highly comorbid with Bipolar Disorder (BP) and this comorbidity is associated with high morbidity and dysfunction. We sought to better understand the clinical characteristics and familiality of comorbid BP + CD by examining children with BP with and without co-morbid CD. METHODS: 357 subjects with BP were derived from two independent datasets of youth with and without BP. All subjects were evaluated with structured diagnostic interviews, the Child Behavior Checklist (CBCL), and neuropsychological testing. We stratified the sample of subjects with BP by the presence or absence of CD and compared the two groups on measures of psychopathology, school functioning, and neurocognitive functioning. First-degree relatives of subjects with BP +/- CD were compared on rates of psychopathology in relatives. RESULTS: Subjects with BP + CD compared to BP without CD had significantly more impaired scores on the CBCL Aggressive Behavior (p < 0.001), Attention Problems (p = 0.002), Rule-Breaking Behavior (p < 0.001), Social Problems (p < 0.001), Withdrawn/Depressed clinical scales (p = 0.005), the Externalizing Problems (p < 0.001), and Total Problems composite scales(p < 0.001). Subjects with BP + CD had significantly higher rates of oppositional defiant disorder (ODD) (p = 0.002), any SUD (p < 0.001), and cigarette smoking (p = 0.001). First-degree relatives of subjects with BP + CD had significantly higher rates of CD/ODD/ASPD and cigarette smoking compared to first-degree relatives of subjects without CD. LIMITATIONS: The generalization of our findings was limited due to a largely homogeneous sample and no CD only comparison group. CONCLUSIONS: Given the deleterious outcomes associated with comorbid BP + CD, further efforts in identification and treatment are necessary.