Broad Trauma Initiative  

The Broad Trauma Initiative, led by Dr. Karestan Koenen, seeks to understand the mechanisms by which trauma, occurring over the life course, but especially in childhood, gets into the bodies of patients and shapes how they think, feel, and behave, often for the remainder of their lives. Although much is known about the effects of trauma, little is known about the biological mechanisms and pathways it impacts. The Initiative is centered around four focus areas: Neurobiology & Organismal Biology, Genomics & Biobanks, Pediatric Trauma, and Community Engagement with the ultimate goal of improving the health and well-being of trauma survivors.

Biology of Adversity Project

In the Biology of Adversity Project at the Broad Institute, we are working to uncover biological pathways affected by many forms of adversity, stress, and trauma and identifying measurable markers — what we call “molecular scars” — that alter individuals’ biological responses to stress, impact childhood development, and subsequently alter health outcomes.  Learn about how we aim to discover and characterize long-lasting damage to specific genes, cell types, and pathways through our Molecular Atlas of Adversity and Mapping Trauma Epigenomes in Human Populations projects here. The Biology of Adversity Project is led by Drs. Jason Buenrostro and Karestan Koenen. 

Trauma, Violence and Women’s Health within and across generations 

Dr. Koenen collaborates on many projects related to trauma, especially gender-based violence, and women’s health over the life course and across generations. 

Across a number of studies, Drs. Koenen, Rebecca Lawn, and Audrey Murchland have investigated whether women’s experience of gender-based violence, including in non-contact forms, is linked to later-life cardiovascular health. For example, we have shown that women’s experiences of workplace sexual harassment was associated with an increased risk of hypertension. Recent work includes whether women’s experiences of stalking and intimate partner violence increase their risk of cardiovascular disease.

We are currently exploring whether maternal exposure to intimate partner violence pre-, during, and post- pregnancy is associated with their offspring’s blood pressure, smoking, and overweight status in adulthood, which may place the offspring at adulthood risk of cardiovascular disease. Key projects include:

• Gender-based violence and cardiovascular disease among women with Drs. Rebecca Lawn and Audrey Murchland 
• Interpersonal violence and dementia with Dr. Audrey Murchland
• Intimate partner violence among mothers and offspring health with Dr. Rebecca Lawn  

Psychiatric Genomics Consortium for PTSD

The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD) was founded in 2013 with the goal of conducting the first meta-analysis of genome-wide association study (GWAS) data for symptoms and diagnoses of PTSD. Since then our GWASs have grown to include over 130,000 cases with PTSD and 1 million controls of European Ancestry and over 13,000 cases and 40,000 controls of admixed ancestry and have led to the identification of 95 genome-wide significant loci and 43 potential causal genes.  This work is led by Drs. Karestan Koenen, Caroline Nievergelt, Kerry Ressler, and Murray Stein in conjunction with 200 other investigators from 12 countries. 

Design Microbiome-Based Therapies to Prevent and Ameliorate PTSD

This study aims to combine integrative molecular age assessments with deep phenotyping and longitudinal neuroimaging after trauma with the hope of discovering new predictors and mechanistic insights that enhance prevention and treatment of posttraumatic psychiatric outcomes.  This study is being led by Drs. Karestan Koenen and Yang-Yu Liu.

Epigenomic Predictors of PTSD and Traumatic Stress in an African American Cohort 

The overall goal of this study is to provide mechanistic insight into how social context, both positive and negative, affects brain-related epigenomic variation to impact risk of posttraumatic stress disorder (PTSD) and traumatic stress in a prospective, community-based cohort of African Americans.  This study is being led by Drs. Monica Uddin, Allison Aiello, and Derek Wildman.

Evidence-based treatment for PTSD and cardiovascular risk 

Posttraumatic stress disorder (PTSD) is an often disabling, yet treatable, mental disorder that increases risk of cardiovascular disease, but it is unclear whether PTSD treatment can reduce incidence of cardiovascular disease. By analyzing 20 years of comprehensive electronic health record data on evidence-based treatment, PTSD symptoms, and cardiovascular disease outcomes in a large, diverse sample of veterans, the proposed project aims to understand the impact of evidence-based treatment for PTSD on cardiovascular disease risk.  This study is being led by Drs. Jennifer Sumner, Jamie Gradus, and Brian Shriner.

Posttraumatic Stress Disorder and Accelerated Aging in Women

The purpose of this research is to better understand whether posttraumatic stress disorder (PTSD) causes accelerated aging in women and to identify underlying disease mechanisms.  Principal Investigators Drs. Karestan Koenen and Laura Kubzansky are evaluating if PTSD is prospectively associated with patterns of cognitive decline, examining the relation of PTSD with DNA methylation and shortened leukocyte telomere length, and examining how PTSD influences accelerated aging by examining symptom clusters as well as mediators and modifiers.

Genetics of PTSD in African Ancestry Populations: Enhancing discovery by addressing inequality

This study aims to accelerate genetic discovery for posttraumatic stress disorder (PTSD) by addressing the under-representation of African populations in PTSD genetic research.  As part of the study, researchers are increasing the sample bank of participants from the African continent and diaspora, performing analyses to expand PTSD risk loci discovery, and improving polygenic risk score accuracy for PTSD in these populations.  This research is led by Drs. Karestan Koenen, Caroline Nievergelt, Dickens Akena, Lukoye Atwoli, and Segun Fatumo.

