Early-onset Mood Disorders Research Articles

Factors Associated with High Parent- and Youth-Rated Irritability Score in Early-Onset Mood Disorders: A Cross-Sectional Study with the Affective Reactivity Index (ARI).

Correct classification of irritability is extremely important to assess prognosis and treatment indications of juvenile mood disorders. We assessed factors associated with low versus high parent- and self-rated irritability using the affective reactivity index (ARI) in a sample of 289 adolescents diagnosed with a bipolar or a major depressive disorder. Bivariate analyses were followed by multilinear logistic regression model. Factors significantly and independently associated with high versus low parent-rated ARI score were: more severe emotional dysregulation and bipolar disorders diagnosis. Factors significantly and independently associated with high versus low self-rated ARI score were: lower children depression rating scale (CDRS-R) difficulty of having fun item score, greater children depression inventory (CDI-2) self-report score, more severe emotional dysregulation, and greater CDRS-R appetite disturbance item score. High parent-rated irritability was strictly related with a bipolar disorder diagnosis, whereas high youth-rated irritability was related to depressive phenotype characterized by appetite/food-intake dysregulation, mood lability, and less anhedonia and apathy.

Identifying predictive factors for mood recurrence in early-onset major mood disorders: A 4-year, multicenter, prospective cohort study

We investigate the predictive factors of the mood recurrence in patients with early-onset major mood disorders from a prospective observational cohort study from July 2015 to December 2019. A total of 495 patients were classified into three groups according to recurrence during the cohort observation period: recurrence group with (hypo)manic or mixed features (MMR), recurrence group with only depressive features (ODR), and no recurrence group (NR). As a result, the baseline diagnosis of bipolar disorder type 1 (BDI) and bipolar disorder type 2 (BDII), along with a familial history of BD, are strong predictors of the MMR. The discrepancies in wake-up times between weekdays and weekends, along with disrupted circadian rhythms, are identified as a notable predictor of ODR. Our findings confirm that we need to be aware of different predictors for each form of mood recurrences in patients with early-onset mood disorders. In clinical practice, we expect that information obtained from the initial assessment of patients with mood disorders, such as mood disorder type, family history of BD, regularity of wake-up time, and disruption of circadian rhythms, can help predict the risk of recurrence for each patient, allowing for early detection and timely intervention.

Characteristics of children with autism and unspecified intellectual developmental disorder (intellectual disability) presenting with severe self-injurious behaviours

Objective: This study aims to delineate the characteristics of severe self-injurious behaviors (SIB) in a cohort of children with autism and unspecified intellectual developmental disorder (UIDD) (intellectual disability) and examine potential risk factors for developing SIB. Methods: A retrospective chart review studied characteristics of severe SIB in 30 children with autism spectrum disorder (ASD) and UIDD referred to a tertiary care center. Characteristics examined include genetic syndromes, brain MRI abnormalities, verbal ability, adaptive functioning, SIB frequency and severity, age of onset, number of psychopharmacological agents, irritability, hyperactivity, stereotypy, psychiatric and physical comorbidities, among others. Descriptive and bivariate analysis were applied to explore potential relationships between factors. Results: Children with severe SIB exhibit this behaviour with high frequency, inflicting moderate to severe injury. Most children in the study sample are non-verbal and have ASD (93.3%; n = 28) with psychiatric (96.7%; n = 29) and physical (90%; n = 27) comorbidities. Overall SIB improvement using the Clinical Global Impression, Improvement Score (CGI-I) was 3.0 (minimally improved). A minority were much or very much improved following appropriate intervention. Conclusions: The severity of SIB is much higher in this sample than previously noted in the literature. Severe SIB is associated with ADHD, early onset mood disorders, tics, avoidant restrictive food intake disorder and Obsessive-Compulsive Disorder.

