We report a familial case of the nephrogenic syndrome of inappropriate antidiuresis (NSIAD), including 30-year followup data on two patients. The proband and one maternal uncle presented in their infancy with severe recurrent hyponatremia, and clinical pictures consistent with the syndrome of inappropriate antidiuretic hormone (SIADH) in the absence of an elevated ADH level. They were both confirmed to be hemizygous for the R137C mutation on the V2R gene (AVPR2), the same locus of the gain of function mutation demonstrated in the original reports of this condition. The proband's mother was identified as an asymptomatic carrier of this X-linked condition. Our case describes a favourable long-term outcome for NSIAD, in particular, successful treatment with oral urea during the infancy period, and with self-regulated precautions on fluid intake into adult life.

Purpose

To investigate the association between social isolation and loneliness, how they relate to depression, and whether these associations are explained by genetic influences.

Methods

We used data from the age-18 wave of the Environmental Risk Longitudinal Twin Study, a birth cohort of 1116 same-sex twin pairs born in England and Wales in 1994 and 1995. Participants reported on their levels of social isolation, loneliness and depressive symptoms. We conducted regression analyses to test the differential associations of isolation and loneliness with depression. Using the twin study design, we estimated the proportion of variance in each construct and their covariance that was accounted for by genetic and environmental factors.

Results

Social isolation and loneliness were moderately correlated (r = 0.39), reflecting the separateness of these constructs, and both were associated with depression. When entered simultaneously in a regression analysis, loneliness was more robustly associated with depression. We observed similar degrees of genetic influence on social isolation (40 %) and loneliness (38 %), and a smaller genetic influence on depressive symptoms (29 %), with the remaining variance accounted for by the non-shared environment. Genetic correlations of 0.65 between isolation and loneliness and 0.63 between loneliness and depression indicated a strong role of genetic influences in the co-occurrence of these phenotypes.

Conclusions

Socially isolated young adults do not necessarily experience loneliness. However, those who are lonely are often depressed, partly because the same genes influence loneliness and depression. Interventions should not only aim at increasing social connections but also focus on subjective feelings of loneliness.

Objective

In healthy, nonobese, adolescent males and females to: (1) Determine the relationship between fitness and energy intake; (2) assess the effect of five-weeks endurance training on energy intake and food choice and (3) compare food record assessments of energy intake with doubly-labeled water (DLW) measurement of total energy expenditure (TEE).

Design

(1) Cross sectional analysis of fitness and food intake and (2) Prospective, randomized, controlled interventional study of endurance-type exercise training in 44 females and 44 males (age range, 15-17 y).

Measurements

Pre and end interventional three day food records were successfully collected from 32 females (15 controls, 17 trained) and 39 males (19 controls, 20 trained). Fitness was assessed from cycle ergometry as peak oxygen uptake normalized both to thigh muscle mass and body weight. Thigh muscle mass was measured by magnetic resonance imaging. TEE using the DLW technique was measured in 12 females (6 controls, 6 trained) and 20 males (10 controls, 10 trained) during weeks 4-5 of the exercise training program (simultaneously with the second assessment of food records). Food record data were analyzed using the Minnesota Nutrition Data System.

Results

Fitness was correlated with self reported total caloric intake in males but not females. In females, there was a significant increase in fat intake (19.8+/-9%, P < 0.05) and a significant decrease in carbohydrate intake (-9.8+/-4%) in the trained subjects. No changes were observed in the control subjects. Energy expenditure (2072+/-52 kcal/d) was significantly greater than the estimated energy intake (1520+/-112 kcal/d, P < 0.007) during the intervention in the trained, but not control, subjects. However, there was no weight change in either control or trained subjects. In males, no changes were observed in food choice in either control or trained subjects. Similar to the females, energy expenditure (2425+/-22 kcal/d) was significantly greater than the estimated energy intake (2168+/-117 kcal/d, P < 0.05) during the intervention in the trained, but not control, subjects. No weight changes were observed in either group.

