PTSD: Neurobiological and Clinical Aspects PDF

Trauma and Related Disorders Introduction In the DSM 5, trauma- and stressor-related disorders are disorders in which exposure to a traumatic or stressful event is listed explicitly as a diagnostic criterion. Today we will discuss: Post-traumatic stress disorder (PTSD) ...

Trauma and Related Disorders Introduction In the DSM 5, trauma- and stressor-related disorders are disorders in which exposure to a traumatic or stressful event is listed explicitly as a diagnostic criterion. Today we will discuss: Post-traumatic stress disorder (PTSD) History of Post- Traumatic Stress Disorder (PTSD) Soldier’s heart (American Civil War); “Shell shock” (WWI); combat fatigue (WWII); delayed stress (Vietnam war) Finally included as a formal diagnostic entity in 1980 (DSM- III); initially met with suspicion Now: biomarkers Included as an “Anxiety Disorder” up until DSM 5; now part of trauma and related disorders Clinical Features of PTSD Essential feature of PTSD is development of characteristic symptoms following exposure to one or more traumatic events Examples of traumatic events: Exposure to war (combatant or civilian), threatened or actual physical assault, threatened or actual sexual violence Clinical presentation varies; can be predominately fear/anxiety, anhedonic/dysphoric, arousal/reactive, or dissociative or a combination PTSD Diagnostic Features A. Confirmed experience of trauma (exposure to actual or threatened death, serious injury, or sexual violence), either by directly experiencing or witnessing the event, or hearing about the event of a close friend or family member In first responders, this can be manifest as repeated or extreme exposure to aversive traumatic events B. Presence of intrusion symptoms Recurrent, involuntary and intrusive distressing memories or dreams Dissociative reactions (e.g., flashbacks) Intense prolonged psychological distress and physiological response to cues associated with the trauma PTSD Diagnostic Features (2) C. Persistent avoidance of stimuli associated with the event D. Negative alterations in cognitions and mood associated with the event, e.g., Inability to remember details associated with trauma Negative beliefs about self, expectations (e.g., “I am bad”, “no one can be trusted”) Feelings of detachment or estrangement from others F. Marked alterations in arousal and reactivity associated with traumatic events, as evidenced by at least two of: Irritability, angry outbursts Reckless, self-destructive behavior Hypervigilance Exaggerated startle response Problems with concentration Sleep disturbances Has to have significantly impacted psychological well-being for at least 1 month PTSD Epidemiology U.S. projected lifetime risk for PTSD at age 75 years is 8.7% 12 month prevalence is about 3.5% Canada: projected lifetime risk is 9.2% Current rate (1-month) is 2.4% (2008) Sex differences: PTSD more prevalent among females than males across the lifespan and experience PTSD for a longer duration Probably due to greater exposure to traumatic events (e.g., rape) High risk for suicidality WHAT IS THE NEURAL BASIS OF PTSD? Fear circuitry  Medial Prefrontal Cortex (mPFC) appraises threat  If threat  signals to amygdala/HPA  Amygdala signals to hippocampus (learn about context) and hypothalamus (activates brainstem response to fear) Fear circuitry: traumatic events Amygdala hypersensitive Prefrontal cortex activity reduced (ineffectively inhibits amygdala) Results in: Hypervigilance Intrusion symptoms Avoidance of stimuli associated with trauma Cognitive distortions This is adaptive This is PTSD structural Anatomical findings Significantly reduced volume of the hippocampus; ventral medial portion of the prefrontal cortex (vmPFC) However, may represent premorbid features What does this mean? Hippocampus is not able to use contextual cues in the environment to signal safety; vmPFC fails to maintain extinction of conditioned emotional responses once traumatic learning is no longer relevant Reduced cortical capacity to inhibit fear and other negative emotional responses Gene x Environment Interactions Functional Anatomical Diff erences Exaggerated amygdala activation in response to trauma-related stimuli as well as generic stimuli Traumatic event serves as unconditioned stimulus that becomes paired with stimuli associated with the trauma E.g., odors, sounds These then can elicit fear response; will activate the amygdala Exaggerated response also coupled with reduced mPFC activity Different symptoms of ptsd correlate with distinct circuits Neurobiologica l Diff erences PTSD patients show enhanced stress activation – both SAM and HPA pathways Altered adrenaline, noradrenaline, and cortisol levels Dysregulated signaling of noradrenalin considered biomarker of PTSD Associated with hyperarousal, nightmares, flashbacks What causes this? Theory: Excessively strong adrenergic response to traumatic event may mediate formation of durable traumatic memories If we block cortisol or noradrenaline/adrenaline immediately post-trauma, will this prevent the traumatic memory formation? PTSD: PHARMACOLOGICAL Treatment Administration of propranolol (a beta- receptor antagonist  prevents binding of noradrenaline) within hours following trauma exposure reduces likelihood of developing PTSD Seems to prevent consolidation of memories 10-day regimen of 40 mg of propanolol 4 x / day (initiated within 20 h of trauma) leads to reduced physiological reactivity to trauma cues 3 months post-trauma However, data have been mixed; highly criticized Seems to be most effective when administered upon memory reactivation Treatment (2): PTSD and cannabis use Individuals with PTSD are at increased odds of using cannabis PTSD patients have higher numbers of cannabinoid receptors & lower levels of endocannabinoids Suggests dysregulated eCB system post- trauma Self-medicating? However! Smoking cannabis (high levels of THC) associated with worsening PTSD Hill et al., 2013 symptoms whereas cannabidiol (CBD) may effectively decrease symptoms Seems to be effective at reducing the consolidation of fear memory; enhances fear extinction New target: enhancing the eCB activity (instead of using exogenous cannabis compounds)