Examining parent and child agreement in the diagnosis of adolescent depression

Background: The diagnosis of depression in adolescents relies on identifying the presence of specific core and additional symptoms. Symptoms can be identified using structured or unstructured interviews and a range of questionnaire measures, which are completed by the young person and by a parent or carer. The aim of this research was to examine the inter- and intra-rater reliability of parent report and adolescent self-report of depression symptoms. Method: In a sample of parent-child dyads, where young people aged 13-17 were referred to a mental health service for depression, we examined adolescents’ (n = 46) and parents’ (n = 46) independent responses to the Schedule for Affective Disorders and Schizophrenia in School-Age Children (Kaufman et al., 1997) and the Mood and Feelings Questionnaire (Costello & Angold, 1988). Results: In the clinical interview, diagnostic criteria were more often met based on the adolescent’s report, and adolescents endorsed more symptoms of depression than their parents. Tentative results also suggest that parent-child agreement about specific symptoms was low. Comparing different measures of depression revealed that adolescent report on the questionnaire and interview was significantly correlated. However, there was no significant correlation between parent questionnaire and interview report. Conclusion: These results suggest that relying solely on parents to identify depression in their children may result in young people with depression being missed and therefore untreated. Young people themselves should be encouraged and enabled to recognise the symptoms of depression, and have an established pathway to services that offer assessment and treatment

The developmental environment, epigenetic biomarkers and long-term health

Evidence from both human and animal studies has shown that the prenatal and early postnatal environments influence susceptibility to chronic disease in later life and suggests that epigenetic processes are an important mechanism by which the environment alters long-term disease risk. Epigenetic processes, including DNA methylation, histone modification and non-coding RNAs, play a central role in regulating gene expression. The epigenome is highly sensitive to environmental factors in early life, such as nutrition, stress, endocrine disruption and pollution, and changes in the epigenome can induce long-term changes in gene expression and phenotype. In this review we focus on how the early life nutritional environment can alter the epigenome leading to an altered susceptibility to disease in later life

Prenatal famine exposure, health in later life and promoter methylation of four candidate genes

Poor nutrition during fetal development can permanently alter growth, cardiovascular physiology and metabolic function. Animal studies have shown that prenatal undernutrition followed by balanced postnatal nutrition alters deoxyribonucleic acid (DNA) methylation of gene promoter regions of candidate metabolic control genes in the liver. The aim of this study was to investigate whether methylation status of the proximal promoter regions of four candidate genes differed between individuals exposed to the Dutch famine in utero. In addition, we determined whether methylation status of these genes was associated with markers of metabolic and cardiovascular disease and adult lifestyle. Methylation status of the GR1-C (glucocorticoid receptor), PPAR? (peroxisome proliferator-activated receptor gamma), lipoprotein lipase and phosphatidylinositol 3 kinase p85 proximal promoters was investigated in DNA isolated from peripheral blood samples of 759 58-year-old subjects born around the time of the 1944–45 Dutch famine. We observed no differences in methylation levels of the promoters between exposed and unexposed men and women. Methylation status of PPAR? was associated with levels of high-density lipoprotein cholesterol and triglycerides as well as with exercise and smoking. Hypomethylation of the GR promoter was associated with adverse adult lifestyle factors, including higher body mass index, less exercise and more smoking. The previously reported increased risk of cardiovascular and metabolic disease after prenatal famine exposure was not associated with differences in methylation status across the promoter regions of these candidate genes measured in peripheral blood. The adult environment seems to affect GR and PPAR? promoter methylation

Role of DNA methyltransferase 1 on the altered eNOS expression in human umbilical endothelium from intrauterine growth restricted fetuses

