Mihaela Aslan

Bio: Mihaela Aslan is an academic researcher from Yale University. The author has contributed to research in topics: Veterans Affairs & Bipolar disorder. The author has an hindex of 18, co-authored 47 publications receiving 2916 citations. Previous affiliations of Mihaela Aslan include United States Department of Veterans Affairs & Veterans Health Administration.

Prolonged Grief Disorder: Psychometric Validation of Criteria Proposed for DSM-V and ICD-11

Abstract: Background: Bereavement is a universal experience, and its association with excess morbidity and mortality is well established. Nevertheless, grief becomes a serious health concern for a relative few. For such individuals, intense grief persists, is distressing and disabling, and may meet criteria as a distinct mental disorder. At present, grief is not recognized as a mental disorder in the DSM-IV or ICD-10. The goal of this study was to determine the psychometric validity of criteria for prolonged grief disorder (PGD) to enhance the detection and potential treatment of bereaved individuals at heightened risk of persistent distress and dysfunction. Methods and Findings: A total of 291 bereaved respondents were interviewed three times, grouped as 0–6, 6–12, and 12– 24 mo post-loss. Item response theory (IRT) analyses derived the most informative, unbiased PGD symptoms. Combinatoric analyses identified the most sensitive and specific PGD algorithm that was then tested to evaluate its psychometric validity. Criteria require reactions to a significant loss that involve the experience of yearning (e.g., physical or emotional suffering as a result of the desired, but unfulfilled, reunion with the deceased) and at least five of the following nine symptoms experienced at least daily or to a disabling degree: feeling emotionally numb, stunned, or that life is meaningless; experiencing mistrust; bitterness over the loss; difficulty accepting the loss; identity confusion; avoidance of the reality of the loss; or difficulty moving on with life. Symptoms must be present at sufficiently high levels at least six mo from the death and be associated with functional impairment. Conclusions: The criteria set for PGD appear able to identify bereaved persons at heightened risk for enduring distress and dysfunction. The results support the psychometric validity of the criteria for PGD that we propose for inclusion in DSM-V and ICD-11. Please see later in the article for the Editors’ Summary.

Childhood maltreatment as a risk factor for adult cardiovascular disease and depression.

Abstract: BACKGROUND: Traumatic experiences in childhood are linked to adult depression and cardiovascular disease. Depression is twice as common in women than men, and depression after cardiovascular events is more common in women than men. However, sex differences in these relationships have not been comprehensively investigated using a nationally representative sample in which demographic factors related to these illnesses can be controlled. METHOD: Data come from the Part 2 sample of the U.S. National Comorbidity Survey, a nationally representative sample containing over 5000 adults. Relationships between childhood maltreatment (sexual abuse, physical abuse, neglect), adult depression (DSM-III-R), and cardiovascular disease were examined using multiple logistic regression models with a specific emphasis on the evaluation of sex differences. RESULTS: Childhood maltreatment was associated with a significant increase in cardiovascular disease for women only and with a significant increase in lifetime depression for both genders. A history of childhood maltreatment removed the natural protection against cardiovascular disease for women and depression for men. Although depression and cardiovascular disease were correlated, depression did not contribute to the prediction of cardiovascular disease in women when controlling for history of childhood maltreatment. CONCLUSIONS: Gender is important in evaluating potential psychiatric and physical correlates of childhood maltreatment. Maltreatment is a potent risk factor for cardiovascular disease in women and for depression in both women and men. Effective clinical assessment should recognize the role of childhood abuse or neglect in adult health and disease. Research on the consequences of childhood maltreatment should focus on both psychiatric and physical outcomes. Language: en

Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program.

Abstract: Objective:Anxiety disorders are common and often disabling. The goal of this study was to examine the genetic architecture of anxiety disorders and anxiety symptoms, which are also frequently comor...

Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions.

Abstract: Major depressive disorder is the most common neuropsychiatric disorder, affecting 11% of veterans. Here we report results of a large meta-analysis of depression using data from the Million Veteran Program, 23andMe, UK Biobank and FinnGen, including individuals of European ancestry (n = 1,154,267; 340,591 cases) and African ancestry (n = 59,600; 25,843 cases). Transcriptome-wide association study analyses revealed significant associations with expression of NEGR1 in the hypothalamus and DRD2 in the nucleus accumbens, among others. We fine-mapped 178 genomic risk loci, and we identified likely pathogenicity in these variants and overlapping gene expression for 17 genes from our transcriptome-wide association study, including TRAF3. Finally, we were able to show substantial replications of our findings in a large independent cohort (n = 1,342,778) provided by 23andMe. This study sheds light on the genetic architecture of depression and provides new insight into the interrelatedness of complex psychiatric traits. This bi-ancestral genome-wide association study of major depressive disorder (MDD) identified 178 risk variants. The results advance understanding of the biology of MDD and hint at new treatment possibilities.

Social and Emotional Aging

Abstract: The past several decades have witnessed unidimensional decline models of aging give way to life-span developmental models that consider how specific processes and strategies facilitate adaptive aging. In part, this shift was provoked by the stark contrast between findings that clearly demonstrate decreased biological, physiological, and cognitive capacity and those suggesting that people are generally satisfied in old age and experience relatively high levels of emotional well-being. In recent years, this supposed "paradox" of aging has been reconciled through careful theoretical analysis and empirical investigation. Viewing aging as adaptation sheds light on resilience, well-being, and emotional distress across adulthood.

Genetic mechanisms of critical illness in Covid-19.

Abstract: Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10−8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice. A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.