Youth meeting episodic symptom and impairment criteria for bipolar disorder: an epidemiological inquiry

BACKGROUND: Little is known about short-duration episodes of mania-like symptoms in youth. Here we determine the prevalence, morbid associations, and contribution to social impairment of a phenotype characterised by episodes during which symptom and impairment criteria for mania are met, but DSM-IV duration criteria are not (Bipolar not otherwise specified; BP-NOS). METHODS: A cross-sectional national survey of a sample (N=5326) of 8-19 year olds from the general population using information from parents and youth. Outcome measures were prevalence rates and morbid associations assessed by the Developmental and Well-Being Assessment, and social impairment assessed by the impact scale of the Strengths and Difficulties Questionnaire. RESULTS: While only seven individuals (0.1%) met definite or probable DSM-IV criteria for BPI or BPII, the prevalence of BP-NOS was 10-fold higher, 1.1% by parent report and 1.5% by youth report. Parent-youth agreement was very low: κ=0.02, p>0.05 for BP-NOS. Prevalence and episode duration for BP-NOS did not vary by age. BP-NOS showed strong associations with externalising disorders. After adjusting for a dimensional measure of general psychopathology, self-reported (but not parent-reported) BP-NOS remained associated with overall social impairment. CONCLUSIONS: BP meeting full DSM-IV criteria is rare in youth. BP-NOS, defined by episodes shorter than those required by DSM-IV, but during which DSM-IV symptom and impairment criteria are met, is commoner and may be associated with social impairment that is beyond what can be accounted for by other psychopathology. These findings support the importance of research into these short episodes during which manic symptoms are met in youth but they also call into question the extent to which BP-NOS in youth is a variant of DSM-IV BP - superficially similar symptoms may not necessarily imply deeper similarities in aetiology or treatment response

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

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

Do childhood externalizing disorders predict adult depression? A meta-analysis

Childhood externalizing disorders have been linked to adult affective disorders, although some studies fail to substantiate this finding. Multiple longitudinal cohort studies identifying childhood psychopathology and their association with adult psychiatric illness have been published. To examine the association between childhood externalizing symptoms or disorders and the development of adult depression across cohorts, a meta-analysis was performed. Potential studies were identified using a PubMed search through November 2013. All published, prospective, longitudinal, community-sampled cohort studies of children (≤ 13 years) with externalizing symptoms or disorders (aggression, conduct problems, oppositional defiant disorder, conduct disorder), reassessed in adulthood (≥ 18 years) for depressive disorders (major depressive disorder, depressive disorder NOS, or dysthymic disorder) were included. A random effects model was used to summarize the pooled effect sizes. Ancillary analyses considered covariates that could account for variance among studies. Ten studies representing eight cohorts of children initially assessed at age 13 or younger (N = 17,712) were included in the meta-analysis. Childhood externalizing behavior was associated with adult depressive disorders (OR = 1.52, 95% confidence interval = 1.27-1.80, p < 0.0001). Utilizing Orwin's Fail-safe N approach, 263 studies with a mean odds ratio of 1.0 would have to be added to the analysis before the cumulative effect would become trivial. Externalizing psychopathology in childhood is associated with the development of unipolar depressive disorders in adulthood

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

Detecting the subtle shape differences in hemodynamic responses at the group level

The nature of the hemodynamic response (HDR) is still not fully understood due to the multifaceted processes involved. Aside from the overall amplitude, the response may vary across cognitive states, tasks, brain regions, and subjects with respect to characteristics such as rise and fall speed, peak duration, undershoot shape, and overall duration. Here we demonstrate that the fixed-shape or adjusted-shape methods may fail to detect some shape subtleties. In contrast, the estimated-shape method (ESM) through multiple basis functions can provide the opportunity to identify some subtle shape differences and achieve higher statistical power at both individual and group levels. Previously, some dimension reduction approaches focused on the peak magnitude, or made inferences based on the area under the curve or interaction, which can lead to potential misidentifications. By adopting a generic framework of multivariate modeling (MVM), we showcase a hybrid approach that is validated by simulations and real data. Unlike the few analyses that were limited to main effect, two- or three-way interactions, we extend the approach to an inclusive platform that is more adaptable than the conventional GLM, achieving a practical equipoise among representation, false positive control, statistical power, and modeling flexibility

Longitudinal Stability of Genetic and Environmental Influences on Irritability: From Childhood to Young Adulthood.

