Young Adult ADHD Symptoms in the General Population and Neurocognitive Impairment.

OBJECTIVE: Neurocognitive impairments are associated with child and adult ADHD in clinical settings. However, it is unknown whether adult ADHD symptoms in the general population are associated with the same pattern of cognitive impairment. We examined this using a prospective, population-based cohort spanning birth to age 25 years. METHODS: We examined associations between self-reported adult ADHD symptoms and cognitive task performance (attention and response inhibition) in adulthood and childhood. RESULTS: Self-rated ADHD symptoms at age 25 were associated with poorer performance in age 25 cognitive tasks capturing ADHD-related functioning (attention B = -0.03, 95% CI [0.05, -0.01], p = .005; response inhibition B = -0.03, 95% CI [-0.05, -0.01], p = .002). CONCLUSIONS: Neurocognitive impairments linked to adult ADHD symptoms in the general population, are similar to those found in people with childhood ADHD symptoms and are consistent with findings in adult ADHD clinical samples.

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.

Childhood attention-deficit hyperactivity disorder problems and mid-life cardiovascular risk: prospective population cohort study.

BACKGROUND: It is well-known that childhood attention-deficit hyperactivity disorder (ADHD) is associated with later adverse mental health and social outcomes. Patient-based studies suggest that ADHD may be associated with later cardiovascular disease (CVD) but the focus of preventive interventions is unclear. It is unknown whether ADHD leads to established cardiovascular risk factors because so few cohort studies measure ADHD and also follow up to an age where CVD risk is evident. AIMS: To examine associations between childhood ADHD problems and directly measured CVD risk factors at ages 44/45 years in a UK population-based cohort study (National Child Development Study) of individuals born in 1958. METHOD: Childhood ADHD problems were defined by elevated ratings on both the parent Rutter A scale and a teacher-rated questionnaire at age 7 years. Outcomes were known cardiovascular risk factors (blood pressure, lipid measurements, body mass index and smoking) at the age 44/45 biomedical assessment. RESULTS: Of the 8016 individuals assessed both during childhood and at the biomedical assessment 3.0% were categorised as having childhood ADHD problems. ADHD problems were associated with higher body mass index (B = 0.92 kg/m2, s.d. = 0.27-1.56), systolic (3.5 mmHg, s.d. = 1.4-5.6) and diastolic (2.2 mmHg, s.d. = 0.8-3.6) blood pressure, triglyceride levels (0.24 mol/l, s.d. = 0.02-0.46) and being a current smoker (odds ratio OR = 1.6, s.d. = 1.2-2.1) but not with LDL cholesterol. CONCLUSIONS: Childhood ADHD problems predicted multiple cardiovascular risk factors by mid-life. These findings, when taken together with previously observed associations with cardiovascular disease in registries, suggest that individuals with ADHD could benefit from cardiovascular risk monitoring, given these risk factors are modifiable with timely intervention.

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.

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.

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.

Variable Emergence of Autism Spectrum Disorder Symptoms From Childhood to Early Adulthood.

OBJECTIVE: Autism spectrum disorder (ASD) is currently considered an early-onset neurodevelopmental condition. Follow-up studies of clinic-ascertained autism suggest that autistic symptoms typically decline with age, although symptom improvement is limited for some. To date there have been no population-based prospective studies investigating the natural history of autistic symptoms from childhood to adulthood. The aim of this study was to characterize the development and heterogeneity of autistic symptoms in a population-based cohort from childhood to age 25. METHODS: Data were analyzed in a prospective U.K. population-based cohort (ALSPAC). Trajectories were derived using five assessments of the parent-rated Social and Communication Disorders Checklist (SCDC) spanning ages 7-25. Additional measures were used to validate symptom trajectories. RESULTS: Three distinct SCDC symptom trajectory classes were identified: low (88.5%), declining (5.0%), and late-emerging (6.5%). Both the declining and late-emerging trajectory classes were associated with child and adult ASD measures, low IQ, communication problems, peer problems, and worse adult functioning compared with the low trajectory class. Male sex was associated with a higher likelihood of being in the declining trajectory class (odds ratio=2.84, 95% CI=2.19, 3.69). This sex difference was not observed in the late-emerging class (odds ratio=1.00, 95% CI=0.80, 1.24) compared with the low trajectory class. CONCLUSIONS: ASD symptom levels that emerged early tended to decline across development, although impairment was still present in adulthood for some. For others, autistic symptoms emerged across adolescence and adulthood. This challenges our current understanding that ASD symptoms inevitably first manifest early in development.

