The role of inflammation in the effects of peer victimisation and stressful life events on mental health in childhood.

Background: Peer victimisation represents a salient stressor during childhood. However, studies investigating the mechanism of its impact on children's mental health typically examine socio-cognitive factors as mediators. The current study sought to provide novel insight through testing a potential biological mechanism, inflammation. It also tested for pathway-specific effects by comparing how inflammation may mediate the effect of peer victimisation and that of another important stressor in childhood: adverse life events. Method: Data from 4,583 participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) were used. Path analysis was carried out to investigate whether inflammation (IL-6 and CRP) at age 9 years mediates the effect of peer victimisation and stressful life events at age 8 years on internalising (peer and emotional) or externalising (hyperactivity and conduct) problems (measured at age 11 years), both before and after adjustment for potential confounders. Results: IL-6 partially mediated the effect of peer victimisation on peer problems, even after adjustment for potential confounders. Inflammation did not mediate the effect of stressful life events on either type of internalising problems. Neither stressor predicted externalising problems via inflammation. Conclusion: We did not find evidence that inflammation mediates the effect of stressful life events on mental health in childhood when they are considered alongside experiences of peer victimisation. Inflammation may already represent a form of biological embedding of peer victimisation in the early years.

The role of mild stressors in children's cognition and inflammation: positive and negative impacts depend on timing of exposure.

Although the impact of stressful life events (SLEs) on mental health is well-established, the research on the impact of such stressors on cognitive outcomes has produced mixed results. Arguably, the timing and severity of exposure may play a key role. In this study, we shed light on the relationship between timing of exposure to relatively minor SLEs and cognitive ability in children, while taking into account the role of a plausible biological mediator: inflammation. Using data from the Avon Longitudinal Study of Parents and Children, a general population birth cohort, we explored the role of relatively minor SLEs, experienced during two crucial developmental stages: up to transition to school (1-4.5 years) and up to transition to puberty (5.5-8.5 years). We then tested if they may impact differently on inflammatory markers (serum C-reactive protein [CRP] and interleukin 6 [IL-6]) at age 9 and general intelligence, measured with the Wechsler Abbreviated Scale of Intelligence at age 15. Data (n = 4,525) were analyzed using path analysis while controlling for covariates. We found that when relatively minor stressful events were experienced up to transition to school they were significantly associated with higher IQ at age 15, whereas when experienced up to transition to puberty they were significantly associated with higher levels of IL-6 at age 9. Results were robust to adjustment for relevant covariates, including IQ at age 8. Mild stressors in childhood may result in positive (i.e., improved cognition) or negative (i.e., inflammation) outcomes depending on the timing of exposure.

Decision-making difficulties mediate the association between poor emotion regulation and eating disorder symptoms in adolescence.

BACKGROUND: The emergence of eating problems during childhood increases the risk for eating disorders (EDs) during young adulthood. Previous studies highlight a relationship between poor self-regulation and onset of eating pathology. In this study, we investigated whether this association is mediated by decision-making difficulties. METHODS: To test this hypothesis, we used data from the Millennium Cohort Study. Decision-making performance was assessed with the Cambridge Gambling Task at age 11. Principal components analysis was used to derive an index of ED symptoms at age 14. The trajectories of scores of two subscales of the Child Social Behaviour Questionnaire, Independence and Self-Regulation (ISR) and Emotional Dysregulation (EmotDy), were modelled from ages 3 to 7 years in a latent growth curve analysis. The individual predicted values of the intercept (set at baseline, 3 years) and the slope (rate of annual change) were then used in the mediation analysis. RESULTS: In our sample of 11 303 individuals, there was evidence for mediation by three measures of decision-making at age 11 (poor quality of decision-making, delay aversion and low risk-adjustment) in the association between EmotDy across ages 3-7 and ED symptoms at age 14 even after the adjustment for relevant covariates. We found no evidence of association between ISR and ED symptoms. CONCLUSION: Our findings suggest that emotion regulation processes during childhood may be relevant for the future onset of ED symptoms via their association with decision-making skills. These findings, obtained from a large, representative, sample, shed light on the relationship between self-regulation, decision-making and symptoms of EDs.