Reduced fetal growth associates with endothelial dysfunction and cardiovascular risk in both young and adult offspring and the nitric oxide (NO) system has been implicated in these effects. Epigenetic processes are likely to underlie such effects, but there is to date no evidence that endothelial dysfunction in early life results from epigenetic processes on key genes in the NO system, such as NOS3 (eNOS) and ARG2 (arginase-2). We determined basal DNA methylation status in NOS3 and ARG2 promoters, and DNA methyltransferase 1 (DNMT1) effect on eNOS and arginase-2 expression using human endothelial cells isolated from umbilical arteries (HUAEC) and veins (HUVEC) from control and intrauterine growth restricted (IUGR) fetuses. Compared with cells from control pregnancies, eNOS protein and mRNA levels were increased in HUAEC, but decreased in HUVEC, from IUGR, while arginase-2 levels were increased in IUGR-HUVEC. The NOS3 promoter showed a decrease in DNA methylation at CpG -352 in IUGR-HUAEC, and an increase in IUGR-HUVEC, when compared with control cells. Methylation in the hypoxia response element of the NOS3 promoter was increased in IUGR-HUAEC and decreased in HUVEC. Methylation in the AGR2 promoter in IUGR-HUVEC was decreased in a putative HRE, and without changes in IUGR-HUAEC. Silencing of DNMT1 expression normalized eNOS expression in IUGR endothelial cells, and restored the normal response to hypoxia in HUVEC, without effects on arginase-2. This data suggest that eNOS expression in IUGR-derived endothelial cells is programmed by altered DNA methylation, and can be reversed by transient silencing of the DNA methylation machinery.<br/

Effect of maternal diet and body condition on glucose metabolism and skeletal muscle structure in mature adult sheep offspring

Early life nutrition is implicated in the risk of metabolic diseases (e.g. type 2 diabetes) in adulthood. Low birth-weight was associated with defects in the skeletal muscle insulin-signalling pathway of young adult men (1), and insulin resistance was associated with changes in myofibre composition (2). In sheep, maternal undernutrition reduced fetal skeletal muscle myofibre density and composition (3). Recently we reported that lower body condition score (BCS) led to increased fasting glycaemia, mild glucose intolerance and impaired initial insulin secretory response in adult offspring (4). We hypothesised that this would worsen with age, and that altered skeletal muscle structure and insulin signalling pathways are involved. Ewes were established, by dietary manipulation, at a BCS of 2 (lower (L) n = 10) or &gt;3 (higher (H) n = 14) before and during pregnancy (4). In male offspring at 4.04±0.02 years plasma glucose and insulin concentrations were measured during a glucose tolerance test (0.5 g/kg body weight i.v.) and rams were killed by an overdose of barbiturate (i.v. 145 mg/kg). We analysed a) insulin-signalling proteins by Western blotting in abdominal fat and vastus muscle (m.); b) glucose uptake in isolated strips of vastus and soleus m.(5); c) myofibre density and cross-sectional area (CSA) by immunostaining with anti-fast skeletal myosin (3). Data are mean±SE and were analysed by Student’s t test. Glucose tolerance was similar between groups. Basal glucose uptake was similar in L and H group soleus and vastus m. isolated strips. However insulin-stimulated uptake tended to be reduced in the soleus m. only of L rams (H 1.01±0.06; L 0.84±0.07 pmol.min.mg, p&lt;0.1). In vastus, but not soleus, m. total myofibre density (H 343±15; L 294±14 fibres/mm2, p&lt;0.05) and fast myofibre density (H 226±10; L 194±10 fibres/mm2, p&lt;0.05) was lower in L rams. Slow myofibre density tended to be lower in L rams (H 117±7; L 100±6 fibres/mm2, p&lt;0.1). Myofibre CSA was unaltered. Protein levels of (i) Akt1 were lower in the vastus m. (L=83±7% of H, p&lt;0.05), and tended to be lower in abdominal fat (L=71±7% of H, p&lt;0.1), of L rams; (ii) GLUT-4 were increased (L=157±6% of H, p&lt;0.001), and (iii) IGF-IR tended to be reduced (L=78±12% of H, p&lt;0.1), in the vastus m. of L rams. Reduced signalling through Akt1 may therefore mediate the decreased vastus m. myofibre density in L rams resulting in reduced glucose tolerance of the young adult offspring (4). However in mature adulthood, glucose tolerance and glucose uptake into vastus m. was not altered by maternal BCS, and thus the impact of reduced myofibre density may be offset in part by increased GLUT-4. Such adaptations may lead to complications in metabolic control in an overabundant postnatal nutrient environment