PTSD

Post-Traumatic Stress Disorder (PTSD) is a trauma- and stressor-related disorder that may develop following exposure to actual or threatened death, serious injury, or sexual violence. It is characterised by four symptom clusters: intrusion (unwanted re-experiencing), avoidance, negative alterations in cognition and mood, and alterations in arousal and reactivity. PTSD can occur after direct experience, witnessing, or learning about the traumatic event of a close family member or friend, or repeated/extreme exposure to aversive details (e.g., first responders). References: DSM-5-TR, StatPearls (NCBI Bookshelf).

Post-Traumatic Stress Disorder (PTSD) is a trauma- and stressor-related disorder that may develop following exposure to actual or threatened death, serious injury, or sexual violence. It is characterised by four symptom clusters: intrusion (unwanted re-experiencing), avoidance, negative alterations in cognition and mood, and alterations in arousal and reactivity. PTSD can occur after direct experience, witnessing, or learning about the traumatic event of a close family member or friend, or repeated/extreme exposure to aversive details (e.g., first responders). DSM-5-TR classifies it under Trauma- and Stressor-Related Disorders. It is a serious, disabling, and potentially chronic condition but is highly treatable with evidence-based therapies.

Intrusion symptoms: recurrent, involuntary, intrusive distressing memories of the traumatic event; recurrent distressing dreams; dissociative reactions (flashbacks - acting/feeling as if the event is recurring); intense or prolonged psychological distress to internal/external trauma cues; marked physiological reactions to cues. Avoidance: avoidance of distressing memories, thoughts, or feelings related to the event; avoidance of external reminders (people, places, activities, situations). Negative cognitions and mood: inability to recall key aspects of the trauma; persistent negative beliefs about self, others, or the world; distorted blame of self/others; persistent negative emotions (fear, horror, anger, guilt, shame); diminished interest in activities; feeling detached/estranged from others; persistent inability to experience positive emotions (emotional numbing). Alterations in arousal and reactivity: irritable behaviour/angry outbursts; reckless or self-destructive behaviour; hypervigilance; exaggerated startle response; concentration difficulties; sleep disturbance.

Trauma exposure is necessary but not sufficient. Risk factors for developing PTSD given trauma exposure include: Trauma-related: greater severity, duration, and proximity of the traumatic event; interpersonal trauma (especially sexual assault) confers higher PTSD risk than accidental or natural disaster trauma; repeated trauma exposure; lack of social support immediately after trauma. Individual: female sex (2x PTSD risk for equivalent trauma); prior trauma history; prior mental health diagnosis; neuroticism; dissociation during or after the traumatic event (peritraumatic dissociation); genetic vulnerability (FKBP5, CRHR1, ADCYAP1R1 genes).

Post-trauma: lack of social support; subsequent life stressors; lack of access to mental health care.

PTSD involves a failure of adaptive fear processing and extinction. Fear conditioning: the traumatic event creates strong fear associations; hippocampal failure to contextualise the memory leads to generalised fear responses. HPA axis: disrupted in PTSD (often low basal cortisol, enhanced cortisol suppression on low-dose dexamethasone - contrasting with depression); inadequate glucocorticoid suppression of fear memory consolidation. Amygdala hyperreactivity: the amygdala responds excessively to trauma-related and general threat cues. Prefrontal cortex hypoactivity: reduced ventromedial PFC (vmPFC) activity impairs extinction of fear memories and emotional regulation. Hippocampal volume reduction: impairs contextual memory processing, contributing to intrusive, context-free trauma memories. Noradrenergic hyperactivation: explains hyperarousal symptoms and is the rationale for prazosin treatment of PTSD nightmares.

Global: lifetime prevalence ~7-8% in the general population; widely varying by country and trauma exposure rates (highest in conflict-affected regions). USA: ~7-8% lifetime prevalence; ~3.5% 12-month prevalence (NIMH). High-risk populations: combat veterans (15-30% lifetime in Vietnam veterans; 10-20% in OEF/OIF veterans); sexual assault survivors (approximately 50% develop PTSD); disaster survivors; first responders; refugees and displaced persons. Female:male ratio approximately 2:1 despite males experiencing more trauma overall, reflecting differential trauma type (females more often experience sexual/interpersonal violence). Approximately 50% of PTSD cases resolve within 3 months; chronic PTSD (>1 year) occurs in ~30% of cases. Comorbidity: MDD (~50%), anxiety disorders, substance use (~50%), suicidal ideation.

