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.\ud - 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).\ud - 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.\ud - 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

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

Atypical neural responses to vocal anger in attention-deficit/hyperactivity disorder

Background Deficits in facial emotion processing, reported in attention-deficit/hyperactivity disorder (ADHD), have been linked to both early perceptual and later attentional components of event-related potentials (ERPs). However, the neural underpinnings of vocal emotion processing deficits in ADHD have yet to be characterised. Here, we report the first ERP study of vocal affective prosody processing in ADHD. Methods Event-related potentials of 6–11-year-old children with ADHD (n = 25) and typically developing controls (n = 25) were recorded as they completed a task measuring recognition of vocal prosodic stimuli (angry, happy and neutral). Audiometric assessments were conducted to screen for hearing impairments. Results Children with ADHD were less accurate than controls at recognising vocal anger. Relative to controls, they displayed enhanced N100 and attenuated P300 components to vocal anger. The P300 effect was reduced, but remained significant, after controlling for N100 effects by rebaselining. Only the N100 effect was significant when children with ADHD and comorbid conduct disorder (n = 10) were excluded. Conclusion This study provides the first evidence linking ADHD to atypical neural activity during the early perceptual stages of vocal anger processing. These effects may reflect preattentive hyper-vigilance to vocal anger in ADHD

Effector Functions of Natural Killer Cell Subsets in the Control of Hematological Malignancies.

Treatment of hematological malignant disorders has been improved over the last years, but high relapse rate mainly attributable to the presence of minimal residual disease still persists. Therefore, it is of great interest to explore novel therapeutic strategies to obtain long-term remission. Immune effector cells, and especially natural killer (NK) cells, play a crucial role in the control of hematological malignancies. In this regard, the efficiency of allogeneic stem cell transplantation clearly depends on the immune-mediated graft versus leukemia effect without the risk of inducing graft versus host disease. Alloreactive donor NK cells generated following hematopoietic stem cell transplantation ameliorate the outcome of leukemia patients; in addition, in vivo transfer of in vitro expanded NK cells represents a crucial tool for leukemia treatment. To improve NK cell effector functions against resistant leukemia cells, novel immunotherapeutic strategies are oriented to the identification, isolation, expansion, and administration of particular NK cell subsets endowed with multifunctional anti-tumor potential and tropism toward tumor sites. Moreover, the relationship between the emergence and persistence of distinct NK cell subsets during post-graft reconstitution and the maintenance of a remission state is still rather unclear

Extracellular calcium reduction strongly increases the lytic capacity of pneumolysin from streptococcus pneumoniae in brain tissue

Background. Streptococcus pneumoniae causes serious diseases such as pneumonia and meningitis. Its major pathogenic factor is the cholesterol-dependent cytolysin pneumolysin, which produces lytic pores at high concentrations. At low concentrations, it has other effects, including induction of apoptosis. Many cellular effects of pneumolysin appear to be calcium dependent. Methods. Live imaging of primary mouse astroglia exposed to sublytic amounts of pneumolysin at various concentrations of extracellular calcium was used to measure changes in cellular permeability (as judged by lactate dehydrogenase release and propidium iodide chromatin staining). Individual pore properties were analyzed by conductance across artificial lipid bilayer. Tissue toxicity was studied in continuously oxygenated acute brain slices. Results. The reduction of extracellular calcium increased the lytic capacity of the toxin due to increased membrane binding. Reduction of calcium did not influence the conductance properties of individual toxin pores. In acute cortical brain slices, the reduction of extracellular calcium from 2 to 1 mM conferred lytic activity to pathophysiologically relevant nonlytic concentrations of pneumolysin. Conclusions. Reduction of extracellular calcium strongly enhanced the lytic capacity of pneumolysin due to increased membrane binding. Thus, extracellular calcium concentration should be considered as a factor of primary importance for the course of pneumococcal meningitis

Mood lability and psychopathology in youth

Background. Mood lability is a concept widely used. However, data on its prevalence and morbid associations are scarce. We sought to establish the occurrence and importance of mood lability in a large community sample of cildren and adolescents by testing a priori hypotheses.Method. Cross-sectional data were taken from a national mental health survey including 5326 subjects aged 8-79 years in the UK. The outcomes were prevalence and characteristics of mood lability and its associations with psychopathology and overall impairment.Results. Mood lability occurred in more than 5% of the population of children and adolescents, both by parent and self-report. Mood lability was strongly associated with a wide range of psychopathology and was linked to significant impairment even in the absence of psychiatric disorders. Mood lability was particularly strongly associated with co-morbidity between internalizing and externalizing disorders, even when adjusting for the association with individual disorders. The pattern of results did not change after excluding youth with bipolar disorder or with episodes of elated mood.Conclusions. Clinically significant mood lability is relatively common in the community. Our findings indicate that mood lability is not a mere consequence of other psychopathology in that it is associated with significant impairment even in the absence of psychiatric diagnoses. Moreover, the pattern of association of mood lability with co-morbidity suggests that it could be a risk factor shared by both internalizing and externalizing disorders. Our data point to the need for greater awareness of mood lability and its implications for treatment