The relationship between morningness-eveningness and mood symptoms and quality of life in euthymic state of mood disorders: Results from a prospective observational cohort study

BackgroundThe clinical importance of morningness-eveningness, especially in mood disorders, is prevailing. The differential relation of chronotype with diagnoses of early-onset mood disorders, mood symptoms, anxiety, and quality of life was evaluated. MethodsEarly-onset mood disorder patients [n = 419; 146 major depressive disorder (MDD); 123 bipolar I disorder (BDI); 150 bipolar II disorder (BDII)] from the Mood Disorder Cohort Research Consortium were assessed for chronotype using the composite scale for morningness (CSM) and its association with clinical variables obtained during the clinician-verified euthymic state. ResultsThe mean total CSM of BDI was significantly higher than MDD and BDII (p < 0.001). In all types of mood disorders, higher total CSM was associated with lower Quick inventory of depressive symptomatology (p < 0.005) and higher WHO quality of life (p < 0.005). Such negative correlations between the total CSM and Montgomery-Asberg depression rating were significant in MDD and BDI (p < 0.05) and marginally significant in BDII (p = 0.077). CSM was a significant contributor to quality of life in BDI (p < 0.001) and BDII (p = 0.011), but it was not for MDD. LimitationsThe defined ‘euthymic state’ that may not fully reflect the remission of episode; limited generalizability due to clinical characteristic of early-onset mood disorder; the disparity between diurnal preference measured by the CSM and chronotype; possible effects of the last mood episode polarity and medication; and, lack of control group. ConclusionLess eveningness was associated with less severe depressive symptoms and better quality of life. This suggests that morningness may reduce residual depressive symptoms and recover function of patients.

Bipolar II disorder has the highest prevalence of seasonal affective disorder in early-onset mood disorders: Results from a prospective observational cohort study.

Many mood disorder patients experience seasonal changes in varying degrees. Studies on seasonality have shown that bipolar disorder has a higher prevalence rate in such patients; however, there is limited research on seasonality in early-onset mood disorder patients. This study estimated the prevalence of seasonality in early-onset mood disorder patients, and examined the association between seasonality and mood disorders. Early-onset mood disorder patients (n = 378; 138 major depressive disorder; 101 bipolar I disorder; 139 bipolar II disorder) of the Mood Disorder Cohort Research Consortium and healthy control subjects (n = 235) were assessed for seasonality with Seasonality Pattern Assessment Questionnaire (SPAQ). A higher global seasonality score, an overall seasonal impairment score, and the prevalence of seasonal affective disorder (SAD) and subsyndromal SAD showed that mood disorder subjects had higher seasonality than the healthy subjects. The former subject group had a significantly higher mean overall seasonal impairment score than the healthy subjects (p < .001); in particular, bipolar II disorder subjects had the highest prevalence of SAD, and the diagnosis of bipolar II disorder had significantly higher odds ratios for SAD when compared to major depression and bipolar I disorder (p < .05). Early-onset mood disorders, especially bipolar II disorder, were associated with high seasonality. A thorough assessment of seasonality in early-onset mood disorders may be warranted for more personalized treatment and proactive prevention of mood episodes.

Mood disorders with onset in early adulthood and socio-economic outcomes over the long run

Abstract Background Mood disorders have been associated with poor socioeconomic outcomes, but there is a lack of large-scale population-based studies on the topic. We examined associations between bipolar disorder and depression with an onset between ages 15 and 25, and subsequent socio-economic outcomes (employment, income and educational attainment) using Danish registry data. Methods All individuals (n = 2 390 127; 49% women) born in Denmark between 1955 and 1990, who were alive at their 25th birthday were included. Employment status, wage or self-employment earnings, and educational attainment were assessed annually from the age of 25 to 58 (years 1980 to 2015). Mood disorder diagnosis was obtained from the Danish Psychiatric Central Register. The associations were examined using logistic regression analyses. Results At the age of 30, 46% of individuals with bipolar disorder and 35% of individuals with depression were not employed, and 52% of individuals diagnosed with bipolar disorder and 42% of individuals with depression did not have any secondary or post-secondary education. Bipolar disorder and depression were associated with increased and increasing risk (at age 30: bipolar disorder, OR 7.21, 95% CI 6.54 to 7.96; depression, OR 4.07, 95% CI 3.93 to 4.22) of not being employed over the follow-up. Similarly, both bipolar disorder and depression were associated with increased risk of not completing secondary or post-secondary education (at the age of 30, bipolar disorder: OR 3.21, 95% CI 2.92 to 3.54; depression: OR 2.81, 95% CI 2.71 to 2.91), but this difference become smaller over the follow-up. An individual with bipolar disorder or depression earned around 36% and 51%, respectively, of the earnings earned by an individual without mood disorders. Conclusions Mood disorders diagnosed in early adulthood are associated with lasting poor socioeconomic outcomes over the long run. Key messages Early onset mood disorders are associated with consistently, and in some cases increasingly, poorer socioeconomic outcomes over time. An individual with early onset bipolar disorder or depression earned around third and half, respectively, of the earnings earned by an individual without early onset mood disorders.

