Publications by authors named "Monica Uddin"

Article Synopsis
  • The study explores the biological differences linked to PTSD by examining DNA methylation changes in blood, suggesting they could indicate susceptibility or effects of trauma.
  • Conducted by the Psychiatric Genomics Consortium, the research included nearly 5,100 participants to identify specific genetic markers associated with PTSD.
  • Results showed 11 significant CpG sites related to PTSD, with some also showing correlations between blood and brain tissue methylation, highlighting their potential role in understanding PTSD biology.
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Article Synopsis
  • Researchers aimed to create and validate Methylation Risk Scores (MRS) using machine learning to identify individuals at risk for PTSD based on genomic and trauma exposure data.
  • The study developed three models: eMRS (which combines trauma exposure and methylation data), MoRS (which relies only on methylation data), and MoRSAE (which adjusts MoRS for trauma exposure).
  • The eMRS model showed the best performance with a 92% accuracy, and all models were able to predict post-deployment PTSD significantly, suggesting that including trauma exposure improves risk assessment.
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Article Synopsis
  • The study investigates the link between post-traumatic stress disorder (PTSD) and differences in DNA methylation, a type of gene regulation, in blood samples from individuals diagnosed with PTSD compared to trauma-exposed controls.
  • Researchers conducted a large-scale analysis involving over 5,000 participants from various civilian and military studies, using standardized procedures for PTSD assessment and DNA methylation testing.
  • The results revealed 11 specific DNA methylation sites associated with PTSD, and found similarities in methylation patterns between blood and brain tissues, suggesting a biological basis for the condition.
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The mRNA-seq data analysis is a powerful technology for inferring information from biological systems of interest. Specifically, the sequenced RNA fragments are aligned with genomic reference sequences, and we count the number of sequence fragments corresponding to each gene for each condition. A gene is identified as differentially expressed (DE) if the difference in its count numbers between conditions is statistically significant.

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Major depressive disorder (MDD) is a debilitating and prevalent mental disorder with a high disease burden. Despite a wide array of different treatment options, many patients do not respond to initial treatment attempts. Selection of the most appropriate treatment remains a significant clinical challenge in psychiatry, highlighting the need for the development of biomarkers with predictive utility.

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Article Synopsis
  • PTSD genetics have been difficult to study compared to other psychiatric disorders, limiting our biological understanding of the condition.
  • A large-scale meta-analysis involving over 1.2 million individuals identified 95 genome-wide significant loci, with 80 being new discoveries related to PTSD.
  • Researchers identified 43 potential causal genes linked to neurotransmitter activity, developmental processes, synaptic function, and immune regulation, enhancing our knowledge of the neurobiological systems involved in PTSD.
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Thirty years after the 1994 genocide against the Tutsi in Rwanda, children of survivors are being increasingly documented to be at higher risk compared to their peers for adverse mental health outcomes. However, no studies in Rwanda have empirically explored family psychosocial factors underlying this intergenerational transmission of trauma. We investigated family psychosocial factors that could underlie this transmission in 251 adult Rwandan children of survivors (mean age = 23.

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Background: Incorporating genomic data into risk prediction has become an increasingly useful approach for rapid identification of individuals most at risk for complex disorders such as PTSD. Our goal was to develop and validate Methylation Risk Scores (MRS) using machine learning to distinguish individuals who have PTSD from those who do not.

Methods: Elastic Net was used to develop three risk score models using a discovery dataset (n = 1226; 314 cases, 912 controls) comprised of 5 diverse cohorts with available blood-derived DNA methylation (DNAm) measured on the Illumina Epic BeadChip.

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Article Synopsis
  • - A new multi-ancestry genome-wide association study (GWAS) of major depression (MD) analyzed data from 88,316 cases and 902,757 controls, representing various ancestries including African, East Asian, South Asian, and Hispanic/Latin American.
  • - The study discovered 53 novel genetic loci significantly linked to MD, with fewer existing European ancestry loci proving relevant to other ancestry groups.
  • - A transcriptome-wide association study in this research identified 205 new genes associated with MD, highlighting the importance of diverse ancestry in genetic research for better understanding and finding relevant genes.
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The link between childhood adversity and adulthood depression is well-established; however, the underlying mechanisms are still being explored. Recent research suggests biological age may mediate the relationship between childhood adversity and depression in later life. This study examines if biological age mediates the relationship between childhood adversity and depression symptoms using an expanded set of biological age measures in an urban population-based cohort.

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Article Synopsis
  • PTSD genetics are harder to study compared to other mental health disorders, resulting in limited biological insights from past research.
  • A large-scale analysis involving over 1.2 million individuals found 95 significant genetic loci related to PTSD, with 80 being new discoveries.
  • The study identified 43 potential causal genes linked to neurotransmitters, synaptic function, and immune responses, enhancing understanding of PTSD's biological mechanisms and suggesting new research directions.
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Background: Historical trauma experienced by Indigenous peoples of North America is correlated with health disparities and is hypothesized to be associated with DNA methylation. Massive group traumas such as genocide, loss of land and foodways, and forced conversion to Western lifeways may be embodied and affect individuals, families, communities, cultures, and health. This study approaches research with Alaska Native people using a community-engaged approach designed to create mutually-beneficial partnerships, including intentional relationship development, capacity building, and sample and data care.

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Observational studies have shown an association between post-traumatic stress disorder (PTSD) and ischemic stroke (IS) but given the susceptibility to confounding it is unclear if these associations represent causal effects. Mendelian randomization (MR) facilitates causal inference that is robust to the influence of confounding. Using two sample MR, we investigated the causal effect of genetic liability to PTSD on IS risk.

