Faculty Bibliography

Improving meaningful outcomes is the main goal of clinical care for mental disorders. Traditionally, the focus in clinical research and practice has been on outcome domains that refer to symptom severity or service use (e.g., hospitalization), relate to categorical diagnoses, and favour clinician-rated measures. More recently, self-rated and dimensional as well as transdiagnostic outcome domains have gained traction, and functioning, quality of life and well-being/life satisfaction, along with the construct of personal recovery, have become a stronger focus. These key multidimensional outcome domains need to be properly defined and assessed. Further, the concepts of "functional" and "personal" recovery need to be differentiated. "Functional recovery" is defined by observed functioning across the domains of self-care, social interactions, leisure time activities, and educational or vocational activities. "Personal recovery" involves the subjective sense of living a personally meaningful life, irrespective of whether symptoms continue, or ongoing/intermittent support is needed. Despite the multi-stakeholder relevance of these outcome domains, no comprehensive account of how to measure them is available. To fill this gap, we provide here an overview of the main tools to assess functioning, quality of life/well-being/life satisfaction, and personal recovery outcomes across mental disorders in adults, aiming to also identify additional needs that should be addressed. We identified tools that can be used in clinical and research practice to assess people with the following mental health conditions: anxiety disorders, bipolar disorder, dementias, eating disorders, major depressive disorder, obsessive-compulsive and related disorders, personality disorders, post-traumatic stress disorder, schizophrenia, and substance use disorders. Both transdiagnostic and disorder-specific measures are described. Suggested tools were selected keeping feasibility and scalability needs in mind. The incorporation of these measures in both research and clinical care will enrich patient assessment as well as treatment planning and evaluation, increasing the likelihood of enhanced outcomes in people living with mental disorders.

OBJECTIVE:Attention-deficit/hyperactivity disorder (ADHD) is associated with lower birth weight, but also with obesity in childhood. Findings on the direction of this association are mixed. This study investigated the relationship between weight and ADHD from birth across development. METHOD/METHODS:We used data from the Millennium Cohort Study (MCS), collected at 7 time points between age 9 months and 17 years. ADHD diagnosis status and scores on the Strength and Difficulties Questionnaire (SDQ) were used to create an ADHD group and a control group. Random intercept cross-lagged panel models were conducted in female individuals (n = 4,051) and male individuals (n = 3,857) to examine bidirectional associations between body mass index (BMI) z scores and SDQ scores between ages 3 and 17 years. Analyses were adjusted for common risk factors for ADHD and obesity, such as sex assigned at birth, multiple births, and ADHD medication status. RESULTS:Children in the ADHD group were significantly lighter in weight at birth than the control group (t[5674] = 2.65, 95% CI = 0.02, 0.14, p = .008) and were significantly more likely to have obesity at age 5 years onward (odds ratio range = 1.57-2.46, relative risk range 0.98-2.29). Path analyses conducted separately for male and female individuals showed that higher ADHD symptoms in female individuals at ages 7, 11, and 14 years significantly predicted higher BMI z scores at ages 11, 14, and 17 years, respectively. In male individuals, this association was seen only between ages 11 and 14 years (β = 0.07; 95% CI = 0.04-0.10, p < .001). CONCLUSION/CONCLUSIONS:Results suggest that interventions for children with ADHD, and their parents, should begin as soon as possible, ideally prenatally. Developmental sex differences should be considered.

