Sex Differences in ADHD: Review and Priorities for Future Research.

PURPOSE OF REVIEW: In childhood, attention-deficit/hyperactivity disorder (ADHD) is diagnosed three to 16 times more frequently in males compared to females, yet in adulthood, nearly equivalent numbers of males and females are diagnosed with ADHD. Relatively few studies have prioritized examination of sex differences in ADHD even though sex differences may have critical implications for the identification and treatment of ADHD in females and males. This review highlights current research on sex differences in ADHD across the lifespan that has emerged from cross-sectional and prospective longitudinal studies of youth, adult-ascertained samples, and registry studies. RECENT FINDINGS: Accumulating research suggests that both males and females with ADHD experience widespread impairment across the lifespan. Some evidence of sex differences emerged, although effects have generally been modest in size. Continued research that includes females and males with ADHD is needed to clarify the nature of sex differences in ADHD. Research that focuses on equitable identification of ADHD in males and females, disentangles the effects of sex and gender, probes underlying mechanisms of sex differences, and addresses the clinical impact of sex differences in ADHD must be prioritized.

Social and Monetary Reward Processing in Youth with Early Emerging Personality Pathology: An RDoC-Informed Study.

Very little is known about the mechanisms underlying the development of personality disorders, hindering efforts to address early risk for these costly and stigmatized disorders. In this study, we examined associations between social and monetary reward processing, measured at the neurophysiological level, and personality pathology, operationalized through the Level of Personality Functioning (LPF), in a sample of early adolescent females (Mage = 12.21 years old, SD = 1.21). Female youth with (n = 80) and without (n = 30) a mental health history completed laboratory tasks assessing social and monetary reward responsiveness using electroencephalogram (EEG) and completed ratings of personality pathology. Commonly co-occurring psychopathology, including depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) were also assessed. At the bivariate level, significant associations did not emerge between psychopathology and reward processing variables. When covarying symptoms of depression, anxiety, ADHD, ODD, and CD, an enhanced reward positivity (RewP) component to social reward feedback (accounting for response to social rejection) was associated with higher levels of personality impairment. Results were specific to social rather than monetary reward processing. Depression, anxiety, and ODD also explained unique variance in LPF. These findings suggest that alterations in social reward processing may be a key marker for early emerging personality pathology. Future work examining the role of social reward processing on the development of LPF across adolescence may guide efforts to prevent the profound social dysfunction associated with personality pathology.

Gender differences in transdiagnostic domains and function of adults measured by DSM-5 assessment scales at the first clinical visit: a cohort study.

BACKGROUND: Measurement-based care has been called for as best practice in psychiatric care and learning health systems and use of transdiagnostic measures was suggested as part of the DSM-5. Our objective is to examine gender differences in first visit socioeconomic, transdiagnostic, and functional characteristics of a dynamic, real-world measurement-based care cohort. METHODS: Transdiagnostic, functional, and clinical measures were collected from 3,556 patients at first visit in an ambulatory psychiatric clinic. All patients were evaluated at the first visit by board-certified psychiatrists or licensed clinical psychologists. Demographic variables and clinical diagnoses were collected from the Electronic Medical Record. Self-report measures were collected that assessed transdiagnostic symptoms (DSM-5 Level 1 Cross-cutting Measure and Level 2 symptom scales), disability, alcohol use, attention deficit hyperactivity disorder (ADHD) symptoms, depression, anxiety, mania, suicidal thoughts and behaviors, and trauma exposure. RESULTS: Men and women did not differ in age, BMI, household income, high school graduation rate, race, or ethnicity, but women were more likely to be formerly married and less likely to have commercial insurance. Compared to men, women reported significantly higher overall psychopathology on the transdiagnostic Level 1 Cross-cutting measure and had higher depression, anxiety, sleep, anger, ADHD combined presentation, and suicidality severity. Women also had higher disability scores than men. However, men reported higher alcohol, tobacco and substance use, and more risky behavior than women. Trauma exposure differed significantly by gender; men reported more exposure to accidents, war-related trauma, serious accidents, and major disasters and women reported more unwanted sexual contact. CONCLUSIONS: This cross-sectional study of a transdiagnostic, ecologically-valid real-word measurement-based care cohort demonstrates gender differences in socioeconomic factors, trauma exposure, transdiagnostic symptoms, and functioning.

