Longitudinal studies have revealed that raised levels of inflammatory markers and trauma in childhood are associated with psychopathology in adulthood.

To examine whether inflammation in childhood mediates the effects of genetic risk and trauma on psychopathology in early adulthood.

Measures of trauma exposure, inflammation and psychopathology were collected from the Avon Longitudinal Study of Parents and Children. Exposure to trauma was measured from 5 to 11 years of age; C-reactive protein and interleukin-6 levels were measured at 9 years; and depression, anxiety disorders, negative symptoms and psychotic experiences were assessed at 24 years. Polygenic risk scores (PRSs) were created for schizophrenia, depression, anxiety and psychotic experiences. Mediation analyses were conducted using imputed data (N: 7859 to 8700) to investigate whether inflammation mediated the associations of genetic risk and childhood trauma with psychopathology.

Most psychiatric PRSs were associated with multiple psychopathological outcomes in adulthood, with the exception of the PRS for psychotic experiences. Childhood trauma was associated with all psychopathology. However, there was no strong evidence that inflammatory markers in childhood mediated associations among PRSs, trauma and psychopathology. Sensitivity analyses using outcomes from age 18 and PRSs based on single-nucleotide polymorphisms that met more stringent standards of evidence of association gave results consistent with those of our primary analyses.

We found little evidence that interleukin-6 or C-reactive protein mediated the pathway between genetic liability for psychiatric phenotypes or trauma and subsequent psychopathology. Longitudinal investigation of other inflammatory and non-inflammatory pathways is required to identify modifiable targets and inform novel treatment strategies for individuals at genetic or trauma-related risk of psychiatric illness.

Peripheral inflammatory markers, including serum interleukin 6 (IL-6), are associated with depression, but less is known about how these markers associate with depression at different stages of the life course.

We examined the associations between serum IL-6 levels at baseline and subsequent depression symptom trajectories in two longitudinal cohorts: ALSPAC (age 10–28 years; N = 4,835) and UK Biobank (39–86 years; N = 39,613) using multilevel growth curve modeling. Models were adjusted for sex, BMI, and socioeconomic factors. Depressive symptoms were measured using the Short Moods and Feelings Questionnaire in ALSPAC (max time points = 11) and the Patient Health Questionnaire-2 in UK Biobank (max time points = 8).

Higher baseline IL-6 was associated with worse depression symptom trajectories in both cohorts (largest effect size: 0.046 [ALSPAC, age 16 years]). These associations were stronger in the younger ALSPAC cohort, where additionally higher IL-6 levels at age 9 years was associated with worse depression symptoms trajectories in females compared to males. Weaker sex differences were observed in the older cohort, UK Biobank. However, statistically significant associations (pFDR <0.05) were of smaller effect sizes, typical of large cohort studies.

These findings suggest that systemic inflammation may influence the severity and course of depressive symptoms across the life course, which is apparent regardless of age and differences in measures and number of time points between these large, population-based cohorts.

Few studies have examined how parenting influences the associations between prenatal maternal stress and children's mental health. The objectives of this study were to examine the sex-specific associations between prenatal maternal stress and child internalizing and externalizing symptoms, and to assess the moderating effects of parenting behaviors on these associations.

This study is based on 15 963 mother–child dyads from the Norwegian Mother, Father, and Child Cohort Study (MoBa). A broad measure of prenatal maternal stress was constructed using 41 self-reported items measured during pregnancy. Three parenting behaviors (positive parenting, inconsistent discipline, and positive involvement) were assessed by maternal report at child age 5 years. Child symptoms of internalizing and externalizing disorders (depression, anxiety, attention-deficit hyperactivity disorder, conduct disorder, and oppositional-defiant disorder) were assessed by maternal report at age 8. Analyses were conducted using structural equation modeling techniques.

Prenatal maternal stress was associated with child internalizing and externalizing symptoms at age 8; associations with externalizing symptoms differed by sex. Associations between prenatal maternal stress and child depression, and conduct disorder and oppositional-defiant disorder in males, became stronger as levels of inconsistent discipline increased. Associations between prenatal maternal stress and symptoms of attention-deficit hyperactivity disorder in females were attenuated as levels of parental involvement increased.

This study confirms associations between prenatal maternal stress and children's mental health outcomes, and demonstrates that these associations may be modified by parenting behaviors. Parenting may represent an important intervention target for improving mental health outcomes in children exposed to prenatal stress.