Neurobiological mechanisms: Fear circuit dysregulation - amygdala hyperactivation, vmPFC and ACC hypoactivation (impaired fear extinction), hippocampal volume reduction. Noradrenergic hyperactivation: elevated urinary norepinephrine, exaggerated startle, nightmares - target for prazosin, propranolol. HPA axis: low basal cortisol (distinct from MDD), enhanced negative feedback - may reflect a defence against excessive cortisol toxicity after trauma. Serotonergic: serotonin transporter function and BDNF alterations contribute. Neuropeptide Y (NPY): reduced in PTSD; associated with resilience. Inflammatory mediators: elevated cytokines and CRP. Genetic: epigenetic modifications of stress response genes (FKBP5 methylation, glucocorticoid receptor signalling) are altered by trauma exposure.

The prefrontal cortex, which helps us think clearly and calm our reactions, may be underactive—like a weak brake on the fear system. Noradrenaline, a chemical that sharpens alertness, can be released too readily, contributing to hypervigilance and nightmares. In simple terms: the brain is trying to protect us by staying hyper-alert, but this backfires, causing ongoing distress. Trauma-focused therapy helps the brain learn that memories are safe to process; medication can reduce the overactive alarm. Clinical interview: Obtain detailed trauma history (type, severity, timing); assess all four symptom clusters; onset, duration (symptoms must persist >1 month), and functional impact. Exclusion of substances/medications as cause. Key assessment tools: PTSD Checklist for DSM-5 (PCL-5): 20-item self-report; Clinician-Administered PTSD Scale (CAPS-5): gold-standard structured interview; Primary Care PTSD Screen for DSM-5 (PC-PTSD-5): brief 5-item screen for primary care. Suicide risk assessment is mandatory (comorbid SI is common). Dissociation assessment (DES-II). Physical examination: assess for traumatic brain injury (TBI), chronic pain, somatic complaints related to trauma.

DSM-5-TR Criteria (for adults, adolescents, and children >6): A. Exposure to actual or threatened death, serious injury, or sexual violence (direct, witnessed, learned of loved one, repeated/extreme exposure). B. Intrusion symptoms (>=1 of 5). C. Avoidance (>=1 of 2). D. Negative cognitions/mood (>=2 of 7). E. Arousal/reactivity alterations (>=2 of 6). F. Duration >1 month. G. Significant distress or impairment. H. Not attributable to substances or medical condition. Specifiers: With dissociative symptoms (depersonalisation or derealisation); With delayed expression (full criteria not met until >=6 months post-event). Separate criteria exist for PTSD in children aged 6 and under, with developmentally sensitive symptom descriptions. ICD-11: PTSD (6B40) defined more narrowly (intrusion, avoidance, hyperarousal - 3 clusters). Complex PTSD (6B41) added for chronic, repeated trauma.

CAPS-5 (Clinician-Administered PTSD Scale for DSM-5): the gold-standard diagnostic interview; assesses severity of each symptom criterion. PCL-5 (PTSD Checklist): 20-item self-report corresponding to DSM-5 criteria; cutoff >=31-33 suggests PTSD. PC-PTSD-5: 5-item screen for primary care and military settings. Harvard Trauma Questionnaire (HTQ): for refugee/cross-cultural settings. Assessment of comorbidities: PHQ-9 (depression), GAD-7 (anxiety), AUDIT (alcohol), DAST (drugs), C-SSRS (suicide). Neuropsychological testing when TBI or cognitive impairment is suspected.

Acute Stress Disorder (ASD): same symptoms but 3 days-1 month post-trauma; if persists >1 month, reassess for PTSD. Adjustment disorder: less specific symptoms, not necessarily traumatic stressor, lacks full PTSD symptom clusters. MDD: depressive features overlap; PTSD additionally has intrusion and hyperarousal.