The Disruptive Behavior Disorders Rating Scale: Updated Factor Structure, Measurement Invariance, and National Caregiver Norms.

OBJECTIVE: To provide the first caregiver-report national norms for the Disruptive Behavior Disorders Rating Scale (DBDRS) and an updated evaluation of its factor structure and measurement invariance across child sex, informant sex, and child age. METHODS: Caregivers of children aged 5-12 years (N = 962) based in the United States completed the four DBDRS subscales. Using both severity scoring and dichotomous scoring procedures, confirmatory factor analyses supported a four-factor model of inattentive and hyperactive/impulsive symptoms, oppositional defiant symptoms, and conduct disorder symptoms. RESULTS: Measurement invariance was supported, indicating that the DBDRS functions similarly across demographic characteristics. Boys were reported to have more severe symptoms than girls (Cohen's d = 0.33 [inattention], 0.30 [hyperactivity/impulsivity], 0.18 [oppositional defiant disorder], 0.14 [conduct disorder]), female caregivers rated ADHD symptoms as more severe than male caregivers (ds = 0.15 and 0.19 for inattention and hyperactivity/impulsivity, respectively), and older children were reported to experience more inattention than younger children (d = 0.18). Overall, group differences were modest in magnitude. CONCLUSION: This psychometric study supports the continued use of the DBDRS in school-aged youth and will enhance the measure's clinical and research utility by providing the first caregiver-report norms.

Reinforcement-based responsiveness, depression, and anhedonia: A multi-method investigation of intergenerational risk.

Offspring of depressed parents are at an increased risk for depression. Reward- and punishment-based systems might be mechanisms linking maternal outcomes to offspring depression and anhedonia. The current study was designed to investigate the intergenerational relations between maternal markers of reward and punishment responsiveness and their offspring's depression and anhedonia in a community sample of 40 mother (mean age = 44.5; SD = 6.82) and adolescent (mean age = 14.73; SD = 1.25; 52.5% female) dyads. Maternal markers of reward and punishment responsiveness were captured using self-report, behavioral, and neurophysiological methods, and self-reported depression and anhedonia symptoms were used as outcomes among the adolescent offspring. Maternal self-reported reward responsiveness and punishment learning rates were differentially associated with depression across male and female offspring. Regarding anhedonia, maternal punishment learning rate was positively related to adolescent anhedonia regardless of offspring biological sex. Maternal reward learning rate was also positively associated with anhedonia among male offspring. In general, low concurrence across self-report, behavioral, and neurophysiological markers of reward and punishment responsiveness was found. The results from the current study suggest that learning-rates on reinforcement-based behavioral tasks may be important objective markers to consider when evaluating intergenerational risk.

Borderline personality features and altered social feedback processing in emerging adults: An EEG study.

The goal of this study was to examine social feedback processing among emerging adults with borderline personality features (BPF). Participants (N = 118; 66.9% female) completed ratings of BPF and a computerized peer interaction task designed to measure processing of rejection and acceptance cues at the neurophysiological (i.e., electroencephalogram [EEG]), behavioral, and self-report levels. When covarying symptoms of depression and social anxiety, greater BPF were associated with heightened neural processing of social acceptance cues, accounting for reactivity to neutral and rejection cues, as demonstrated by an enhanced reward positivity (RewP) component. Additionally, BPF were associated with less adaptive voting in response to peer acceptance, such that emerging adults with higher BPF made fewer votes to keep peers in the game who had provided acceptance feedback to participants. These neural and behavioral patterns associated with BPF highlight the potential role of social reward processing in borderline personality. Specifically, emerging adults high in BPF show a hyper-responsiveness to social acceptance at the neural level but difficulty modulating behavioral responses in an adaptive way to obtain more social rewards. Future research replicating these effects across development may guide efforts to address and prevent the profound social dysfunction associated with BPF.

