Validation of the Strengths and Difficulties Questionnaire (SDQ) emotional subscale in assessing depression and anxiety across development.

Emotional disorders are common in childhood, and their prevalence sharply increases during adolescence. The Strengths and Difficulties Questionnaire (SDQ) is widely used for screening emotional and behavioural difficulties in children and young people, but little is known about the accuracy of the emotional subscale (SDQ-E) in detecting emotional disorders, and whether this changes over development. Such knowledge is important in determining whether symptom changes across age are due to developmental or measurement differences. This study assessed the validity of the SDQ-E and two individual items (low mood and general worry) in differentiating between cases and non-cases of Major Depressive Disorder (MDD), Generalised Anxiety Disorder (GAD), and other anxiety disorders across ages 7, 10, 13, 15, and 25 years in a UK population cohort. Analyses showed moderate accuracy of the subscale in discriminating cases of MDD (AUC = 0.67-0.85), and high accuracy for discriminating cases of GAD (AUC = 0.80-0.93) and any anxiety disorder (AUC = 0.74-0.83) compared to non-cases. The SDQ-E performed well across ages and sex, and generally performed better than the two individual items. Together our findings validate the SDQ-E as a screen for emotional disorders during childhood, adolescence, and early adulthood, and as a tool for longitudinal research on depression and anxiety disorders.

Developing and validating a prediction model of adolescent major depressive disorder in the offspring of depressed parents.

BACKGROUND: Parental depression is common and is a major risk factor for depression in adolescents. Early identification of adolescents at elevated risk of developing major depressive disorder (MDD) in this group could improve early access to preventive interventions. METHODS: Using longitudinal data from 337 adolescents at high familial risk of depression, we developed a risk prediction model for adolescent MDD. The model was externally validated in an independent cohort of 1,384 adolescents at high familial risk. We assessed predictors at baseline and MDD at follow-up (a median of 2-3 years later). We compared the risk prediction model to a simple comparison model based on screening for depressive symptoms. Decision curve analysis was used to identify which model-predicted risk score thresholds were associated with the greatest clinical benefit. RESULTS: The MDD risk prediction model discriminated between those adolescents who did and did not develop MDD in the development (C-statistic = .783, IQR (interquartile range) = .779, .778) and the validation samples (C-statistic = .722, IQR = -.694, .741). Calibration in the validation sample was good to excellent (calibration intercept = .011, C-slope = .851). The MDD risk prediction model was superior to the simple comparison model where discrimination was no better than chance (C-statistic = .544, IQR = .536, .572). Decision curve analysis found that the highest clinical utility was at the lowest risk score thresholds (0.01-0.05). CONCLUSIONS: The developed risk prediction model successfully discriminated adolescents who developed MDD from those who did not. In practice, this model could be further developed with user involvement into a tool to target individuals for low-intensity, selective preventive intervention.

Practitioner Review: Attention-deficit hyperactivity disorder and autism spectrum disorder - the importance of depression.

Young people with neurodevelopmental disorders, such as attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), show high rates of mental health problems, of which depression is one of the most common. Given that depression in ASD and ADHD is linked with a range of poor outcomes, knowledge of how clinicians should assess, identify and treat depression in the context of these neurodevelopmental disorders is much needed. Here, we give an overview of the latest research on depression in young people with ADHD and ASD, including possible mechanisms underlying the link between ADHD/ASD and depression, as well as the presentation, assessment and treatment of depression in these neurodevelopmental disorders. We discuss the implications for clinicians and make recommendations for critical future research in this area.

Depression in young people.

Depression rates in young people have risen sharply in the past decade, especially in females, which is of concern because adolescence is a period of rapid social, emotional, and cognitive development and key life transitions. Adverse outcomes associated with depression in young people include depression recurrence; the onset of other psychiatric disorders; and wider, protracted impairments in interpersonal, social, educational, and occupational functioning. Thus, prevention and early intervention for depression in young people are priorities. Preventive and early intervention strategies typically target predisposing factors, antecedents, and symptoms of depression. Young people who have a family history of depression, exposure to social stressors (eg, bullying, discordant relationships, or stressful life events), and belong to certain subgroups (eg, having a chronic physical health problem or being a sexual minority) are at especially high risk of depression. Clinical antecedents include depressive symptoms, anxiety, and irritability. Evidence favours indicated prevention and targeted prevention to universal prevention. Emerging school-based and community-based social interventions show some promise. Depression is highly heterogeneous; therefore, a stepwise treatment approach is recommended, starting with brief psychosocial interventions, then a specific psychological therapy, and then an antidepressant medication.