Does decision-making at age 11 predict prodromal eating pathology at ages 14 and 17? A prospective, observational, UK population-based cohort study.

OBJECTIVES: We examined whether decision-making at age 11 and 14 is associated with prodromal eating pathology at age 14 and whether it would persist across adolescence and also be present at age 17. DESIGN: This prospective, observational, population-based cohort study used a longitudinal design. SETTING: Data from the Millennium Cohort Study (MCS), a UK longitudinal cohort study involving 19 244 families from England, Scotland, Wales and Northern Ireland, were analysed. PARTICIPANTS: We modelled data from 8922 boys and girls aged 11, 14 and 17 (MCS sweeps 5, 6 and 7). PRIMARY AND SECONDARY OUTCOMES: We investigated decision-making using the risk-taking, quality of decision-making, deliberation time, delay aversion and risk adjustment subscales of the Cambridge Gambling Task and prodromal eating pathology through binary response items measuring: body dissatisfaction (whether the participant perceived their body as being too overweight); intention to lose weight (whether participants reported a strong desire to lose weight); dietary restriction (whether participants reported actively eating less to influence their shape/weight) and excessive exercise (whether participants reported exercising in a driven way in order to influence weight/shape). Data were analysed using latent class analysis and logistic regression. RESULTS: Lower scores on quality of decision-making (OR=0.46) and deliberation time (OR=0.99) at age 14 were associated with prodromal eating pathology at both ages 14 and 17 (all p<0.05), indicating an association between less frequently opting to bet on the most likely outcome and taking less time to decide on which bet to choose and the persistence of prodromal eating pathology over adolescence. Lower deliberation time (OR=0.99) and delay aversion (OR=0.62) at 11 and lower risk-taking scores at 14 (OR=0.43) were associated with the absence of prodromal eating pathology at 14 and 17 (all p<0.05), indicating that a moderate approach under conditions of risk in childhood and mid-adolescence is associated with reduced eating pathology across adolescence. CONCLUSIONS: Training advantageous decision-making might protect from later prodromal eating pathology.

The role of inflammatory markers and cortisol in the association between early social cognition abilities and later internalising or externalising problems: Evidence from a UK birth cohort.

OBJECTIVE: Deficits in social cognition are associated with internalising (emotional and peer problems) and externalising (conduct problems and hyperactivity/inattention) symptoms in youth. It has been suggested that stress may be one of the mechanisms underlying these associations. However, no empirical studies have investigated if physiological stress can explain the prospective associations between social cognition deficits and internalising and externalising symptoms in the general youth population. This study addressed this question and focused on two indicators of physiological stress, dysregulated diurnal cortisol patterns and systemic inflammation. METHOD: Participants were 714 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK population-based birth cohort. Bayesian structural equation modelling was used to investigate a) the associations of social cognition abilities at ages 8, 11, and 14 years with internalising and externalising problems at age 17 years and b) the potential mediating effects of cortisol parameters at age 15 years and inflammatory markers [interleukin 6 (IL-6) and C-reactive protein (CRP)] at ages 9 and 16 years. RESULTS: We found that social cognition difficulties were associated with later internalising and externalising problems. Flattened diurnal cortisol slope was associated with hyperactivity/inattention problems two years later. Lower morning cortisol partially mediated the direct association between social communication deficits at 8 years and hyperactivity/inattention and conduct problems at 17 years, even after adjustments for inflammation and confounders (for hyperactivity/inattention: indirect effect = 0.07, 95% CI [0.00, 0.18], p = .042; for conduct problems: indirect effect = 0.04, 95% CI [0.00, 0.11], p = .040). We did not find a significant association between systemic inflammation and social cognition difficulties, internalising problems, or externalising problems. CONCLUSION: Our findings suggest that part of the effect of social communication difficulties in childhood on externalising problems in adolescence was mediated by lower morning cortisol. Hence, our study indicates that the hypoactivity of the hypothalamic-pituitary-adrenal (HPA) axis may be one of the physiological mechanisms linking some social cognition deficits to externalising problems.

