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Related Concept Videos

Post-traumatic Stress Disorder01:27

Post-traumatic Stress Disorder

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Post-traumatic stress disorder (PTSD) is a psychiatric condition that arises following exposure to traumatic events such as natural disasters, forced displacement, or severe accidents. It significantly impairs individuals' ability to cope with daily activities and disrupts their emotional and psychological equilibrium.
Symptoms and Behavioral Manifestations
A spectrum of distressing symptoms characterizes PTSD. Recurrent flashbacks, where individuals involuntarily relive traumatic events,...
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Stress is a multifaceted response to events perceived as challenging or threatening, highlighting physical, emotional, cognitive, and behavioral reactions. Physically, stress can lead to fatigue, sleep disruptions, and various health issues such as frequent colds, chest pains, and nausea. Emotionally, it can manifest as anxiety, depression, irritability, and anger triggered by both minor and major life events. Cognitively, it may result in difficulty in concentration, memory, and...
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The stress response system, also known as the fight-or-flight response, is the body's automatic physiological reaction to perceived threats. Hans Selye introduced the concept of General Adaptation Syndrome (GAS) to describe the predictable pattern of changes that occur in response to stress. GAS consists of three sequential stages: alarm, resistance, and exhaustion. This model helps explain how chronic stress can contribute to health problems.
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Psychological Responses to Stress01:20

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Psychological responses to stress encompass the various cognitive and emotional reactions individuals experience when faced with challenging or threatening situations, such as a job loss. Prolonged exposure to stressors can disturb emotional balance, increasing negative emotions (e.g., anxiety and sadness) and diminishing positive emotions (e.g., joy and satisfaction). These persistent emotional shifts are associated with an increased risk of both physical illness and mental health issues, such...
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Physiological Foundation of Stress01:24

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Stress triggers a coordinated physiological response involving the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This dual activation ensures that the body is prepared for both immediate and prolonged stress management. The process begins with the perception of a stressor. This initial phase activates the SNS, leading to the rapid release of adrenaline (epinephrine) from the adrenal glands.
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Related Experiment Video

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Single-Nucleus Transcriptome Profiling of Dorsolateral Prefrontal Cortex: Mechanistic Roles for Neuronal Gene

Chris Chatzinakos1, Cameron D Pernia1, Filomene G Morrison1

  • 1Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Mass. (Chatzinakos, Pernia, Iatrou, McCullough, Schuler, Snijders, DiPietro, Soliva Estruch, Anastasopoulos, Bowlby, Hartmann, N.M. Ressler, Carlezon, K.J. Ressler, Daskalakis); Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Mass. (Chatzinakos, Pernia, Iatrou, Schuler, Snijders, DiPietro, Soliva Estruch, Anastasopoulos, Bowlby, Daskalakis); National Center for PTSD, VA Boston Healthcare System, Boston (Morrison, Wolf, Logue, Miller); Department of Psychiatry (Morrison, Wolf, Logue, Miller), Department of Neurology (Huber), and Department of Biomedical Genetics (Logue), Boston University School of Medicine, Boston; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (Soliva Estruch, Snijders); RG Neurohomeostasis, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Bonn, Bonn, Germany (Bajaj, Gassen); Department of Radiology, University Hospital Basel, University of Basel, Basel, Switzerland (Anastasopoulos); Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore (Bharadwaj, Kleinman); Department of Psychiatry, University of California San Diego, La Jolla (Maihofer, Nievergelt); Center for Excellence in Stress and Mental Health (Maihofer, Nievergelt) and Research Service (Maihofer, Nievergelt), Veterans Affairs San Diego Healthcare System, San Diego; Department of Psychiatry, Yale University School of Medicine, New Haven, Conn. (Krystal, Girgenti); Psychiatry Service, VA Connecticut Healthcare System, West Haven (Krystal, Girgenti); National Center for PTSD, Clinical Neurosciences Division, U.S. Department of Veterans Affairs, West Haven, Conn. (Krystal, Girgenti); Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore (Kleinman); Pathology and Laboratory Medicine, VA Boston Healthcare System, Boston (Huber); Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, and Broad Institute of MIT and Harvard, Cambridge, Mass. (Kellis); Department of Biostatistics, Boston University School of Public Health, Boston (Logue).

The American Journal of Psychiatry
|July 26, 2023
PubMed
Summary

This study reveals cell-type-specific gene expression differences in the brain for posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Findings highlight distinct stress response mechanisms and potential biomarkers for these conditions.

Keywords:
Biological MarkersGenetics/GenomicsGlucocorticoidMajor Depressive DisorderPosttraumatic Stress DisorderRNA Sequencing

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are linked to the dorsolateral prefrontal cortex (DLPFC).
  • Previous bulk-tissue RNA sequencing (RNA-seq) studies lack cell-type resolution for understanding disease mechanisms.

Purpose of the Study:

  • To conduct the first single-nucleus RNA-seq (snRNA-seq) study on postmortem brain tissue from individuals with PTSD.
  • To elucidate cell-type-specific transcriptomic pathology in PTSD and compare it with MDD.

Main Methods:

  • Single-nucleus RNA sequencing (snRNA-seq) was performed on 32 DLPFC samples from individuals with PTSD, MDD, and controls.
  • A replication sample of 15 DLPFC samples was analyzed.
  • Differential gene expression and pathway analyses were conducted on approximately 415,000 nuclei.

Main Results:

  • Significant differentially expressed genes (snDEGs) were identified in excitatory and inhibitory neurons, and astrocytes, but not in bulk tissue.
  • PTSD samples showed a higher replication rate for snDEGs compared to MDD.
  • Glucocorticoid signaling pathways were differentially enriched in neurons in PTSD versus MDD, with distinct regulatory directions.

Conclusions:

  • The findings underscore cell-type-specific mechanisms in the brain's stress response for PTSD and MDD.
  • This study highlights the necessity of examining cell-type-specific gene expression for understanding these disorders.
  • The results suggest novel biomarkers and potential therapeutic targets for PTSD and MDD.