Medical Journal of Babylon-Vol. 11- No. 1 -2014 مجلة بابل الطبية- المجلد الحادي عشر

مجلة بابل الطبية- المجلد الحادي عشر - العدد ال ول - Medical Journal of Babylon-Vol. 11 - No. 1 -201 4 201 4

Review Article

Received 3 December 2013 Accepted 3 March 2014 Abstract After 2003, there is almost no day without an explosion or terrorist attacks in Iraq. The effects of repeated explosions extended to cover all aspects of life and places, where the negative effects of destruction, devastation and death continue. Consequently, the psychological and social effects are one of the most important negative effects which remain for long periods as a result of these traumatic experiences, as well as, the experiences of severe psychological stress had an evident impact on most individuals who have experienced such traumatic events. Usually, our communities have no sufficient interest in psychological care for disaster survivor, despite the fact that the psychological effects of disasters have often more impact than organic effects [1]. This review article highlights to the history, diagnosis and pathogenesis of posttraumatic stress disorder (PTSD). Keyword: posttraumatic stress disorder, diagnosis, pathogenesis, DSM-IV, ICD–10. اضطراب ما بعد الصدمة: تاريخه وتشخيصه موامراضيته: مقالة مرجعية الخلصة يكاد ل يمر يوم في العراق بعد عام 2003 دون حصول انفجار أو هجمة ارهابية. ان آثار النفجارات المتكررة يمتد ليشمل جميع مناحي الحياة، حيث تستمر الثار السلبية المترتبة على الدمار والخراب والموت. وبالتالي، فإن الثار النفسية والجتماعية هي واحدة من اهم الثار السلبية التي تبقى لفترات طويلة نتيجة لهذه الخبرات الصادمة. وكذلك، كان هنالك تأثير واضح لخبرات الجهاد النفسي الشديد على معظم الفراد الذين عانوا من مثل هذه الحداث الصادمة. وعادة فان مجتمعاتنا ل تهتم بشكل كافي في مجال الرعاية النفسية للناجين من الكوارث، على الرغم من أن الثار النفسية للكوارث في كثير من الحيان تكون أكثر تأثيرا من الثار .الجسدية .يسلط هذا المقال الضوء تاريخ وتشخيص موامراضيه اضطراب ما بعد الصدمة DSM-IV ، ICD–10 ،الكلمات المفتاحية: اضطراب ما بعد الصدمة، التشخيص، المراضية

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Page and Oppenheim contradicted the disorder (PTSD) for the first time original connection drawn by Erichsen. among the anxiety disorders in the Oppenheim with his study on traumatic DSM classification[2]. neurosis is the first one who introduces For extensive understanding of this term and then placed the main seat post-traumatic stress disorder, it is of the disturbance in the cerebrum. The necessary to delve into the history of term “trauma,” that till then had been the discovery, historical connotations utilized exclusively in surgery, was and review of literatures. thus introduced into psychiatry. Also, Unfortunately, the basic Oppenheim illustrates the frequent experiences in human history are the involvement of the heart in traumatic violence and war. Shay J. mentions neurosis: “The abnormal excitability of that Homer’s Iliad includes powerful the cardiac nervous system is an almost images of war traumatization and constant symptom of traumatic stresses that Achilles feels with neurosis, only in few instances is there sadness, disappointed withdrawal, and serious cardiac disease” [3]. Myers [9] feelings of guilt toward deaths of and da Costa [10] originate the concept comrades; sometimes, Achilles feels as of “irritability of the heart” so normally if he is dead himself and is prompted in soldiers with combat experience that to berserk-like anger. In poetry and they gave it a term for diagnosis: fiction, another examples of how to “irritable heart” or “soldier’s heart.” handle with traumatization, as in the Another term commonly used story of Oliver Twist by Charles in German-speaking countries around Dickens, who talk about a boy the turn of the 20th century is tolerating to cope with the early death “Schreckneurose” which mean (fright of his parents[7]. Daly RJ illustrates a neurosis) which was invented by witness of the Great Fire of London in Kraepelin [11], who set the personal 1666 who wrote, “How strange that to shock in the foreground. this very day I cannot sleep at night In the same time, another area without great fear of being over-come of enhancement concerning trauma by fire? And last night I lay awake etiology began at France, where until almost 2 o’clock in the morning Charcot [12] and Janet [13] referred to because I could not stop thinking about the importance of traumatic experience the fire.” It is an exemplary way to for the origin of hysterical or describe thought intrusions here [8]. dissociative symptoms. Janet [13] One of the earlier articles gives emphasis to the role of published in medical literature on the dissociation as the central process in subject of PTSD is the article of the the genesis of posttraumatic symptoms. English surgeon Erichsenin 1866, who During the second half of the attributed obvious psychological 19th century in Paris, an argument was abnormalities that follow railway presented Tardieu [14] the specialist in accidents to microtraumas of the spinal forensic medicine recorded the sexual cord that later led to the concept of the abuse of children. This argument was “railroad spine syndrome.” The varied rejected by Fournier as range of symptoms described involves “pseudologiaphantastica ” in children anxiety, tiredness, irritability, defective who falsely accuse their parents of memory, sleep disturbance, incest. nightmares, perceptual disorders, The term “shell-shock” was dizziness, noise in the ear, and limbs presented into the psychiatrist literature pain. Erichsen notices that speech can in 1915 by the British military also be influenced. Later the surgeons