Types of Eating Disorder Prodrome in Adolescence: The Role of Decision Making in Childhood.

Psychiatric disorders like eating disorders (EDs) might be underpinned by differences in decision making. However, little previous research has investigated this potential relationship using longitudinal data. This study aimed to understand how components of decision making (delay aversion, risk adjustment, risk taking, quality of decision making and deliberation time) measured by the Cambridge Gambling Task in the United Kingdom's Millennium Cohort Study (MCS; n = 11,303; female = 50.17%) at age 11 might explain clusters/types of ED prodrome involving body dissatisfaction, intention to lose weight, dietary restraint, excessive exercise and significant under/overweight measured in the MCS at age 14. Latent class analysis revealed two groups within the cohort: a non-prodromal eating pathology group, who were more likely to be of "average" weight, according to the UK90, with minimal disordered attitudes and behaviors in relation to eating and weight; and a second group with prodromal eating pathology, who had more body dissatisfaction, a desire to lose weight, were using dietary restriction and exercise to influence weight and were more likely to be "overweight" according to the UK90. Logistic regression showed that, after adjustment for confounding, higher risk-taking scores were associated with a 60% greater probability of being in the prodromal eating pathology group (b = 0.47, OR = 1.60, p < 0.01), and higher scores on quality of decision making were associated with a 30% lower probability of being in the prodromal eating pathology group (b = -0.34, OR = 0.70, p < 0.05). Helping young people to engage in moderate risk taking and improving decision making might reduce the later presence of ED prodromes.

Decision-Making in Childhood Predicts Prodromal Eating Pathology in Adolescence.

OBJECTIVE: Differences in decision-making under conditions of risk have been observed cross-sectionally in clinical groups of people with eating disorders but have never been studied longitudinally or in large cohorts. We investigated whether responses on the Cambridge Gambling Task (CGT), measured in the Millennium Cohort Study in childhood, would predict prodromal eating pathology in adolescence. METHOD: Regression models were built to explore relationships between CGT variables at age 11 years and prodromal eating pathology (body dissatisfaction, intention to lose weight, dietary restriction, significant under/overweight, and excessive exercise) at 14 years. RESULTS: In 11,303 boys and girls, those with better quality decision-making were 34% less likely to show an intention to lose weight (b = -0.40, odds ratio [OR] = 0.66, p < 0.05) and 34% less likely to be overweight (b = -0.41, relative risk ratio [RRR] = 0.66, p < 0.05). Those with higher risk-taking were 58% more likely to report dietary restriction (b = 0.45, OR = 1.58, p < 0.05) and 46% more likely to report excessive exercise (b = 0.38, OR = 1.46, p < 0.05). In the complete-cases sample, higher risk-adjustment scores were associated with a 47% increased risk of underweight (b = 0.39, RRR = 1.47, p < 0.05), and better quality of decision-making was associated with a 46% lower risk of overweight (b = -0.60, RRR = 0.54, p < 0.05). CONCLUSION: Disadvantageous decision-making in childhood may predict prodromal eating pathology in adolescence and might represent a prevention target.

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.

Endocannabinoid system mediates the association between gut-microbial diversity and anhedonia/amotivation in a general population cohort.