Investigating the associations between irritability and hot and cool executive functioning in those with ADHD.

BACKGROUND: Irritability is especially pertinent to those with Attention Deficit Hyperactivity Disorder (ADHD) as it is highly prevalent and associated with a more severe clinical presentation and poorer longitudinal outcomes. Preliminary evidence suggests that top-down cognitive processes taking place in emotional contexts (i.e., hot executive functions) as opposed to those evoked in abstract scenarios (i.e., cool executive functions) may be relevant to the presentation of irritability in ADHD. This study explored the cognitive mechanisms underlying irritability in young people with ADHD, hypothesising that irritability would be associated with hot, but not cool, executive function impairments. METHODS: Our sample included 219 individuals with ADHD. A composite irritability score was derived extracting items from a parent interview, with scores ranging from 0 to 5. Associations were investigated using linear regression analyses, between irritability and four hot tasks measuring sensitivity to risk, risk-taking behaviour following reward or punishment, acceptance of reward delay and reaction to unfair behaviour from others, and two cool tasks measuring set-shifting and motor inhibition. RESULTS: As hypothesised, there were no significant associations between irritability and cool executive functions in those with ADHD; however, contrary to expectations, there was also no significant evidence that hot executive functions were associated with irritability. CONCLUSIONS: These results, in a large well characterised sample and using a comprehensive task battery, suggest that the variation in irritability in those with ADHD may not be associated with differences in hot or cool executive function performance.

Exploring ADHD Symptoms and Associated Impairment across Development.

OBJECTIVE: ADHD symptoms typically decline with age, but less is known about whether the presentation of specific ADHD symptoms differs across development. This study aimed to examine the frequency and associated impairment of specific ADHD symptoms in childhood, adolescence, and young adulthood. METHOD: A prospective, longitudinal cohort, the Avon Longitudinal Study of Parents and Children, was utilized (N = 2,327). ADHD symptoms and impairment were assessed using the Development and Well Being Assessment at ages 7, 15, and 25. RESULTS: Specific ADHD symptom frequencies and their associated impairment varied across development for the majority of symptoms, although easily distracted was one of the most commonly reported symptoms at each age, and difficulty sustaining attention was consistently associated with high levels of impairment. CONCLUSION: These findings suggest differences in the presentations of ADHD symptoms across development: current understanding of how ADHD presents in childhood/adolescence may not be generalizable to young adulthood.

The antecedents and outcomes of persistent and remitting adolescent depressive symptom trajectories: a longitudinal, population-based English study.