Complex PTSD (ICD-11): chronic trauma history, additional disturbances in self-organisation (affect dysregulation, negative self-concept, relational disturbances). BPD: overlaps with emotional dysregulation and self-harm; distinguish by trauma focus, identity disturbance pattern, and developmental history. Dissociative disorders: significant dissociation may complicate PTSD; DID (Dissociative Identity Disorder) can result from severe early trauma. TBI: hyperarousal, sleep disturbance, and concentration problems overlap; neurological assessment needed. Substance use disorder: often comorbid and sometimes masking PTSD; address both simultaneously.

Treatment of Post-Traumatic Stress Disorder (PTSD) involves trauma-focused psychotherapy as the primary intervention, with pharmacotherapy as an adjunct. Trauma-Focused Psychotherapy: Prolonged Exposure (PE) involves repeated, systematic confrontation with trauma-related memories and situations that are safe but avoided due to trauma-related fear. It is one of the most strongly evidence-based treatments. Cognitive Processing Therapy (CPT) helps patients identify and challenge unhelpful beliefs related to the trauma (about safety, trust, power, esteem, and intimacy). Eye Movement Desensitisation and Reprocessing (EMDR) uses bilateral stimulation (eye movements, tapping) while processing traumatic memories to facilitate adaptive information processing. All three are recommended as first-line treatments by major guidelines (APA, NICE, VA/DoD). Other Psychotherapies: CBT with cognitive restructuring and exposure components, narrative exposure therapy (for multiple traumas or refugees), and written exposure therapy are effective alternatives. Skills-based therapies (Seeking Safety, Skills Training in Affective and Interpersonal Regulation - STAIR) may be helpful for patients with complex trauma or who are not ready for trauma-focused work. Pharmacotherapy: SSRIs (sertraline, paroxetine - both FDA-approved for PTSD) and SNRIs (venlafaxine) are first-line medications. Prazosin is effective for trauma-related nightmares and sleep disturbance. Atypical antipsychotics may be used adjunctively for severe symptoms or partial SSRI response. Benzodiazepines are not recommended and may impair trauma processing. Mood stabilisers have limited evidence. Complementary Approaches: Mindfulness-based interventions, yoga, and physical exercise have growing evidence as adjuncts to primary treatment. Peer support and group therapy can reduce isolation.

Approximately 50% of cases resolve within 3 months without treatment. Without treatment, many develop chronic PTSD (>1 year). With evidence-based treatment: PE and CPT achieve ~60-80% response rates; 40-60% achieve full remission. Longer duration before treatment initiation, greater severity, and comorbid substance use predict poorer outcomes. Comorbid MDD and personality disorders worsen prognosis. Residual symptoms (especially sleep disturbance and emotional numbing) are common even after treatment. Suicide risk remains elevated for years after trauma. Complex trauma with childhood onset typically requires more intensive and longer-term treatment.

Suicide: elevated risk (~10x general population in severe PTSD). Substance use: alcohol and opioid abuse as self-medication; predicts worse treatment response. Occupational disability: difficulty maintaining employment; high rates of work absence. Relationship difficulties: intimacy avoidance, emotional numbing, irritability, and interpersonal isolation. Health: higher rates of cardiovascular disease, autoimmune disorders, metabolic syndrome, and chronic pain. Medical non-utilisation: trauma-related settings (hospitals, medical procedures) may be avoided, leading to untreated medical conditions. TBI comorbidity: common in combat-related PTSD; compounds cognitive and emotional difficulties.

Primary prevention: immediate post-trauma psychological first aid (social support, information, practical assistance); avoiding benzodiazepines in the immediate post-trauma period (may impair fear extinction). Secondary prevention: early intervention with CBT-based early intervention programs; single-session 'debriefing' is NOT recommended (evidence of harm in some studies). Patient education: PTSD is a normal response to abnormal events; symptoms are not a sign of weakness; effective treatments exist; avoidance maintains PTSD; treatment requires facing trauma memories in a safe, supported way.

