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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]

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]