BACKGROUND: Depression often first emerges in adolescence and, for many, is a lifelong disorder. The long-term clinical course of depression is highly variable. We aimed to examine the adult outcomes of adolescent-onset trajectories of clinically significant depressive symptoms and to identify factors differentiating trajectories that persist and desist in adulthood. METHODS: We included participants from the English population-based Avon Longitudinal Study of Parents and Children with data on depressive symptoms. Self-reported depression symptoms were assessed on ten occasions when participants were age 10·5-25 years using the short Mood and Feelings Questionnaire, and major depressive disorder episodes were assessed at age 13·0 years, 15·0 years, 17·5 years, and 25·0 years. We characterised trajectories of depression symptoms using latent class growth analysis, for which we required depression data at least once from each of three key phases: ages 10·5-13·5 years; 16·5-18·5 years; and 21-25 years. We examined adult outcomes by assessing lifetime suicidal self-harm and functional impairment at age 24·0 years, and employment, education, and the self-reported Strengths and Difficulties Questionnaire at age 25·0 years. FINDINGS: We studied 4234 participants: 2651 (63%) female, 1582 (37%) male, and one individual with missing sex data. The mean age was 10·6 years (SD 0·2) at baseline and 25·8 years (SD 0·5) at the final timepoint. Data on ethnicity were not available in our data set. We identified four depression trajectory classes: adolescent-persistent depression with onset early in adolescence (7%, n≈279), adolescent-limited depression with onset later in adolescence and remittance by adult life (14%, n≈592), adult-increasing depression (25%, n≈1056), and stable-low levels of depression (54%, n≈2307). The adolescent-persistent class was associated with poor adult outcomes for functional impairment (62%), suicidal self-harm (27%), mental health difficulties (25%), and not being in education, employment, or training (16%). Adolescent-limited depression was associated with transient adolescent stress, but by early adulthood functional impairment and mental health difficulties were similar to the stable-low group. Major depressive disorder polygenic score (odds ratio [OR] 1·36, 95% CI 1·04-1·79), adolescent educational attainment (OR 0·47, 0·30-0·74), and any early childhood adversity (OR 2·60, 1·42-4·78), that persisted into adulthood (OR 1·60, 1·38-1·87) distinguished the adolescent-persistent and adolescent-limited groups. INTERPRETATION: The future course of adolescent depression can be differentiated by age at onset during adolescence, adolescent academic attainment, early and persistent adversity, and genetic loading. A detailed social and educational history could be helpful in making clinical decisions about the intensity of interventions for young people with clinically elevated depressive symptoms who seek help. FUNDING: Medical Research Council, Wolfson Centre for Young People's Mental Health, Wolfson Foundation.

ADHD in adults with recurrent depression.

BACKGROUND: Depression is highly heterogeneous in its clinical presentation. Those with attention deficit/hyperactivity disorder (ADHD) may be at risk of a more chronic and impairing depression compared to those with depression alone according to studies of young people. However, no studies to date have examined ADHD in recurrently depressed adults in mid-life. METHOD: In a sample of women in mid-life (n=148) taken from a UK based prospective cohort of adults with a history of recurrent depression, we investigated the prevalence of ADHD and the association of ADHD with clinical features of depression. RESULTS: 12.8% of the recurrently depressed women had elevated ADHD symptoms and 3.4% met DSM-5 diagnostic criteria for ADHD. None of the women reported having a diagnosis of ADHD from a medical professional. ADHD symptoms were associated with earlier age of depression onset, higher depression associated impairment, a greater recurrence of depressive episodes and increased persistence of subthreshold depression symptoms over the study period, higher levels of irritability and increased risk of self-harm or suicide attempt. ADHD symptoms were associated with increased risk of hospitalisation and receiving non-first-line antidepressant medication. LIMITATIONS: ADHD was measured using a questionnaire measure. We focussed on mothers in a longitudinal study of recurrent depression, so the findings may not apply to males or other groups. CONCLUSIONS: Higher ADHD symptoms appear to index a worse clinical presentation for depression. Clinical implications include that in women with early onset, impairing and recurrent depression, the possibility of underlying ADHD masked by depression needs to be considered.

Validation of the short Mood and Feelings Questionnaire in young adulthood.

BACKGROUND: Depression often onsets in adolescence and is associated with recurrence in adulthood. There is a need to identify and monitor depression symptoms across adolescence and into young adulthood. The short Mood and Feelings Questionnaire (sMFQ) is commonly used to measure depression symptoms in adolescence but has not been validated in young adulthood. This study aimed to (1) examine whether the sMFQ is valid in young adulthood, and (2) identify cut-points best capturing DSM-5 depression diagnosis at age 25 METHODS: The sample included participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 25 (n = 4098). Receiver Operating Characteristic analyses examined how well the self-rated sMFQ discriminates between cases and non-cases of DSM-5 Major Depressive Disorder (MDD) classified using the self-rated Development and Well Being Assessment. Sensitivity and specificity values were used to identify cut-points on the sMFQ RESULTS: The sMFQ had high accuracy for discriminating MDD cases from non-cases at age 25. The commonly used cut-point in adolescence (≥12) performed well at this age, best balancing sensitivity and specificity. However, a lower cut-point (≥10) may be appropriate when favouring sensitivity over specificity e.g., in context of screening. Sensitivity analyses suggested similar results for males and females LIMITATIONS: ALSPAC is a longitudinal population cohort that suffers from non-random attrition CONCLUSIONS: The sMFQ is a valid measure of depression in young adults in the general population. It can be used to screen for and monitor depression across adolescence and early adulthood.

