Kerry Ressler

Kerry Ressler
Mclean Hospital, Harvard Medical School · Psychiatry

MD, PhD

About

671
Publications
136,024
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
40,143
Citations
Additional affiliations
August 2015 - August 2015
Howard Hughes Medical Institute
Position
  • Professor and Chief Scientific Officer
July 2008 - present
Howard Hughes Medical Institute
Position
  • Investigator

Publications

Publications (671)
Article
Full-text available
Post-traumatic stress disorder (PTSD) develops in only some people following trauma exposure, but the mechanisms differentially explaining risk versus resilience remain largely unknown. PTSD is heritable but candidate gene studies and genome-wide association studies (GWAS) have identified only a modest number of genes that reliably contribute to PT...
Article
Neuroimaging genetic studies that associate genetic and epigenetic variation with neural activity or structure provide an opportunity to link genes to psychiatric disorders, often before psychopathology is discernable in behavior. Here we review neuroimaging genetics studies with participants who have Posttraumatic Stress Disorder (PTSD). Results s...
Article
Full-text available
DICER1 is an enzyme that generates mature microRNAs (miRNAs), which regulate gene expression post-transcriptionally in brain and other tissues and is involved in synaptic maturation and plasticity. Here, through genome-wide differential gene expression survey of post-traumatic stress disorder (PTSD) with comorbid depression (PTSD&Dep), we find that...
Article
Full-text available
Trajectories toward risk or resilience in psychiatric disorders are influenced by acquired and inherited factors. More recently, evidence from rodent studies suggest that acquired risk factors can be transmitted through non-genomic, epigenetic mechanisms to subsequent generations, potentially contributing to a cycle of disease and disease risk. Her...
Article
Full-text available
Pathological fear and anxiety are highly debilitating and, despite considerable advances in psychotherapy and pharmacotherapy they remain insufficiently treated in many patients with PTSD, phobias, panic and other anxiety disorders. Increasing preclinical and clinical evidence indicates that pharmacological treatments including cognitive enhancers,...
Chapter
Significant progress has been made in the expansion of our understanding of the biological basis of anxiety disorders. Preclinical research examining the biological basis of fear learning, emotional memory regulation, and the expression of fear in animal models has, in conjunction with clinical research in patients with anxiety disorders, promoted...
Article
Full-text available
Background: Inhibition is a critical executive control process and an established neurobiological phenotype of PTSD, yet to our knowledge, no prospective studies have examined this using a contextual cue task that enables measurement of behavioural response and neural activation patterns across proactive and reactive inhibition. Objective: The c...
Article
Full-text available
Exposure to traumatic stress can lead to fear dysregulation, which has been associated with posttraumatic stress disorder (PTSD). Previous work showed that a polymorphism in the PACAP-PAC1R (pituitary adenylate cyclase-activating polypeptide) system is associated with PTSD risk in women, and PACAP ( ADCYAP1 )-PAC1R ( ADCYAP1R1 ) are highly expresse...
Preprint
Individuals with posttraumatic stress disorder (PTSD) are significantly more likely to be diagnosed with cardiovascular disease (CVD; e.g., myocardial infarction, stroke). The evidence for this link is so compelling that the National Institutes of Health convened a working group to determine gaps in the current literature, including the need for la...
Article
Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals...
Article
Full-text available
The ability to associate temporally segregated information and assign positive or negative valence to environmental cues is paramount for survival. Studies have shown that different projections from the basolateral amygdala (BLA) are potentiated following reward or punishment learning1–7. However, we do not yet understand how valence-specific infor...
Article
Full-text available
Genome-wide association studies (GWAS) have identified several risk loci for post-traumatic stress disorder (PTSD); however, how they confer PTSD risk remains unclear. We aimed to identify genes that confer PTSD risk through their effects on brain protein abundance to provide new insights into PTSD pathogenesis. To that end, we integrated human bra...
