Childhood Trajectories of Hyperactivity/Inattention Symptoms and Diurnal Cortisol in Middle Adolescence: Results from a UK Birth Cohort

Objective: Children with attention-deficit/hyperactivity disorder (ADHD) show hypoactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Whether the association between hyperactivity/inattention symptoms with HPA axis dysfunction holds in the general child population too is not clear. // Method: We assessed associations between longitudinal trajectories of hyperactivity/inattention symptoms during ages 4 to 13 years and basal cortisol profiles at age 15 in a British general population cohort. // Results: Adolescents with persistently high levels of hyperactivity/inattention symptoms since childhood showed lower total morning cortisol and a smaller diurnal decline, even after adjusting for confounders. No associations were found between any of the symptom trajectories and cortisol awakening response, diurnal slope or daily output of cortisol. // Conclusion: This study provides evidence for hypocortisolism among adolescents with chronic hyperactivity/inattention symptoms in the general population

Change in decision-making skills and risk for eating disorders in adolescence: A population based study

Background: Despite the growing interest in the involvement of decision-making under conditions of risk in the onset of eating disorders in adolescence, no studies have investigated how the development of decision-making across that period may influence such a risk. Using data from the Millennium Cohort Study this study explored whether changes in performance on the Cambridge Gambling Task (CGT) between age 11 and age 14 were associated with presence of eating disorder (ED) symptoms at age 14. Methods: Latent class analysis was used to identify groups with distinct profiles based on their responses to questions investigating eating and dieting at age 14. CGT change scores were used as predictors of latent class membership in a logistic regression while accounting for confounders. Results: In our sample of 11,303 participants, the best class solution was a two-class one reflecting high and low risk for ED symptoms. Higher risk-taking scores and lower quality of decision-making scores at age 11 were associated with increased odds of belonging to the high-risk group at age 14. Risk-taking was reduced from age 11 to age 14, but a smaller reduction was associated with a higher probability of being in the higher risk group at age 14. The change over time in the other CGT measures was not associated with risk for ED symptoms. Conclusions: Atypical change in risk-taking from early to middle adolescence may be implicated in the risk of ED symptoms in middle adolescence. These results should be replicated in clinical samples

Prenatal and childhood adverse life events, inflammation and depressive symptoms across adolescence

Background No study has investigated the role of inflammation in explaining the association between early exposures to adverse life events and depressive symptoms in adolescence. Method Using data from the Avon Longitudinal Study of Parents and Children, we tested if inflammatory markers [serum C-reactive protein (CRP) and interleukin 6 (IL-6)] at age 9 years mediate the association between adverse life events, measured separately for the prenatal (since the beginning of pregnancy) and the childhood (ages 0–9 years) periods, and the development of depressive symptoms at ages 10–17 years. Data (n = 4,263) were analyzed using mediation analysis in a latent growth curve modeling framework. Results Depressive symptoms at the beginning of adolescence (age 10) were associated with the number of prenatal events, the number of events around birth and the increase in events over time in childhood (ages 0–9), even after adjustment for confounders. IL-6 partially mediated the association between increasing exposure to events over time in childhood and depressive symptoms at the beginning of adolescence. IL-6 did not mediate any other association between events and symptoms. There was no evidence for mediation by CRP, which was generally unrelated to exposure to events. Limitations The small size of the mediation effect and the robust direct effects of events prenatally and around birth suggest there are multiple routes from early stressors to adolescent depression. Conclusions In the general adolescent population, increasing exposure to psychosocial stressors over time during childhood is associated with the early onset of depressive symptoms, partly via increasing levels of plasma IL-6

Internalizing and externalizing problems across childhood and psychotic-like experiences in young-adulthood: The role of developmental period

