ptsd Flashcards
what is the definition/ criteria of PTSD
an exposure to a traumatic event that involves actual or threatened death, serious injury or sexual violence through:
directly experiencing the trauma
witnessing the events occur to others
learning that traumatic events occurred to a close family member
experiencing extreme or repeated exposure of trauma to others
give some background on PTSD
occurs due to a traumatic event so severe that it breaks the stress response management
most people exposed to trauma do not develop PTSD
individuals with PTSD have underlying physiological differences that result in a failure to recover, the trauma unmasks the physiology
trauma itself also alters the physiology
some of the underlying physiological difference is genetic and epigenetics play a large role
rate of PTSD increases with intimacy of violence
higher rate for child abuse than natural disasters
what is the usual time course for a trauma response
after trauma most individuals have PTSD symptoms for days to weeks; usual response
up to one month: acute stress disorder
longer than one month: PTSD
most individuals symptoms resolve by 3 months
delayed onset PTSD is rare
PTSD can last months to lifetime
what is PTSD prevalence in american war veterans of iraq and afghan wars?
14-20% out of 2.7 million
what are symptoms required for PTSD
re experiencing the trauma; intrusive memories, flashbacks, nightmares, reacting to cues
avoidance and numbing; avoided thoughts, reminders, diminished interest in activities
negative cognitions and mood associated with the trauma
hyperarousal; hypervigilance, irritability, insomnia, startle, poor concentration
pathophysiology: increased heart rate and skin conductance in response to trauma related cues
low basal cortisol levels, raised catecholamine levels
how is fear conditioning associated w ptsd
fear conditioning is a behavioural paradigm in which organisms learn to predict aversive events; such as pavlovian conditioning, long after the precipitating traumatic event environmental cues will continue to serve as triggers for a similar physiologic response
just speaking about event can be trigger; may lead to avoidance of therapy
fear conditioning is adaptive to a dangerous environment; it is essential for survival, however the same behaviour is maladaptive when returned to safety, PTSD is the failure to unlearn adaptive thoughts and behaviours on the return to safety
what brain areas are involved in PTSD
amygdala, hypothalamus, hippocampus, brainstem etc
what neurotransmitters are involved in ptsd
CRH: wide circuit throughout brain
catecholamines: higher NA, flood of NA after traumatic event is key in encoding traumatic memories
serotonin, GABA, glutamate, NPY, endogenous opioids
describe some circuitry involved in ptsd in amygdala
in the amygdala: the basal nucleus of amygdala transmits to central nucleus of amygdala (NA flood), which transmits to VTA via DA pathways, raphe nuclei via 5HT , locus coeruleus via NA pathways
amygdala activity is exaggerated in individuals with ptsd, and is positively correlated with symptom severity
what structures other than the amygdala are altered in ptsd
the insular and dorsal anterior cingulate cortex are also hyper active in ptsd, these structures may modulate the amygdalas expression of fear
the ventromedial prefrontal cortex which also modulates (in this case reduces) the amygdalas expression of fear is diminished in ptsd
there are both hypo and hyper reactivity observed in hippocampus
compare mild stress to extreme stress in the prefrontal cortex
in mild stress the PFC inhibits the amygdala, there are optimum na, da and 5ht levels and there is increased alpha 1/2 activation
in extreme stress the amygdala dominates and there is increased alpha 1/2 activation and excessive DA1R and 5HT2R activation
activation in pfc is mediated by the amygdala through the VTA, raphe nuclei and locus coeruleus
what is the HPA axis
the hypothalamic-pituitary-adrenal axis; body’s fundemental stress response, hypothalamus releases cortocotropin releasing hormone, the anterior pituitar releases adrenocorticotropin causing the adrenal cortex to release cortisol, is the bodys fundemental stress response, people with higher levels of glucocorticoid receptor (for cortisol) are better at detecting cortisol and so recover from stress more quickly
how does cortisol change in ptsd
cortisol is lower in combat veterans than controls
hypothalamic corticotropin releasing hormone release increased in combat veterans
increased negative feedback inhibitions of HPA axis
overall reduced glucocorticoid signalling and exaggerated negative feedback
cortisol alterations in ptsd reflect pre existing conditions; genetic variants in genes NR3C1 and FKBP5 are key
describe memory reconsolidation in ptsd
every time a memory is recalled it is momentarily made labile and then needs to be reconsolidated, during this process the memory may be updated or changed based on new experience; can occur alone or within context of therapy, may lead to fear extinction (better) or memory made worse
what are risk factors for ptsd
severity and nature of trauma
history of childhood adversity/trauma
history of poor coping
low social support
family history of trauma (genetics?)
low heart rate variability, low cortisol, other physiologic variables
describe the genetics of ptsd
most studied and relevant;
5ht transporter gene; linked to risk for depression and increased amygdala reactivity, no overall association w ptsd but potential GxE interactions with level of trauma exposure, risk allele does not predict ptsd but “interacts” w environment to predict increased risk of ptsd
FKBP5: moderate risk for ptsd
variant of COMT gene linked to increased risk for ptsd
SNP in BDNF
describe epigenetics of ptsd
low maternal grooming in early life led to stress sensitive animals in adulthood; via decreased expression of the GR receptor through hypermethylation of the NR3C1 (gene encoding GR) promoter
there is an association between methylation status of the orthologous exon 1F promoter in human NR3C1 in hippocampus and history of childhood trauma; decreased GR expression and increased DNA methylation of NR3C1 promoter
describe FKBP51 in ptsd
fkbp51 (the protein) regulates the stress response by modulating the binding of stress hormones (cortisol/glucocorticoids) to GR
incorrect expression of the gene (FKBP5) has been linked w a range of mood disorder in humans
polymorphisms of this gene w the environment may predict mood disorders; early life stress may lead to long lasting demethylation of the gene, leads to switching off the GC signalling needed to turn off stress response, there is an increased resistance to glucocorticoids in ptsd
how is ptsd treated without drugs
prevention: risk is high for military personnel, emergency first responders and journalistic war correspondents; prevention by promoting good mental health, adaptive methods for coping in the face of adversity, resilience training
management: psychotherapy is first line of treatment over drugs, designed to reverse the lasting impact of fear conditioning; psychotherapy can reverse DNA methylation patterns associated w ptsd
psychotherapy: over time exposure to the conditioned stimulus in a safe environment without the expected adverse outcome can lead to habituation (weakening of intensity of response to the stimulus) and extinction (conditioned stimulus is no longer associated w aversive unconditioned stimulus)
current psychotherapies; CBT, exposure therapy (drop out rate v high), eye movement desensitisation and reprocessing
what medications may be used for ptsd
only 2 medications had received FDA approval for ptsd in 2015; both SSRIs ( sertraline and paroxetine)
beta blockers may be useful in reducing early encoding
morphine may be used during early resuscitation; protective effect, may reduce initial encoding
D-cycloserine facilitated fear extinction may enhance effects of therapy by enhancing plasticity, it is a NMDA partial agonist, may accelerate therapy
SSRIs have downstream effect of increased BDNF expression and enhance plasticity
activation of CB1 receptor facilitates extinction of aversive/ traumatic memories in rats
evidence of dysregulated endocannabinoid system in neuropsychiatric patients
dexamethasone (GR agonist) facilitated fear extinction, reduces FKBP5 mRNA expression in amygdala, via changes to DNA methylation, leads to enhanced fear extinction