Design and Methods of the Mood Disorder Cohort Research Consortium (MDCRC) Study.

The Mood Disorder Cohort Research Consortium (MDCRC) study is designed as a naturalistic observational prospective cohort study for early-onset mood disorders (major depressive disorders, bipolar disorders type 1 and 2) in South Korea. The study subjects consist of two populations: 1) patients with mood disorders under 25 years old and 2) patients with mood disorders within 2 years of treatment under 35 years old. After successful screening, the subjects are evaluated using baseline assessments and serial follow-up assessments at 3-month intervals. Between the follow-up assessments, subjects are dictated to check their own daily mood status before bedtime using the eMood chart application or a paper mood diary. At the regular visits every 3 months, inter-visit assessments are evaluated based on daily mood charts and interviews with patients. In addition to the daily mood chart, sleep quality, inter-visit major and minor mood episodes, stressful life events, and medical usage pattern with medical expenses are also assessed. Genomic DNA from blood is obtained for genomic analyses. From the MDCRC study, the clinical course, prognosis, and related factors of early-onset mood disorders can be clarified. The MDCRC is also able to facilitate translational research for mood disorders and provide a resource for the convergence study of mood disorders.

Early onset mood disorders and first alcohol use in the general population

BackgroundMood disorders and alcohol use are common in the general population and often occur together. This study explored how early onset mood disorders relate to age of first alcohol use in the Australian general population. MethodsDiscrete time survival analysis modelled the odds of first alcohol use among those with, versus without, an early onset DSM-IV mood disorders (major depression, dysthymia or bipolar disorder). Data came from the 2007 Australian National Survey of Mental Health and Wellbeing (N=8841). ResultsEarly onset mood disorders as an overall class were not significantly related to the odds of first alcohol use in any given year. On examining the different types of mood disorders individually early onset bipolar disorder was a significant predictor of first alcohol use. The analysis then looked at interactions with time and found that after the age of 14 years the presence of an early onset mood disorder significantly increased the odds of first alcohol use by 32%. LimitationsRetrospective recall was used to determine age of onset data which is subject to known biases and replication is recommended in some subgroup analysis due to smaller sample sizes. ConclusionsMood disorders, particularly bipolar disorder, act as unique risk factors for first alcohol use in the general population and show significant interactions with developmental timing. The findings point to the potential utility of prevention programs that target alcohol use and mood disorders together from early adolescence.

Recognizing Depression, Anxiety, and Externalizing Behaviors in Children of a Parent with Mood Disorders: Weekly Symptom Monitoring in the Child Network

High levels of depression, anxiety and externalizing disorders are common in the general population of children in the USA. These disorders are further dramatically increased in the offspring of a parent with bipolar disorder followed up prospectively for 7 years or in the offspring of a parent with unipolar depression followed up for 20 years, yet few receive early or adequate treatment. This is particularly problematic as early onset mood disorders have a more difficult course and outcome than adult onset illness, and are associated with long delays to first treatment, which is an additional independent risk factor for a poor outcome.

The serotonergic system in mood disorders and suicidal behaviour

A stress-diathesis explanatory model of suicidal behaviour has proved to be of heuristic value, and both clinical and neurobiological components can be integrated into such a model. A trait deficiency in serotonin input to the anterior cingulate and ventromedial prefrontal cortex is found in association with suicide, and more recently non-fatal suicidal behaviour, and is linked to decision-making and suicide intent by imaging and related studies in vivo. The same neural circuitry and serotonin deficiency may contribute to impulsive aggressive traits that are part of the diathesis for suicidal behaviour and are associated with early onset mood disorders and greater risk for suicidal behaviour. Other brain areas manifest deficient serotonin input, that is, a trait related to recurrent major depressive disorder and bipolar disorder. Thus the serotonin system is involved in both the diathesis for suicidal behaviour in terms of decision-making, and to a major stressor, namely episodes of major depression.