Conclusions

Fitness is associated with increased self-reported energy intake in males but not females, while exercise training led to alterations in food selection (greater fat and reduced carbohydrate) only in females. These observations could reflect specific gender differences, or, alternatively, the generally lower levels of fitness in the females. The apparent negative energy balance without evidence for weight loss in both the trained males and females suggests a systematic under reporting of food intake during exercise programs in adolescents, and indicates the possibility that errors in self reported food intake might be greater during transitions from one level of energy expenditure to another.

Objectives

To test whether childhood maltreatment was a predictor of (1) having low educational qualifications and (2) not being in education, employment, or training among young adults in the United Kingdom today.

Methods

Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative UK cohort of 2232 twins born in 1994 to 1995. Mothers reported on child maltreatment when participants were aged 5, 7, 10, and 12 years. Participants were interviewed about their vocational status at age 18 years.

Results

The unadjusted odds of having low educational qualifications or of not being in education, employment, or training at age 18 years were more than 2 times greater for young people with a childhood history of maltreatment versus those without. These associations were reduced after adjustments for individual and family characteristics. Youths who reported having a supportive adult in their lives had better education outcomes than did youths who had less support.

Conclusions

Closer collaboration between the child welfare and education systems is warranted to improve vocational outcomes for maltreated youths.

Background

Associations of socioenvironmental features like urbanicity and neighborhood deprivation with psychosis are well-established. An enduring question, however, is whether these associations are causal. Genetic confounding could occur due to downward mobility of individuals at high genetic risk for psychiatric problems into disadvantaged environments.

Methods

We examined correlations of five indices of genetic risk [polygenic risk scores (PRS) for schizophrenia and depression, maternal psychotic symptoms, family psychiatric history, and zygosity-based latent genetic risk] with multiple area-, neighborhood-, and family-level risks during upbringing. Data were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins born in 1994-1995 and followed to age 18 (93% retention). Socioenvironmental risks included urbanicity, air pollution, neighborhood deprivation, neighborhood crime, neighborhood disorder, social cohesion, residential mobility, family poverty, and a cumulative environmental risk scale. At age 18, participants were privately interviewed about psychotic experiences.

Results

Higher genetic risk on all indices was associated with riskier environments during upbringing. For example, participants with higher schizophrenia PRS (OR = 1.19, 95% CI = 1.06-1.33), depression PRS (OR = 1.20, 95% CI = 1.08-1.34), family history (OR = 1.25, 95% CI = 1.11-1.40), and latent genetic risk (OR = 1.21, 95% CI = 1.07-1.38) had accumulated more socioenvironmental risks for schizophrenia by age 18. However, associations between socioenvironmental risks and psychotic experiences mostly remained significant after covariate adjustment for genetic risk.

Conclusion

Genetic risk is correlated with socioenvironmental risk for schizophrenia during upbringing, but the associations between socioenvironmental risk and adolescent psychotic experiences appear, at present, to exist above and beyond this gene-environment correlation.

Fluorescence microscopy is one of the most important tools in cell biology research because it provides spatial and temporal information to investigate regulatory systems inside cells. This technique can generate data in the form of signal intensities at thousands of positions resolved inside individual live cells. However, given extensive cell-to-cell variation, these data cannot be readily assembled into three- or four-dimensional maps of protein concentration that can be compared across different cells and conditions. We have developed a method to enable comparison of imaging data from many cells and applied it to investigate actin dynamics in T cell activation. Antigen recognition in T cells by the T cell receptor (TCR) is amplified by engagement of the costimulatory receptor CD28. We imaged actin and eight core actin regulators to generate over a thousand movies of T cells under conditions in which CD28 was either engaged or blocked in the context of a strong TCR signal. Our computational analysis showed that the primary effect of costimulation blockade was to decrease recruitment of the activator of actin nucleation WAVE2 (Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2) and the actin-severing protein cofilin to F-actin. Reconstitution of WAVE2 and cofilin activity restored the defect in actin signaling dynamics caused by costimulation blockade. Thus, we have developed and validated an approach to quantify protein distributions in time and space for the analysis of complex regulatory systems.

