Emotional Pain, Not Fear, Weighs More Heavily on Individuals with PTSD

New research is challenging the long-held view of post-traumatic stress disorder (PTSD) as a fear-based disorder. In a new study, 68% of trauma-exposed individuals reported that emotional pain (guilt, shame, sadness, loss of joy) impaired their daily functioning more than fear. The findings from this research in Biological Psychiatry, published by Elsevier, underscore the need to broaden PTSD models beyond fear and re-evaluate treatment pathways accordingly.

PTSD affects approximately 8% of individuals and often co-occurs with depression and anxiety. The DSM-5 defines PTSD based on 20 symptoms spanning intrusion, avoidance, negative mood and cognition, and hyper-arousal. In this study across two independent samples, researchers identified two distinct PTSD profiles—one centered on fear (flashbacks and hyper-arousal symptoms), and another on emotional pain (symptoms of guilt, shame, anhedonia).

“For some, trauma inflicts not just fear, but a moral or existential wound, shattering beliefs about oneself, others, or the world; For others, it deepens pre-existing negative schemas, reinforcing guilt, shame, or worthlessness. These internalized and meaning-laden responses often give rise to persistent emotional pain,” says first author Ziv Ben-Zion, PhD, Yale School of Medicine, VA Connecticut Healthcare System, and University of Haifa.

Senior investigator Ilan Harpaz-Rotem, PhD, Yale School of Medicine, Yale University, and VA Connecticut Healthcare System, adds, “Basic science, including the research done in our lab at Yale, has focused for years on fear learning and safety updating, with minimal attention to the toll of other negative emotions associated with PTSD. We started thinking that fear and emotional pain are potentially driven by two different biological systems that play a critical role in defining how to tailor pharmacological and psychological treatments for PTSD.”

The research was conducted in two phases. In Study 1, using a large online sample of 838 trauma-exposed individuals, researchers mapped how fear and emotional pain relate to specific PTSD symptoms through network analysis. Study 2, a unique longitudinal neuroimaging study of 162 recent trauma survivors, used whole-brain connectivity at one-month post-trauma to predict symptom severity 14 months later for the two profiles identified in Study 1 (Fear and Emotional Pain). Connectivity patterns robustly predicted chronic fear-based symptoms but not emotional pain, suggesting mechanistic differences between these profiles.

This is one of the first studies to integrate subjective emotional experience, symptom network structure, and neurobiological prediction to differentiate PTSD profiles.

John Krystal, MD, Editor of Biological Psychiatry, comments, “One of the most challenging aspects of mental health care is simply and accurately characterizing the actual emotional symptoms associated with psychiatric disorders. People may use different words to describe the same experience, and they may apply the same descriptor to different experiences. Neuroimaging may provide a strategy to help to untangle this state of affairs.”

Dr. Krystal continues, “This study identifies distinct emotional symptoms that are associated with PTSD: fear and emotional pain. These two experiences are represented by different circuits in the brain, and they are differentially associated with other PTSD symptoms. Fear was associated with increased arousal, nightmares, and intrusive trauma memories, while emotional pain was associated with depression-like symptoms and insomnia.”

“Rather than proposing a new diagnostic category, our goal is to sharpen the clinical understanding of PTSD by identifying the emotional lens of fear or emotional pain through which trauma is most acutely experienced,” notes Dr. Harpaz-Rotem.

Identifying whether a patient’s distress is primarily driven by fear or by emotional pain could guide more personalized and mechanism-based treatment planning. Fear-driven profiles may respond best to exposure-based therapies, whereas emotional pain may be better addressed through approaches targeting guilt, shame, and negative self-beliefs. This distinction may also help clarify which symptoms are likely to persist chronically.

Dr. Ben-Zion concludes, “PTSD is not a single emotional experience. Our goal was to bring the patient’s subjective emotional reality to the center of the scientific discussion. Recognizing which emotional system is driving a person’s distress can open the door to more precise and compassionate treatment.”

Notes for editors

The article is "Dissecting Fear and Emotional Pain in PTSD: From Symptom Networks to Neural Signatures,” by Ziv Ben-Zion, Erin Z. Basol, Alexander J. Simon, Maayan Abargil, Katherine Samonek, Megan Patterson, Tobias R. Spiller, Or Duek, Stefan Just, Katrin Preller, Jakcob N. Keynan, Roee Admon, Israel Liberzon, Arieh Y. Shalev, Talma Hendler, Ifat Levy, Jutta Joormann, Dustin Scheinost, and Ilan Harpaz-Rotem (https://doi.org/10.1016/j.biopsych.2025.11.016). It is published online in Biological Psychiatry, published by Elsevier.

The article is openly available for 60 days at https://www.biologicalpsychiatryjournal.com/article/S0006-3223(25)01645-2/fulltext.

Copies of the full text and additional information are also available to credentialed journalists upon request; please contact Rhiannon Bugno at [email protected]. Journalists wishing to interview the authors should contact Ziv Ben-Zion, PhD, at [email protected] or [email protected].

This research was supported by an Investigator Imitated Research (IIR) Precision Psychiatry grant from Boehringer Ingelheim (Study 1) and by a grant from the National Institute of Mental Health (NIMH, Study 2, award number R01-MH103287).

The authors’ affiliations and disclosures of financial relationships and conflicts of interests are available in the article.

John H. Krystal, MD, is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial relationships and conflicts of interests are available here.

About Biological Psychiatry

Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms, and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 9^th out of 156 Psychiatry titles and 17^th out of 271 Neurosciences titles in Journal Citation Reports^TM, published by Clarivate. The 2024 Impact Factor score for Biological Psychiatry is 9.0.www.sobp.org/journal

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