Explore the vast range of titles available.

Childhood maltreatment is the most important preventable risk factor for psychiatric disorders. Maltreated individuals typically develop psychiatric disorders at an earlier age, have a more pernicious course, more comorbidities, greater symptom severity, and respond less favorably to treatments than non-maltreated individuals with the same primary DSM-5 diagnosis. Furthermore, maltreated individuals have alterations in stress-susceptible brain regions, hypothalamic-pituitary-adrenal response, and inflammatory marker levels not discernible in their non-maltreated counterparts. Hence, maltreated and non-maltreated individuals with the same primary DSM-5 diagnoses appear to be clinically and neurobiologically distinct. The failure to embody this distinction in DSM-5 has interfered with our ability to discover novel treatments, to recommend currently available treatments most likely to be efficacious, and has been a largely unrecognized confound that has thwarted our ability to identify the biological basis for major psychiatric disorders. Incorporating this distinction into DSM will help transform this sign and symptom-based classification system to a more etiologically informed nosology. We discuss several diagnostic alternatives and recommend the inclusion of a Developmental Trauma Disorder diagnosis for severely dysregulated individuals, of all ages, with numerous comorbidities, who experienced interpersonal victimization and disruptions in attachment, such as emotional maltreatment or neglect. For less severely affected maltreated individuals, we suggest using conventional diagnostic categories, such as major depression, but with an essential modifier indicating a history of childhood maltreatment, or early life stress, to delineate the ecophenotypic variant. Implementing this strategy should improve our ability to effectively diagnose and treat individuals with psychiatric disorders and to accelerate discovery.

Pharmacogenomic technology is a developing field with enthusiastic interest and broad application potential. Three large, controlled studies have been published exploring the benefit of pharmacogenomically guided antidepressant treatment selection. Though all three studies did not show significant benefit of using this technology, these studies laid the foundation for further research that should address the limitations of this previous research and currently available commercial platforms. Future research needs to include large scale pharmacogenomic trials with GWAS analytics across diverse groups with attention to cost-effectiveness models, particularly for cases of treatment resistance and polypharmacy. The application of results from these large scale pharmacogenomic trials must also include exploring optimal EHR user interface design.

The central theme of personalized medicine is the premise that an individual’s unique physiologic characteristics play a significant role in both disease vulnerability and in response to specific therapies. The major goals of personalized medicine are therefore to predict an individual’s susceptibility to developing an illness, achieve accurate diagnosis, and optimize the most efficient and favorable response to treatment. The goal of achieving personalized medicine in psychiatry is a laudable one, because its attainment should be associated with a marked reduction in morbidity and mortality. In this review, we summarize an illustrative selection of studies that are laying the foundation towards personalizing medicine in major depressive disorder, bipolar disorder, and schizophrenia. In addition, we present emerging applications that are likely to advance personalized medicine in psychiatry, with an emphasis on novel biomarkers and neuroimaging.

Depression increases the risk of cardiovascular disease and is a predictor of poor cardiovascular outcomes. The authors outline these epidemiological findings, describe the pathophysiological mechanisms that might underlie the risk of cardiovascular disease in patients with depression, and describe new data on the effects of successful treatment of depression on biological risk factors for coronary artery disease. The close, bidirectional relationship between depression and cardiovascular disease is well established. Major depression is associated with an increased risk of coronary artery disease and acute cardiovascular sequelae, such as myocardial infarction, congestive heart failure, and isolated systolic hypertension. Morbidity and mortality in patients with cardiovascular disease and depression are significantly higher than in patients with cardiovascular disease who are not depressed. Various pathophysiological mechanisms might underlie the risk of cardiovascular disease in patients with depression: increased inflammation; increased susceptibility to blood clotting (owing to alterations in multiple steps of the clotting cascade, including platelet activation and aggregation); oxidative stress; subclinical hypothyroidism; hyperactivity of the sympatho-adrenomedullary system and the hypothalamic–pituitary–adrenal axis; reductions in numbers of circulating endothelial progenitor cells and associated arterial repair processes; decreased heart rate variability; and the presence of genetic factors. Early identification of patients with depression who are at risk of cardiovascular disease, as well as prevention and appropriate treatment of cardiovascular disease in these patients, is an important and attainable goal. However, adequately powered studies are required to determine the optimal treatment regimen for patients with both depression and cardiovascular disorders. Key Points Depression is associated with increased risk of coronary artery disease, and increased morbidity and mortality after myocardial infarction, CABG surgery, congestive heart failure, or mitral valve replacement Depression-associated biological alterations include increased inflammation, a clotting diathesis, decreased variability in heart rate, increased activity of the sympathoadrenal and pituitary–adrenal axes, and a reduction in circulating endothelial progenitor cells Depression-associated biological alterations might mediate the link between depression and cardiovascular disease Results are inconclusive from studies designed to determine whether successful treatment of depression in patients with cardiovascular disease is associated with a reduction in subsequent major cardiac events Further research is required to determine whether normalization of these depression-associated biological alterations, resulting from effective treatment, contribute to a reduced risk of cardiovascular disease

There is a considerable literature on the relationship of thyroid function with risk of depression and responsiveness to depression treatment. This literature is briefly reviewed here, followed by a focus on the incremental advance provided by the findings of Luo et al on autoimmune thyroiditis and suicide attempts.