Objective

To test whether bullied children have an elevated risk of being overweight in young adulthood and whether this association is: (1) consistent with a dose-response relationship, namely, its strength increases with the chronicity of victimization; (2) consistent across different measures of overweight; (3) specific to bullying and not explained by co-occurring maltreatment; (4) independent of key potential confounders; and (5) consistent with the temporal sequence of bullying preceding overweight.

Method

A representative birth cohort of 2,232 children was followed to age 18 years as part of the Environmental Risk Longitudinal Twin Study. Childhood bullying victimization was reported by mothers and children during primary school and early secondary school. At the age-18 follow-up, we assessed a categorical measure of overweight, body mass index, and waist-hip ratio. Indicators of overweight were also collected at ages 10 and 12. Co-twin body mass and birth weight were used to index genetic and fetal liability to overweight, respectively.

Results

Bullied children were more likely to be overweight than non-bullied children at age 18, and this association was (1) strongest in chronically bullied children (odds ratio = 1.69; 95% confidence interval [CI] = 1.21-2.35); (2) consistent across measures of overweight (body mass index: b = 1.12; 95% CI = 0.37-1.87; waist-hip ratio: b = 1.76; 95% CI = 0.84-2.69); (3) specific to bullying and not explained by co-occurring maltreatment; (4) independent of child socioeconomic status, food insecurity, mental health, and cognition, and pubertal development; and (5) not present at the time of bullying victimization, and independent of childhood weight and genetic and fetal liability.

Conclusion

Childhood bullying victimization predicts overweight in young adulthood.

Background

Labour market disengagement among youths has lasting negative economic and social consequences, yet is poorly understood. We compared four types of work-related self-perceptions, as well as vulnerability to mental health and substance abuse problems, among youths not in education, employment or training (NEET) and among their peers.

Methods

Participants were from the Environmental Risk (E-Risk) longitudinal study, a nationally representative UK cohort of 2,232 twins born in 1994-1995. We measured commitment to work, job-search effort, professional/technical skills, 'soft' skills (e.g. teamwork, decision-making, communication), optimism about getting ahead, and mental health and substance use disorders at age 18. We also examined childhood mental health.

Results

At age 18, 11.6% of participants were NEET. NEET participants reported themselves as committed to work and searching for jobs with greater diligence than their non-NEET peers. However, they reported fewer 'soft' skills (B = -0.98, p < .001) and felt less optimistic about their likelihood of getting ahead in life (B = -2.41, p < .001). NEET youths also had higher rates of concurrent mental health and substance abuse problems, but these did not explain the relationship with work-related self-perceptions. Nearly 60% of NEET (vs. 35% of non-NEET) youths had already experienced ≥1 mental health problem in childhood/adolescence. Associations of NEET status with concurrent mental health problems were independent of pre-existing mental health vulnerability.

Conclusions

Our findings indicate that while NEET is clearly an economic and mental health issue, it does not appear to be a motivation issue. Alongside skills, work-related self-perceptions and mental health problems may be targets for intervention and service provision among this high-risk population.

This paper presents multilevel findings on adolescents' victimization exposure from a large longitudinal cohort of twins. Data were obtained from the Environmental Risk (E-Risk) Longitudinal Twin Study, an epidemiological study of 2,232 children (1,116 twin pairs) followed to 18 years of age (with 93% retention). To assess adolescent victimization, we combined best practices in survey research on victimization with optimal approaches to measuring life stress and traumatic experiences, and introduce a reliable system for coding severity of victimization. One in three children experienced at least one type of severe victimization during adolescence (crime victimization, peer/sibling victimization, Internet/mobile phone victimization, sexual victimization, family violence, maltreatment, or neglect), and most types of victimization were more prevalent among children from low socioeconomic backgrounds. Exposure to multiple victimization types was common, as was revictimization; over half of those physically maltreated in childhood were also exposed to severe physical violence in adolescence. Biometric twin analyses revealed that environmental factors had the greatest influence on most types of victimization, while severe physical maltreatment from caregivers during adolescence was predominantly influenced by heritable factors. The findings from this study showcase how distinct levels of victimization measurement can be harmonized in large-scale studies of health and development.