ADHD and depression: investigating a causal explanation.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is associated with later depression and there is considerable genetic overlap between them. This study investigated if ADHD and ADHD genetic liability are causally related to depression using two different methods. METHODS: First, a longitudinal population cohort design was used to assess the association between childhood ADHD (age 7 years) and recurrent depression in young-adulthood (age 18-25 years) in N = 8310 individuals in the Avon Longitudinal Study of Parents and Children (ALSPAC). Second, two-sample Mendelian randomization (MR) analyses examined relationships between genetic liability for ADHD and depression utilising published Genome-Wide Association Study (GWAS) data. RESULTS: Childhood ADHD was associated with an increased risk of recurrent depression in young-adulthood (OR 1.35, 95% CI 1.05-1.73). MR analyses suggested a causal effect of ADHD genetic liability on major depression (OR 1.21, 95% CI 1.12-1.31). MR findings using a broader definition of depression differed, showing a weak influence on depression (OR 1.07, 95% CI 1.02-1.13). CONCLUSIONS: Our findings suggest that ADHD increases the risk of depression later in life and are consistent with a causal effect of ADHD genetic liability on subsequent major depression. However, findings were different for more broadly defined depression.

Assessment of age-at-onset criterion for adult attention-deficit hyperactivity disorder.

To investigate the accuracy of the age-at-onset criterion in those who meet other DSM-5 criteria for attention-deficit hyperactivity disorder, using a prospective population cohort we compared four different approaches to asking those aged 25 years (n = 138) when their symptoms started. Receiver operating characteristic curves showed variation between the approaches (χ(3) = 8.99, P = 0.03); all four showed low discrimination against symptoms that had been assessed when they were children (area under the curve: 0.57-0.68). Asking adults to recall specific symptoms may be preferable to recalling at what age symptoms started. However, limitations to retrospective recall add to debate on the validity of ADHD age-at-onset assessment.

Investigating attention-deficit hyperactivity disorder and autism spectrum disorder traits in the general population: What happens in adult life?

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are generally considered early-onset disorders so most research has therefore tended to focus on children. Differences between ADHD/ASD in adult life and childhood have been noted, but few population-based studies have examined them in adulthood. Furthermore, the interpretation of findings is hampered by changes in measure and from parent report to self-report. METHOD: We examined continuous/trait measures of parent- and self-rated ADHD and ASD in adulthood (age 25 years) in a UK prospective longitudinal sample ALPSAC (the Avon Longitudinal Study of Parents and Children), using many of the same measures that parents reported on in childhood (N = 6,064). Our aim was to investigate these traits in this population for mean-level sex differences, overlaps with other cognitive, learning and communication problems and their associations with polygenic risk scores (PRS) for neuropsychiatric disorders (ADHD, ASD, schizophrenia, depression and anxiety). RESULTS: ADHD and ASD traits in adulthood, as in childhood, showed associations with childhood cognitive, learning and communication problems and adult communication/language measures, although less so for self-ratings than parent-ratings. Males had higher ADHD and ASD trait levels, but this was not as marked as in childhood. In adulthood, ADHD (both parent- and self-rated) and ASD (parent-rated) symptoms showed associations with ADHD PRS; self-reported ADHD also showed association with depression PRS, whereas self-reported ASD did not show strong PRS associations. CONCLUSIONS: Our findings suggest that in young adults, ADHD and ASD symptoms have similar characteristics as they do in childhood. Associations with other cognitive, learning and communication problems, and ADHD PRS were somewhat less pronounced for self-reported adult ADHD and ASD symptoms, suggesting that even at age 25, parent reports, where available, could be clinically useful.

A Digital Intervention for Adolescent Depression (MoodHwb): Mixed Methods Feasibility Evaluation.

