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Background: Prenatal maternal stress is increasingly recognized as a risk factor for offspring mental health challenges. DNA methylation may be a mechanism, but few studies directly tested mediation. These few integrative studies are reviewed along with studies from three research areas: prenatal maternal stress and child mental health, prenatal maternal stress and child DNA methylation, and child mental health and DNA methylation.Methods: We conducted a narrative review of articles in each research area and the few published integrative studies to evaluate the state of knowledge.Results: Prenatal maternal stress was related to greater offspring internalizing and externalizing symptoms and to greater offspring peripheral DNA methylation of the NR3C1 gene. Youth mental health problems were also related to NR3C1 hypermethylation while epigenome-wide studies identified genes involved in nervous system development. Integrative studies focused on infant outcomes and did not detect significant mediation by DNA methylation though methodological considerations may partially explain these null results.Limitations: Operationalization of prenatal maternal stress and child mental health varied greatly. The few published integrative studies did not report conclusive evidence of mediation by DNA methylation.Conclusions: DNA methylation likely mediates the association between prenatal maternal stress and child mental health. This conclusion still needs to be tested in a larger number of integrative studies. Key empirical and statistical considerations for future research are discussed. Understanding the consequences of prenatal maternal stress and its pathways of influence will help prevention and intervention efforts and ultimately promote well-being for both mothers and children. [ABSTRACT FROM AUTHOR]

Background Optimal maternal nutrition during pregnancy has been linked to better cognitive and behavioral development in children. However, its influence on the effects of suboptimal postnatal exposures like reduced stimulation and support in the home is not known. Objectives To examine the effect of maternal pregnancy diet on executive function and/or behavioral development in children raised in suboptimal home environments. Methods Data were provided by 808 mother–infant dyads from the Canadian Maternal-Infant Research on Environmental Chemicals–Child Development study. Maternal pregnancy diet was self-reported using the Healthy Eating Index 2010 questionnaire. Stimulation and support in the home was assessed using the Home Observation for Measurement of the Environment (HOME) when children were 3–4 y old. Child executive function was reported by mothers at this age using the Behavior Rating Inventory of Executive Functioning–Preschool Edition, and child behavior was assessed using the Behavior Assessment System for Children–2nd Edition. We examined the interaction of maternal pregnancy diet and postnatal HOME scores on child executive function and behavior using linear regression adjusted for maternal education, postpartum depression, prepregnancy BMI, and smoking. Results Maternal pregnancy diet was associated with an increasingly positive association with child working memory (β: 0.21; 95% CI: 0.82, 3.41; P =  0.001), planning (β: 0.17; 95% CI: 0.38, 2.84; P =  0.007), and adaptability (β: –0.13; 95% CI: –1.72, –0.08; P =  0.032) as levels of postnatal stimulation decreased. Conclusions The positive association of maternal pregnancy diet quality and executive function and adaptability in 3- to 4-y-olds appeared to increase with decreasing levels of postnatal stimulation and support. These results suggest that overall maternal pregnancy diet could be linked to better child neurodevelopment in families experiencing barriers to providing stimulation and support to children in their home. [ABSTRACT FROM AUTHOR]

Background and Objectives: Depression has been associated with alterations in social functioning. Decoding and understanding others' mental states and adaptive reasoning are important for social functioning. This study examined theory of mind (ToM) and socio-moral reasoning (SMR) in adolescent girls with and without depression. Within the depression group, we examined associations between relevant clinical features (depression severity, anxiety symptoms and borderline personality traits) and ToM and SMR.Methods: A cross-sectional study was conducted, whereby 43 adolescent girls (mean age = 16.19, SD = 1.24) meeting full or subthreshold criteria for depression and 40 adolescent girls (mean age = 15.44, SD = 1.24) with no psychiatric diagnosis were recruited. ToM was assessed using the Movie for the Assessment of Social Cognition; SMR was evaluated via the Socio-Moral Reasoning Aptitude Level task.Results: Analyses of covariance indicated that adolescents with depression did not differ from controls in ToM abilities but showed lower socio-maturity scores on the SMR task. This difference disappeared after controlling for the number of words used to justify responses. Amongst adolescents with depression, multiple linear regression analyses revealed that higher levels of borderline personality traits were associated with lower levels of mentalization (ToM task), and more severe depressive symptoms were associated with lower socio-moral maturity stages (SMR task) LIMITATIONS: Directional associations were not studied, and the sample included only girls.Conclusions: Findings may help to explain clinical heterogeneity in social cognitive functioning observed in individuals with depression. [ABSTRACT FROM AUTHOR]

Background: Subthreshold depression is highly prevalent in adolescence, but compared to major depressive disorder, the clinical impact is under-researched. The aim of this review was to compare subthreshold depression and major depressive disorder in adolescents by reviewing available literature on epidemiology, risk factors, illness trajectories, brain anatomy and function, genetics, and treatment response.Methods: We conducted a scoping review of papers on subthreshold depression and major depressive disorder in adolescence published in English. Studies in adults were included when research in adolescence was not available.Results: We found that individuals with subthreshold depression were similar to individuals with major depressive disorder in several regards, including female/male ratio, onset, functional impairment, comorbidity, health care utilization, suicidal ideation, genetic predisposition, brain alterations, and treatment response. Further, subthreshold depression was about two times more common than major depressive disorder.Limitations: The definition of subthreshold depression is highly variable across studies. Adolescent-specific data are limited in the areas of neurobiology and treatment.Conclusions: The findings of the current review support the idea that subthreshold depression is of clinical importance and provide evidence for a spectrum, versus categorical model, for depressive symptomatology. Given the frequency of subthreshold depression escalating to major depressive disorder, a greater recognition and awareness of the significance of subthreshold depression in research, clinical practice and policy-making may facilitate the development and application of early prevention and intervention. [ABSTRACT FROM AUTHOR]