Attention-deficit/hyperactivity disorder (ADHD) was once thought to be solely a childhood condition. Now it is well established that it can persist into adulthood, with an estimated worldwide prevalence of around 2.5%. Additionally, up to 70% of individuals with childhood-onset ADHD continue to experience impairing symptoms as adults, even if they no longer meet the criteria for a formal diagnosis. The validity of adult ADHD initially faced strong criticism. Today, empirical research supports its descriptive validity (identifying characteristic signs and symptoms), predictive validity (concerning specific outcomes, courses, and responses to treatment), and concurrent validity (evidence related to its underlying causes and biological mechanisms). Despite this progress, unresolved questions and ongoing debates about adult ADHD persist. This paper summarizes current empirical evidence, alongside uncertainties and controversies, regarding the definition, epidemiology, diagnosis, etiology, neurobiology, and management of ADHD in adults. Crucially, we also include perspectives from individuals with lived experience of this condition, highlighting their views on unmet needs and priorities for improving care. Key uncertainties and controversies on adult ADHD include: a) the possibility of late-onset ADHD; b) the significance of emotional dysregulation as a core symptom; c) the definition and characterization of functional impairment; d) the persistence of comorbid psychiatric and somatic conditions after accounting for confounders; e) the relevance of executive dysfunction in the definition of the condition; f) the use of objective diagnostic measures; g) the long-term effects of treatments; and h) the role of non-pharmacological interventions. Further research on adult ADHD is urgently needed. Funding for studies on this condition lags behind that for childhood ADHD and other mental disorders in adulthood. Hopefully, efforts by clinicians, researchers and other stakeholders will ultimately help ensure that adults with ADHD are better understood, supported, and empowered to thrive.

OBJECTIVE:To evaluate the association between attention-deficit/hyperactivity disorder (ADHD) and atypical sensory processing patterns. METHOD/METHODS:For this systematic review and meta-analysis, PubMed, Embase, and Web of Science were searched from their inception until June 30, 2024. Studies examining sensory processing patterns using questionnaires in participants with a diagnosis of ADHD compared with healthy controls were included. The study risk of bias was assessed using a modified Newcastle-Ottawa Scale. A random-effects meta-analysis was conducted using R Version 4.3.1 software, considering sensory modulation severity atypicities as the primary outcome. The risk of publication bias was explored, and sensitivity analyses were conducted to test the robustness of findings. RESULTS:= 97%). Heterogeneity was high in all analyses. Only 9 studies were deemed at overall low risk of bias. CONCLUSION/CONCLUSIONS:Even though available ADHD clinical guidelines do not specifically mention the need to assess sensory processing in ADHD, this meta-analysis suggests that this should be systematically explored in the evaluation of children and adults referred for ADHD. PLAIN LANGUAGE SUMMARY/CONCLUSIONS:This systematic review and meta-analysis examined 30 studies including over 5,000 participants to assess the link between attention-deficit/hyperactivity disorder (ADHD) and atypical sensory processing. Findings show that individuals with ADHD experience significantly higher sensory sensitivity, sensory avoidance, sensory seeking, and low sensory registration compared to controls. Given their impact on daily functioning, assessing sensory processing could improve clinical evaluations for both children and adults with ADHD. STUDY REGISTRATION INFORMATION/UNASSIGNED:Association between ADHD and sensory processing disorder: A systematic review and meta-analysis; https://www.crd.york.ac.uk/PROSPERO/view/CRD42022325271. DIVERSITY & INCLUSION STATEMENT/UNASSIGNED:We actively worked to promote sex and gender balance in our author group. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science.

OBJECTIVE:This study aimed at identifying moderators of efficacy of stimulants against placebo to inform personalized recommendations for treatment in preschool children (< 6 years) with attention-deficit/hyperactivity disorder (ADHD). METHOD/METHODS:We acquired individual-level participant data from two randomized placebo-controlled trials (RCTs) of preschool ADHD: MAPPA (8-week methylphenidate, 102 participants, Brazil) and SPD489-347 (6-week lisdexamfetamine, 148 participants, US). We evaluated the moderator and predictor effects of baseline demographic (age, sex, race, ethnicity, maternal educational level) and baseline clinical (ADHD symptom severity, intelligence quotient, number of psychiatric comorbidities) characteristics, as available, on endpoint ADHD symptom severity scores. Data from each study were analyzed separately with linear mixed-effects model for repeated measures. For categorical variables, we also computed treatment effects (i.e., stimulants versus placebo) within subgroups and, when possible, pooled them alongside subgroup data from PATS (5-week methylphenidate, 165 participants, US) in random-effects meta-analyses. RESULTS:Stimulants had greater efficacy against placebo in White children compared to Black children considering data from US studies. Older age was not a moderator of greater efficacy of stimulants against placebo, nor was it associated with worse ADHD symptom severity at endpoint. Greater baseline ADHD symptom severity was associated with higher ADHD symptom severity at endpoint independently of the assigned treatment group. CONCLUSION/CONCLUSIONS:Race, but not older age or baseline ADHD symptom severity, may moderate the efficacy of stimulants for preschool ADHD. Given the post hoc nature of subgroup analyses, the findings should be interpreted as exploratory and viewed as hypothesis for confirmation in future studies.