Article
Posttraumatic stress disorder (PTSD) is prevalent and associated with significant morbidity. Mild traumatic brain injury (mTBI) concurrent with psychiatric trauma may be associated with PTSD. Prior studies of PTSD‐related structural brain alterations have focused on military populations. The current study examined correlations between PTSD, acute m...
Article
Objective: Dissociation, a disruption or discontinuity in psychological functioning, is often linked with worse psychiatric symptoms; however, the prognostic value of dissociation after trauma is inconsistent. Determining whether trauma-related dissociation is uniquely predictive of later outcomes would enable early identification of at-risk traum...
Preprint
Background Melanocortin 4 receptor (MC4R) activity in the hypothalamus is crucial for regulation of metabolism and food intake. The peptide ligands for the MC4R are associated with feeding, energy expenditure, and also with complex behaviors that orchestrate energy intake and expenditure, but the downstream neuroanatomical and neurochemical targets...
Preprint
Background Trauma-related pathological dissociation is a multidimensional and disabling phenomenon that involves disruptions or discontinuities in psychological functioning. Despite its prevalence, personal and societal burden, dissociation remains underappreciated in clinical practice, and it lacks a synthesized neurobiological model that could pl...
Article
Background Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated alteration in covariance of structural networks associated with PTSD in regions that demonstrate the case-control differences in cortical thickness (CT) and surface area (SA). Methods Neuroimaging and clinical data were aggregated fro...
Article
Full-text available
Post-traumatic stress disorder (PTSD) is a maladaptive and debilitating psychiatric disorder, characterized by re-experiencing, avoidance, negative emotions and thoughts, and hyperarousal in the months and years following exposure to severe trauma. PTSD has a prevalence of approximately 6-8% in the general population, although this can increase to...
Article
Biomedical research has grown increasingly cooperative through the sharing of consortia-level epigenetic data. Since consortia preprocess data prior to distribution, new processing pipelines can lead to different versions of the same dataset. Similarly, analytic frameworks evolve to incorporate cutting-edge methods and best practices. However, it r...
Article
Full-text available
Doublecortin (DCX) has long been implicated in, and employed as a marker for, neurogenesis, yet little is known about its function in non-neurogenic brain regions, including the amygdala. This study sought first to explore, in rodents, whether fear learning and extinction modulate amygdala DCX expression and, second, to assess the utility of periph...
Article
Background Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over...
Preprint
Full-text available
Schizophrenia is a chronic mental illness that is amongst the most debilitating conditions encountered in medical practice. A recent landmark schizophrenia study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This study -- and most...
Article
Posttraumatic stress disorder (PTSD) is a highly impairing psychiatric condition, and women are twice as likely as men to receive a diagnosis. It is thought that chronic arousal and physiological stress place individuals with PTSD at greater risk for cardiovascular disease (CVD). Sex differences in CVD are also well established. For example, premen...
Article
Background: Researchers are increasingly investigating therapeutic response associated with new patient subgroups as a way to improve electroconvulsive therapy (ECT) treatment outcomes and reduce adverse events. This study is the first to examine baseline cognitive impairment status as a predictor of clinical outcome in first acute-course ECT pati...
Article
Full-text available
The current study investigated the relationship between trauma exposure and psychopathology in a sample of predominately African-American women of low socioeconomic status (SES). Women (N = 7430) were recruited from medical clinics at two large public hospitals in Atlanta, GA, from 2005 to 2017. Women were assessed for sociodemographics, life-cours...
Article
Attempts to correlate blood levels of brain-derived neurotrophic factor (BDNF) with post-traumatic stress disorder (PTSD) have provided conflicting results. Some studies found a positive association between BDNF and PTSD diagnosis and symptom severity, while others found the association to be negative. The present study investigated whether serum l...
Article
Full-text available
Background Type 2 diabetes mellitus (T2DM) is a major public health problem in the United States. Although cardiovascular autonomic functioning, blood glucose control, and inflammation are known to play a role in T2DM, the interaction between these variables remains largely unexplored, particularly in the context of stress. To address this gap, we...
