Adolescent Irritability: Phenotypic Associations and Genetic Links With Depressed Mood

OBJECTIVE: Irritability has been proposed to underlie the developmental link between oppositional problems and depression. However, little is known about the genetic and environmental influences on irritability and its overlap with depression. This paper tests the hypothesis that the association between irritability and depression is accounted for by genetic factors. As such, it draws on the notion of “generalist genes” i.e., genes of general effect that underlie phenotypic overlap between disorders. METHOD: The G1219 study, a UK-based twin sample (N=2651), was used in a cross-sectional and longitudinal design. Irritable and headstrong/hurtful dimensions of oppositional behavior were derived using factor analysis. Regression was used to estimate the association between depression and delinquency. Multivariate genetic analyses were used to estimate the genetic overlap between irritability versus headstrong/hurtful behaviors with depression and delinquency respectively. RESULTS: Irritability showed a significantly stronger phenotypic relationship with depression than delinquency, whereas headstrong/hurtful behaviors were more strongly related to delinquency than depression. In multivariate genetic analyses, the genetic correlation between irritability and depression (0.70; CI: 0.59-0.82) was significantly higher than that between irritability and delinquency (0.57; CI: 0.45-0.69); conversely, the genetic correlation between headstrong/hurtful behaviors and delinquency (0.80; CI: 0.72-0.86) was significantly higher than that between headstrong/hurtful behaviors and depression (0.46; CI: 0.36-0.57). In longitudinal models, the phenotypic association between irritability at Time 1 and depression at Time 2 was accounted for by the genetic association between irritability and depression at Time1. CONCLUSIONS: The findings are consistent with the theory that genes with general effects underlie the relationship between irritability and depression

Pathways from maternal depressive symptoms to adolescent depressive symptoms:the unique contribution of irritability symptoms

BACKGROUND: The authors tested three possible pathways linking prenatal maternal depressive symptoms to adolescent depressive symptoms. These pathways went through childhood Irritability Symptoms, Anxiety/Depressive Symptoms or Conduct Problems. METHOD: Data were collected from 3,963 mother–child pairs participating in the Avon Longitudinal Study of Parents and Children. Measures include maternal depressive symptoms (pre‐ and postnatal); toddler temperament (2 years); childhood (7–13 years) irritability symptoms, anxiety/depressive symptoms, conduct problems, and adolescent depressive symptoms (16 years). RESULTS: Irritability Symptoms: This pathway linked sequentially – prenatal maternal depressive symptoms, toddler temperament (high perceived intensity and low perceived adaptability), childhood irritability symptoms, and adolescent depressive symptoms. Anxiety/Depressive symptoms: This pathway linked sequentially – prenatal maternal depressive symptoms, toddler temperament (negative perceived mood), childhood anxiety/depressive symptoms, and adolescent depressive symptoms. Childhood conduct problems were not associated with adolescent depressive symptoms, above and beyond irritability symptoms and anxiety/depressive symptoms. CONCLUSIONS: Results suggest evidence for two distinct developmental pathways to adolescent depressive symptoms that involve specific early and midchildhood features

The use of the development and well-being assessment (DAWBA) in clinical practice: a randomized trial

The development and well-being assessment (DAWBA) has been used in various epidemiological studies, whereas the clinical value of the instrument needs support from further studies. In particular, it is important to document how the use of the DAWBA influences clinical decision-making. The present study employed the DAWBA in a consecutive series of 270 new referrals to a large public child and adolescent psychiatric service in Zurich, Switzerland. ICD-10 based diagnoses were obtained from clinicians for all patients and reliability of DAWBA expert raters was calculated. The DAWBA diagnoses were randomly disclosed (n=144) or not disclosed (n=126) before clinical decision-making. The reliability of DAWBA expert diagnoses was very satisfactory and the agreement under the disclosed versus the non-disclosed condition amounted to 77 versus 68% for internalizing disorders and to 63 versus 71% for externalizing disorders. The increment in agreement due to disclosure of the DAWBA diagnosis was significant for internalizing disorders. Access to DAWBA information was more likely to prompt clinicians to add an extra diagnosis. Professional background and degree of clinical experience did not affect diagnostic agreement. Overall, diagnostic agreements between DAWBA expert diagnoses and clinical diagnoses were in the fair to moderate range and comparable to previous studies with other structured diagnostic interviews. The inclusion of the DAWBA into the clinical assessment process had an impact on diagnostic decision-making regarding internalizing disorders but not regarding externalizing disorder

