Post-traumatic stress disorder: a psychiatric disorder requiring urgent attention

Abstract

Post-traumatic stress disorder (PTSD) is a severe and heterogenous psychiatric disorder that was first defined as a mental disorder in 1980. Currently, the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and the International Classification of Diseases 11th Edition (ICD-11) offer the most widely accepted diagnostic guidelines for PTSD. In both diagnostic categories, experiencing a traumatic event (TE) is the necessary criterion for diagnosing PTSD. The TEs described in the DSM-5 include actual or threatened death, serious injury, sexual violence, and other extreme stressors, either directly or indirectly. More than 70% of adults worldwide are exposed to a TE at least once in their lifetime, and approximately 10% of individuals develop PTSD after experiencing a TE. The important features of PTSD are intrusion or re-experiencing fear memories, pervasive sense of threat, active avoidance, hyperarousal symptoms, and negative alterations of cognition and mood. Individuals with PTSD have high comorbidities with other psychiatric diseases, including major depressive disorder, generalized anxiety disorder, and substance use disorder. Multiple lines of evidence suggest that the pathophysiology of PTSD is complex, involving abnormal neural circuits, molecular mechanisms, and genetic mechanisms. A combination of both psychotherapy and pharmacotherapy is used to treat PTSD, but has limited efficacy in patients with refractory PTSD. Because of the high prevalence, heavy burden, and limited treatments, PTSD is a psychiatric disorder that requires urgent attention. In this review, we summarize and discuss the diagnosis, prevalence, TEs, pathophysiology, and treatments of PTSD and draw attention to its prevention.

Keywords: animal models; comorbidity; pathophysiology; post-traumatic stress disorder; traumatic events; treatments.

Figure 1:

Yearly growth in the number of post-traumatic stress disorder publications from 1980 to 2021. The number of annual publications was obtained by searching PubMed using the search terms “post-traumatic stress disorder” and “PTSD”. Online publications 1980 to 2021 are tallied. PTSD, post-traumatic stress disorder.

Figure 2:

Different names for post-traumatic stress disorder used in different historical periods. PTSD, Post-traumatic stress disorder; WWI, World war I; WWII, World war II.

Figure 3:

Symptom clusters in the DSM-5 and ICD-11 for post-traumatic stress disorder. The diagnostic criteria for post-traumatic stress disorder include four symptom clusters in the DSM-5 (A) and three symptom clusters in the ICD-11 (B). The complex post-traumatic stress disorder in the ICD-11 consists of six symptom clusters (B). CPTSD, Complex post-traumatic stress disorder; DSM-5, Diagnostic and statistical manual of mental disorders fifth edition; ICD-11, International classification of diseases 11th edition.

Figure 4:

Physical or psychosocial stressors used to generate animal models of post-traumatic stress disorder. Physical or psychosocial stressors are employed as trauma-like events to establish animal models of post-traumatic stress disorder. Many models are defined by the type of trauma that animals are exposed to. PTSD, post-traumatic stress disorder.

Figure 5:

Abnormal activities of brain regions in patients with post-traumatic stress disorder. (A) Functional neuroimaging shows increased activity in the amygdala, dACC and insular cortex; and decreased activity in the mPFC, rACC and hippocampus in patients with PTSD. dACC: Dorsal anterior cingulate cortex; mPFC: Medial prefrontal cortex; rACC: Rostral anterior cingulate cortex. (B) Hypoactivity of the vmPFC results in the inability of the cortex to inhibit amygdala, and hyperactivity of the dACC contributes to the increased activity of amygdala in patients with PTSD, and then the amygdala outputs to other emotional nucleus associated with fear conditioning after integrating information. PTSD, post-traumatic stress disorder; vmPFC, ventromedial prefrontal cortex; dACC, dorsal anterior cingulate cortex.

Figure 6:

Hypoactivity of the hypothalamic-pituitary-adrenal axis in patients with post-traumatic stress disorder. CRH concentrations in cerebrospinal fluid are higher in PTSD compared to control subjects. But patients with PTSD show enhanced cortisol feedback inhibition of ACTH secretion at the level of the pituitary in PTSD and a blunted ACTH response to CRH. Low circulating levels of cortisol may lead to an adaptation of the HPA axis to increase GR sensitivity and increase negative feedback inhibition of the HPA axis. PTSD, post-traumatic stress disorder; CRH, corticotropin releasing hormone; ACTH, adrenocorticotropin; GR, glucocorticoid receptors. (Figure modified from Yehuda et al. 2015 [180].)

Figure 7:

Common treatments for post-traumatic stress disorder. Psychotherapies are first-line treatments for PTSD. A combination of psychological therapy and pharmacotherapy can enhance treatment outcomes for PTSD. Sertraline and paroxetine are the only two FDA-approved drugs to treat PTSD. Neuromodulation has been used to reduce symptoms of refractory PTSD. The effect of treatments labeled with dotting wheel needs to be further studied. PTSD, Post-traumatic stress disorder; PE, prolonged exposure; EMDR, Eye movement desensitization and reprocessing; ACT, Acceptance and commitment therapy; CPT, Cognitive processing therapy; MDMA, 3, 4,-Methylenedioxmethamphetamine; ECT, Electroconvulsive therapy; rTMS, Repetitive transcranial magnetic stimulation; DBS, Deep brain stimulation.