BACKGROUND: Treatment and prevention guidelines highlight the key role of health information and evidence-based psychosocial interventions for adolescent depression. Digital health technologies and psychoeducational interventions have been recommended to help engage young people and to provide accurate health information, enhance self-management skills, and promote social support. However, few digital psychoeducational interventions for adolescent depression have been robustly developed and evaluated in line with research guidance. OBJECTIVE: We aimed to evaluate the feasibility, acceptability, and potential impact of a theory-informed, co-designed digital intervention program, MoodHwb. METHODS: We used a mixed methods (quantitative and qualitative) approach to evaluate the program and the assessment process. Adolescents with or at elevated risk of depression and their parents and carers were recruited from mental health services, school counselors and nurses, and participants from a previous study. They completed a range of questionnaires before and after the program (related to the feasibility and acceptability of the program and evaluation process, and changes in mood, knowledge, attitudes, and behavior), and their Web usage was monitored. A subsample was also interviewed. A focus group was conducted with professionals from health, education, social, and youth services and charities. Interview and focus group transcripts were analyzed using thematic analysis with NVivo 10 (QSR International Pty Ltd). RESULTS: A total of 44 young people and 31 parents or carers were recruited, of which 36 (82%) young people and 21 (68%) parents or carers completed follow-up questionnaires. In all, 19 young people and 12 parents or carers were interviewed. Overall, 13 professionals from a range of disciplines participated in the focus group. The key themes from the interviews and groups related to the design features, sections and content, and integration and context of the program in the young person's life. Overall, the participants found the intervention engaging, clear, user-friendly, and comprehensive, and stated that it could be integrated into existing services. Young people found the "Self help" section and "Mood monitor" particularly helpful. The findings provided initial support for the intervention program theory, for example, depression literacy improved after using the intervention (difference in mean literacy score: 1.7, 95% CI 0.8 to 2.6; P<.001 for young people; 1.3, 95% CI 0.4 to 2.2; P=.006 for parents and carers). CONCLUSIONS: Findings from this early stage evaluation suggest that MoodHwb and the assessment process were feasible and acceptable, and that the intervention has the potential to be helpful for young people, families and carers as an early intervention program in health, education, social, and youth services and charities. A randomized controlled trial is needed to further evaluate the digital program.

Adult mood problems in children with neurodevelopmental problems: evidence from a prospective birth cohort followed to age 50.

PURPOSE: Specific child neurodevelopmental (ND) disorders such as ADHD and learning problems are associated with concurrent and future (up to early adulthood) mood problems. However, it is unclear whether findings generalise to population traits as well as diagnoses, to general as well as specific neurodevelopmental domains, and whether risk associations extend to later adulthood or diminish with age. METHODS: We used data from a UK cohort of children born in 1958, the National Child Development Study (NCDS). ND problems were assessed at ages 7 and 11 years with parent- and teacher ratings of restlessness, hyperactivity and motor co-ordination difficulties, and by individual tests of reading, arithmetic and general cognitive ability. Mood (depression/anxiety) problems were assessed using the Malaise symptom screen at 23, 33, 42, and 50 years. Factor analyses were conducted to assess whether the specific neurodevelopmental domains could be aggregated into a general "ND" latent factor as well as specific factors. Associations with mood outcomes were then tested. RESULTS: A bi-factor model with a general "ND" latent factor and specific "motor" and "cognition" factors fits the data well. The specific cognition and motor factor scores were associated with mood problems in early adulthood only. The "ND" factor demonstrated associations with mood problems at each adult follow-up (men - age 23 years: ß = 0.17; age 33: ß = 0.16; age 42: ß = 0.14; age 50: ß = 0.16; women - 23 years: ß = 0.25; 33 years: ß = 0.26; 42 years: ß = 0.14; 50 years: ß = 0.16; all ps < 0.01). Interactions by sex indicated that the association between this general factor and mood problems was more pronounced for women than men at ages 23 years (ß = 0.09, p = 0.005) and 33 years (ß = 0.10, p = 0.003), but not at 42 or 50 years (ps > 0.8). CONCLUSIONS: Our results suggest that, in a population-based cohort, a general, childhood neurodevelopmental difficulty factor is stably associated with mood problems in adult life.

Using Genetics to Examine a General Liability to Childhood Psychopathology.

Psychiatric disorders show phenotypic as well as genetic overlaps. There are however also marked developmental changes throughout childhood. We investigated the extent to which, for a full range of early childhood psychopathology, a general "p" factor was explained by genetic liability, as indexed by multiple different psychiatric polygenic risk scores (PRS) and whether these relationships altered with age. The sample was a UK, prospective, population-based cohort with psychopathology data at age 7 (N = 8161) and age 13 (N = 7017). PRS were generated from large published genome-wide association studies. At both ages, we found evidence for a childhood "p" factor as well as for specific factors. Schizophrenia and attention-deficit/hyperactivity disorder (ADHD) PRS were associated with this general "p" factor at both ages but depression and autism spectrum disorder (ASD) PRS were not. We also found some evidence of associations between schizophrenia, ADHD and depression PRS with specific factors, but these were less robust and there was evidence for developmental changes.

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.

Brief report: a comparison of child mental health inequalities in three UK population cohorts.

