Summary Unipolar depressive disorder in adolescence is common worldwide but often unrecognised. The incidence, notably in girls, rises sharply after puberty and, by the end of adolescence, the 1 year ...prevalence rate exceeds 4%. The burden is highest in low-income and middle-income countries. Depression is associated with substantial present and future morbidity, and heightens suicide risk. The strongest risk factors for depression in adolescents are a family history of depression and exposure to psychosocial stress. Inherited risks, developmental factors, sex hormones, and psychosocial adversity interact to increase risk through hormonal factors and associated perturbed neural pathways. Although many similarities between depression in adolescence and depression in adulthood exist, in adolescents the use of antidepressants is of concern and opinions about clinical management are divided. Effective treatments are available, but choices are dependent on depression severity and available resources. Prevention strategies targeted at high-risk groups are promising.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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.
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.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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.
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).
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.
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.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: Early-onset major depressive disorder (MDD) is common in individuals at high familial risk of depression and is associated with poor long-term mental health, social, and educational ...outcomes. OBJECTIVES: To examine the developmental pathways that lead to first-episode adolescent-onset MDD (incident cases) in those at high familial risk and to postulate a theoretically informed model that enables simultaneous testing of different pathways to incident adolescent-onset MDD composed of contributions from familial/genetic and social risk factors, as well as effects via specific clinical antecedents. DESIGN, SETTING, AND PARTICIPANTS: This investigation was a 4-year longitudinal study (April 2007 to March 2011) among offspring of depressed parents in the general community. Analyses were conducted between September 1, 2015, and May 27, 2016. Participants were 337 families in whom the index parent (315 mothers and 22 fathers) had experienced at least 2 episodes of MDD (recruited through primary care) and among whom there was a biologically related child in the age range of 9 to 17 years living with the index parent (197 girls and 140 boys with a mean SD age of 12.4 2.0 years) at baseline. Offspring with MDD before the study or at baseline (n = 27), offspring with an episode of MDD that had remitted by follow-up (n = 4), and offspring with missing baseline MDD data (n = 2) were excluded. Ninety-two percent (279 of 304) of families completed the follow-up. MAIN OUTCOMES AND MEASURES: The primary outcome was new-onset offspring MDD, and the secondary outcome was the total DSM-IV MDD symptom score. RESULTS: On average, children and adolescents had a mean (SD) of 1.85 (1.74) (range, 0-8.5) DSM-IV symptoms of MDD at follow-up. Twenty (6 males and 14 females) had new-onset MDD, with a mean (SD) age at onset of 14.4 (2.0) years (range, 10-18 years). Irritability (β = 0.12, P = .03) and fear and/or anxiety (β = 0.38, P < .001) were significant independent clinical antecedents of new adolescent-onset MDD, but disruptive behavior (β = −0.08, P = .14) and low mood (β = −0.03, P = .65) were not. The results were similar for the DSM-IV symptom count at follow-up. All the measured familial/genetic and social risk indicators directly influenced risk for new-onset MDD rather than indirectly through acting on dimensional clinical antecedents. CONCLUSIONS AND RELEVANCE: There are multiple pathways to first-onset adolescent depression in individuals at familial risk. Irritability and fear/anxiety may be additional clinical phenomena to be included as targets in primary preventive interventions focusing on the child. In addition to targeting these phenomena in parents and children, depression prevention methods in high-risk groups may need to take into consideration social risks, such as poverty and psychosocial adversity.
IMPORTANCE: Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder that shows clinical and genetic overlap with other childhood neurodevelopmental disorders. ...Levels of ADHD symptoms typically decline across childhood and adolescence, although they remain elevated for some individuals. The determinants of symptom persistence and decline are not yet fully understood. OBJECTIVES: To test the hypothesis that genetic risk variant load for ADHD (indexed by polygenic risk scores PRS), but not for other psychiatric disorders, is associated with population-based ADHD symptom trajectories across childhood and adolescence, and to examine whether higher genetic liability for ADHD is correlated with total number of additional neurodevelopmental disorders (multimorbidity) in childhood. DESIGN, SETTING, AND PARTICIPANTS: The Avon Longitudinal Study of Parents and Children, an ongoing prospective population-based cohort study, has been collecting data on 14 701 children, including 9757 with data on symptoms of ADHD at multiple time points, since September 6, 1990. The primary exposure variables, PRS, were generated using results of a genome-wide association study from the Psychiatric Genomics Consortium. Childhood multimorbidity scores (ages 7-9 years) were measured by total impairments in 4 domains known to share genetic liability with ADHD: IQ, social communication, pragmatic language, and conduct. Data analysis was conducted from March 1 to September 8, 2016. MAIN OUTCOMES AND MEASURES: Attention-deficit/hyperactivity disorder symptom trajectories from ages 4 to 17 years (7 time points). RESULTS: Among 9757 children with data on symptoms of ADHD at multiple time points (age range, 4-17 years; 4968 boys and 4789 girls), 4 ADHD symptom trajectories were identified: low (82.6%), intermediate (7.7%), childhood-limited (5.8%), and persistent (3.9%). Mean (SE) PRS for ADHD were higher in children in the persistent trajectory (0.254 0.069) compared with each of the other 3 trajectories (low, –0.018 0.014, χ21 = 14.67, P < .001, odds ratio, 1.31; intermediate, 0.054 0.055, χ21 = 4.70, P = .03, odds ratio, 1.22; and childhood-limited, 0.017 0.060, χ21 = 6.50, P = .01, odds ratio, 1.27). Findings were specific to PRS for ADHD; PRS for other psychiatric conditions did not differ across trajectories. The proportion of children with multimorbidity was also highest in those in the persistent trajectory (42.5%; 95% CI, 33.9%-51.1%; P < .001) and was associated with persistence of ADHD symptoms independent of PRS. CONCLUSIONS AND RELEVANCE: Persistence of ADHD symptoms across childhood and adolescence in the general population is associated with higher PRS for ADHD. Childhood multimorbidity was also associated with persistence of ADHD symptoms and may help to identify children with ADHD whose symptoms are most likely to continue into adolescence.
