**6. Neurobiology**

Neurobiological research indicates that PTSD may be associated with stable neurobiological alterations in both the central and autonomic nervous systems[26]. Psycho physiological alterations associated with PTSD include hyper arousal of the sympathetic nervous system, increased sensitivity and augmentation of the acoustic-startle eye blink reflex, a reducer pattern of auditory evoked cortical potentials, and sleep abnormalities. Neuropharmacologic and neuroendocrine abnormalities have been detected in the noradrenergic, hypothalamic-pituitary-adrenocortical, and endogenous opioid systems[27]. There is increasing evidence that PTSD is associated with biological alterations or abnormalities. Individuals with PTSD have an atypical stress response. Instead of producing increases in cortisol, a stress related hormone, the usual hypothalamic-pituitary axis mechanisms are disrupted and result in lower than expected levels of the hormone[28]. PTSD symptoms may result when a traumatic event causes an overactive adrenaline response, which creates deep neurological patterns in the brain. These patterns can persist long after the event that triggered the fear, making an individual hyper-responsive to future fearful situations. Brain catecholamine levels are low, and corticotropin-releasing factor (CRF) concentrations are high. Together, these findings suggest abnormality in the hypothalamic-pituitary-adrenal (HPA) axis. Trauma victims who develop post-traumatic stress disorder often have higher levels of other stimulating hormones (catecholamines) under normal conditions in which the threat of trauma is not present as well as lower levels of cortisol. This combination of higher than normal arousal levels and lower than normal levels of the "calming" hormones of the changes creates the conditions for PTSD. The amygdala is the brain region that alerts the body to danger and activates hormonal systems.

increases the likelihood of developing the disorder[22]. It may be that people who have fewer supports and limited inter-personal coping skills are more likely to develop PTSD[21]. Studies of concentration camp survivors and prisoners of war suggest that even given sufficient trauma intensity and duration most of those who are exposed develop PTSD. A positive relationship has been found between trauma intensity and the likelihood of PTSD[22]. People who have been injured or perceived the event as life threatening are more likely to develop PTSD than those with less severe trauma. Human caused traumatic events such as assaults and murder have a more powerful impact than accidents and natural disasters. Among crime victims, individuals who have suffered more brutal trauma have higher frequencies of PTSD – torture (54%), rape (49%); badly beaten (32%), and other sexual assault (24%)[21]. Dissociation during the trauma, peritraumatic dissociation, is associated

There is evidence that susceptibility to PTSD is hereditary. For twin pairs exposed to combat in Vietnam, having a monozygotic (identical) twin with PTSD was associated with an increased risk of the co-twin having PTSD compared to twins that were dizygotic (nonidentical twins)[23]. Recently, it has been found that several single-nucleotide polymorphisms (SNPs) in FK506 binding protein 5 (FKBP5) interact with childhood trauma to predict severity of adult PTSD[24]. These findings suggest that individuals with these SNPs who are abused as children are more susceptible to PTSD as adults. Another recent study found a single SNP in a putative estrogen response element on ADCYAP1R1 (encodes pituitary adenylate cyclase-activating polypeptide type I receptor or PAC1) to predict PTSD

Neurobiological research indicates that PTSD may be associated with stable neurobiological alterations in both the central and autonomic nervous systems[26]. Psycho physiological alterations associated with PTSD include hyper arousal of the sympathetic nervous system, increased sensitivity and augmentation of the acoustic-startle eye blink reflex, a reducer pattern of auditory evoked cortical potentials, and sleep abnormalities. Neuropharmacologic and neuroendocrine abnormalities have been detected in the noradrenergic, hypothalamic-pituitary-adrenocortical, and endogenous opioid systems[27]. There is increasing evidence that PTSD is associated with biological alterations or abnormalities. Individuals with PTSD have an atypical stress response. Instead of producing increases in cortisol, a stress related hormone, the usual hypothalamic-pituitary axis mechanisms are disrupted and result in lower than expected levels of the hormone[28]. PTSD symptoms may result when a traumatic event causes an overactive adrenaline response, which creates deep neurological patterns in the brain. These patterns can persist long after the event that triggered the fear, making an individual hyper-responsive to future fearful situations. Brain catecholamine levels are low, and corticotropin-releasing factor (CRF) concentrations are high. Together, these findings suggest abnormality in the hypothalamic-pituitary-adrenal (HPA) axis. Trauma victims who develop post-traumatic stress disorder often have higher levels of other stimulating hormones (catecholamines) under normal conditions in which the threat of trauma is not present as well as lower levels of cortisol. This combination of higher than normal arousal levels and lower than normal levels of the "calming" hormones of the changes creates the conditions for PTSD. The amygdala is the brain region that alerts the body to danger and activates hormonal systems.

with risk for PTSD[21].

**6. Neurobiology** 

diagnosis and symptoms in females[25].

After a month in this heightened state with stress hormones elevated and cortisol levels lowered, further physical changes, such as heightened hearing develop. This cascade of physical changes, one triggering another, suggests that early intervention may be the key to heading off the effects of post-traumatic stress disorder.