The Genetics of Eating Disorders Study

The Genetics of Eating Disorders Study is a collaboration between McLean Hospital, the Harvard Chan School and the Broad Institute to learn about how eating disorders like anorexia nervosa and bulimia nervosa affect individuals across the United States and how these conditions are shaped by genetic factors.  To find out more about the study in either English and Spanish and to learn about participating in the study, click here. 

NeuroGAP-Psychosis 2.0

The Neuropsychiatric Genetics of African Populations-Psychosis (NeuroGAP-Psychosis) study 2.0 expands on the work of the first NeuroGAP-Psychosis study.  The goal of NeuroGAP-Psychosis 1.0 and 2.0 is to better understand the environmental and genetic risk factors for schizophrenia and bipolar disorder by increasing representation of participants of African ancestry, which have been under-represented in psychiatric genomic research to date.   Recruitment for NeuroGAP-Psychosis 2.0 is taking place in Durban, South Africa and Nairobi, Kenya.  This study is a collaboration between the Harvard Chan School, the Broad Institute, University of KwaZulu-Natal, and Aga Khan University Medical College, East Africa and led by Drs. Karestan Koenen, Bonga Chiliza, and Lukoye Atwoli. 

Populations Underrepresented in Mental Illness Association Studies (PUMAS)

PUMAS project aimed to remediate the historical underrepresentation of African and Latin American populations in psychiatric genetics through large-scale genetic association studies of individuals diagnosed with a serious mental illness.  The study collected blood and saliva samples from participants in Brazil, Colombia, Ethiopia, and the United States, which were then low-pass whole genome sequenced (WGS) and exome sequenced.  The new data, in combination with additional sample banks, created a 120,000 sample WGS dataset, allowing for sufficient statistical power for genetic discovery and improving the precision of fine-mapping of known loci.

To learn about additional research studies and capacity building initiatives, please click below.

Global Initiative for Neuropsychiatric Genetics Education in Research (GINGER)

Neuropsychiatric Genetics of African Populations-Psychosis study 1.0 (NeuroGAP-Psychosis 1.0)

Neuropsychiatric Genetics of Mexican Populations (NeuroMex)

STAIR Coach in Kenya 

The STAIR Coach pilot study aims to examine the feasibility and acceptability of a low cost, low intensity treatment, called Skills Training in Affective and Interpersonal Regulation (STAIR), delivered through a mobile-based application (app), called STAIR Coach for use in Kenya. Participants with probable PTSD receive 10 weeks of treatment delivered through the STAIR Coach app and have five bi-weekly video sessions with a facilitator trained in the use of STAIR.  Participants complete baseline, mid-treatment, and follow-up assessments. Upon completion of the STAIR Coach pilot study, we aim to adapt the STAIR Coach mobile app for use in Kenya using participatory co-design workshops informed by human centered design.

Preventing Mental Disorders Among Women Internally Displaced by War in Ukraine: The SHAWL Trial

This project is adapting and evaluating a single-session Acceptance and Commitment Therapy (ACT) group intervention aimed towards preventing mental disorders among women displaced by the war in Ukraine. ACT is an evidence-based intervention that uses acceptance, mindfulness, and behavior change processes to improve psychological flexibility. 

Substance Use Prevention for Recently displaced Adults (SUPRA)

War and humanitarian emergencies may exacerbate substance use, but the incidence and prevalence of unhealthy substance use in humanitarian settings, including Ukraine, are currently largely unknown. This lack of data limits the ability to tailor targeted, effective preventive substance use interventions for these mobile populations. We are conducting an epidemiological substance use survey among internally displaced persons in Ukraine.  We then plan to develop an intervention based on these results and test it in a pilot randomized controlled trial.

Contrast Breathing and PTSD

Posttraumatic stress disorder (PTSD) is characterized by persistent activation of stress responses, regulated by the autonomic nervous system, and can present as elevated heart rate, blood pressure, and reduced heart rate variability.  The Contrast Breathing and PTSD study is a 12-week intervention assessing whether sequences of yogic breathing known as “Bhramari Pranayama” followed by hyperventilation and breath retention can lead to improvements in heart rate variability and decreases in inflammation, resting heart rate, and blood pressure. The intervention is being led by Drs. Antonia Seligowski and Mike Osborn at Massachusetts General Hospital. 

Dynamic Volitional Respiratory Modulation Treatment Development Study

Dynamic Volitional Respiratory Modulation (DVRM) is a type of trance breathing and therapeutic breathwork that aims to improve physiological and psychological health. This mixed-methods study examines whether sessions of DVRM can lead to changes in well-being, with the long-term goal of establishing whether DVMR can provide therapeutic benefits at a population level. Drs. Karestan Koenen, Kristina Korte, and David Magone are leading this study.

Neurophysiological Correlates of Dynamic Volitional Respiratory Modulation (DVRM)

This is a pilot investigation into the neurophysiological correlates of Dynamic Volitional Respiratory Modulation (DVRM), a type of trance breathing and therapeutic breathwork. This study uses magnetic resonance imaging (MRI) to obtain cerebral resting-state maps before and after DVRM sessions. It assesses changes in functional connectivity patterns with resting-state networks following DVRM.  The study also uses MRI to capture dynamic changes in brain activity and respiratory gas exchange measures during DVRM and investigate the relationship between breathing patterns, breath retentions, and neural network connectivity in real-time.  Drs. Kenneth Kwong, Susan Whitfield Gabrieli, and Karestan Koenen at Massachusetts General Hospital are leading this study.