Anhedonia and amotivation are debilitating symptoms and represent unmet therapeutic needs in a range of clinical conditions. The gut-microbiome-endocannabinoid axis might represent a potential modifiable target for interventions. Based on results obtained from animal models, we tested the hypothesis that the endocannabinoid system mediates the association between gut-microbiome diversity and anhedonia/amotivation in a general population cohort. We used longitudinal data collected from 786 volunteer twins recruited as part the TwinsUK register. Our hypothesis was tested with a multilevel mediation model using family structure as random intercept. The model was set using alpha diversity (within-individual gut-microbial diversity) as predictor, serum and faecal levels of the endocannabinoid palmitoylethanolamide (PEA) as mediator, and anhedonia/amotivation as outcome. PEA is considered the endogenous equivalent of cannabidiol, with increased serum levels believed to have anti-depressive effects, while increased stool PEA levels, reflecting increased excretion, are believed to have opposite, detrimental, effects on mental health. We therefore expected that either reduced serum PEA or increased stool PEA would mediate the association between microbial diversity and anhedonia amotivation. Analyses were adjusted for obesity, diet, antidepressant use, sociodemographic and technical covariates. Data were imputed using multiple imputation by chained equations. Mean age was 65.2 ± 7.6; 93% of the sample were females. We found a direct, significant, association between alpha diversity and anhedonia/amotivation (ß = -0.37; 95%CI: -0.71 to -0.03; P = 0.03). Faecal, but not serum, levels of the endocannabinoid palmitoylethanolamide (PEA) mediated this association: the indirect effect was significant (ß = -0.13; 95%CI: -0.24 to -0.01; P = 0.03), as was the total effect (ß = -0.38; 95%CI: -0.72 to -0.04; P = 0.03), whereas the direct effect of alpha diversity on anhedonia/amotivation was attenuated fully (ß = -0.25; 95%CI: -0.60 to 0.09; P = 0.16). Our results suggest that gut-microbial diversity might contribute to anhedonia/amotivation via the endocannabinoid system. These findings shed light on the biological underpinnings of anhedonia/amotivation and suggest the gut microbiota-endocannabinoid axis as a promising therapeutic target in an area of unmet clinical need.

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.

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.

Trajectories of internalising and externalising symptoms and inflammation in the general child population.

BACKGROUND: Elevations in inflammatory marker levels have been shown to precede internalising and externalising problems in the general child population. One study has found the reverse, that elevations in inflammatory marker levels in childhood follow internalising and externalising problems. However, the authors did not explore the role of the course of these problems in childhood or adjust for a number of potential confounders including psychosocial stressors and prenatal and perinatal exposures. AIMS: To investigate the association in childhood between the growth of internalising and externalising symptoms and levels of inflammatory markers, while accounting for potential confounders. METHODS: Using data from the Avon Longitudinal Study of Parents and Children, we tested the association between the trajectories of internalising (emotional and social) and externalising (hyperactivity and conduct) problems, at ages 4, 6, 8 and 9 years, and levels of C-reactive protein (CRP) and interleukin 6 (IL-6) at age 9 years. We analysed data (n = 4525) using latent growth curve modelling and linear regression. RESULTS: Children who had increasing levels of internalising symptoms over childhood were more likely to have higher levels of CRP and IL-6 at 9 years of age, even after adjustment for confounders. A one-unit increase in the rate of annual change of internalising symptoms was related to an increase of 12% and 8% in the level of CRP and IL-6, respectively. However, there was no evidence for an association between externalising symptoms and either inflammatory marker. CONCLUSIONS: This study is the first step towards identifying a robust pathway, via increases in emotional and social difficulties, to elevated inflammation in healthy children. This association, if causal, suggests that effective interventions for children experiencing chronic emotional and social difficulties could also have physical health benefits.

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.

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.

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.

Correction to: Main and interactive effects of inflammation and perceived neighbourhood cohesion on psychological distress: results from a population-based study in the UK.

The article "Main and interactive effects of inflammation and perceived neighbourhood cohesion on psychological distress: results from a population-based study in the UK", written by "Efstathios Papachristou, Eirini Flouri, Theodora Kokosi and Marta Francesconi", was originally published electronically on the publisher's Internet portal (currently SpringerLink) on 25 February 2019 without open access.

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

OBJECTIVE: To explore whether paternal psychological distress is related to the longitudinal course of child problem behavior after accounting for maternal psychological distress. METHOD: We used data from the Millennium Cohort Study (MCS), a large general-population birth cohort in the United Kingdom. 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 behavior was measured with the Strengths and Difficulties Questionnaire at these ages. Data were analyzed using growth curve modeling, 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 behavior that 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 nonbiological 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 in girls. CONCLUSION: There was evidence for a robust association between psychological distress in fathers and problem behavior in their offspring. Our findings suggest that the mental health of both fathers and mothers is important for the behavior of their children.