Treatment with stimulants and the risk of COVID-19 complications in adults with ADHD.

Adults with attention deficit hyperactivity disorder (ADHD) have shown higher infection rates and worse outcomes from COVID-19. Stimulant medications are prescribed as the first-line treatment for ADHD in adults and mitigate risk of negative ADHD-related health outcomes, but little is known about the association between stimulant medications and COVID-19 outcomes. The objective of this study was to assess the risks of severe COVID-19 outcomes among people with ADHD who were prescribed stimulant medications versus those who were not. This retrospective cohort study used electronic health records in the TriNetX research database. We assessed records of adults with ADHD diagnosed with COVID-19 between January 1, 2020 and June 30, 2021. The stimulant cohort consisted of 28,011 people with at least one stimulant prescription; the unmedicated cohort comprised 42,258 people without prescribed stimulants within 12 months prior to their COVID infection. Multiple logistic regression modeling was utilized to assess the presence of critical care services or death within 30 days after the onset of COVID diagnoses, controlling for patient demographics, and comorbid medical and mental health conditions. The stimulant cohort was less likely to utilize emergency department, hospital, and intensive care services than the unmedicated cohort, and had significantly lower 30-day mortality. Further research, including prospective studies, is needed to confirm and refine these findings.

Associations among ADHD symptoms, ODD symptoms, and borderline personality features: A network analysis.

Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are common childhood syndromes that exhibit a high degree of comorbidity. Both ADHD and ODD symptoms in childhood predict higher levels of borderline personality features (BPF) later in development. Yet ADHD, ODD, and BPF each consist of a heterogeneous group of symptoms, and symptom-level associations between these groups remain unclear. The present study examined symptom-level associations, as well as sex differences in symptom-level associations, among ADHD, ODD, and BPF using network analysis. Caregivers of 962 children between the ages of 5 and 12 completed rating scales of ADHD, ODD, and BPF. Assessment of Bridge Expected Influence indicated a number of bridge symptoms linking ADHD to ODD; these bridge symptoms were primarily from the hyperactive-impulsive (rather than the inattentive) dimension of ADHD (e.g., blurts out answers, leaves seat, runs excessively). A smaller number of bridge symptoms were identified linking ADHD and ODD to BPF, and these bridge symptoms were different for girls versus boys. Overall, several ADHD hyperactive-impulsive symptoms were related to the BPF item gets in trouble for doing things without thinking, and the ODD item touchy/easily annoyed was related to the BPF item goes back and forth between different feelings. Moreover, whereas we observed stronger links between ODD antagonistic symptoms (e.g., blames others) and BPF among girls, we observed stronger links between ODD oppositional symptoms (e.g., defies/refuses to comply) and BPF among boys. Taken together, results provide a more nuanced, symptom-level understanding of the overlap among ADHD, ODD, and BPF.

The Impact of ADHD on Maternal Quality of Life.

Childhood attention-deficit/hyperactivity disorder (ADHD) is associated with substantial burden to caregiver quality of life (QoL). However, a paucity of work has focused on quantifying QoL among caregivers of adolescents with a history of ADHD. The purpose of the current study was (1) to quantify maternal QoL in a sample of mothers of adolescents with and without childhood ADHD; and (2) to examine predictors (i.e., parent and child characteristics and behavior) associated with maternal QoL. Participants included mothers of adolescents with (N = 110) and without ADHD (N = 90) ranging in age from 13 to 18 (M = 16.09, 92% male). The Quality Adjusted Life-Year (QALY) was used to calculate maternal QoL using two health domains (i.e., anxiety/depression and disruption in daily activities) commonly impacted by raising youth with ADHD. QALYs are valued monetarily to estimate disease burden. Mothers of adolescents with childhood ADHD experienced significantly worse QoL relative to mothers in the comparison group. Maternal depression, as well as adolescent age, ADHD status, and discipline problems significantly predicted lower levels of maternal QALY health status index, with ADHD being the strongest predictor. This is equal to a reduction in 1.96 QALYs when summed over the course of a child's lifetime and is associated with a loss of $98,000 to $196,000. Results of the investigation help to further elucidate the health impacts incurred by families of adolescents with ADHD and have important public health implications. Further, parental QoL should be considered when conceptualizing the financial and negative health impact of ADHD.