Ancient: trauma responses described in soldiers throughout history (Achilles in the Iliad, 'soldier's heart' in the American Civil War, 'shell shock' in WWI, 'combat fatigue' in WWII, 'gross stress reaction' in DSM-I). Vietnam veterans' advocacy drove formalisation in DSM-III (1980) as 'Post-Traumatic Stress Disorder.' Recognition of PTSD in civilians (sexual assault survivors, disaster victims) followed. DSM-5 (2013) moved PTSD from Anxiety Disorders to new Trauma- and Stressor-Related Disorders chapter. ICD-11 (2019) introduced Complex PTSD as a separate diagnosis for chronic/repeated trauma.

Military PTSD and veterans' care have driven much of the research and public awareness. The veteran mental health crisis, particularly in post-9/11 US veterans (22 veteran suicides per day statistic, though contested), has resulted in massive investment in PTSD research and treatment. #MeToo movement increased recognition of sexual trauma and PTSD in survivors. Cultural and gender barriers to PTSD disclosure persist in military culture (stigma of perceived weakness). PTSD in refugees and asylum seekers is a growing global public health concern.

MDMA-assisted psychotherapy: Phase III RCT (Mitchell et al., 2021, Nature Medicine) showed 67% response vs 32% placebo; FDA Breakthrough Therapy. Stellate ganglion block: sympathetic nervous system intervention showing preliminary efficacy for hyperarousal. Psychedelic-assisted therapies: psilocybin, ketamine being studied. Prevention: propranolol administered immediately post-trauma to prevent PTSD (results mixed); cortisol administration for ICU survivors. Neuromodulation: rTMS targeting right lateral PFC. Digital interventions: app-based PE (PTSD Coach app), internet-delivered CBT. Biomarkers: FKBP5, NPY, glucocorticoid receptor signalling as predictors of risk and treatment response.

APA. (2022). DSM-5-TR. APA Publishing. Foa EB, et al. (2019). Prolonged Exposure Therapy Manual. Treatments That Work, Oxford. Mitchell JM, et al. (2021). MDMA-assisted therapy for severe PTSD. Nature Medicine, 27, 1025-1033. VA/DoD Clinical Practice Guidelines for PTSD. 2023 update. Sadock BJ, et al. (Eds.). (2024). Kaplan & Sadock's Comprehensive Textbook of Psychiatry (11th ed.). Wolters Kluwer. StatPearls. PTSD. NCBI Bookshelf NBK559129.

StatPearls: PTSD (NCBI Bookshelf)

NIMH: PTSD

National Center for PTSD (VA)

Crisis resources: 988 (US); Crisis Text Line: text HOME to 741741.

events can have on an individual's mental health. The DSM criteria for PTSD involve experiencing a traumatic event, the presence of specific symptoms such as intrusive memories or nightmares, avoidance behaviors, negative changes in mood and cognition, and heightened arousal. The inclusion of PTSD in the DSM has contributed to better understanding, diagnosis, and treatment of individuals who have experienced trauma. The management of PTSD is complex, as each case of trauma is individualized, and specific symptoms of PTSD vary from case to case. Prevention and treatment methods involve psychological interventions as well as pharmacotherapy. Etiology Individuals who experience trauma may or may not develop long-term mental health sequela as a result of the trauma. However, the DSM-5-TR defines trauma as an essential characteristic of those who develop PTSD. Trauma (in the context of PTSD) is defined as exposure to actual or threatened death, serious injury, or sexual violence. This includes directly experiencing the traumatic event, witnessing a person experiencing trauma, or learning that the traumatic event occurred to a close family member or friend. There are various psychological theories proposed to explain trauma's capacity to cause PTSD. The shattered assumptions theory was proposed by Janoff-Bulman in 1992. This theory suggests that traumatic events can change how individuals perceive themselves and the world as compared to their views before the traumatic experience. This theory has preliminary assumptions, including: "the world is benevolent," "the world is meaningful," and "the self is worthy." After trauma, the foundation for these inherited assumptions is weakened or "shattered." Psychodynamic psychology emphasizes the systematic study of how life experiences may relate to the current psychological forces on the mind, which impact behavior and emotions.

