Joseph Biederman’s research while affiliated with Massachusetts General Hospital and other places

Objective Stimulant medications are the main treatment for Attention Deficit Hyperactivity Disorder (ADHD), but overall treatment efficacy in adults has less than a 60% response rate. This study aimed to identify neural and cognitive markers predictive of longitudinal improvement in response to stimulant treatment in drug-naïve adults with ADHD. Method We used diffusion tensor imaging (DTI) and executive function measures with 36 drug-naïve adult ADHD patients in a prospective study design. Results Structural connectivity (measured by fractional anisotropy, FA) in striatal regions correlated with ADHD clinical symptom improvement following stimulant treatment (amphetamine or methylphenidate) in better medication responders. A significant positive correlation was also found between working memory performance and stimulant-related symptom improvement. Higher pre-treatment working memory scores correlated with greater response. Conclusion These findings provide evidence of pre-treatment neural and behavioral markers predictive of longitudinal treatment response to stimulant medications in adults with ADHD.

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.

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.

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.

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.

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.

Objective: Although group findings document that executive function deficits (EFDs) contribute to the morbidity associated with adult attention-deficit/hyperactivity disorder (ADHD), it is unclear whether easy-to-use assessment methods can aid in the identification of EFDs at the individual level. The aim of the present study was to assess whether the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), a well-standardized, self-report instrument that assesses behavioral concomitants of EFDs, can serve that purpose. Methods: 1,090 consecutively referred 18- to 55-year-old adults of both sexes who were clinically referred for the evaluation and treatment of ADHD between June 2016 and December 2021 completed a battery of scales assessing several non-overlapping domains of functioning. Because the BRIEF Global Executive Composite (GEC) offers a single point summary of all other BRIEF-A scales, we used receiver operator characteristic (ROC) curves to identify the optimal cutoff on the BRIEF-A GEC to categorize patients as having executive dysfunction. Results: We averaged the optimal BRIEF-A GEC cut-points from the ROC curve analyses to categorize patients with (N = 480; 44%) and without (N = 610; 56%) EFDs (BRIEF-A GEC score ≥ 70 or < 70, respectively). Adults with ADHD with EFDs had significantly more severe ADHD symptoms (ADHD Self-Report Scale scores ≥ 24: 94% vs 41%, P < .001); higher levels of psychopathology (Adult Self Report Total Problems T-scores ≥ 64: 75% vs 19%, P < .001), emotional dysregulation (69% vs 23%, P < .001), mind wandering (84% vs 48%, P < .001), and symptoms of autism (Social Responsiveness Scale T-scores ≥ 66: 24% vs 3%, P < .001); and worse quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire mean scores: 44.4 ± 8.2 vs 51.9 ± 8.5, P = .001) compared to those without EFDs. There were no major differences in outcomes by age, sex, or race. Conclusions: The BRIEF-A helped identify a sizeable minority of adults with ADHD with behavioral concomitants of EFDs that added substantial morbidity and disability beyond that expected by having ADHD alone.

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.