Sex differences in anxiety and depression in children with attention deficit hyperactivity disorder: Investigating genetic liability and comorbidity.

It is unknown why attention deficit hyperactivity disorder (ADHD) is more common in males, whereas anxiety and depression show a female population excess. We tested the hypothesis that anxiety and depression risk alleles manifest as ADHD in males. We also tested whether anxiety and depression in children with ADHD show a different etiology to typical anxiety and depression and whether this differs by sex. The primary clinical ADHD sample consisted of 885 (14% female) children. Psychiatric symptoms were assessed using standardized interviews. Polygenic risk scores (PRS) were derived using large genetic studies. Replication samples included independent clinical ADHD samples (N = 3,794; 25.7% female) and broadly defined population ADHD samples (N = 995; 33.4% female). We did not identify sex differences in anxiety or depression PRS in children with ADHD. In the primary sample, anxiety PRS were associated with social and generalized anxiety in males, with evidence of a sex-by-PRS interaction for social anxiety. These results did not replicate in the broadly defined ADHD sample. Depression PRS were not associated with comorbid depression symptoms. The results suggest that anxiety and depression genetic risks are not more likely to lead to ADHD in males. Also, the evidence for shared etiology between anxiety symptoms in those with ADHD and typical anxiety was weak and needs replication.

Investigating the validity of the Strengths and Difficulties Questionnaire to assess ADHD in young adulthood.

Attention Deficit Hyperactivity Disorder (ADHD) symptoms typically onset early and persist into adulthood for many. Robust investigation of symptom continuity and discontinuity requires repeated assessments using the same measure, but research is lacking into whether measures used to assess ADHD symptoms in childhood are also valid in adulthood. The Strengths and Difficulties Questionnaire (SDQ) is widely used to assess ADHD symptoms in children, but little is known about its utility in adulthood. The aim of this study was to assess the validity of the SDQ hyperactivity/ADHD subscale to distinguish between cases and non-cases of DSM-5 ADHD at age 25 years in a UK population cohort (N = 4121). ADHD diagnosis was derived using the Barkley Adult ADHD Rating Scale-IV. Analyses suggested that the self-rated SDQ ADHD subscale had high validity in distinguishing ADHD cases/non-cases in young adulthood (area under the curve=0.90, 95% CI=0.87-0.93) and indicated a lower cut-point for identifying those who may have an ADHD diagnosis in this age group compared to that currently recommended for younger ages. Findings were similar for parent-reports. Our findings suggest that the SDQ is suitable for ADHD research across different developmental periods, which will aid the robust investigation of ADHD from childhood to young adulthood.

What explains the link between childhood ADHD and adolescent depression? Investigating the role of peer relationships and academic attainment.

There is increasing evidence that childhood Attention-Deficit Hyperactivity Disorder (ADHD) elevates risk of later depression, but the mechanisms behind this association are unclear. We investigated the relationship between childhood ADHD symptoms and late-adolescent depressive symptoms in a population cohort, and examined whether academic attainment and peer problems mediated this association. ALSPAC (Avon Longitudinal Study of Parents and Children) is an ongoing prospective longitudinal population-based UK cohort that has collected data since September 1990. 2950 individuals with data on parent-reported ADHD symptoms in childhood (7.5 years) and self-reported depressive symptoms in late adolescence (17.5 years) were included in analyses. 2161 individuals with additional data at age 16 years on parent-reported peer problems as an indicator of peer relationships and formal examination results (General Certificate of Secondary Education; GCSE) as an indicator of academic attainment were included in mediation analyses. Childhood ADHD symptoms were associated with higher depressive symptoms (b = 0.49, SE = 0.11, p < 0.001) and an increased odds of clinically significant depressive symptoms in adolescence (OR = 1.27, 95% CI 1.15-1.41, p < 0.001). The association with depressive symptoms was mediated in part by peer problems and academic attainment which accounted for 14.68% and 20.13% of the total effect, respectively. Childhood ADHD is associated with increased risk of later depression. The relationship is mediated in part by peer relationships and academic attainment. This highlights peer relationships and academic attainment as potential targets of depression prevention and intervention in those with ADHD. Future research should investigate which aspects of peer relationships are important in conferring later risk for depression.