Stressful life events, inflammation and emotional and behavioural problems in children: A population-based study.

OBJECTIVE: To test the hypothesis that higher plasma levels of inflammatory markers due to exposure to adverse life events may lead to internalising and externalising symptoms in children. METHOD: Using data from 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 explain the longitudinal association between adverse life events (at ages 1-9 and 9-11 years) and internalising and externalising symptoms (at ages 9 and 11 years). Data (n = 4583) were analysed using cross-lagged panel modelling to take into account reciprocal associations and reverse causality, and path analyses to test for mediation. Gender, ethnicity, body mass index, maternal education, paternal social class and maternal depression were used as potential confounders. RESULTS: CRP was not associated with adverse life events. There was evidence for partial mediation by IL-6 such that exposure to adverse life events was associated with increased levels of IL-6 later, in turn associated with later internalising symptoms. These associations were robust to adjustment for confounders. IL-6 did not explain part of the opposite association, that of earlier internalising symptoms and later life events, nor did it explain either direction of the association between life events and externalising symptoms. CONCLUSION: Our findings suggest a pathway that may connect early psychosocial adversity and childhood internalising symptoms via higher plasma levels of inflammatory markers, such as IL-6.

Main and interactive effects of inflammation and perceived neighbourhood cohesion on psychological distress: results from a population-based study in the UK.

PURPOSE: Low neighbourhood cohesion and increased levels of inflammation are independent predictors of psychological distress. In this study we explored if they also interact to predict it. METHODS: Our sample was 9,393 adult participants of the UK Household Longitudinal Study (UKHLS), a large longitudinal household panel study in the UK. Inflammation was measured using C-reactive protein levels. Perceived neighbourhood cohesion was measured using a 13-item questionnaire. Psychological distress was measured with the General Health Questionnaire-12. RESULTS: Perceived neighbourhood cohesion and inflammation retained their significant main effects on psychological distress even after adjustment for confounders (age, gender, ethnicity, partner status, education, smoking status, obesity and urbanicity). The effect of neighbourhood cohesion was larger. However, we did not find evidence for an interactive association between the two. CONCLUSIONS: Perceived neighbourhood cohesion was inversely related to psychological distress, over and above other important person- and neighbourhood-level characteristics. Inflammation was also associated with psychological distress, albeit less strongly. If these associations are causal, they suggest that promoting neighbourhood cohesion can alleviate some of the burden associated with psychological distress.

Investigating the link between drug-naive first episode psychoses (FEPs), weight gain abnormalities and brain structural damages: Relevance and implications for therapy.

Evidence suggests that obesity and overweight may be associated with severe brain structural abnormalities and poor cognitive and functional outcomes in the general population. Despite these observations and the high prevalence of weight gain abnormalities in patients with psychosis spectrum disorders (PSDs), no studies have investigated the impact that these metabolic disturbances may have on brain structures and development in the earliest stages of PSDs. In the present review we shed light on the association between weight gain and brain structural abnormalities that may affect the course of illness in drug-naïve FEPs. Given the lack of studies directly investigating this issue, we firstly identified and critically evaluated the literature assessing weight gain abnormalities and gray or white matter (GM, WM) volumes (either globally or in specific regions of interest) in otherwise healthy obese/overweight adolescents and young adults. We then compared the results of this systematic review with those of two recent meta-analysis investigating GM and WM abnormalities in drug-naïve FEPs. Weight gain in otherwise healthy subjects was consistently associated with frontal and temporal GM atrophy and with reduced integrity of WM in the corpus callosum. Of relevance, all these brain regions are affected in drug-naïve FEPs, and their integrity is associated with clinical, cognitive and functional outcomes. The underlying mechanisms that may explain the association between weight gain, adiposity, and brain damage in both healthy subjects and drug-naïve FEPs are widely discussed. On the basis of this knowledge, we tried: a) to deduce an integrative model for the development of obesity in psychosis spectrum disorders; b) to identify the key vulnerability factors underlying the association between weight gain and psychosis; c) to provide information on new potential targets of intervention.