There are substantial health disparities between children from low and higher income families. The study aimed to test changes in child mental health inequalities across three large UK population cohorts of 11-year-old children assessed in 1999, 2004 and 2012 as part of the British Child and Adolescent Mental Health Surveys and Millennium Cohort Study. Child mental health was assessed using parent and teacher versions of the Strengths and Difficulties Questionnaire. There were substantial differences in parent and teacher reported symptom scores between children from low and higher income families in each cohort. Differences in parent-reported symptoms increased over time (ES 0.35 [95% CI 0.20, 0.49] in 1999, ES 0.39 [95% CI 0.17, 0.61] in 2004, ES 0.54 [95% CI 0.49, 0.58] in 2012); cohort interaction: p = 0.01). This study found that marked child mental health inequalities exist. The mental health gap between advantaged and disadvantaged children has not reduced over the last 20 years and may be getting worse.

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.

Developmental Contributions of Schizophrenia Risk Alleles and Childhood Peer Victimization to Early-Onset Mental Health Trajectories.

OBJECTIVE: Twin studies suggest that genetic factors contribute to continuity in mental health problems and that environmental factors are the major contributor to developmental change. The authors investigated the influence of psychiatric risk alleles on early-onset mental health trajectories and whether the trajectories were subsequently modified by exposure to childhood victimization. METHODS: The sample was a prospective U.K. population-based cohort, the Avon Longitudinal Study of Parents and Children. The developmental trajectories of emotional problems were estimated in childhood (approximately ages 4-8 years) and adolescence (approximately ages 12-17 years). Psychiatric risk alleles were indexed by polygenic risk scores (PRS) for schizophrenia using genome-wide association study results from the Psychiatric Genomics Consortium. Chronic peer victimization in late childhood (ages 8.5 and 10.5 years) was assessed as an index of environmental exposure. Individuals with sufficient data on emotional problems, the PRS, and victimization were included in the main analyses (N=3,988). RESULTS: Higher schizophrenia PRSs were associated with a trajectory of early-onset increasing emotional problems (odds ratio=1.18, 95% CI=1.02-1.36) compared with a trajectory of low-stable emotional problems. Subsequent exposure to victimization increased the likelihood of transitioning from a trajectory of low-stable emotional problems during childhood (before exposure) to an increasing trajectory in adolescence (after exposure) (odds ratio=2.59, 95% CI=1.48-4.53). CONCLUSIONS: While the early development of emotional problems was associated with genetic risk (schizophrenia risk alleles), the subsequent course of emotional problems for those who might otherwise have remained on a more favorable trajectory was altered by exposure to peer victimization, which is a potentially modifiable environmental exposure.

Characterizing Developmental Trajectories and the Role of Neuropsychiatric Genetic Risk Variants in Early-Onset Depression.

Importance: Depression often first manifests in adolescence. Thereafter, individual trajectories vary substantially, but it is not known what shapes depression trajectories in youth. Adult studies suggest that genetic risk for schizophrenia, a psychiatric disorder with a neurodevelopmental component, may contribute to an earlier onset of depression. Objective: To test the hypothesis that there are distinct trajectories of depressive symptoms and that genetic liability for neurodevelopmental psychiatric disorders (eg, schizophrenia, attention deficit/hyperactivity disorder [ADHD]), as well as for major depressive disorder (MDD), contribute to early-onset depression. Design, Setting, and Participants: The Avon Longitudinal Study of Parents and Children is an ongoing, prospective, longitudinal, population-based cohort that has been collecting data since September 6, 1990, including data on 7543 adolescents with depressive symptoms at multiple time points. The present study was conducted between November 10, 2017, and August 14, 2018. Main Outcomes and Measures: Trajectories based on self-reported depressive symptoms dichotomized by the clinical cutpoint; MDD, schizophrenia, and ADHD polygenic risk score (PRS) were predictors. Results: In 7543 adolescents with depression data on more than 1 assessment point between a mean (SD) age of 10.64 (0.25) years and 18.65 (0.49) years (3568 [47.3%] male; 3975 [52.7%] female), 3 trajectory classes were identified: persistently low (73.7%), later-adolescence onset (17.3%), and early-adolescence onset (9.0%). The later-adolescence-onset class was associated with MDD genetic risk only (MDD PRS: odds ratio [OR], 1.27; 95% CI, 1.09-1.48; P = .003). The early-adolescence-onset class was also associated with MDD genetic risk (MDD PRS: OR, 1.24; 95% CI, 1.06-1.46; P = .007) but additionally with genetic risk for neurodevelopmental disorders (schizophrenia PRS: OR, 1.22; 95% CI, 1.04-1.43; P = .01; ADHD PRS: OR, 1.32; 95% CI, 1.13-1.54; P < .001) and childhood ADHD (χ21 = 6.837; P = .009) and neurodevelopmental traits (pragmatic language difficulties: OR, 1.31; P = .004; social communication difficulties: OR, 0.68; P < .001). Conclusions and Relevance: The findings of this study appear to demonstrate evidence of distinct depressive trajectories, primarily distinguished by age at onset. The more typical depression trajectory with onset of clinically significant symptoms at age 16 years was associated with MDD genetic risk. The less-common depression trajectory, with a very early onset, was particularly associated with ADHD and schizophrenia genetic risk and, phenotypically, with childhood ADHD and neurodevelopmental traits. Findings are consistent with emerging evidence for a neurodevelopmental component in some cases of depression and suggest that the presence of this component may be more likely when the onset of depression is very early.