Brain volumes in psychotic youth with schizophrenia and mood disorders

We sought to test the hypothesis that deficits in grey matter volume are characteristic of psychotic youth with early-onset schizophrenia-spectrum disorders (EOSS) but not of psychotic youth with early-onset mood disorders (EOMD). We used magnetic resonance imaging to examine brain volume in 24 psychotic youth (13 male, 11 female) with EOSS (n = 12) or EOMD (n = 12) and 17 healthy controls (10 male, 7 female). We measured the volume of grey and white matter using an automated segmentation program. After adjustment for age and intracranial volume, whole brain volume was lower in the EOSS patients than in the healthy controls (p = 0.001) and EOMD patients (p = 0.002). The EOSS patients had a deficit in grey matter volume (p = 0.005), especially in the frontal (p = 0.003) and parietal (p = 0.006) lobes, with no significant differences in white matter volume. The main limitations of our study were its small sample size and the inclusion of patients with depression and mania in the affective group. Adolescents with EOSS have grey matter deficits compared with healthy controls and psychotic adolescents with EOMD. Our results suggest that grey matter deficits are not generally associated with psychosis but may be specifically associated with schizophrenia. Larger studies with consistent methods are needed to reconcile the contradictory findings among imaging studies involving psychotic youth.

Tagging SNP association study of the IL‐1β gene (IL1B) and childhood‐onset mood disorders

Given substantial evidence for IL-1beta involvement in the etiology of depression, the IL1B gene is a strong candidate for involvement in susceptibility to depressive disorders. However, association studies investigating this, to date, have been limited to just two polymorphisms (rs1143627[-31T/C] and rs16944[-511C/T]) that constitute only a fraction of the genetic variation that is actually present across this gene in the population. Here, in a family-based association study of childhood-onset mood disorders (COMD), characterized by onset of depression before the age of 15, we have used a gene-wide approach, employing a panel of five tagging SNPs spanning the entire gene. Based on TDT analyses of both individual alleles and haplotypes, in a study sample of 646 families (with 782 affected children), none of the SNPs, including those implicated in transcriptional regulation of the gene, showed evidence for association with COMD. This is the largest and most comprehensive study of IL1B in relation to mood disorders that has been carried out, to date. The results do not support the involvement of IL1B as a major factor in genetic risk for early-onset mood disorders.

Diurnal cortisol profiles and evening cortisol in post-pubertal adolescents scoring high on the Children's Depression Inventory

Early-onset mood disorders have become a significant public health problem in recent years. The Children's Depression Inventory (CDI) is a commonly used self-report measure. We studied the relation of CDI cut-offs to biological markers of depression such as the diurnal cortisol rhythm and evening cortisol. In 58 post-pubertal adolescents (29 boys and 29 girls, M(age)=15.1 years), the diurnal cortisol profile was derived from three saliva samples, collected at awakening, at noon and in the evening on a week-end day. Longitudinal repeated measurements regression revealed that the group with CDI>18 (high depressive symptoms) clearly had a higher and flatter diurnal rhythm with elevated evening cortisol compared to either the group with CDI between 13 and 18 (moderate depressive symptoms) or CDI<13 (low depressive symptoms). Multinomial logistic regression indicated that evening cortisol was useful in classifying the adolescents in the high depressive symptoms group, while awakening and noon cortisol were not. Our results indicate that the type of high flattened profiles sometimes seen in individuals who are clinically depressed according to diagnostic interviews can also be identified with a self-report inventory, at high levels of symptom reporting. Given the complexity of conducting diagnostic interviews, this result bears clinical relevance.