Background: Psychopathology in childhood and adolescence, commonly indexed by co-occurring internalizing and externalizing problem behaviors, has been found to predict psychotic-like experiences (PLEs) in adults. However, studies to date have rarely examined internalizing and externalizing problem behaviors simultaneously or identified in which developmental period do these problem behaviors predict PLEs in adults. This study tests to what extent internalizing and externalizing problem behaviors in childhood (4–9 years) or adolescence (11–16 years) predict PLEs in young-adulthood (18 years). Methods: Parent-rated child internalizing and externalizing problems on the Strengths and Difficulties Questionnaire at ages 4, 6, 8, 9, 11, 13, and 16 years from the Avon Longitudinal Study of Parents and Children (N = 4717) were modelled using two-piece latent growth curve modelling to predict clinician-rated PLEs at age 18 years, controlling for confounders (gender, ethnicity, socio-economic status, parental education and stressful life events) assessed prior to baseline at age 4 years. Results: Controlling for confounders, an increase in childhood internalizing problems from 4 to 9 years and externalizing problems at baseline (at 4 years) predicted PLEs at 18 years, explaining 9.5% of the variance in adult PLEs. These associations were independent to controls for any changes in adolescent internalizing and externalizing problems from 11 to 16 years. Conclusions: High baseline levels of externalizing problems and increasing internalizing problems throughout childhood can predict PLEs at 18 years. Externalizing problems around the transition to primary school and internalizing problems throughout childhood may be particularly helpful in informing risk of PLEs in young-adulthood

Prenatal and childhood adversity and inflammation in children: A population-based longitudinal study

BACKGROUND: Stressful life events experienced during childhood and early prenatal development have been associated with inflammation during childhood. However, no study has considered these two exposures jointly, or has investigated the effect of their interaction. METHODS: In the Avon Longitudinal Study of Parents and Children, a general-population birth cohort, we explored if inflammatory markers [serum C-reactive protein (CRP) and interleukin 6 (IL-6)] at age 9 years were related to early prenatal events (at 18 weeks pregnancy), childhood events (measured on seven occasions at ages 0-9 years) and their interaction (n=3,915). Latent growth curve modelling estimated trajectories of childhood events, and linear regression explored associations of prenatal and childhood events with inflammatory markers. Models controlled for ethnicity, socioeconomic status and body mass index, were stratified by gender and considered both unweighted and weighted (by impact) event exposures. RESULTS: Even after adjustment for confounders and prenatal events, both the intercept and the slope of number of childhood events were associated with IL-6, but only in females. The significant effect of the slope held for both weighted (by impact) and unweighted event specifications. Prenatal events were not associated with either inflammatory marker when childhood events were controlled. There was no evidence for synergistic effects of prenatal and childhood events. CONCLUSION: Independently of prenatal adverse life events, the number and increase in number of adverse life events experienced in childhood were associated positively with plasma levels of inflammatory markers, such as IL-6, in girls. This gender specificity warrants further research

Reprint of: Internalising symptoms mediate the longitudinal association between childhood inflammation and psychotic-like experiences in adulthood

Psychotic-like experiences (PLEs) are part of a continuum of psychosis. Previous longitudinal studies highlighted a relationship between peripheral inflammation during childhood and onset of PLEs in adulthood. In this study, we tested if this association is mediated by internalising and externalising symptoms experienced during childhood and adolescence. To test this hypothesis, we used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). We investigated a subsample of 4525 individuals from this cohort with data on interleukin 6 (IL-6) and C-reactive protein (CRP) in childhood (age 9 years). We measured PLEs at age 18 years, and we used latent growth curve modelling to estimate longitudinal trajectories of internalising and externalising symptoms from ages 9 to 16 years. The individual predicted values of the intercept (set at baseline, 9 years) and the slope (rate of annual change) were then used in the mediation analysis. There was evidence for full mediation by the intercept of internalising symptoms. Our findings suggest that inflammation during childhood may be relevant for the future onset of PLEs via its association with a high level of internalising symptoms. These findings, although obtained from a non-clinical population, provide an additional step in advancing knowledge on the relationship between inflammation and symptoms of the psychosis continuum