Adverse childhood experiences and adult mood problems: evidence from a five-decade prospective birth cohort.

BACKGROUND: Retrospectively recalled adverse childhood experiences (ACEs) are associated with adult mood problems, but evidence from prospective population cohorts is limited. The aims of this study were to test links between prospectively ascertained ACEs and adult mood problems up to age 50, to examine the role of child mental health in accounting for observed associations, and to test gender differences in associations. METHODS: The National Child Development Study is a UK population cohort of children born in 1958. ACEs were defined using parent or teacher reports of family adversity (parental separation, child taken into care, parental neglect, family mental health service use, alcoholism and criminality) at ages 7-16. Children with no known (n = 9168), single (n = 2488) and multiple (n = 897) ACEs were identified in childhood. Adult mood problems were assessed using the Malaise inventory at ages 23, 33, 42 and 50 years. Associations were examined separately for males and females. RESULTS: Experiencing single or multiple ACEs was associated with increased rates of adult mood problems after adjustment for childhood psychopathology and confounders at birth [2+ v. 0 ACEs - men: age 23: odds ratio (OR) 2.36 (95% confidence interval (CI) 1.7-3.3); age 33: OR 2.40 (1.7-3.4); age 42: OR 1.85 (1.4-2.4); age 50: OR 2.63 (2.0-3.5); women: age 23: OR 2.00 (95% CI 1.5-2.6); age 33: OR 1.81 (1.3-2.5); age 42: OR 1.59 (1.2-2.1); age 50: OR 1.32 (1.0-1.7)]. CONCLUSIONS: Children exposed to ACEs are at elevated risk for adult mood problems and a priority for early prevention irrespective of the presence of psychopathology in childhood.

Identifying Novel Types of Irritability Using a Developmental Genetic Approach.

OBJECTIVE: Irritability, which is strongly associated with impairment and negative outcomes, is a common reason for referral to mental health services but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. The authors used a developmental approach to test the hypothesis that there are several forms of irritability, including a "neurodevelopmental/ADHD-like" type, with onset in childhood, and a "depression/mood" type, with onset in adolescence. METHODS: Data were analyzed from the Avon Longitudinal Study of Parents and Children, a prospective U.K. population-based cohort. Irritability trajectory classes were estimated for 7,924 individuals with data at multiple time points across childhood and adolescence (four possible time points from approximately ages 7 to 15). Psychiatric diagnoses were assessed at approximately ages 7 and 15. Psychiatric genetic risk was indexed by polygenic risk scores (PRSs) for attention deficit hyperactivity disorder (ADHD) and depression, derived using large genome-wide association study results. RESULTS: Five irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), late-childhood limited (5.2%), and high-persistent (2.4%). The early-onset high-persistent trajectory was associated with male preponderance, childhood ADHD (odds ratio=108.64, 95% CI=57.45-204.41), and ADHD PRS (odds ratio=1.31, 95% CI=1.09-1.58). The adolescent-onset increasing trajectory was associated with female preponderance, adolescent depression (odds ratio=5.14, 95% CI=2.47-10.73), and depression PRS (odds ratio=1.20, 95% CI=1.05-1.38). Both the early-onset high-persistent and adolescent-onset increasing trajectory classes were associated with adolescent depression diagnosis and ADHD PRS. CONCLUSIONS: The developmental context of irritability may be important in its conceptualization: early-onset persistent irritability may be more neurodevelopmental/ADHD-like and later-onset irritability more depression/mood-like. These findings have implications for treatment as well as nosology.

Irritability in ADHD: association with later depression symptoms.