Article
Full-text available
Background Cross-sectional studies have found that individuals with posttraumatic stress disorder (PTSD) exhibit deficits in autonomic functioning. While PTSD rates are twice as high in women compared to men, sex differences in autonomic functioning are relatively unknown among trauma-exposed populations. The current study used a prospective design...
Article
Background : Previous work has indicated that differences in neurocognitive functioning may predict the development of adverse post-traumatic neuropsychiatric sequelae (APNS). Such differences may be vulnerability factors or simply correlates of APNS-related symptoms. Longitudinal studies that measure neurocognitive functioning at the time of traum...
Article
Full-text available
Objective: Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic lo...
Preprint
The ability of the medial prefrontal cortex (mPFC) to exert top-down control of behavior is affected by stress. The molecular response of mPFC to stress is incompletely understood, however, in part because of the region’s cellular heterogeneity. Here we used single nucleus RNA sequencing (snRNAseq) to map specific molecular cell types within the mP...
Preprint
Experience-dependent learning depends on synaptic plasticity. While plasticity in individual synapses has been extensively investigated, the mechanisms underlying coordinated changes across sets of synapses on multiple dendrites, likely needed to encode effective adaptations to a salient stimulus, are not well understood. The extracellular matrix i...
Article
Many reports have documented the relationship between post-traumatic stress disorder (PTSD) and substance use. Substance use is commonly comorbid with PTSD and is a risk factor for trauma exposure. The aim of this study was to prospectively examine how recent substance use, abuse, or dependence influenced the development of PTSD in the context of a...
Preprint
Objective A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behaviour. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. Method Here, we examine this issue through two approaches: (i) an e...
Article
Posttraumatic stress disorder (PTSD) is associated with lower gray matter volume (GMV) in brain regions critical for extinction of learned threat. However, relationships among volume, extinction learning, and PTSD symptom development remain unclear. We investigated subcortical brain volumes in regions supporting extinction learning and fear-potenti...
Preprint
Full-text available
Alcohol intake progressively increases after prolonged consumption of alcohol, but relatively few new therapeutics targeting development of alcohol use disorder (AUD) have been validated. Here, we conducted a genome-wide RNA-sequencing (RNA-seq) analysis in mice exposed to different modes (acute vs chronic) of ethanol drinking. We focused on transc...
Article
Full-text available
Active-duty Army personnel can be exposed to traumatic warzone events and are at increased risk for developing post-traumatic stress disorder (PTSD) compared with the general population. PTSD is associated with high individual and societal costs, but identification of predictive markers to determine deployment readiness and risk mitigation strategi...
Article
Importance A substantial proportion of the 40 million people in the US who present to emergency departments (EDs) each year after traumatic events develop posttraumatic stress disorder (PTSD) or major depressive episode (MDE). Accurately identifying patients at high risk in the ED would facilitate the targeting of preventive interventions. Objecti...
Article
Childhood maltreatment, occurring in up to 20-30% of the population, remains far too common, and incorporates a range of active and passive factors, from abuse, to neglect, to the impacts of broader structural and systemic adversity. Despite the effects of childhood maltreatment and adversity on a wide range of adult physical and psychological nega...
Article
Full-text available
Posttraumatic stress disorder can be viewed as a disorder of fear dysregulation. An abundance of research suggests that the prefrontal cortex is central to fear processing—that is, how fears are acquired and strategies to regulate or diminish fear responses. The current review covers foundational research on threat or fear acquisition and extinctio...
Article
Full-text available
Women are at higher risk for developing posttraumatic stress disorder (PTSD) compared to men, yet little is known about the biological contributors to this sex difference. One possible mechanism is differential immunological and neuroendocrine responses to traumatic stress exposure. In the current prospective study, we aimed to identify whether sex...
Article
Full-text available
A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for,...
Article
Full-text available
Post-traumatic stress disorder (PTSD) is a heterogeneous condition evidenced by the absence of objective physiological measurements applicable to all who meet the criteria for the disorder as well as divergent responses to treatments. This study capitalized on biological diversity observed within the PTSD group observed following epigenome-wide ana...