Depression is a common and serious mental illness that begins early in life. An association between cardiovascular disease (CVD) and subsequent depression is clear in adults. We examined associations between individual CVD risk factors and depression in young people.

We searched MEDLINE, EMBASE, and PsycINFO databases from inception to 1 January 2020. We extracted data from cohort studies assessing the longitudinal association between CVD risk factors [body mass index (BMI), smoking, systolic blood pressure (SBP), total cholesterol, high-density lipoprotein] and depression, measured using a validated tool in individuals with mean age of 24 years or younger. Random effect meta-analysis was used to combine effect estimates from individual studies, including odds ratio (OR) for depression and standardised mean difference for depressive symptoms.

Based on meta-analysis of seven studies, comprising 15 753 participants, high BMI was associated with subsequent depression [pooled OR 1.61; 95% confidence interval (CI) 1.21–2.14; I2 = 31%]. Based on meta-analysis of eight studies, comprising 30 539 participants, smoking was associated with subsequent depression (pooled OR 1.73; 95% CI 1.36–2.20; I2 = 74%). Low, but not high, SBP was associated with an increased risk of depression (pooled OR 3.32; 95% CI 1.68–6.55; I2 = 0%), although this was based on a small pooled high-risk sample of 893 participants. Generalisability may be limited as most studies were based in North America or Europe.

Targeting childhood/adolescent smoking and obesity may be important for the prevention of both CVD and depression across the lifespan. Further research on other CVD risk factors including blood pressure and cholesterol in young people is required.

Childhood infections are associated with adult psychosis and depression, but studies of psychotic experiences (PEs) and depressive symptoms in childhood, adolescence, and early-adulthood are scarce. Previous studies have typically examined severe infections, but studies of common infections are also scarce.

Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort, we examined associations of the number of infections in childhood from age 1.5 to 7.5 years with depressive symptom scores at age 10, 13, 14, 17, 18, and 19 years, and with PEs at 12 and 18 years. We performed additional analysis using infection burden (‘low’ = 0–4 infections, ‘medium’ = 5–6, ‘high’ = 7–9, or ‘very high’ = 10–22 infections) as the exposure.

The risk set comprised 11 786 individuals with childhood infection data. Number of childhood infections was associated with depressive symptoms from age 10 (adjusted beta = 0.14; standard error (s.e.) = 0.04; p = <0.01) to 17 years (adjusted beta = 0.17; s.e. = 0.08; p = 0.04), and with PEs at age 12 (suspected/definite PEs: adjusted odds ratio (OR) = 1.18; 95% confidence interval (CI) = 1.09–1.27). These effect sizes were larger when the exposure was defined as very high infection burden (depressive symptoms age 17: adjusted beta = 0.79; s.e. = 0.29; p = 0.01; suspected/definite PEs at age 12: adjusted OR = 1.60; 95% CI = 1.25–2.05). Childhood infections were not associated with depressive/psychotic outcomes at age 18 or 19.

Common early-childhood infections are associated with depressive symptoms up to mid-adolescence and with PEs subsequently in childhood, but not with these outcomes in early-adulthood. These findings require replication including larger samples with outcomes in adulthood.

Peripheral low-grade inflammation in depression is increasingly seen as a therapeutic target. We aimed to establish the prevalence of low-grade inflammation in depression, using different C-reactive protein (CRP) levels, through a systematic literature review and meta-analysis.

We searched the PubMed database from its inception to July 2018, and selected studies that assessed depression using a validated tool/scale, and allowed the calculation of the proportion of patients with low-grade inflammation (CRP >3 mg/L) or elevated CRP (>1 mg/L).

After quality assessment, 37 studies comprising 13 541 depressed patients and 155 728 controls were included. Based on the meta-analysis of 30 studies, the prevalence of low-grade inflammation (CRP >3 mg/L) in depression was 27% (95% CI 21–34%); this prevalence was not associated with sample source (inpatient, outpatient or population-based), antidepressant treatment, participant age, BMI or ethnicity. Based on the meta-analysis of 17 studies of depression and matched healthy controls, the odds ratio for low-grade inflammation in depression was 1.46 (95% CI 1.22–1.75). The prevalence of elevated CRP (>1 mg/L) in depression was 58% (95% CI 47–69%), and the meta-analytic odds ratio for elevated CRP in depression compared with controls was 1.47 (95% CI 1.18–1.82).

