Understanding PTSD

In his early theories of the mind, Sigmund Freud hypothesised that traumatic experiences such as war, accidents, or assault could leave lasting psychological effects. With advances in research, these responses are now formally recognised as post-traumatic stress disorder (PTSD) (Schrader & Ross, 2021). As defined by the Diagnostic and Statistical Manual of Mental Disorders, PTSD is a complex psychiatric condition that develops following exposure to severe trauma, including threatened death, injury, or violence (Zhang et al., 2025). PTSD frequently co-occurs with other disorders, such as depression, anxiety, and substance use, which intensify symptom severity, increase suicidal behaviour, and reduce treatment effectiveness. Manifesting with significant heterogeneity, research indicates that there are over 636,120 possible symptom combinations (Zhang et al., 2025).

Symptoms and Clinical Impact

According to the National Institute for Health and Care Excellence (NICE) guidelines, a diagnosis of PTSD requires at least nine symptoms drawn from five categories: intrusion, avoidance, negative mood, dissociation, and arousal. Intrusion symptoms may include distressing memories, nightmares, or flashbacks. Avoidance can involve staying away from places, people, or conversations linked to the trauma. Negative mood may be shown through negative beliefs, persistent low mood, and feelings of detachment. Arousal symptoms include irritability, exaggerated startle responses, poor concentration, and disturbed sleep (NICE, 2025). In more recent conflicts, underreporting of symptoms remains a persistent issue due to fears of stigma and job loss, while civilians face a lack of insurance coverage for specialised treatment (Schrader & Ross, 2021).

Biological Mechanisms of PTSD

Features of PTSD, including fear, hyperarousal, avoidance, and intrusive symptoms such as flashbacks, are thought to arise from disruptions in brain circuitry and neurochemical regulation. Structural and functional abnormalities are consistently observed in the amygdala, anterior cingulate cortex, hippocampus, and prefrontal cortex, which together mediate threat detection, emotional regulation, and contextual memory processing (Al Jowf et al., 2023). Neuroimaging studies report that amygdala hyperactivity, coupled with reduced prefrontal regulation, impairs the ability to suppress fear responses, while hippocampal alterations disrupt contextual processing of traumatic memories (Ben-Zion et al., 2024).

Excessive noradrenergic activity is linked to hyperarousal and intrusive symptoms, while disruptions in serotonin and dopamine signalling contribute to anxiety, mood dysregulation, and altered reward processing.

Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis connects stress exposure to maladaptive cortisol responses and long-term physiological and psychological consequences (Ben-Zion et al., 2024). Collectively, these findings highlight PTSD as a disorder rooted in disrupted brain circuits, impaired connectivity, and imbalances in key neurotransmitter and stress-regulation systems.

Treatment approaches

Effective treatment for PTSD requires a multidisciplinary approach that combines treatment modalities. First-line interventions are trauma-focused psychotherapies that have proven useful in the treatment of PTSD, specifically cognitive behavioural therapy (CBT) and eye movement desensitisation and reprocessing (EMDR) therapy, which have been shown to reduce the emotional impact of traumatic memories by helping patients process distressing experiences and develop healthier coping mechanisms (Al Jowf et al., 2023).

Pharmacological treatment is often considered when psychotherapy alone is insufficient. NICE guidelines recommend using a selective serotonin reuptake inhibitor (SSRI), such as sertraline or venlafaxine (NICE, 2025). These medications act by modulating serotonin and noradrenaline levels in the brain and have been shown to reduce symptoms of anxiety and fear in individuals with PTSD (Williams et al., 2022). In addition, antipsychotics such as risperidone may be considered for adults with PTSD who experience disabling behaviour, such as severe hyperarousal or psychotic symptoms (NICE, 2025).

Prevention and future directions

Exposure to trauma cannot always be avoided, so preventing PTSD remains a challenge. However, the social-ecological model emphasises risk factors at individual, relationship, community, and societal levels. Preventive measures range from accessible hotlines and early counselling to broader public health initiatives such as awareness campaigns and anti-discrimination policies (Al Jowf et al., 2023). PTSD biomarkers, though currently limited to research, have the potential to improve early detection, diagnosis, and prognosis by reflecting underlying biological processes and disease risk (Zhang et al., 2025).