Screening for ADHD in a general outpatient psychiatric sample of adults.

Adults (n = 805) seeking outpatient psychiatric care completed the Adult ADHD Self-Report Scale (ASRS) and measures of impairment and co-occurring psychopathology as part of a measurement-based care initiative. Diagnostic indicators of ADHD (i.e., formal diagnosis and/or medication treatment) were recorded from the electronic medical record (EMR). Agreement between screening positive for ADHD and EMR indicators for the diagnosis was explored, and clinical characteristics of adults identified with ADHD using these indicators were examined. Lastly, the contribution of ADHD to functional impairment was examined, controlling for the contribution of other demographic and psychiatric comorbidities. In the full sample, 54.78% of adults screened positive for ADHD based on the ASRS, and using EMR indicators, only 11.93% of adults were identified with ADHD. Agreement emerged between self-reported ADHD and ADHD EMR indicators, although adults screening positive for ADHD generally reported greater psychiatric complexity relative to adults identified with ADHD in the EMR. ADHD was associated with clinical impairment even when controlling for other psychiatric comorbidities. The considerable difference in prevalence of ADHD based on self-report screening versus EMR indicators suggests that ADHD may be overlooked in adult psychiatric care. Findings point to the importance of assessing adult ADHD in routine psychiatric care.

The Impact of Irritability and Callous Unemotional Traits on Reward Positivity in Youth with ADHD and Conduct Problems.

Children with attention-deficit/hyperactivity disorder (ADHD) and conduct problems exhibit significant variability in functioning and treatment response that cannot be fully accounted for by differences in symptom severity. Reward responsivity (RR) is a potential transdiagnostic means to account for this variability. Irritability and callous-unemotional (CU) traits moderate associations between both ADHD and conduct problems with multiple realms of functioning. Both are theorized to be associated with RR, but associations in clinical samples are unknown. In 48 youth ages 5-12 with ADHD referred for treatment of conduct problems, we examined RR using a guessing task where participants select a door icon to win and lose money. Analyses focused on the reward positivity (RewP) event-related potential in response to gain and loss feedback, which reliably peaks approximately 300 ms after feedback. Frequentist and Bayesian approaches assessed main effects of ADHD, Conduct Disorder (CD) and non-irritable Oppositional Defiant Disorder (ODD) symptoms with RR, plus interactions between symptoms and affective dimensions (irritability, CU). CD and ODD were hypothesized to be associated with altered RR, with irritability and CU moderating these associations. Across models, a reliable CD x irritability interaction emerged, indicating enhanced RewP when irritability was elevated and CD symptoms were low. CU did not moderate any associations with RR, and little support was found for associations between RR and other symptom domains. As neural response to reward varied with levels of irritability and CD symptoms, RR may hold potential as a clinically-relevant biomarker in youth with ADHD and conduct problems.

Inhibitory Control, Conduct Problems, and Callous Unemotional Traits in Children with ADHD and Typically Developing Children.

Compared children with CP/ADHD, CPCU/ADHD, ADHD-only, and controls on two measures of inhibitory control: a Simon/flanker task that measured response selection and a stop signal task that measured response inhibition. Results showed: (a) ADHD was associated with both measures of inhibitory control; (b) control children had better overall performance and ADHD-only had worse response selection than the CP groups; and (c) children with CPCU/ADHD had better response inhibition than children with ADHD-only or CP/ADHD. Results suggest inhibitory control dysfunction is associated with ADHD rather than CP and that response inhibition dysfunction distinguishes children with CP/ADHD from children with CPCU/ADHD.

Psychometric Properties of Parent Ratings on the Inventory of Callous-Unemotional Traits in a Nationally Representative Sample of 5- to 12-Year-Olds.