The use of Attention-Deficit/Hyperactivity Disorder (ADHD) medications during pregnancy is increasing, raising concerns about potential long-term effects on offspring. This study investigates in utero exposure to methylphenidate, amphetamines and atomoxetine and risk of offspring neurodevelopmental disorders (NDDs). The population-based cohort study identified from Swedish registers included 861,650 children born by 572,731 mothers from 2008-2017. We categorized exposure based on redeemed medication during pregnancy and compared exposed children to those whose mothers discontinued medication before conception. Main outcomes were any NDD, including ADHD and autism spectrum disorder (ASD). Cox proportional hazards regression estimated hazard ratios (HRs), adjusting for maternal psychiatric and sociodemographic factors. Sensitivity analyses included stratifications by medication type, timing, and duration of exposure, and sibling comparisons. We also performed a meta-analysis combining data from the present study with those from a previous Danish study. Results showed no increased risk for any NDD (HR_adjusted 0.95, 95% CI 0.82-1.11), ADHD (HR_adjusted 0.92, 95% CI 0.78-1.08), or ASD (HR_adjusted 0.86, 95% CI 0.63-1.18). Sensitivity analyses showed consistent patterns of no increased risks across different exposure durations, medication types and between siblings. Meta-analyses further supported the findings (pooled HR for any NDD 1.00, 95% CI 0.83;1.20). Our study provides evidence that in utero exposure to ADHD medications does not increase the risk of long-term NDDs in offspring. This study replicates safety data for methylphenidate and extends it with new safety data on amphetamines and atomoxetine. These findings are crucial for informing clinical guidelines and helping healthcare providers and expectant mothers make informed decisions.

Children presenting comorbid attention-deficit/hyperactivity disorder (ADHD) and depression symptoms have higher risks of later suicidal ideation and attempt. However, it is unclear to what extent this risk stems from individual differences in the genetic predisposition for ADHD and/or depression. We investigated the unique and combined contribution of genetic predisposition to ADHD and depression to suicidal ideation and attempt by early adulthood. Data were from two longitudinal population-based birth cohorts, the Quebec Longitudinal Study of Child Development and the Quebec Newborn Twin Study (total N = 1207). Genetic predisposition for ADHD and depression were measured using polygenic scores. Suicidal ideation and attempt by age 20 years were self-reported via questionnaires. Across the two cohorts, suicidal ideation and attempt were reported by 99 (8.2%) and 75 (6.1%) individuals, respectively. A higher polygenic score for depression was associated with significantly higher risk of suicidal ideation and attempt, while no significant associations were found for ADHD polygenic score. However, we found an interaction between polygenic scores for depression and ADHD in the association with suicide attempt (P = 0.012), but not suicidal ideation (P = 0.897). The association between polygenic score for depression and suicide attempt was significantly stronger for individuals with a higher polygenic score for ADHD. Individuals scoring ≥ 1-SD above the mean for both polygenic scores were at increased risk for suicide attempt compared to individuals with lower scores (OR 4.03, CI 1.64-9.90), as well as compared to individuals scoring ≥ 1-SD above the mean in only depression (OR 2.92, CI 1.01-8.50) or only ADHD (OR 4.88, CI 1.56-15.26) polygenic scores. Our findings suggest that genetic predisposition for ADHD and depression contributes to increase the risk of suicide attempt in a multiplicative, rather that additive, way. Our results contribute to our understanding of the etiology of suicide risk and may inform screening and risk stratification.