In 1890, Jean-Martin Charcot argued that psychological trauma was the origin of all mental illness. Over time, this has been refuted, but it is acknowledged that trauma (and particularly early life trauma) can have a profound impact on the development of mental illness. A psychodynamic psychological view of posttraumatic stress relates particularly to unconscious decisions of trust. Individuals who experience trauma can have difficulty trusting that the world can be a safe place or trusting that individuals will not emotionally or physically harm them. Behavioral scientists have also contributed to understanding trauma's impact on cognitive processes. A conditioned response of learned fear can occur after exposure to a significant stimulus, which is usually the case in the context of PTSD. Individuals exposed to repeated traumas (such as those experiencing domestic or parental abuse) can develop a conditioned response to trauma. The presence or absence of support after trauma can both increase or decrease the risk of PTSD. Individuals who have a well-established support system are less likely to develop PTSD after a traumatic event. Likewise, individuals who feel isolated after trauma or have a poor social support system are more likely to develop an acute stress disorder and/or PTSD. The risk of PTSD after a traumatic event is further increased by lower educational level, lower socioeconomic status, childhood adversity, gender, race, physical injury (including traumatic brain injury), and initial severity of the reaction to the trauma. Epidemiology The lifetime prevalence of PTSD ranges from 6.1% to 9.2% from national samples of the general adult population of the United States and Canada. The 1-year prevalence rates range from 3.5% to 4.7%. In the Western Hemisphere, certain populations have been found to have a higher prevalence of PTSD, including indigenous peoples and refugees. Lower prevalence rates of PTSD have been found outside of the Western Hemisphere, but the reason for lower PTSD rates in the Eastern Hemisphere is not well understood. Intentional trauma has been found to have a greater association with PTSD than accidental trauma or nonviolent trauma. Repeated trauma and increasing duration of trauma exposure are also associated with a higher risk of PTSD. Males and females both commonly develop PTSD after trauma, but females are known to be more predisposed to PTSD, with slight variations depending on the type of traumatic experience. Pathophysiology The initial response to trauma is associated with the pathophysiology of PTSD. The response is characterized by a surge of adrenaline from sympathetic nervous system stimulation. Physiologically, this can lead to tachycardia, rising blood pressure, and further neuroendocrine responses such as the release of cortisol and other catecholamines. When the trauma stimulus is prolonged or repeated, a conditioned behavioral response leading to acute stress disorder or PTSD can occur. Neuroanatomically, the amygdala has significant responsibility for threat detection and fear response. Magnetic resonance imaging (MRI) studies of individuals with PTSD have revealed nonspecific findings, including reduced total brain volume, although the results are not consistent. The amygdala is part of the ancient brain evolutionarily, meaning that its activation is primary and typically toned down by the frontal cortex as cognition and learned behaviors develop. In patients with PTSD, the toning down capacity of the frontal lobe is dysregulated compared to those without PTSD. This observation may partially explain the imaging findings of reduced brain volume in those individuals with chronic PTSD. Neurotransmitter levels have been investigated in those with PTSD, including serotonin, dopamine, epinephrine, norepinephrine, glutamate, and gamma-aminobutyric acid (GABA). Neurotransmitter levels in patients with PTSD have had inconsistent findings but still form the basis of an approach for treatment with psychotropic medications. History and Physical The presentation of PTSD is variable in both the history of