The psychometric properties of the parent-report version of the Inventory of Callous-Unemotional Traits (ICU) in school-aged children requires further examination. In a nationally representative sample of U.S. children (N = 1,064, M age = 8.42, 51.7% boys), the current study examined the factor structure, measurement invariance, and the moderating role of parent rated ICU scores on conduct problems. Results supported (a) a two-factor model consisting of a CU factor and a limited prosocial emotions (LPE) factor; (b) an invariant structure of the ICU across child sex, as well as (to a lesser extent) across child age and parent sex; and (c) the moderating role of the LPE factor on the relationship between conduct problems and relevant outcomes (i.e., impairment, need for treatment). Normative data on the parent-report version of the ICU for elementary-aged school children in the United States were also presented. Clinical implications regarding use of the parent-report version of the ICU for school-aged children are discussed.

Interactive Effects of Parent Emotion Socialization and Child Physiological Reactivity in Predicting Adolescent Borderline Personality Disorder Features.

Theories suggest that a transaction between child biological vulnerability and parent emotion socialization underlies the development of borderline personality disorder (BPD) features. Yet, few studies have examined the interaction between these factors prospectively in at-risk samples. Consequently, this study tested whether parental reactions to children's negative emotions moderated the effect of the child's physiological reactivity to stress in predicting adolescent BPD features in a sample of youth with and without clinical elevations in attention deficit/hyperactivity disorder (ADHD). Participants were 61 children (52% female) and parents (90% mothers). When children were 9-13 years old, their physiological reactivity to a social stressor was assessed based on respiratory sinus arrhythmia (RSA) and skin conductance level (SCL) reactivity; parents also reported on their supportive and non-supportive reactions to their child's negative emotions. Children were followed-up four to five years later at ages 14-18 years old and their BPD features were assessed based on parent and adolescent report. Significant interactions between children's SCL reactivity and parental reactions to children's negative emotions were found in predicting adolescent BPD features. Children with low SCL reactivity to social stress and parents high in supportive/low in non-supportive reactions were lowest in adolescent BPD features. However, greater SCL reactivity predicted greater adolescent BPD features specifically when the parent was high in support or low in non-support. Childhood ADHD symptoms also significantly predicted greater adolescent BPD features. Findings suggest that children with different patterns of SCL reactivity may respond differently to parental reactions to their emotions.

Caregiver Strain Questionnaire-Short Form 11 (CGSQ-SF11): A Validation Study.

Caregiver strain is associated with caregiver and child well-being and clinical outcomes. The present study examined the psychometric properties of a revised 11-item measure of caregiver strain, the Caregiver Strain Questionnaire-Short Form 11 (CGSQ-SF11). In a sample of 962 caregivers, we found support for a three-factor model of the CGSQ-SF11, consisting of objective (e.g., financial impact), subjective internalized (e.g., sadness about the child's problems), and subjective externalized (e.g., anger directed toward the child) strain factors. Measurement invariance was supported across multiple demographic and clinical groups, and all three subscales displayed high internal consistency. Convergent validity was also supported through positive correlations with measures of child psychopathology symptoms and psychosocial impairment. Moreover, caregiver strain was associated with number of child disorders as well as breadth of child symptoms across both internalizing and externalizing domains. Findings provide initial validation of the CGSQ-SF11 as a comprehensive yet brief measure of caregiver strain.

Family-based treatments for attention-deficit/hyperactivity disorder: A review of family functioning outcomes in randomized controlled trials from 2010 to 2019.

This review details advances in randomized controlled trials of family-based treatments for attention-deficit/hyperactivity disorder (ADHD) conducted in the United States from 2010 to 2019, and the impact of these treatments on the domain of family functioning. Twenty-two studies were included in the review and three types of family treatments, integrated parent-child treatments, parent-directed treatments, and youth treatments with adjunctive parent involvement, were identified for children and adolescents. Studies point to considerable advancements in consideration of understudied and diverse populations, and results of the review show all three types of family interventions for ADHD should be considered well-established interventions addressing family functioning. Practical guidelines are offered, and future directions for research are discussed.