About a quarter of patients with depression show evidence of low-grade inflammation, and over half of patients show mildly elevated CRP levels. There are significant differences in the prevalence of low-grade inflammation between patients and matched healthy controls. These findings suggest that inflammation could be relevant to a large number of patients with depression.

Prenatal infections have been proposed as a putative risk factor for a number of psychiatric outcomes across a continuum of severity. Evidence on eating disorders is scarce. We investigated whether exposure to prenatal maternal infections is associated with an increased risk of disordered eating and weight and shape concerns in adolescence in a large UK birth cohort.

We used data from the Avon Longitudinal Study of Parents and Children. The primary exposure was maternal experience of infections at any time in pregnancy. Study outcomes were presence of any, monthly or weekly disordered eating at 14 and 16 years of age, and weight and shape concerns at 14 years. We defined the causal effect of the exposure on these outcomes using a counterfactual framework adjusting our analyses for a number of hypothesised confounders, and imputing missing confounder data using multiple imputation.

In total, 4884 children had complete exposure and outcome data at age 14 years, and 4124 at 16 years. Exposed children had a greater risk of reporting weekly disordered eating at both age 14 [risk difference (RD) 0.9%, 95% confidence interval (CI) −0.01 to 1.9, p = 0.08] and 16 (RD 2.3%, 95% CI 0.6–3.9, p < 0.01), though evidence of an association was weak at age 14 years. Exposed children also had greater weight and shape concerns at age 14 years (mean difference 0.15, 95% CI 0.05–0.26, p < 0.01).

Exposure to prenatal maternal infection is associated with greater risk of disordered eating in adolescence. This association could be explained by in utero processes leading to impaired neurodevelopment or altered immunological profiles. Residual confounding cannot be excluded.

Schizophrenia is associated with impaired neurodevelopment as indexed by lower premorbid IQ. We examined associations between erythrocyte sedimentation rate (ESR), a marker of low-grade systemic inflammation, IQ, and subsequent schizophrenia and other non-affective psychoses (ONAP) to elucidate the role of neurodevelopment and inflammation in the pathogenesis of psychosis.

Population-based data on ESR and IQ from 638 213 Swedish men assessed during military conscription between 1969 and 1983 were linked to National Hospital Discharge Register for hospitalisation with schizophrenia and ONAP. The associations of ESR with IQ (cross-sectional) and psychoses (longitudinal) were investigated using linear and Cox-regression. The co-relative analysis was used to examine effects of shared familial confounding. We examined mediation and moderation of effect between ESR and IQ on psychosis risk.

Baseline IQ was associated with subsequent risk of schizophrenia (adjusted HR per 1-point increase in IQ = 0.961; 95% confidence interval (CI) 0.960–0.963) and ONAP (adjusted HR = 0.973; 95% CI 0.971–0.975). Higher ESR was associated with lower IQ in a dose-response fashion. High ESR was associated with increased risk for schizophrenia (adjusted HR = 1.14; 95% CI 1.01–1.28) and decreased risk for ONAP (adjusted HR = 0.85; 95% CI 0.74–0.96), although these effects were specific to one ESR band (7–10 mm/hr). Familial confounding explained ESR-IQ but not ESR-psychoses associations. IQ partly mediated the ESR-psychosis relationships.

Lower IQ is associated with low-grade systemic inflammation and with an increased risk of schizophrenia and ONAP in adulthood. Low-grade inflammation may influence schizophrenia risk by affecting neurodevelopment. Future studies should explore the differential effects of inflammation on different types of psychosis.

To identify training needs of the next generation of psychiatrists and barriers in prescribing first-generation antipsychotics (FGAs). We have surveyed psychiatry trainees in East Anglia with regard to their training experience, knowledge and attitudes to the use of oral FGAs as regular medication.

Two-thirds of trainees were aware that first- and second-generation antipsychotics (SGAs) have similar efficacy, and a similar proportion perceived the older drugs to have more or ‘stronger’ side-effects. Lack of training experience was noted as the second leading concern for prescribing FGAs. A quarter of trainees received no training exposure to the older drugs and two-thirds had never initiated these drugs themselves. Although nearly 90% of trainees felt confident about initiating an oral SGA as a regular medication, only about 40% felt confident with FGAs (P<0.001).

The survey highlights worrying gaps in training. FGAs can be used effectively, minimising side-effects, by careful dose titration, avoiding antipsychotic polypharmacy, high-dose, and high-potency drugs, thus ensuring they are not lost to future generations of psychiatrists.