Bipolar disorder and disruptive mood dysregulation in children and adolescents:assessment, diagnosis and treatment

Bipolar disorder (BD) is a heritable psychiatric condition, that is, associated with lifelong distress and impairment. There has been a long-standing interest in the early-life origins of BD, not least because as many as 50% of adults with BD report onset of their symptoms during childhood and adolescence.1 In this article, we present evidence on the assessment and treatment of BD and related conditions in young people. We also discuss the recent controversy about BD in children and adolescents that has led to the introduction of the diagnosis of disruptive mood dysregulation disorder (DMDD) by the Diagnostic and Statistical Manual for Mental Disorders (DSM)-5

Social anxiety symptoms and their relationship with suicidal ideation and depressive symptoms in adolescents: A prospective study

Background: Social anxiety disorder typically emerges in adolescence and its symptoms often co‐occur with depression and suicidal ideation. It is important to understand whether social anxiety symptoms precede depression and suicidal ideation in youth. This study aimed to investigate the temporal associations between baseline social anxiety and later suicidal ideation and depressive symptoms in a community youth sample. Methods: The Wellcome Trust NSPN (Neuroscience in Psychiatry Network) study recruited 2397 youth aged 14–24 in the United Kingdom to participate in a prospective observational study. Participants were assessed for symptoms of social anxiety, generalised anxiety, depression and suicidal ideation at baseline, 1‐year follow‐up, and 2‐year follow‐up. We conducted multiple linear regression analyses and mediation analyses to examine whether baseline social anxiety was associated with 2‐year suicidal ideation and depressive symptoms (excluding suicide‐related items), and whether these associations were mediated by 1‐year depressive symptoms. The study was preregistered on the Open Science Framework. Results: Results from multiple linear regression analyses indicated that baseline social anxiety symptoms were associated with 2‐year suicidal ideation (β = 0.07, p < 0.05, 95% CI [0.02, 0.12]) and 2‐year depressive symptoms (β = 0.08, p < 0.05, 95% CI [0.02, 0.13]), after controlling for baseline predicted variable. Furthermore, 1‐year depressive symptoms significantly mediated the relationship between baseline social anxiety symptoms and 2‐year suicidal ideation (β = 0.04, 95% CI [0.02, 0.05]), and the relationship between baseline social anxiety symptoms and 2‐year depressive symptoms (β = 0.06, 95% CI [0.03, 0.08]) after adjusting for age, sex, and other covariates. Conclusions: We found evidence that baseline social anxiety symptoms were associated with 2‐year suicidal ideation and 2‐year depressive symptoms via 1‐year depressive symptoms in non‐clinical adolescents. These results may have important implications for targeted psychological interventions

Developmental pathways from childhood conduct problems to early adult depression:findings from the ALSPAC cohort

BackgroundPathways from early-life conduct problems to young adult depression remain poorly understood.AimsTo test developmental pathways from early-life conduct problems to depression at age 18.MethodData (n = 3542) came from the Avon Longitudinal Study of Parents and Children (ALSPAC). Previously derived conduct problem trajectories (ages 4-13 years) were used to examine associations with depression from ages 10 to 18 years, and the role of early childhood factors as potential confounders.ResultsOver 43% of young adults with depression in the ALSPAC cohort had a history of child or adolescent conduct problems, yielding a population attributable fraction of 0.15 (95% CI 0.08-0.22). The association between conduct problems and depression at age 18 was considerable even after adjusting for prior depression (odds ratio 1.55, 95% CI 1.24-1.94). Early-onset persistent conduct problems carried the highest risk for later depression. Irritability characterised depression for those with a history of conduct problems.ConclusionsEarly-life conduct problems are robustly associated with later depressive disorder and may be useful targets for early intervention