2 مجلة بابل الطبية- المجلد الحادي عشر - العدد ال ول - Medical Journal of Babylon-Vol. 11 - No. 1 -201 4 201 4 accomplished the dream content psychiatrist C. S. Myers [15]. After awakens them. Also, Kardiner [20] discovering that the shell-shock differentiated the normal action syndrome was found in soldiers who syndrome from its alteration through had not contributed in actual fighting, trauma in terms of the he discriminated between “shell symptomatology. This differentiation concussion”, in which a neurological led to the term physioneurosis, disturbance could obviously be emphasizing the prevalence of recognized as a result of a physical physiological changes. At this period, injury, and the actual shell-shock the diagnoses of “combat fatigue” or syndrome, in which an emotional “combat exhaustion” had been also shock produced by extreme stress was fairly popular [21]. considered as enough for its causation The first edition of the [16]. diagnostic and statistical manual of At the beginning of the 20th mental disorders (DSM-I) [22] century, natural disasters were dealt introduced in 1952 the diagnosis of with from a psychiatric point of view. “gross stress reaction,” to describe the Earthquake at Messina (1907) was combat reactions after World War II investigated by Stierlin [17] and found and after the Korean War. The that 25% of the victims underwent diagnosis seemed to be defensible for from nightmares and sleep disturbance. situations of extreme demands or stress Also, Prasad [18] describes the situations which occurred as a emotional problems of the survivors consequence of acts of war or natural after a disastrous earthquake in India. disasters which were capable of Adler [19] presents an excellent causing abnormal behavior in clinical depiction of posttraumatic individuals who had previously been consequences in the survived people of entirely normal. the Boston Coconut Grove fire, with Many psychiatric reports was emphasis on nightmares, avoidance published about the consequences of behavior, and insomnia. natural disasters during the period that Abram Kardiner [20] in 1941 followed, such as the Mississippi published a book entitled "The tornado of 1953 [23], the sinking of the Traumatic Neuroses of War", a book Andrea Doria of 1957 [24], the Alaska that is considered as an exceptional earth-quake of 1962 [25] and the contribution to the field of Bristol flood disaster of 1968 [26]. psychotraumatology with very detailed A group of specialists from the clinical descriptions. Kardiner [20] American Psychological Association considered the amnesia as a defensive published the second edition of the method of the personality as a whole Diagnostic and Statistical Manual of and as a collapse of ego resources. He Mental Disorders (DSM-II), at the end refers to night-mares with a threat of of the 1960s [27]. They introduced the annihilation or very aggressive dreams. name “Transient situational The contraction of the ego according to disturbance” instead of “gross stress Kardiner [20] is the key process, it is a, reaction.” In the mid-1970s, the lack an inhibitory process and represented in DSM-II of operational criteria, the as the primary symptom, and all others diagnosis limited reliability, and many being secondary. Kardiner[20] saw, the missing links led to a commission sleep disturbances were caused by an within the American Psychiatric increased susceptibility to external Association to create more detailed stimuli, preventing the patients from symptom profiles. The sub- falling asleep, and when sleep is