The use of complementary, alternative and integrative medicine (CAIM) is highly prevalent among autistic individuals, with up to 90% reporting having used CAIM at least once in their lifetime. However, the evidence base for the effects of CAIM for autism remains uncertain. Here, to fill this gap, we conducted an umbrella review of meta-analyses exploring the effects of CAIM in autism across the lifespan and developed a web platform to disseminate the generated results. Five databases were searched (up to 31 December 2023) for systematic reviews with meta-analyses exploring the effects of CAIM in autism. Independent pairs of investigators identified eligible papers and extracted relevant data. Included meta-analyses were reestimated using a consistent statistical approach, and their methodological quality was assessed with AMSTAR-2. The certainty of evidence generated by each meta-analysis was appraised using an algorithmic version of the GRADE framework. This process led to the identification of 53 meta-analytic reports, enabling us to conduct 248 meta-analyses exploring the effects of 19 CAIMs in autism. We found no high-quality evidence to support the efficacy of any CAIM for core or associated symptoms of autism. Although several CAIMs showed promising results, they were supported by very low-quality evidence. The safety of CAIMs has rarely been evaluated, making it a crucial area for future research. To support evidence-based consideration of CAIM interventions for autism, we developed an interactive platform that facilitates access to and interpretation of the present results ( https://ebiact-database.com ).

OBJECTIVE:To examine the effects of drug treatment for attention deficit/hyperactivity disorder (ADHD) on suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality. DESIGN/METHODS:Emulation of target trials. SETTING/METHODS:Linkage of national registers in Sweden, 2007-20. PARTICIPANTS/METHODS:People aged 6-64 years with a new diagnosis of ADHD, who either started or did not start drug treatment for ADHD within three months of diagnosis. MAIN OUTCOME MEASURES/METHODS:First and recurrent events of five outcomes over two years after ADHD diagnosis: suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality. RESULTS:90.1 per 1000 person years; incidence rate ratio 0.98, 0.96 to 1.01). The reduced rates were more pronounced among individuals with previous events, with incidence rate ratios ranging from 0.79 (0.72 to 0.86) for suicidal behaviours to 0.97 (0.93 to 1.00) for accidental injuries. For recurrent events, drug treatment for ADHD was significantly associated with reduced rates of all five outcomes, with incidence rate ratios of 0.85 (0.77 to 0.93) for suicidal behaviours, 0.75 (0.72 to 0.78) for substance misuse, 0.96 (0.92 to 0.99) for accidental injuries, 0.84 (0.76 to 0.91) for transport accidents, and 0.75 (0.71 to 0.79) for criminality. CONCLUSIONS:Drug treatment for ADHD was associated with beneficial effects in reducing the risks of suicidal behaviours, substance misuse, transport accidents, and criminality but not accidental injuries when considering first event rate. The risk reductions were more pronounced for recurrent events, with reduced rates for all five outcomes. This target trial emulation study using national register data provides evidence that is representative of patients in routine clinical settings.

The directionality of the relationship between adolescent alcohol consumption and mental health difficulties remains poorly understood. This study investigates the longitudinal relationship between alcohol use frequency, internalizing and externalizing symptoms from the ages of 11 to 17. We conducted a random-intercept cross-lagged panel model across three timepoints (ages: 11yrs, 14yrs, 17yrs; 50.4% female) in the Millennium Cohort Study (N = 10,647). Survey weights were used to account for attrition. At each timepoint, past month alcohol use frequency was self-reported, parents and cohort members reported internalizing/externalizing symptoms using the Strengths and Difficulties Questionnaire. We controlled for alcohol expectancies, sex, and four cumulative risk indices (perinatal risk, early childhood adverse parenting, longitudinal parent-level risk occurrence, and persistent household socioeconomic deprivation). More frequent past month alcohol use at age 11 predicted increased internalizing symptoms at age 14 (β = 0.06; p =.01). More frequent past month alcohol use at age 14 predicted increased externalizing symptoms at age 17 (β = 0.11; p <.001). Increased internalizing symptoms consistently predicted reduced alcohol use at the next timepoint throughout the study period (11 years: β= -0.04; p =.03; 14 years: β= -0.09; p <.001). Increased externalizing symptoms at age 11 predicted increased alcohol consumption at age 14 (β = 0.06; p =.004). Frequent adolescent alcohol consumption represents a significant risk for subsequent mental health difficulties. Externalizing symptoms and alcohol use frequency appear to exacerbate one another. Internalizing symptoms may reduce the risk of frequent alcohol consumption. Incorporating routine alcohol screening into adolescent mental health treatment settings could reduce the risk of comorbid externalizing and alcohol use disorders.