the illness and the clinical symptomatology. Trauma is broad, and risks for certain types of trauma vary depending on patient characteristics such as age, gender, geographic location, family and marital status, and presence of a physical disability. Types of trauma include sexual assault, mass political conflict and displacement (refugee), military or combat exposure, physical injury, and medical illness. Due to the broad range of possible traumas, it is essential to understand individual patient backgrounds and social history. Additionally, adult patients with PTSD commonly suffer from symptoms as a result of childhood trauma, which can be far in the distant past compared to the time of clinical evaluation. Duration of symptoms since the traumatic event is significant to note as this distinguishes PTSD from other psychiatric disorders (such as acute stress disorder). Dissociative symptoms may be present in patients with PTSD, and when these symptoms are present, they must be distinguished from a prior dissociative disorder. Dissociative symptoms include the following: Depersonalization: Feeling disconnected from one's body and feeling "lost" or "floating above my body." Derealization: Feeling as if the surrounding world is not real, such as watching the world from a dreamlike state. Discussing trauma with patients who are being evaluated for PTSD requires an approach with sensitivity. In the context of sexual assault trauma, the gender of the provider and patient should be taken into consideration, as many patients who are survivors of sexual assault may have difficulty being in an interview room alone with the gender of their perpetrator. Some patients can talk about past trauma with ease, while others are not able to discuss details without experiencing acute symptoms. When engaging in a discussion of trauma details, it is important to respect patient boundaries on the topic and ask how deeply or superficially the patient prefers to discuss the topic. These are foundational concepts of trauma-informed interventions. Notably, the specific details of the trauma are usually not necessary for obtaining a PTSD diagnosis. Specific details of trauma are only necessary for certain types of psychotherapeutic treatments, which the patient should consent to before initiating. General questioning about symptoms related to trauma is usually an optimal approach for a first diagnostic interview where developing therapeutic rapport is essential. General questions can include the following: Do you think about the traumatic event more than you would like to? Do you have nightmares or flashbacks related to the trauma? Do you avoid people or triggers associated with the trauma? Are you struggling with feelings of persistent sadness? The mental status examination (MSE), conducted during psychiatric evaluations, is crucial in assessing individuals with PTSD. However, it is necessary to note that the specific elements and findings of the examination can vary depending on each case of PTSD. Components of the MSE should include the following: Appearance: Scars, wounds, and other deformities may be present due to prior traumatic experiences. Attitude and Behavior: PTSD can commonly lead to hypervigilant behavior. Eye contact should observed. Affect: Patients with PTSD may present fearful, anxious, apathetic, or depressed. Affect may change depending on the conversation, and the range of affect should be observed. PTSD may present with constricted affect consistent with feeling numb. Thought content: Thought content should be evaluated to assess suicide ideations and self-harm behaviors. Thought process: For patients with persistent and exaggerated negative beliefs after trauma, the thought process may deviate from linear. Insight: Patients with PTSD commonly have a fair understanding of their illness, although specific populations of patients may minimize their symptoms. Patients with PTSD may have difficulty understanding how...

treatment of PTSD in the general population favor psychotherapeutic interventions, such as PE or cognitive processing therapies (CPTs), over pharmacologic ones. Similarly, CBT for insomnia (CBT-I) is favored over pharmacologic interventions for PTSD- related insomnia. While more research is needed to assess the efficacy of these interventions for patients with TBI, particularly moderate and severe TBI, preliminary studies suggest that evidence-based psychotherapies for PTSD may still be useful in this population. However, therapies may require modifications for patients with persistent cognitive and physical impairments. For instance, exposure therapies may require reconstructing memories to offset amnesia, simplification of homework, and more frequent repetition. Given their safety and tolerability in patients with TBI, SSRIs represent a reasonable first-line treatment strategy in PTSD associated with TBI. An open-label study of prazosin—effective for PTSD-related nightmares in the general population—in patients with TBI found improvements in cognitive performance, sleep, and headaches; however, the largest RCT to date of prazosin versus placebo for PTSD-related nightmares was negative. Given the possibility of adverse cognitive side effects, anticholinergic medications and benzodiazepines should be avoided. Finally, consideration of other conditions contributing to poor sleep quality and PTSD symptoms, such as obstructive sleep apnea, should be incorporated into psychiatric management. Anxiety Disorders The available data suggests that post-TBI anxiety disorders are common; may take the form of any anxiety-spectrum disorder; and tend to co-occur with depression. Of the individual anxiety disorders, generalized anxiety disorder may be the most common following TBI, but data has been inconsistent. A meta-analysis of 22 studies, comprised of 1,145 subjects with TBIs of mixed severities and postinjury durations, estimated the prevalence of generalized anxiety disorder to range from 2% to 28%, with a pooled estimate of 11%. Rates of panic disorder following TBI range from 6% to 14%. One study found that TBI conferred double the risk of developing panic disorder compared to other traumatic injuries. TBI also doubled the risk of developing agoraphobia, with 7% of patients with TBI experiencing this condition. The estimated prevalence of specific phobias post TBI, while based on limited data, appears to be similar to that of the general population (1– 10% versus 8–12%, respectively). One study found that among patients who experienced TBI due to a motor vehicle accident, the specific phobias that subsequently developed involved transportation. Another group found that a substantial proportion of individuals with TBI experience a phobic- like fear of falling, which at times may interfere with activities. One study found that 5% of patients with TBI developed social anxiety disorder, twice the rate of those who experienced other types of injuries. Although obsessive-compulsive disorder is no longer classified with other anxiety disorders by the DSM-5, its estimated prevalence (1% to 5%) does not appear significantly elevated above that of the general population. Previous experimental and clinical studies on the neurobiology of anxiety disorders have emphasized the etiologic role of disrupted prefrontal modulation of limbic and paralimbic circuits involving medial and orbital prefrontal cortices, the amygdala, and the hippocampus. A recent meta-analysis of structural and functional neuroimaging correlates of syndromal post-TBI anxiety found a broad range of regional and circuit alterations reported among studies. Although the most frequently implicated regional alterations involved components of the default mode network, the methodologic heterogeneity and a limited number of included studies prevent definitive conclusions. Additional investigations on the neurobiological correlates of anxiety disorders post TBI are needed. The evidence base for the treatment of anxiety disorders in TBI