Novel therapies such as MDMA-assisted psychotherapy show strong promise in clinical trials and may soon become approved adjunct treatments, as they reduce avoidance, facilitate trauma processing, strengthen therapeutic alliance, and enhance emotional reappraisal beyond core PTSD symptoms (Kangaslampi & Zijlmans, 2024). Emerging approaches such as neurofeedback, brain stimulation, and artificial intelligence (AI) in diagnosis and treatment planning illustrate the evolving future of PTSD care. Particularly, machine learning (ML) offers potential for earlier symptom detection, personalised treatment strategies, and improved monitoring of patient progress, enabling more targeted and effective interventions (Wan et al., 2024).

Although progress in biomedical research is revealing the neurobiological underpinnings of PTSD, its mechanism remains only partly understood, highlighting the need for continued investigation. Hwang and colleagues, in a recent 2025 study published in Nature , identified gene expression changes in specific brain cell types associated with PTSD. These alterations involve dysregulation of pathways related to glucocorticoid signalling, GABAergic transmission, and neuroinflammation, providing insight into the molecular mechanisms underlying PTSD (Hwang et al., 2025).

Seeking help is a vital step for individuals experiencing PTSD, and a range of support services is available to facilitate recovery. Non-profit organisations such as Mind, Combat Stress, and PTSD UK play a crucial role in providing resources, raising awareness, and advocating for those affected by the disorder.

References

Al Jowf, G. I., Ahmed, Z. T., Reijnders, R. A., de Nijs, L., & Eijssen, L. M. T. (2023). To Predict, Prevent, and Manage Post-Traumatic Stress Disorder (PTSD): A Review of Pathophysiology, Treatment, and Biomarkers. Int J Mol Sci , 24 (6). https://doi.org/10.3390/ijms24065238

Ben-Zion, Z., Korem, N., Fine, N. B., Katz, S., Siddhanta, M., Funaro, M. C., Duek, O., Spiller, T. R., Danbock, S. K., Levy, I., & Harpaz-Rotem, I. (2024). Structural Neuroimaging of Hippocampus and Amygdala Subregions in Posttraumatic Stress Disorder: A Scoping Review. Biol Psychiatry Glob Open Sci , 4 (1), 120-134. https://doi.org/10.1016/j.bpsgos.2023.07.001

Hwang, A., Skarica, M., Xu, S., Coudriet, J., Lee, C. Y., Lin, L., Terwilliger, R., Sliby, A. N., Wang, J., Nguyen, T., Li, H., Wu, M., Dai, Y., Duan, Z., Srinivasan, S. S., Zhang, X., Lin, Y., Cruz, D., Deans, P. J. M., . . . Girgenti, M. J. (2025). Single-cell transcriptomic and chromatin dynamics of the human brain in PTSD. Nature , 643 (8072), 744-754. https://doi.org/10.1038/s41586-025-09083-y

Iqbal, J., Huang, G. D., Xue, Y. X., Yang, M., & Jia, X. J. (2023). The neural circuits and molecular mechanisms underlying fear dysregulation in posttraumatic stress disorder. Front Neurosci , 17 , 1281401. https://doi.org/10.3389/fnins.2023.1281401

Kangaslampi, S., & Zijlmans, J. (2024). MDMA-assisted psychotherapy for PTSD in adolescents: rationale, potential, risks, and considerations. Eur Child Adolesc Psychiatry , 33 (11), 3753-3764. https://doi.org/10.1007/s00787-023-02310-9

NICE. (2025). Post-traumatic stress disorder: diagnosis . https://cks.nice.org.uk/topics/post-traumatic-stress-disorder/diagnosis/diagnosis/

Schrader, C., & Ross, A. (2021). A Review of PTSD and Current Treatment Strategies. Mo Med , 118 (6), 546-551. https://www.ncbi.nlm.nih.gov/pubmed/34924624

Wan, R., Wan, R., Xie, Q., Hu, A., Xie, W., Chen, J., & Liu, Y. (2024). Current Status and Future Directions of Artificial Intelligence in Post-Traumatic Stress Disorder: A Literature Measurement Analysis. Behav Sci (Basel) , 15 (1). https://doi.org/10.3390/bs15010027

Zhang, C., Haim-Nachum, S., Prasad, N., Suarez-Jimenez, B., Zilcha-Mano, S., Lazarov, A., Neria, Y., & Zhu, X. (2025). PTSD subtypes and their underlying neural biomarkers: a systematic review. Psychol Med , 55 , e153. https://doi.org/10.1017/S0033291725001229