A Web-Based Psychoeducational Intervention for Adolescent Depression: Design and Development of MoodHwb.

BACKGROUND: Depression is common in adolescence and leads to distress and impairment in individuals, families and carers. Treatment and prevention guidelines highlight the key role of information and evidence-based psychosocial interventions not only for individuals but also for their families and carers. Engaging young people in prevention and early intervention programs is a challenge, and early treatment and prevention of adolescent depression is a major public health concern. There has been growing interest in psychoeducational interventions to provide accurate information about health issues and to enhance and develop self-management skills. However, for adolescents with, or at high risk of depression, there is a lack of engaging Web-based psychoeducation programs that have been developed with user input and in line with research guidelines and targeted at both the individual and their family or carer. There are also few studies published on the process of development of Web-based psychoeducational interventions. OBJECTIVE: The aim of this study was to describe the process underlying the design and development of MoodHwb (HwbHwyliau in Welsh): a Web-based psychoeducation multimedia program for young people with, or at high risk of, depression and their families, carers, friends, and professionals. METHODS: The initial prototype was informed by (1) a systematic review of psychoeducational interventions for adolescent depression; (2) findings from semistructured interviews and focus groups conducted with adolescents (with depressive symptoms or at high risk), parents or carers, and professionals working with young people; and (3) workshops and discussions with a multimedia company and experts (in clinical, research, and multimedia work). Twelve interviews were completed (four each with young people, parents or carers, and professionals) and six focus groups (three with young people, one with parents and carers, one with professionals, and one with academics). RESULTS: Key themes from the interviews and focus groups were: aims of the program, design and content issues, and integration and context of the program. The prototype was designed to be person-centered, multiplatform, engaging, interactive, and bilingual. It included mood-monitoring and goal-setting components and was available as a Web-based program and an app for mobile technologies. CONCLUSIONS: MoodHwb is a Web-based psychoeducational intervention developed for young people with, or at high risk of, depression and their families and carers. It was developed with user input using qualitative methods as well as user-centered design and educational and psychological theory. Further research is needed to evaluate the effectiveness of the program in a randomized controlled trial. If found to be effective, it could be implemented in health, education, youth and social services, and charities, to not only help young people but also families, carers, friends, and professionals involved in their care.

The impact of schizophrenia and mood disorder risk alleles on emotional problems: investigating change from childhood to middle age.

BACKGROUND: Previous studies find that both schizophrenia and mood disorder risk alleles contribute to adult depression and anxiety. Emotional problems (depression or anxiety) begin in childhood and show strong continuities into adult life; this suggests that symptoms are the manifestation of the same underlying liability across different ages. However, other findings suggest that there are developmental differences in the etiology of emotional problems at different ages. To our knowledge, no study has prospectively examined the impact of psychiatric risk alleles on emotional problems at different ages in the same individuals. METHODS: Data were analyzed using regression-based analyses in a prospective, population-based UK cohort (the National Child Development Study). Schizophrenia and major depressive disorder (MDD) polygenic risk scores (PRS) were derived from published Psychiatric Genomics Consortium genome-wide association studies. Emotional problems were assessed prospectively at six time points from age 7 to 42 years. RESULTS: Schizophrenia PRS were associated with emotional problems from childhood [age 7, OR 1.09 (1.03-1.15), p = 0.003] to mid-life [age 42, OR 1.10 (1.05-1.17), p < 0.001], while MDD PRS were associated with emotional problems only in adulthood [age 42, OR 1.06 (1.00-1.11), p = 0.034; age 7, OR 1.03 (0.98-1.09), p = 0.228]. CONCLUSIONS: Our prospective investigation suggests that early (childhood) emotional problems in the general population share genetic risk with schizophrenia, while later (adult) emotional problems also share genetic risk with MDD. The results suggest that the genetic architecture of depression/anxiety is not static across development.