Cytokine Genes TNF, IL1A, IL1B, IL6, IL1RN and IL10, and Childhood-Onset Mood Disorders

Background/Aims: Inflammatory cytokines induce a behavioral syndrome, known as sickness behavior, that strongly resembles symptoms typically seen in depression. This resemblance has led to the theory that an imbalance of inflammatory cytokine activity may be a contributing factor in depressive disorders. Support for this is found in multiple lines of evidence, such as the effects of cytokines on the activities of the hypothalamic-pituitary-adrenal axis, serotonin and brain-derived neurotrophic factor, and hippocampal function, all of which are implicated in the etiology of depression. In addition, associations between inflammatory activity and depressive symptomology have been documented in a number of studies, and the depressogenic effects of cytokine therapy are well known. Accordingly, given that depression has a substantial genetic basis, genes involved in the regulation of inflammatory cytokine activity are strong candidates for involvement in genetic susceptibility to depressive disorders. Here, we have tested 6 key genes of this type, TNF, IL1A, IL1B, IL6, IL1RN and IL10, as candidates for involvement in childhood-onset mood disorders. Methods: In this study of 384 families, each ascertained through a child with depression diagnosed before the age of 15 years, 11 polymorphisms of known or likely functional significance (coding and regulatory variants) were analyzed. Results: Testing for biased transmission of alleles from parents to their affected offspring, we found no evidence for an association between childhood-onset mood disorders and any of the polymorphisms, either individually or as haplotypes. Conclusion: The present study does not support the involvement of the TNF, IL1A, IL1B, IL6, IL1RN and IL10 variants as major genetic risk factors contributing to early-onset mood disorders.

Pituitary gland volume in adolescent and young adult bipolar and unipolar depression

Few studies have examined pituitary gland size in mood disorders, particularly in adolescents. We hypothesized increase in the pituitary gland size in early-onset mood disorders. Thirty subjects between the ages of 13 and 20 years participated in the study. Three groups (control, bipolar I depression and unipolar depression) of 10 subjects each (4 male, 6 female) underwent volumetric magnetic resonance imaging at 1.5 T. Analysis of covariance (covarying for age, sex and intracranial volume) revealed a significant difference in pituitary gland volume amongst the groups [F(2,24) = 7.092, p = 0.014]. Post hoc analysis revealed that controls had a significantly smaller pituitary gland volume than both bipolar patients (p = 0.019) and depressed patients (p = 0.049). Bipolar and depressed subjects did not differ significantly from each other with regard to pituitary gland volume (p = 0.653). Control females had larger pituitary glands than control males [F(1,8) = 10.523, p = 0.012], but no sex differences were noted in the mood disorder groups. Pituitary glands are enlarged in adolescents with mood disorders compared to controls. Healthy young females have larger pituitary glands than males, but such a difference is not evident in individuals with unipolar depression or bipolar disorder. These findings provide new evidence of abnormalities of the pituitary in early onset mood disorders, and are consistent with neuroendocrine dysfunction in early stages of such illnesses.

Social neuroscience of child and adolescent depression

The social neuroscience of child and adolescent depression is inherently multidisciplinary. Depressive disorders beginning early in life can have serious developmental and functional consequences. Psychopathology research has described depression’s defining clinical and contextual features, and intervention research has characterized its response to treatment and prevention programs. Neuroendocrine, electrophysiological, and neuroimaging studies have identified core neurobiological aspects of early-onset mood disorders. These areas are reviewed using a developmental social neuroscience perspective for integrating disparate observations. The paper introduces a dynamic adaptive systems framework, and it discusses hedonic capacity, stress sensitivity, ruminative self-focus, and attentional impairments as fundamental components of mood disorders.

Neurodevelopmental antecedents of early-onset bipolar affective disorder.

Developmental impairments have been identified as a risk factor for early-onset schizophrenia. Affective symptoms are more common in children and adolescents with disordered neurodevelopmental than in healthy controls. To test the hypothesis that severe early-onset mood disorders are associated with developmental antecedents. We retrospectively identified 38 adolescent cases (15 female, 23 male; mean age 14.4 years, range 11-18) who met ICD-10 Research Diagnostic Criteria for a manic episode, bipolar affective disorder or psychotic depression, and 41 controls (25 female, 16 male, mean age 14.2 years, range 11-18) with depression but without psychotic features. Cases were significantly more likely to have experienced delayed language, social or motor development (OR 5.5, 95% CI = 1.4-21.6, P = 0.01), in particular those who develop psychotic symptoms (OR 7.2, 95% CI = 1.8-28.6, P = 0.003). Compared to early-onset unipolar depression, neurodevelopmental antecedents are over-represented in early-onset bipolar disorder. The validity of this finding was supported by contemporaneous IQ scores that are not subject to the same potential biases as case-note ratings.