Young people whose parents have depression have a greatly increased risk of developing a psychiatric disorder, but poor outcomes are not inevitable. Identification of the contributors to mental ...health resilience in young people at high familial risk is an internationally recognised priority. Our objectives were to identify protective factors that predict sustained good mental health in adolescents with a parent with depression and to test whether these contribute beyond what is explained by parent illness severity.
The Early Prediction of Adolescent Depression study (EPAD) is a prospective longitudinal study of offspring of parents with recurrent depression. Parents with recurrent major depressive disorder, co-parents, and offspring (aged 9–17 years at baseline) were assessed three times over 4 years in a community setting. Offspring outcomes were operationalised as absence of mental health disorder, subthreshold symptoms, or suicidality on all three study occasions (sustained good mental health); and better than expected mental health (mood and behavioural symptoms at follow-up lower than predicted given severity of parental depression). Family, social, cognitive, and health behaviour predictor variables were assessed using interview and questionnaire measures.
Between February and June, 2007, we screened 337 families at baseline, of which 331 were eligible. Of these, 262 completed the three assessments and were included in the data for sustained mental health. Adolescent mental health problems were common, but 53 (20%) of the 262 adolescents showed sustained good mental health. Index parent positive expressed emotion (odds ratio 1·91 95% CI 1·31–2·79; p=0·001), co-parent support (1·90 1·38–2·62; p<0·0001), good-quality social relationships (2·07 1·35–3·18; p=0·001), self-efficacy (1·49 1·05–2·11; p=0·03), and frequent exercise (2·96 1·26–6·92; p=0·01) were associated with sustained good mental health. Analyses accounting for parent depression severity were consistent, but frequent exercise only predicted better than expected mood-related mental health (β=–0·22; p=0·0004) not behavioural mental health, whereas index parents' expression of positive emotions predicted better than expected behavioural mental health (β=–0·16; p=0·01) not mood-related mental health. Multiple protective factors were required for offspring to be free of mental health problems (zero or one protective factor, 4% sustained good mental health; two protective factors, 10%; three protective factors, 13%, four protective factors, 38%; five protective factors, 48%).
Adolescent mental health problems are common, but not inevitable, even when parental depression is severe and recurrent. These findings suggest that prevention programmes will need to enhance multiple protective factors across different domains of functioning.
Sir Jules Thorn Charitable Trust, Economic and Social Research Council.
Schizophrenia typically onsets after puberty but is often preceded by observable childhood neurodevelopmental impairments. Whether these childhood antecedents index genetic liability is unknown. We ...used polygenic risk scores derived from a patient discovery sample as indicators of the genetic liability of schizophrenia. Our aim was to identify the early childhood manifestations of this liability in a UK population-based cohort.
The study sample was the Avon Longitudinal Study of Parents and Children, a prospective population-based cohort study of 14701 children. Data were primarily analysed with regression-based analyses. Polygenic risk score were generated from a published Psychiatric Genomics Consortium genome-wide association study. Outcomes were childhood (age 4-9 years) dimensional measures in four developmental domains with 12 indicators: cognition and learning, social and communication, emotion and mood regulation, and behaviour (n=5100-6952).
At age 7-9 years, schizophrenia polygenic risk scores showed associations with lower performance intelligence quotient (β -0·056, OR 1·13 95% CI 1·04-1·23), poorer social understanding (β -0·032, OR 1·08 1·00-1·17), worse language intelligibility and fluency (β -0·032, OR 1·10 1·02-1·20), more irritability (β 0·032, OR 1·07 1·01-1·14), and more headstrong behaviour (β 0·031, OR 1·08 1·02-1·15). The schizophrenia polygenic risk scores also predicted social and behavioural impairments as early as age 4 years.
Childhood cognitive, social, behavioural, and emotional impairments, implicated as antecedents to schizophrenia in high-risk, developmental studies, might represent early manifestations of genetic liability.
Medical Research Council.
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