OBJECTIVE: Little is known about genetic influences on juvenile irritability and whether such influences are developmentally stable and/or dynamic. This study examined the temporal pattern of genetic and environmental effects on irritability using data from a prospective, four-wave longitudinal twin study. METHOD: Parents and their twin children (N=2,620 children) from the Swedish Twin Study of Child and Adolescent Development reported on the children's irritability, defined using a previously identified scale from the Child Behavior Checklist. RESULTS: Genetic effects differed across the sexes, with males exhibiting increasing heritability from early childhood through young adulthood and females exhibiting decreasing heritability. Genetic innovation was also more prominent in males than in females, with new genetic risk factors affecting irritability in early and late adolescence for males. Shared environment was not a primary influence on irritability for males or females. Unique, nonshared environmental factors suggested strong effects early for males followed by an attenuating influence, whereas unique environmental factors were relatively stable for females. CONCLUSIONS: Genetic effects on irritability are developmentally dynamic from middle childhood through young adulthood, with males and females displaying differing patterns. As males age, genetic influences on irritability increase while nonshared environmental influences weaken. Genetic contributions are quite strong in females early in life but decline in importance with age. In girls, nonshared environmental influences are fairly stable throughout development.The National Institutes of Health/National Institute of Mental HealthPublishe

Deficits in attention to emotional stimuli distinguish youth with severe mood dysregulation from youth with bipolar disorder.

Studying attention in the context of emotional stimuli may aid in differentiating pediatric bipolar disorder (BD) from severe mood dysregulation (SMD). SMD is characterized by chronic irritability, arousal, and hyper-reactivity; SMD youth frequently receive a BD diagnosis although they do not meet DSM-IV criteria for BD because they lack manic episodes. We compared 57 BD (14.4 +/- 2.9 years old, 56% male), 41 SMD (12.6 +/- 2.6 years old, 66% male), and 33 control subjects (13.7 +/- 2.5 years old, 52% male) using the Emotional Interrupt task, which examines how attention is impacted by positive, negative, or neutral distracters. We compared reaction time (RT) and accuracy and calculated attention interference scores by subtracting performance on neutral trials from emotional trials. Between-group analyses indicated that SMD subjects had significantly reduced attention interference from emotional distracters relative to BD and control subjects. Thus, attention in SMD youth was not modulated by emotional stimuli. This blunted response in SMD youth may contribute to their affective and behavioral dysregulation

fMRI predictors of treatment outcome in pediatric anxiety disorders

A growing number of studies have found evidence that anxiety and depressive disorders are associated with atypical amygdala hyperactivation, which decreases with effective treatment. Interest has emerged in this phenomenon as a possible biological marker for individuals who are likely to benefit from tailored treatment approaches. The present study was designed to examine relationships between pre-treatment amygdala activity and treatment response in a sample of anxious children and adolescents. Participants, who were diagnosed predominantly with Generalized Anxiety Disorder (GAD), underwent functional magnetic resonance imaging (fMRI) scanning prior to treatment with fluoxetine or cognitive behavioral therapy (CBT). Results indicated significant negative associations between degree of left amygdala activation and measures of post-treatment symptom improvement in the group as a whole. Taken together with research on associations between adult amygdala activation and treatment response, these findings suggest that patients whose pre-treatment amygdala activity is the strongest may be particularly likely to respond well to such widely used treatments as selective serotonin reuptake inhibitor (SSRI) medications and CBT