Systematic Review and Meta-Analysis: Early Irritability as a Transdiagnostic Neurodevelopmental Vulnerability to Later Mental Health Problems.

OBJECTIVE: Irritability is a transdiagnostic indicator of child and adolescent internalizing and externalizing problems that is measurable from early life. The objective of this systematic review was to determine the strength of the association between irritability measured from 0 to 5 years and later internalizing and externalizing problems, to identify mediators and moderators of these relationships, and to explore whether the strength of the association varied according to irritability operationalization. METHOD: Relevant studies published in peer-reviewed, English-language journals between the years 2000 and 2021 were sought from EMBASE, PsycINFO, MEDLINE, CINAHL, and ERIC. We synthesized studies that included a measure of irritability within the first 5 years of life and reported associations with later internalizing and/or externalizing problems. Methodological quality was assessed using the JBI-SUMARI Critical Appraisal Checklist. RESULTS: Of 29,818 identified studies, 98 met inclusion criteria, with a total number of 932,229 participants. Meta-analysis was conducted on 70 studies (n = 831,913). Small, pooled associations were observed between infant irritability (0-12 months) and later internalizing (r = 0.14, 95% CI = 0.09, 0.20) and externalizing symptoms (r = 0.16, 95% CI = 0.11, 0.21) symptoms. For toddler/preschool irritability (13-60 months), small-to-moderate pooled associations were observed for internalizing (r = 0.21, 95% CI = 0.14, 0.28) and externalizing (r = 0.24, 95% CI = 0.18, 0.29) symptoms. These associations were not moderated by the lag between irritability and outcome assessment, although the strength of the associations varied according to irritability operationalization. CONCLUSION: Early irritability is a consistent transdiagnostic predictor of internalizing and externalizing symptoms in childhood and adolescence. More work is required to understand how to accurately characterize irritability across this developmental period, and to understand mechanisms underlying the relationship between early irritability and later mental health problems. DIVERSITY & INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as living with a disability. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. STUDY PREREGISTRATION INFORMATION: Early irritability as a transdiagnostic neurodevelopmental vulnerability to early onset mental health problems: A systematic review; https://www.crd.york.ac.uk/prospero/; CRD42020214658.

Associations between the human immune system and gut microbiome with neurodevelopment in the first 5 years of life: A systematic scoping review.

The aim of this review was to map the literature assessing associations between maternal or infant immune or gut microbiome biomarkers and child neurodevelopmental outcomes within the first 5 years of life. We conducted a PRISMA-ScR compliant review of peer-reviewed, English-language journal articles. Studies reporting gut microbiome or immune system biomarkers and child neurodevelopmental outcomes prior to 5 years were eligible. Sixty-nine of 23,495 retrieved studies were included. Of these, 18 reported on the maternal immune system, 40 on the infant immune system, and 13 on the infant gut microbiome. No studies examined the maternal microbiome, and only one study examined biomarkers from both the immune system and the gut microbiome. Additionally, only one study included both maternal and infant biomarkers. Neurodevelopmental outcomes were assessed from 6 days to 5 years. Associations between biomarkers and neurodevelopmental outcomes were largely nonsignificant and small in effect size. While the immune system and gut microbiome are thought to have interactive impacts on the developing brain, there remains a paucity of published studies that report biomarkers from both systems and associations with child development outcomes. Heterogeneity of research designs and methodologies may also contribute to inconsistent findings. Future studies should integrate data across biological systems to generate novel insights into the biological underpinnings of early development.