Depression in childhood and adolescence

Objective: To review recent evidence on child and adolescent depression.Method: Narrative review.Results: Rates of unipolar depression are low before puberty, but rise from the early teens, especially among girls. Concurrent comorbidity with both disruptive and emotional disorders is common, especially among younger children; across age, youth depression may be preceded by both anxiety and disruptive behaviour disorders, and increase risk for alcohol problems. Adolescent depression is associated with a range of adverse later outcomes including suicidality, problems in social functioning and poor physical and mental health. Across development, a family history of depression and exposure to stressful life events are the most robust risk factors for depression. Familial transmission involves both psychosocial and heritable processes; genetic and environmental influences also combine to influence risk. Neurocognitive and neuroendocrine pathways have been established, but contributors to the adolescent rise in risk, and the female preponderance later in development, remain to be clarified. Depressed youth benefit from psychological therapy or antidepressant medication or their combination; however, treatment effects are moderate.Conclusions: Despite considerable progress in understanding developmental trajectories to depression, more needs to be done to identify disease mechanisms that may serve as intervention targets early in the life course

Emotion Dysregulation in Attention Deficit Hyperactivity Disorder

Although it has long been recognized that many individuals with attention deficit hyperactivity disorder (ADHD) also have difficulties with emotion regulation, no consensus has been reached on how to conceptualize this clinically challenging domain. The authors examine the current literature using both quantitative and qualitative methods. Three key findings emerge. First, emotion dysregulation is prevalent in ADHD throughout the lifespan and is a major contributor to impairment. Second, emotion dysregulation in ADHD may arise from deficits in orienting toward, recognizing, and/or allocating attention to emotional stimuli; these deficits implicate dysfunction within a striato-amygdalo-medial prefrontal cortical network. Third, while current treatments for ADHD often also ameliorate emotion dysregulation, a focus on this combination of symptoms reframes clinical questions and could stimulate novel therapeutic approaches. The authors then consider three models to explain the overlap between emotion dysregulation and ADHD: emotion dysregulation and ADHD are correlated but distinct dimensions; emotion dysregulation is a core diagnostic feature of ADHD; and the combination constitutes a nosological entity distinct from both ADHD and emotion dysregulation alone. The differing predictions from each model can guide research on the much-neglected population of patients with ADHD and emotion dysregulation

Using arterial spin labeling to examine mood states in youth

Introduction:Little is known about the neural correlates of mood states and the specific physiological changes associated with their valence and duration, especially in young people. Arterial spin labeling (ASL) imaging is particularly well-suited to study sustained cerebral states in young people, due to its robustness to low-frequency drift, excellent interscan reliability, and noninvasiveness. Yet, it has so far been underutilized for understanding the neural mechanisms underlying mood states in youth.Methods:In this exploratory study, 21 healthy adolescents aged 16 to 18 took part in a mood induction experiment. Neutral, sad, and happy mood states were induced using film clips and explicit instructions. An ASL scan was obtained following presentation of each film clip.Results:Mood induction led to robust changes in self-reported mood ratings. Compared to neutral, sad mood was associated with increased regional cerebral blood flow (rCBF) in the left middle frontal gyrus and anterior prefrontal cortex, and decreased rCBF in the right middle frontal gyrus and the inferior parietal lobule. A decrease in self-reported mood from neutral to sad condition was associated with increased rCBF in the precuneus. Happy mood was associated with increased rCBF in medial frontal and cingulate gyri, the subgenual anterior cingulate cortex, and ventral striatum, and decreased rCBF in the inferior parietal lobule. The level of current self-reported depressive symptoms was negatively associated with rCBF change in the cerebellum and lingual gyrus following both sad and happy mood inductions.Conclusions:Arterial spin labeling is sensitive to experimentally induced mood changes in healthy young people. The effects of happy mood on rCBF patterns were generally stronger than the effects of sad mood