Attention-deficit/hyperactivity disorder (ADHD) and depression commonly co-occur. Identifying children with ADHD at risk for later depression may allow early intervention and prevention. Irritability is one possible mechanism linking these two disorders. It is common in ADHD and associated with later depression in the general population. Cross-sectional studies suggest an association between irritability and depression in ADHD, but longitudinal research is limited. This study followed up a clinical ADHD sample longitudinally to examine: (1) the association between childhood irritability and later depression symptoms, and (2) whether irritability persistence is important in this association. At baseline, parents (n = 696) completed semi-structured interviews about their child (mean age = 10.9), providing information on child psychopathology, including irritability. A subsample (n = 249) was followed up after a mean of 5.4 years. Parent-completed Mood and Feelings Questionnaires provided information on depressive symptoms at follow-up. Parent-rated structured diagnostic interviews provided information on ADHD diagnosis and irritability at follow-up. Regression analyses examined associations between (i) baseline irritability and depression symptoms at follow-up, and (ii) persistent (vs. remitted) irritability and depression symptoms at follow-up. Analyses controlled for age, gender, depression symptoms, anxiety, ADHD symptoms, and ADHD medication at baseline. Baseline irritability was associated with depression symptoms at follow-up, but the association attenuated after controlling for anxiety and ADHD symptoms. Persistent irritability was associated with depression symptoms at follow-up, after including all covariates. Children with ADHD with persistent irritability are at elevated risk of developing depression symptoms. They may be a target for early intervention and prevention of depression.

Childhood neurodevelopmental difficulties and risk of adolescent depression: the role of irritability.

BACKGROUND: Children with neurodevelopmental disorders are at increased risk of developing depression. Irritability predicts depression in the general population and is common in children with neurodevelopmental disorders. Thus, it is possible that irritability in children with neurodevelopmental disorders contributes to the link with later depression. This study aimed to (a) examine the association between childhood neurodevelopmental difficulties and adolescent depression and (b) test whether irritability explains this association. METHODS: Children with any neurodevelopmental difficulty at the age of 7-9 (n = 1,697) and a selected, comparison group without any neurodevelopmental difficulty (n = 3,177) were identified from a prospective, UK population-based cohort, the Avon Longitudinal Study of Parents and Children. Neurodevelopmental difficulties were defined as a score in the bottom 5% of the sample on at least one measure of cognitive ability, communication, autism spectrum symptoms, attention-deficit/hyperactivity symptoms, reading or motor coordination. The Development and Well-Being Assessment measured parent-reported child irritability at the age of 7, parent-reported adolescent depression at the age of 10 and 13, and self-reported depression at the age of 15. Depression measures were combined, deriving an outcome of major depressive disorder (MDD) in adolescence. Logistic regression examined the association between childhood neurodevelopmental difficulties and adolescent MDD, controlling for gender. Path analysis estimated the proportion of this association explained by irritability. Analyses were repeated for individual neurodevelopmental problems. RESULTS: Childhood neurodevelopmental difficulties were associated with adolescent MDD (OR = 2.11, 95% CI = 1.24, 3.60, p = .006). Childhood irritability statistically accounted for 42% of this association. On examining each neurodevelopmental difficulty separately, autistic, communication and ADHD problems were each associated with depression, with irritability explaining 29%-51% of these links. CONCLUSIONS: Childhood irritability appears to be a key contributor to the link between childhood neurodevelopmental difficulties and adolescent MDD. High rates of irritability in children with autistic and ADHD difficulties may explain elevated rates of depression in the neurodevelopmental group.