Screening is done to improve health outcomes by identifying and effectively treating individuals with unrecognized conditions. Depression screening has been proposed to identify previously unrecognized depression cases. Including individuals already diagnosed or treated for depression in screening test accuracy studies could exaggerate accuracy and the yield of new cases from screening. The present study investigated (1) the proportion of depression screening tool accuracy primary studies published in 2018–2021 that excluded individuals with a confirmed depression diagnosis or who were already undergoing treatment; and (2) whether this has improved since the last review of studies published in 2013–2015, which found that five of 89 (5.6%) primary studies appropriately excluded such individuals. MEDLINE was searched from January 1, 2018 through May 21, 2021 for primary studies on depression screening tool accuracy. Eighteen of 106 (17.0%; 95% Confidence Interval [CI], 11.0% to 25.3%) primary studies excluded currently diagnosed or treated individuals. This was 11.4% (95% CI, 2.8% to 20.0%) greater than in similar studies published in 2013–2015. There has been an improvement since 2015, but the proportion of studies that exclude individuals already known to have depression remains low. This may bias research findings intended to inform clinical practice. [ABSTRACT FROM AUTHOR]

Over the past decade, psychiatric research has been on an important hunt for biomarkers of psychiatric disease. In psychiatry, the term "biomarker" is a broad umbrella term used to identify any biological variable that can be objectively measured and applied to a diagnosis; this includes genetic and epigenetic assessments, hormone levels, measures of neuro-anatomy and many other scientific modalities. However, despite hundreds of studies on the topic being published yearly and other medical specialties having success in discovering biomarkers, clinical psychiatric practice has not had the same success. This paper aims to consolidate the many opinions on the search for psychiatric biomarkers to suggest key methodological and clinical challenges that psychiatric biomarker research faces. Psychiatry as a specialty has many fundamental differences compared to other medical specialties in methods of diagnosing, underlying etiology and disease pathologies that may be limiting the success of biomarker research in itself and puts strict requirements on the research being conducted. The academic and clinical environment in which the research is being conducted also heavily influences the translation of the findings. Finally, once biomarkers are identified, more often than not they are inapplicable to clinical settings, unable to integrate into clinical practice and fail to outperform current diagnostic practices and guidelines. We also make six recommendations for more promising future research in psychiatric biomarkers. • For biomarker research to be successful, multiple techniques must be combined. • There are intricacies unique to psychiatry that make successful biomarker identification difficult. • Improved research methodologies that are easily combined are needed. • Multidisciplinary teams should be involved at all stages of biomarker research. [ABSTRACT FROM AUTHOR]

Exposure to perfluoroalkyl substances (PFAS) has been shown to be neurotoxic in experimental studies, but epidemiological evidence linking prenatal PFAS exposure to child neurodevelopment is equivocal and scarce. To quantify associations between prenatal exposure to legacy PFAS and children's intelligence (IQ) and executive functioning (EF) in a Canadian pregnancy and birth cohort and to determine if these associations differ by child sex. We measured first-trimester plasma concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) in the Maternal-Infant Research on Environmental Chemicals (MIREC) study and assessed children's full-scale (n = 522), performance (n = 517), and verbal (n = 519) IQ using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Children's working memory (n = 513) and ability to plan and organize (n = 514) were assessed using a parent-reported questionnaire, the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P). We quantified associations between individual log2-transformed PFAS exposure and children's IQ and EF using multiple linear regression analyses and evaluated effect modification by child sex. We also used Repeated Holdout Weighted Quantile Sum (WQS) regression models with effect modification by child sex to quantify the effect of combined exposure to all three PFAS chemicals on IQ and EF. All models were adjusted for key sociodemographic characteristics. Geometric mean plasma concentrations (IQR) for PFOA, PFOS and PFHxS were 1.68 (1.10–2.50), 4.97 (3.20–6.20) and 1.09 (0.67–1.60) μg/L respectively. We found evidence of effect modification by child sex in all models examining performance IQ (p <.01). Specifically, every doubling of PFOA, PFOS, and or PFHxS was inversely associated with performance IQ, but only in males (PFOA: B = −2.80, 95% CI: −4.92, −0.68; PFOS: B = −2.64, 95% CI: −4.77, −0.52; PFHxS: B = −2.92, 95% CI: −4.72, −1.12). Similarly, every quartile increase in the WQS index was associated with poorer performance IQ in males (B = −3.16, 95% CI: −4.90, −1.43), with PFHxS contributing the largest weight to the index. In contrast, no significant association was found for females (B = 0.63, 95% CI: −0.99, 2.26). No significant associations were found for EF in either males or females. Higher prenatal PFAS exposure was associated with lower performance IQ in males, suggesting that this association may be sex- and domain-specific. • We assessed associations between PFAS and child neurodevelopment. • PFOS, PFOS and PFHxS were inversely associated with nonverbal IQ in males. • In mixture models, PFHxS was identified as a chemical of concern. • We observed no associations between PFAS and executive functioning. • The association between PFAS and IQ may be sex and domain-specific. [ABSTRACT FROM AUTHOR]