Given the strong cortisol suppression to dexamethasone in PTSD, HPA axis abnormalities are likely predicated on strong negative feedback inhibition of cortisol, itself likely due to an increased sensitivity of glucocorticoid receptors. Some researchers have associated the response to stress in PTSD with long-term exposure to high levels of norepinephrine and low levels of cortisol, a pattern associated with improved learning in animals. Translating this reaction to human conditions gives a pathophysiological explanation for PTSD by a maladaptive learning pathway to fear response through a hypersensitive, hyperreactive and hyperresponsive HPA axis. Low cortisol levels may predispose individuals to PTSD: Swedish soldiers serving in Bosnia and Herzegovina with low pre-service salivary cortisol levels had a higher risk of reacting with PTSD symptoms, following war trauma, than soldiers with normal pre-service levels[29]. Because cortisol is normally important in restoring homeostasis after the stress response, it is thought that trauma survivors with low cortisol experience a poorly contained—that is, longer and more distressing—response, setting the stage for PTSD.

However, there is considerable controversy within the medical community regarding the neurobiology of PTSD. A review of existing studies on this subject showed no clear relationship between cortisol levels and PTSD. Only a slight majority have found a decrease in cortisol levels while others have found no effect or even an increase. Decreased brain volume or volume of specific brain structures have been documented in some adults and children with PTSD [30,31]. The biologic correlates have not yet been fully explored, nor are the implications for intervention established.

Three areas of the brain whose function may be altered in PTSD have been identified: the prefrontal cortex, amygdala and hippocampus. Much of this research has utilised PTSD victims from the Vietnam War. For example, a prospective study using the Vietnam Head Injury Study showed that damage to the prefrontal cortex may actually be protective against later development of PTSD [32]. In a study by Gurvits et al, combat veterans of the Vietnam War with PTSD showed a 20% reduction in the volume of their hippocampus compared with veterans who suffered no such symptoms [33,34]. This finding could not be replicated in chronic PTSD patients traumatized at an air show plane crash in 1988 (Ramstein, Germany) [35]. In human studies, the amygdala has been shown to be strongly involved in the formation of emotional memories, especially fear-related memories. Neuroimaging studies in humans have revealed both morphological and functional aspects of PTSD. The amygdalocentric model of PTSD proposes that it is associated with hyperarousal of the amygdala and insufficient top-down control by the medial prefrontal cortex and the hippocampus particularly during extinction. This is consistent with an interpretation of PTSD as a syndrome of deficient extinction ability. Further animal and clinical research into the amygdala and fear conditioning may suggest additional treatments for the condition.

#### **7. Clinical features**

Describing children's responses to trauma, Terr(1991) presents four specific symptoms characteristic of childhood PTSD: repeatedly perceiving memories of the event through visualization, engaging in behavioral re-enactments and repetitive play related to the event,

Post Traumatic Stress Disorder – An Overview 11

This must have involved both (a) loss of "physical integrity", or risk of serious injury or

One or more of these must be present in the victim: flashback memories, recurring distressing dreams, subjective re-experiencing of the traumatic event(s), or intense negative psychological or physiological response to any objective or subjective reminder of the

avoidance of stimuli associated with the trauma, such as certain thoughts or feelings, or

an expectation that one's future will be somehow constrained in ways not normal to

These are all physiological response issues, such as difficulty falling or staying asleep, or

If all other criteria are present, but 30 days have not elapsed, the individual is diagnosed

The symptoms reported must lead to "clinically significant distress or impairment" of major domains of life activity, such as social relations, occupational activities, or other "important

In preparation for the May 2013 release of the DSM-5, the fifth version of the American Psychiatric Association's diagnostic manual, draft diagnostic criteria was released for public comment, followed by a two-year period of field testing. Proposed changes in DSM-5, to the

 Criterion A (prior exposure to traumatic events) is more specifically stated, and evaluation of an individual's emotional response at the time (current criterion A2) is

Several items in Criterion B (intrusion symptoms) are rewritten to add or augment

 Special consideration is given to developmentally appropriate criteria for use with children and adolescents. This is especially evident in the restated Criterion B intrusion symptoms. Development of age-specific criteria for diagnosis of PTSD is

Criterion C (avoidance and numbing) has been split into "C" and "D":

 avoidance of behaviors, places, or people that might lead to distressing memories; inability to recall major parts of the trauma(s), or decreased involvement in significant

decreased capacity (down to complete inability) to feel certain feelings;

**D: Persistent symptoms of increased arousal not present before** 

problems with anger, concentration, or hypervigilance.

certain distinctions now considered important.

**E: Duration of symptoms for more than 1 month** 

death, to self or others, and (b) an intense negative emotional response.

**A: Exposure to a traumatic event** 

**B: Persistent re-experiencing** 

This involves a sufficient level of:

talking about the event(s);

**C: Persistent avoidance and emotional numbing** 

traumatic event(s).

life activities;

other people.

with 'acute stress disorder'. **F: Significant impairment** 

areas of functioning".

criteria include:

dropped.

ongoing at this time.

fears related to the trauma event, and pessimistic attitudes reflecting a sense of hopelessness about the future and life in general. The behavioral presentation of a child or adolescent experiencing PTSD or symptoms of PTSD may also include problems with verbalization and extremes of disconnections (no close relationships) or false connections (perceiving close relationships where none exist). Additionally, the diagnosis of PTSD cannot be made on the basis of the child's affective presentation alone (e.g. crying, sadness, or expressions of terror).

The symptoms of PTSD include:


Warning symptoms of PTSD: -


*Diagnostic criteria*: The diagnostic criteria for PTSD, stipulated in the Diagnostic and Statistical Manual of Mental Disorders IV (Text Revision) (DSM-IV-TR), may be summarized as [36,37]:
