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There is growing evidence that in utero imbalance immune activity plays a role in the development of neurodevelopmental and psychiatric disorders in children. Mood dysregulation (MD) is a debilitating transnosographic syndrome whose underlying pathophysiological mechanisms could be revealed by studying its biomarkers using the Research Domain Criteria (RDoC) model. Our aim was to study the association between the network of cord serum cytokines, and mood dysregulation trajectories in offsprings between 3 and 8 years of age. We used the data of a study nested in the French birth cohort EDEN that took place from 2003 to 2014 and followed mother-child dyads from the second trimester of pregnancy until the children were 8 years of age. The 2002 mother-child dyads were recruited from the general population through their pregnancy follow-up in two French university hospitals. 871 of them were included in the nested cohort and cord serum cytokine levels were measured at birth. Children's mood dysregulation symptoms were assessed with the Strengths and Difficulties Questionnaire Dysregulation Profile at the ages 3, 5 and 8 years in order to model their mood dysregulation trajectories. Out of the 871 participating dyads, 53% of the children were male. 2.1% of the children presented a high mood dysregulation trajectory whereas the others were considered as physiological variations. We found a significant negative association between TNF-α cord serum levels and a high mood dysregulation trajectory when considering confounding factors such as maternal depression during pregnancy (adjusted Odds Ratio (aOR) = 0.35, 95% Confidence Interval (CI) [0.18–0.67]). Immune imbalance at birth could play a role in the onset of mood dysregulation symptoms. Our findings throw new light on putative immune mechanisms implicated in the development of mood dysregulation and should lead to future animal and epidemiological studies.

Background: Metabolic syndrome (MetS) is a highly prevalent and harmful medical disorder often comorbid with psychosis where it can contribute to cardiovascular complications. As immune dysfunction is a key shared component of both MetS and schizophrenia (SZ), this study investigated the relationship between immune alterations and MetS in patients with SZ, whilst controlling the impact of confounding clinical characteristics including psychiatric symptoms and comorbidities, history of childhood maltreatment and psychotropic treatments. Method: A total of 310 patients meeting DSM-IV criteria for SZ or schizoaffective disorders (SZA), with or without MetS, were systematically assessed and included in the FondaMental Advanced Centers of Expertise for Schizophrenia (FACE-SZ) cohort. Detailed clinical characteristics of patients, including psychotic symptomatology, psychiatric comorbidities and history of childhood maltreatment were recorded and the serum levels of 18 cytokines were measured. A penalized regression method was performed to analyze associations between inflammation and MetS, whilst controlling for confounding factors. Results: Of the total sample, 25% of patients had MetS. Eight cytokines were above the lower limit of detection (LLOD) in more than 90% of the samples and retained in downstream analysis. Using a conservative Variable Inclusion Probability (VIP) of 75%, we found that elevated levels of interleukin (IL)-6, IL-7, IL-12/23 p40 and IL-16 and lower levels of tumor necrosis factor (TNF)-α were associated with MetS. As for clinical variables, age, sex, body mass index (BMI), diagnosis of SZ (not SZA), age at the first episode of psychosis (FEP), alcohol abuse, current tobacco smoking, and treatment with antidepressants and anxiolytics were all associated with MetS. Conclusion: We have identified five cytokines associated with MetS in SZ suggesting that patients with psychotic disorders and MetS are characterized by a specific “immuno-metabolic” profile. This may help to design tailored treatments for this subgroup of patients with both psychotic disorders and MetS, taking one more step towards precision medicine in psychiatry.

Sleep is essential for optimal child development and health during the life course. However, sleep disturbances are common in early childhood and increase the risk of cognitive, metabolic and inflammatory disorders throughout life. Sleep and immunity are mutually linked, and cytokines secreted by immune cells could mediate this interaction. The sleep modulation of cytokines has been studied mostly in adults and adolescents; few studies have focused on school-aged children and none on preschoolers. We hypothesized that night sleep duration affects cytokine levels in preschoolers. In a sample of 687 children from the EDEN French birth cohort, we studied the associations between night sleep duration trajectories from age to 2–5 years old and serum concentrations of four cytokines (Tumor necrosis factor α [TNF-α], Interleukin 6 [IL-6], IL-10, Interferon γ [IFN)-γ] at age 5, adjusting for relevant covariates. As compared with the reference trajectory (≈11h30/night sleep, 37.4% of children), a shorter sleep duration trajectory (

Bipolar disorder (BD) diagnosis currently relies on assessment of clinical symptoms, mainly retrospective and subject to memory bias. BD is often misdiagnosed as Major Depressive Disorder (MDD) resulting in ineffective treatment and worsened clinical outcome. The primary purpose of this study was to identify blood biomarkers that discriminate MDD from BD patients when in a depressed state. We have used clinical data and serum samples from two independent naturalistic cohorts of patients with a Major Depressive Episode (MDE) who fulfilled the criteria of either BD or MDD at inclusion. The discovery and replication cohorts consisted of 462 and 133 patients respectively. Patients were clinically assessed using standard diagnostic interviews, and clinical variables including current treatments were recorded. Blood was collected and serum assessed for levels of 31 cytokines using a sensitive multiplex assay. A penalized logistic regression model combined with nonparametric bootstrap was subsequently used to identify cytokines associated with BD. Interleukin (IL)-6, IL-10, IL-15, IL-27 and C-X-C ligand chemokine (CXCL)-10 were positively associated with BD in the discovery cohort. Of the five cytokines identified as discriminant features in the discovery cohort, IL-10, IL-15 and IL-27 were also positively associated with BD in the replication cohort therefore providing an external validation to our finding. Should our results be validated in a prospective cohort, they could provide new insights into the pathophysiological mechanisms of mood disorders.

Disruption of neurodevelopmental trajectories can alter brain circuitry and increase the risk of psychopathology later in life. While preclinical studies have demonstrated that the immune system and cytokines influence neurodevelopment, whether immune activity and in particular which cytokines at birth are associated with psychopathology remains poorly explored in children. We used data and biological samples from 869 mother-child pairs participating in the French mother-child cohort EDEN. As proxies for immune activity at birth, we measured the levels of 27 cytokines in umbilical cord blood sera (CBS). We then explored the association between CBS cytokine levels and five psychopathological dimensions assessed in 5-year-old children using the Strengths and Difficulties Questionnaire (SDQ). Five cytokines were positively associated with psychopathology: C-X-C motif chemokine Ligand (CXCL)10, interleukin (IL)-10 and IL-12p40 with emotional symptoms, C–C motif chemokine Ligand (CCL)11 with conduct problems, and CCL11, and IL-17A with peer relationships problems. In contrast, seven cytokines were negatively associated with psychopathology: IL-7, IL-15 and Tumor Necrosis Factor (TNF)-β with emotional symptoms, CCL4 and IL-6 with conduct problems, CCL26 and IL-15 with peer relationships problems, and CCL26, IL-7, IL-15, and TNF-α with abnormal prosocial behavior. Without implying causation, these associations support the notion that cytokines influence neurodevelopment in humans and the risk of psychopathology later in life.