Paternal Psychological Distress and Child Problem Behavior from Early Childhood to Middle Adolescence

OBJECTIVE: To explore if paternal psychological distress is related to the longitudinal course of child Problem behaviour after accounting for maternal psychological distress. METHOD: We used data from the Millennium Cohort Study (MCS), a large general-population birth cohort in the UK. Maternal and paternal psychological distress was measured with the Kessler 6-item psychological distress scale (K-6) at child ages 3, 5, 7, 11 and 14 years. Problem behaviour was measured with the Strengths and Difficulties Questionnaire at these ages. Data were analyzed using growth curve modelling, before and after adjustment for confounders (N = 13,442). RESULTS: The effect of paternal psychological distress was weaker than that of maternal psychological distress. However, even after adjustment for maternal psychological distress and confounding, paternal psychological distress predicted all four domains of child Problem behaviour we examined (hyperactivity, conduct, emotional and peer problems). Child problem scores were generally lower in biological father families, but the effect of paternal psychological distress was the same for children in biological and non-biological father families, and did not depend on the level of maternal psychological distress. High levels of paternal psychological distress predicted some problems (emotional symptoms and hyperactivity) more strongly in boys than girls. CONCLUSION: There was evidence for a robust association between psychological distress in fathers and Problem behaviour in their offspring. Our findings suggest that the mental health of both fathers and mothers is important for the behaviour of their children

The proinflammatory cytokine interleukin 18 regulates feeding by acting on the bed nucleus of the stria terminalis

The proinflammatory cytokine IL-18 has central anorexigenic effects and was proposed to contribute to loss of appetite observed during sickness. Here we tested in the mouse the hypothesis that IL-18 can decrease food intake by acting on neurons of the bed nucleus of the stria terminalis (BST), a component of extended amygdala recently shown to influence feeding via its projections to the lateral hypothalamus (LH). We found that both subunits of the heterodimeric IL-18 receptor are highly expressed in the BST and that local injection of recombinant IL-18 (50 ng/ml) significantly reduced c-fos activation and food intake for at least 6 h. Electrophysiological experiments performed in BST brain slices demonstrated that IL-18 strongly reduces the excitatory input on BST neurons through a presynaptic mechanism. The effects of IL-18 are cell-specific and were observed in Type III but not in Type I/II neurons. Interestingly, IL-18-sensitve Type III neurons were recorded in the juxtacapsular BST, a region that contains BST-LH projecting neurons. Reducing the excitatory input on Type III GABAergic neurons, IL-18 can increase the firing of glutamatergic LH neurons through a disinhibitory mechanism. Imbalance between excitatory and inhibitory activity in the LH can induce changes in food intake. Effects of IL-18 were mediated by the IL-18R because they were absent in neurons from animals null for IL-18Rα (Il18ra-/-), which lack functional IL-18 receptors. In conclusion, our data show that IL-18 may inhibit feeding by inhibiting the activity of BST Type III GABAergic neurons

Optimized intermolecular potential for nitriles based on Anisotropic United Atoms model

An extension of the Anisotropic United Atoms intermolecular potential model is proposed for nitriles. The electrostatic part of the intermolecular potential is calculated using atomic charges obtained by a simple Mulliken population analysis. The repulsion-dispersion interaction parameters for methyl and methylene groups are taken from transferable AUA4 literature parameters [Ungerer et al., J. Chem. Phys., 2000, 112, 5499]. Non-bonding Lennard-Jones intermolecular potential parameters are regressed for the carbon and nitrogen atoms of the nitrile group (–C≡N) from experimental vapor-liquid equilibrium data of acetonitrile. Gibbs Ensemble Monte Carlo simulations and experimental data agreement is very good for acetonitrile, and better than previous molecular potential proposed by Hloucha et al. [J. Chem. Phys., 2000, 113, 5401]. The transferability of the resulting potential is then successfully tested, without any further readjustment, to predict vapor-liquid phase equilibrium of propionitrile and n-butyronitrile