The presentation of depression symptoms in attention-deficit/hyperactivity disorder: comparing child and parent reports.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with depression, and outcomes are poor when both are present. Little is known about whether depression symptoms present differently in ADHD compared to the general population, or how reliable young people with ADHD are at reporting these symptoms. This study aimed to describe depression symptoms in a clinical ADHD sample compared to a population sample, and compare self-reports of depression symptoms with parent-reports. METHODS: Two hundred and forty-nine children with ADHD and their parents completed follow-up questionnaires around 5 years after taking part in a Cardiff University ADHD study. Child depression symptoms were measured using parent- and child-reported Mood and Feelings Questionnaires (MFQ) and compared to a population sample with MFQ data (n = 1460). Within both samples, child- and parent-reported depression symptoms were compared. RESULTS: Although the profile of depression symptoms was similar between young people with ADHD and those in the general population, depression symptoms were much more common in the ADHD sample (parent-rated MFQ score = 24.52 vs. 9.39; child-rated = 21.02 vs. 11.86). The most common symptoms in both samples included irritability, restlessness and concentration difficulties, with core depression symptoms such as feeling miserable/unhappy also prominent. Within the ADHD sample, but not the population sample, children reported depression symptoms less frequently than their parents. CONCLUSIONS: Young people with ADHD are at high risk of experiencing symptoms of depression but may under-report the severity of their symptoms. Obtaining parent reports of depression symptoms in this group may be important to avoid missing key indicators of risk.

Sex-specific manifestation of genetic risk for attention deficit hyperactivity disorder in the general population.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is more commonly diagnosed in males than in females. A growing body of research suggests that females with ADHD might be underdiagnosed or receive alternative diagnoses, such as anxiety or depression. Other lines of reasoning suggest that females might be protected from developing ADHD, requiring a higher burden of genetic risk to manifest the disorder. METHODS: We tested these two hypotheses, using common variant genetic data from two population-based cohorts. First, we tested whether females and males diagnosed with anxiety or depression differ in terms of their genetic risk for ADHD, assessed as polygenic risk scores (PRS). Second, we tested whether females and males with ADHD differed in ADHD genetic risk burden. We used three different diagnostic definitions: registry-based clinical diagnoses, screening-based research diagnoses and algorithm-based research diagnoses, to investigate possible referral biases. RESULTS: In individuals with a registry-based clinical diagnosis of anxiety or depression, females had higher ADHD PRS than males [OR(CI) = 1.39 (1.12-1.73)] but there was no sex difference for screening-based [OR(CI) = 1.15 (0.94-1.42)] or algorithm-based [OR(CI) = 1.04 (0.89-1.21)] diagnoses. There was also no sex difference in ADHD PRS in individuals with ADHD diagnoses that were registry-based [OR(CI) = 1.04 (0.84-1.30)], screening-based [OR(CI) = 0.96 (0.85-1.08)] or algorithm-based [OR(CI) = 1.15 (0.78-1.68)]. CONCLUSIONS: This study provides genetic evidence that ADHD risk may be more likely to manifest or be diagnosed as anxiety or depression in females than in males. Contrary to some earlier studies, the results do not support increased ADHD genetic risk in females with ADHD as compared to affected males.

Irritability in ADHD: Associations with depression liability.

BACKGROUND: Irritability and the new DSM-5 diagnostic category of Disruptive Mood Dysregulation Disorder (DMDD) have been conceptualised as related to mood disorder. Irritability is common in Attention Deficit Hyperactivity Disorder (ADHD) but little is known about its association with depression risk in this group. This study aims to establish levels of irritability and prevalence of DMDD in a clinical sample of children with ADHD, and examine their association with anxiety, depression and family history of depression. METHODS: The sample consisted of 696 children (mean age 10.9 years) with a diagnosis of ADHD, recruited from UK child psychiatry and paediatric clinics. Parents completed the Child and Adolescent Psychiatric Assessment, a semi-structured diagnostic interview, about their child. This was used to establish prevalence of DMDD, anxiety disorder and depressive disorder, as well as obtain symptom scores for irritability, anxiety and depression. Questionnaires assessed current parental depression, and family history of depression. RESULT: Irritability was common, with 91% endorsing at least one irritable symptom. 3-month DMDD prevalence was 31%. Children with higher levels of irritability or DMDD were more likely to have comorbid symptoms of anxiety, depression and a family history of depression. LIMITATIONS: Results are based on a clinical sample, so may not be generalizable to children with ADHD in the general population. CONCLUSIONS: Irritability and DMDD were common, and were associated with markers of depression liability. Longitudinal studies are needed to examine the association between irritability and depression in youth with ADHD as they get older.