The significance of limited prosocial emotions among externalizing disorders in children.

Limited Prosocial Emotion (LPE) specifier of conduct disorder (CD) includes lack of remorse or guilt, callousness/lack of empathy, unconcern about performance, and shallow/deficient affect. Given the relatively recent inclusion of the LPE specifier in the Diagnostic and Statistical Manual, fundamental information is still unknown about LPE, such as how common the different domains are, how much they overlap with one another, whether they predict unique variance from each other, and the potential for the LPE specifier as a transdiagnostic facet of externalizing problems. Caregivers (n = 1,50) of children (Mage = 8.42, SD = 2.31) completed a questionnaire assessing individual LPE domains and measures of externalizing symptoms. Results showed that LPE specifier domains were highly related but separable. All LPEs were uniquely associated with oppositional defiant disorder (ODD), CD, and overall impairment after controlling for other LPE items, child sex, and ADHD symptoms. Being unconcerned about performance, emotionally manipulative, and having shallow/deficient affect were uniquely associated with ADHD while controlling for ODD and CD symptomatology. Our findings fit with the historical conceptualization of LPE as a unidimensional construct and contributes to the growing evidence of the potential utility of assessing LPE across externalizing disorders in children. Future research should look to replicate and extend our findings in clinical samples of youth.

Identifying Neural Markers of Peer Dysfunction in Girls with ADHD.

Very little research has prioritized girls with ADHD, despite accumulating evidence showing that girls with ADHD experience broader and more severe peer dysfunction relative to boys with ADHD. Attention to identifying the neural mechanisms underlying the peer difficulties of girls with ADHD is critical in order to develop targeted intervention strategies to improve peer functioning. New efforts to address the peer dysfunction of girls with ADHD are discussed.

A latent profile analysis of borderline personality features and externalizing problems in youth.

OBJECTIVE: This study investigated the co-occurrence of borderline personality disorder (BPD), attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD) features in elementary-aged youth. METHOD: Latent profile analysis characterized subgroups of youth based on the presence of BPD, ADHD, and ODD features, and subgroups were compared on academic, social, and emotional impairment. RESULTS: Seven subgroups were identified, including subgroups with slight, subclinical, clinical, and severe levels of co-occurring BPD, ADHD, and ODD features, and a subgroup of youth with no elevations in these symptom domains. Subgroups of youth with only clinical elevations in ADHD and only clinical levels in BPD features were also identified. Groups differed on level and type of impairment. CONCLUSION: Youth with ADHD and ODD represent a high-risk group likely to also show early prodromal clinical elevations in BPD. Future work is needed to examine the longitudinal outcomes of these subgroups to inform prevention and treatment.

Sex and Emotion Regulation Difficulties Contribute to Depression in Young Adults With Attention-Deficit/Hyperactivity Disorder.

Many young adults with attention-deficit/hyperactivity disorder (ADHD) are at risk for depression. Yet, questions remain about factors associated with the development of depression in young adults with ADHD. This study examined the effects of sex and emotion regulation difficulties on depression in a sample of young adults with (n = 172) and without (n = 730) ADHD. Two aspects of emotion regulation difficulties were examined-impairments in emotional insight (i.e., lack of emotional awareness, nonacceptance of emotion, and lack of emotional clarity) and impairments in behavioral response to emotion (i.e., impulse control difficulties, difficulties engaging in goal-directed behavior, and limited access to emotion regulation strategies). Significant correlations between ADHD and all indices of emotion regulation difficulty emerged. Sex moderated the association between ADHD and lack of emotional awareness, difficulties engaging in goal-directed behavior, and limited access to emotion regulation strategies. Specifically, ADHD was significantly associated with limited emotion regulation awareness for women but not men, while ADHD was associated with greater difficulties engaging in goal-directed behavior and limited access to emotion regulation strategies for women compared to men. These three areas of emotion regulation dysfunction simultaneously mediated the association between ADHD and depression. The findings indicate the importance of considering emotion regulation and sex in understanding depression in young adults with ADHD.