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Article Synopsis
  • - The study introduces a new method, DEHOGT, for analyzing mRNA-seq data to identify differentially expressed genes more effectively by addressing issues like overdispersion and small sample sizes.
  • - DEHOGT uses a heterogeneous overdispersion model and a gene-wise estimation approach, which improves the accuracy and power of detecting gene expression differences across various conditions.
  • - Tests show DEHOGT outperforms traditional methods (like DESeq and EdgeR) in sensitivity and detection of genes that respond to different treatments in microglial cells.
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Experiencing adversity in childhood and adolescence, including stressful life events (SLEs), may accelerate the pace of development, leading to adverse mental and physical health. However, most research on adverse early experiences and biological aging (BA) in youths relies on cross-sectional designs. In 171 youths followed for approximately 2 years, we examined if SLEs over follow-up predicted rate of change in two BA metrics: epigenetic age and Tanner stage.

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Post-traumatic stress disorder (PTSD) is a common and debilitating psychiatric disorder that may occur in individuals exposed to traumatic events such as accidents, interpersonal violence, war, combat, or natural disasters. Additionally, PTSD has been implicated in the development of a variety of chronic conditions including cardiovascular and metabolic diseases, suggesting that the biological alterations associated with the disorder can manifest themselves as chronic diseases in those suffering from PTSD. The biological underpinnings of the disorder are not well understood.

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Adverse social exposures (ASEs) such as low income, low educational attainment, and childhood/adult trauma exposure are associated with variability in brain region measurements of gray matter volume (GMV), surface area (SA), and cortical thickness (CT). These CNS morphometries are associated with stress-related psychiatric illnesses and represent endophenotypes of stress-related psychiatric illness development. Epigenetic mechanisms, such as 5-methyl-cytosine (5mC), may contribute to the biological embedding of the environment but are understudied and not well understood.

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Although the effects of lead, mercury, manganese, and copper on individual disease processes are well understood, estimating the health effects of long-term exposure to these metals at the low concentrations often observed in the general population is difficult. In addition, the health effects of joint exposure to multiple metals are difficult to estimate. Biological aging refers to the integrative progression of multiple physiologic and molecular changes that make individuals more at risk of disease.

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Posttraumatic stress disorder (PTSD) is a heritable (h = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry.

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Epigenomic and neurocognitive studies have provided new perspectives on post-traumatic stress disorder and its intergenerational transmission. This article outlines the lessons learned from community engagement (CE) in such research on Rwandan genocide survivors. A strong trauma-related response was observed within the research project-targeted community (genocide survivors) during explanation of the project.

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Post-traumatic stress disorder (PTSD), which frequently occurs in the aftermath of a psychologically traumatic event is characterized by heightened inflammation. People with PTSD also suffer from a number of comorbid clinical and behavioral disorders that are related to chronic inflammation. Thus, understanding the mechanisms of enhanced inflammation in PTSD can provide insights into the relationship between PTSD and associated comorbid disorders.

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Background: Altered DNA methylation (DNAm) may be one pathway through which early-life adversity (ELA) contributes to adverse mental and physical health outcomes. This study investigated whether the presence versus absence of ELA experiences reflecting the dimensions of threat and deprivation were associated with epigenome-wide DNAm cross-sectionally and longitudinally in a community-based sample of children and adolescents.

Methods: In 113 youths aged 8-16 years with wide variability in ELA, we examined associations of abuse (physical, sexual, emotional; indicating threat-related experiences) and neglect (emotional, physical; indicating deprivation-related experiences) with DNAm assessed with the Illumina EPIC BeadChip array, with DNA derived from saliva.

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The mechanisms through which exposure to differing trauma types become biologically embedded to shape the risk for post-traumatic stress disorder (PTSD) is unclear. DNA methylation (5-mC), particularly in stress-relevant genes, may play a role in this relationship. Here, we conducted path analysis using generalized structural equation modeling to investigate whether blood-derived 5-mC in Nuclear Factor of Activated T Cells 1 (NFATC1) mediates the prospective association between each of five different trauma types ("assaultive violence", "other injury or shocking experience", "learning of trauma to loved one", "sudden, unexpected death of a close friend or relative", and "other") and lifetime PTSD.

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Post-traumatic stress disorder (PTSD) is a psychiatric disorder and patients diagnosed with PTSD often express other comorbid health issues, particularly autoimmune and inflammatory disorders. Our previous reports investigating peripheral blood mononuclear cells (PBMCs) from PTSD patients showed that these patients exhibit an increased inflammatory T helper (Th) cell phenotype and widespread downregulation of microRNAs (miRNAs), key molecules involved in post-transcriptional gene regulation. A combination of analyzing prior datasets on gene and miRNA expression of PBMCs from PTSD and Control samples, as well as experiments using primary PBMCs collected from human PTSD and Controls blood, was used to evaluate TP53 expression, DNA methylation, and miRNA modulation on Th17 development.

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Epigenetic factors modify the effects of environmental factors on biological outcomes. Identification of epigenetic changes that associate with PTSD is therefore a crucial step in deciphering mechanisms of risk and resilience. In this study, our goal is to identify epigenetic signatures associated with PTSD symptom severity (PTSS) and changes in PTSS over time, using whole blood DNA methylation (DNAm) data (MethylationEPIC BeadChip) of military personnel prior to and following combat deployment.

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