Early life stress has been shown to exert profound short- and long-term effects on human physiology both in the central nervous system and peripherally. Early life stress has demonstrated clear association with many psychiatric disorders including major depression, posttraumatic stress disorder, and bipolar disorder. The Diagnostic and Statistics Manuel of Mental Disorders (DSM) diagnostic categorical system has served as a necessary framework for clinical service, delivery, and research, however has not been completely matching the neurobiological research perspective. Early life stress presents a complex dynamic featuring a wide spectrum of physiologic alterations: from epigenetic alterations, inflammatory changes, to dysregulation of the hypothalamic pituitary axis and has further added to the challenge of identifying biomarkers associated with psychiatric disorders. The National Institute of Mental Health’s proposed Research Domain Criteria initiative incorporates a dimensional approach to assess discrete domains and constructs of behavioral function that are subserved by identifiable neural circuits. The current neurobiology of early life stress is reviewed in accordance with dimensional organization of Research Domain Criteria matrix and how the findings as a whole fit within the Research Domain Criteria frameworks.

DNA methylation likely plays a role in the regulation of human stress reactivity. Here we show that in a genome-wide analysis of blood DNA methylation in 85 healthy individuals, a locus in the Kit ligand gene ( KITLG ; cg27512205) showed the strongest association with cortisol stress reactivity ( P =5.8 × 10 −6 ). Replication was obtained in two independent samples using either blood ( N =45, P =0.001) or buccal cells ( N =255, P =0.004). KITLG methylation strongly mediates the relationship between childhood trauma and cortisol stress reactivity in the discovery sample (32% mediation). Its genomic location, a CpG island shore within an H3K27ac enhancer mark, and the correlation between methylation in the blood and prefrontal cortex provide further evidence that KITLG methylation is functionally relevant for the programming of stress reactivity in the human brain. Our results extend preclinical evidence for epigenetic regulation of stress reactivity to humans and provide leads to enhance our understanding of the neurobiological pathways underlying stress vulnerability. Exposure to childhood trauma is a major risk factor for the development of almost all psychiatric disorders. By epigenome-wide studies, here, Houtepen et al . show that DNA methylation at a locus in the Kit ligand gene (KITLG) mediates the relationship between childhood trauma and cortisol stress reactivity.

Social media holds exciting promise for advancing mental health research recruitment, however, the extent and efficacy to which these platforms are currently in use are underexplored. A systematic review was conducted to characterize the current use and efficacy of social media in recruiting participants for mental health research. A literature review was performed using MEDLINE, EMBASE, and PsychINFO. Only non-duplicative manuscripts written in the English language and published between 1/1/2004–3/31/2019 were selected for further screening. Data extracted included study type and design, participant inclusion criteria, social media platform, advertising strategy, final recruited sample size, recruitment location, year, monetary incentives, comparison to other recruitment methods if performed, and final cost per participant. A total of 176 unique studies that used social media for mental health research recruitment were reviewed. The majority of studies were cross-sectional (62.5%) in design and recruited adults. Facebook was overwhelmingly the recruitment platform of choice (92.6%), with the use of paid advertisements being the predominant strategy (60.8%). Of the reviewed studies, substance abuse (43.8%) and mood disorders (15.3%) were the primary subjects of investigation. In 68.3% of studies, social media recruitment performed as well as or better than traditional recruitment methods in the number and cost of final enrolled participants. The majority of studies used Facebook for recruitment at a median cost per final recruited study participant of $19.47. In 55.6% of the studies, social media recruitment was the more cost-effective recruitment method when compared to traditional methods (e.g., referrals, mailing). Social media appears to be an effective and economical recruitment tool for mental health research. The platform raises methodological and privacy concerns not covered in current research regulations that warrant additional consideration. •Social media is increasingly employedin mental health research recruitment.•Compared to traditional methods, social media recruitment offers advantages in cost, speed, and efficiency.•Minimal federal guidance exists in using social media for recruitmentto avoid privacy violations.

Early life adversity (ELA) has long been recognized to negatively impact a variety of health outcomes, with increasingly recognized long-term implications for neurocognitive function. ELA may affect the brain through multiple mechanisms, including chronic inflammation. One potential moderator of the pathway from ELA to neuroinflammation to cognitive dysfunction is sex. ELA may leave females potentially even more vulnerable to cognitive impairment in later life. This review discusses the influence of ELA on cognitive function across much of the lifespan, how inflammation is implicated in this process, and the current state of knowledge regarding sex differences in these relationships. We conclude with a discussion of unanswered questions and suggestions for future research, including the incorporation of genetic data.