remains preliminary. As with trauma-related disorders in TBI, SSRIs are likely the best first-line pharmacotherapy, and medications that could worsen cognition in this vulnerable population, such as benzodiazepines and drugs with anticholinergic effects, should be avoided. Few studies specifically examining psychotherapy (e.g., CBT) for TBI-related anxiety suggest this may be effective as well. Substance-Related and Addictive Disorders Substance-related and addictive disorders are major risk factors for the occurrence of TBI and major determinants of the clinical and psychosocial outcomes post TBI. A prospective study of 197 patients with TBI showed that 42% had blood alcohol levels consistent with legal intoxication at the time of admission to the emergency department and that blood alcohol levels suggested a history of problem drinking among these patients. The authors also observed that the frequency of alcohol abuse and associated disorders diminished immediately after TBI but increased again at 1-year follow-up, although not to preinjury levels. Although alcohol use significantly decreased during the first year after injury, about 25% of the patients reported alcohol-related problems. As expected, preinjury problematic alcohol use predicted alcohol-related problems after TBI. In one study, 60% of patients with alcohol use disorders prior to TBI had resumed problematic alcohol use within 1 year of their injury. Patients who relapsed had significantly less education, showed significantly more severe injury as demonstrated by lower GCS scores and a greater frequency of moderate and severe injuries, had significantly higher frequencies of focal lesions on their initial CT or MRI scans and showed impaired cognitive performance on memory and executive tasks. Conceivably, the combined effects of traumatic injury and the toxicity of chronic substance abuse (particularly alcohol) might produce greater disruption of the neural circuits involved in mood regulation, motivation, and reward processing. In turn, these changes could result in more severe psychopathology, uncontrolled addictive behavior, and poor psychosocial outcome. One study found that inmates with head injuries had higher levels of alcohol and marijuana use, a significantly higher frequency of depression, anxiety, and suicidal thinking, as well as more difficulties in concentrating and controlling violent behavior. Substance use disorders are associated with worse post-TBI outcomes. Individuals with TBI who abuse substances show worse cognitive performance, higher rates of incident depression, decreased employment, and poorer rehabilitation participation in the years following injury than patients with TBI alone. One large study found that, among individuals with TBI, those who had consumed alcohol around the time of their injury were 20% more likely to die of their injuries and were less likely to be able to return home at hospital discharge. The optimal treatment strategy for comorbid substance use disorders and TBI remains to be determined. One study of systematic motivational counseling (SMC) to treat substance abuse comorbidity among patients with TBI found that the SMC group showed significant improvements in motivational structure and a significant reduction in negative affect and the use of addictive substances. However, two RCTs of a brief motivational interviewing and educational intervention targeting alcohol use disorders among patients with TBI did not find effects on alcohol consumption, but one of the studies did indicate that the intervention increased awareness of the negative consequences of alcohol use.

Physical disabilities, such as those which may accompany TBI, can pose barriers to substance abuse treatment, as many treatment programs do not accommodate them. The evidence supporting pharmacologic intervention for alcohol or substance use is limited in the TBI population. A 12-week pilot RCT d