Article
Background Experiences of racial discrimination are linked to a range of negative brain health outcomes, but little is known about how these experiences impact neural architecture, including white matter microstructure, which may partially mediate these outcomes. Our goal was to examine associations between racially discriminatory experiences and w...
Preprint
Full-text available
Genomewide association studies increasingly employ multivariate tests of multiple correlated phenotypes to exploit likely pleiotropy to improve power. Typical multivariate methods produce a global p-value of association between a variant (or set of variants) and multiple phenotypes. When the global test is significant, subsequent interest then focu...
Article
Importance Racial discrimination has a clear impact on health-related outcomes, but little is known about how discriminatory experiences are associated with neural response patterns to emotionally salient cues, which likely mediates these outcomes. Objective To examine associations of discriminatory experiences with brainwide response to threat-re...
Article
Full-text available
This is the initial report of results from the AURORA multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. We focus on n = 666 participants presenting to EDs following a motor vehicle collision (MVC) and...
Article
Full-text available
Disturbed activation or regulation of the stress response through the hypothalamic-pituitary-adrenal (HPA) axis is a fundamental component of multiple stress-related diseases, including psychiatric, metabolic, and immune disorders. The FK506 binding protein 51 (FKBP5) is a negative regulator of the glucocorticoid receptor (GR), the main driver of H...
Article
Full-text available
Posttraumatic stress disorder (PTSD) is a debilitating syndrome with substantial morbidity and mortality that occurs in the aftermath of trauma. Symptoms of major depressive disorder (MDD) are also a frequent consequence of trauma exposure. Identifying novel risk markers in the immediate aftermath of trauma is a critical step for the identification...
Article
Full-text available
Depression is a common condition, but current treatments are only effective in a subset of individuals. To identify new treatment targets, we integrated depression genome-wide association study (GWAS) results (N = 500,199) with human brain proteomes (N = 376) to perform a proteome-wide association study of depression followed by Mendelian randomiza...
Article
Full-text available
Responding to different dynamic levels of stress is critical for mammalian survival. Disruption of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) signaling is proposed to underlie hypothalamic-pituitary-adrenal (HPA) axis dysregulation observed in stress-related psychiatric disorders. In this study, we show that FK506-binding prot...
Article
Full-text available
Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symp...
Article
Biomarkers that predict symptom trajectories after trauma can facilitate early detection or intervention for posttraumatic stress disorder (PTSD) and may also advance our understanding of its biology. Here, we aimed to identify trajectory-based biomarkers using blood transcriptomes collected in the immediate aftermath of trauma exposure. Participan...
Article
Background PTSD is both prevalent and debilitating. While deep transcranial magnetic stimulation (dTMS) has shown preliminary efficacy, exposure therapy remains the most efficacious, though limited, treatment in PTSD. The medial prefrontal cortex (mPFC) is implicated in extinction learning, suggesting that concurrent mPFC stimulation may enhance ex...
Article
Background Evidence-based pharmacological treatments for PTSD are few and of limited efficacy. Prior work suggest that angiotensin type 1 receptor (AT1R) inhibition facilitates fear inhibition and extinction, important for recovery from PTSD. This study tests the efficacy of the AT1R antagonist losartan, an antihypertensive drug, repurposed for the...
Preprint
Prior studies highlight how threat-related arousal may impair hippocampal function. Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may drive arousal responses to alter hippocampal reactivity, and further how these alterations rel...
Article
Full-text available
We sought to find clinical subtypes of posttraumatic stress disorder (PTSD) in veterans 6–10 years post-trauma exposure based on current symptom assessments and to examine whether blood biomarkers could differentiate them. Samples were males deployed to Iraq and Afghanistan studied by the PTSD Systems Biology Consortium: a discovery sample of 74 PT...
Article
Background Impaired contextual fear inhibition is often associated with posttraumatic stress disorder (PTSD). Our previous work has demonstrated that more hippocampal activation during a response inhibition task after trauma exposure was related to greater resilience and fewer future PTSD symptoms. In the current study, we sought to extend our prev...