3 مجلة بابل الطبية- المجلد الحادي عشر - العدد ال ول - Medical Journal of Babylon-Vol. 11 - No. 1 -201 4 201 4 person’s response involved intense commission for “reactive disorders,” fear, helplessness, or horror.” Criterion then came up with the title of A2 followed by the note “In children, “posttraumatic stress disorder” as this may be expressed instead by published in the DSM-III in 1980 [28]. disorganized or agitated behavior.” They were described as specified Criterion B involves “the diagnostic criteria. In third revised traumatic event is persistently re- edition of Diagnostic and Statistical experienced in one (or more) of the Manual of Mental Disorders (DSM-III- following ways: R) in 1987 [29], special classes of 1. Recurrent and intrusive distressing traumatization were described. recollections of the event, including At Geneva, the tenth revision images, thoughts, or perceptions. of the International Classification of Note: In young children, repetitive play Diseases (ICD-10) of World Health may occur in which themes or aspects Organization (WHO) in 1991, under of the trauma are expressed. mental and behavioral disorders 2. Recurrent distressing dreams of the (including disorders of psychological event. development) introduced the clinical Note: In children, there may be descriptions and diagnostic guidelines frightening dreams without of PTSD [30]. recognizable content. More work was done, and more 3. Acting or feeling as if the traumatic precise descriptions of the diagnosis of event were recurring (includes a sense PTSD were listed in the fourth edition of reliving the experience, illusions, of Diagnostic and Statistical Manual of hallucinations, and dissociative Mental Disorders (DSM-IV) in 1994 flashback episodes, including those [31]. that occur on awakening or when Diagnosis of PTSD intoxicated). Nowadays, there are two types Note: In young children, trauma- of diagnosis criteria; DSM-IV [31] and specific reenactment may occur. ICD-10 [30]. In both ICD–10 and 4. Intense psychological distress at DSM–IV, the diagnostic criteria for exposure to internal or external cues PTSD require that the person has been that symbolize or resemble an aspect of exposed to “a stressful event or the traumatic event. situation of exceptionally threatening 5. Physiological reactivity on exposure or catastrophic nature likely to cause to internal or external cues that pervasive distress in almost everyone” symbolize or resemble an aspect of the (according to ICD–10) and eliciting traumatic event.” a response involving “intense fear, Criterion C involves “persistent helplessness or horror” (according to avoidance of stimuli associated with DSM–IV) [32]. the trauma and numbing of general DSM-IV [31] categorized the responsiveness (not present before the criteria into six criterion (A-F), trauma), as indicated by three (or criterion A includes the expose to a more) of the following: traumatic event in which both A1 and 1. Efforts to avoid thoughts, feelings, A2 criterions were present. Criterion or conversations associated with the A1 involves “the person experienced, trauma. witnessed, or was confronted with an 2. Efforts to avoid activities, places, or event or events that involved actual or people that arouse recollections of the threatened death or serious injury, or a trauma. threat to the physical integrity of self or others.” Criterion A2 includes “the

4 مجلة بابل الطبية- المجلد الحادي عشر - العدد ال ول - Medical Journal of Babylon-Vol. 11 - No. 1 -201 4 201 4 reliving of the trauma in intrusive 3. Inability to recall an important memories ("flashbacks") or dreams, aspect of the trauma. occurring against the persisting 4. Markedly diminished interest or background of a sense of "numbness" participation in significant activities. and emotional blunting, detachment 5. Feeling of detachment or from other people, unresponsiveness to estrangement from others. surroundings, anhedonia, and 6. Restricted range of affect (e.g. avoidance of activities and situations unable to have loving feelings). reminiscent of the trauma. Commonly 7. Sense of a foreshortened future (e.g., there is fear and avoidance of cues that does not expect to have a career, remind the sufferer of the original marriage, children, or a normal life trauma. Rarely, there may be dramatic, span.” acute bursts of fear, panic or Criterion D involves “persistent aggression, triggered by stimuli symptoms of increased arousal (not arousing a sudden recollection and/or present before the trauma), as indicated re-enactment of the trauma or of the by two (or more) of the following: original reaction to it. There is usually 1. Difficulty falling or staying asleep. a state of autonomic hyperarousal with 2. Irritability or outbursts of anger. hypervigilance, an enhanced startle 3. Difficulty concentrating. reaction, and insomnia. Anxiety and 4. Hypervigilance. depression are commonly associated 5. Exaggerated startle response.” with the above symptoms and signs, Criterion E includes “duration and suicidal ideation is not infrequent. of disturbance (symptoms in Criteria Excessive use of alcohol or drugs may B, C, and D) is more than 1 month” be a complicating factor.” Criterion F comprises “the ICD-10 [30] specifies the disturbance causes clinically duration of PTSD symptoms by “the significant distress or impairment in onset follows the trauma with a latency social, occupational, or other important period which may range from a few areas of functioning. weeks to months (but rarely exceeds 6 Specify if: Acute—If duration of months). The course is fluctuating but symptoms is < 3 months; Chronic—If recovery can be expected in the duration of symptoms is ≥ 3 months majority of cases. In a small Specify if: With delayed onset—if proportion of patients the condition onset of symptoms is at least 6 months may show a chronic course over many after the stressor.” years and a transition to an enduring In Europe, the ICD-10 [30] is personality change.” more popular [3]. ICD-10 attributes Diagnostic guidelines of PTSD PTSD to “delayed and/or protracted in ICD-10 [30] mention that “This response to a stressful event or disorder should not generally be situation (either short-or long-lasting) diagnosed unless there is evidence that of an exceptionally threatening or it arose within 6 months of a traumatic catastrophic nature, which is likely to event of exceptional severity. A cause pervasive distress in almost "probable" diagnosis might still be anyone (e.g. natural or man-made possible if the delay between the event disaster, combat, serious accident, and the onset was longer than 6 witnessing the violent death of others, months, provided that the clinical or being the victim of torture, manifestations are typical and no terrorism, rape, or other crime).” alternative identification of the ICD-10 [30] documents PTSD disorder (e.g. as an anxiety or symptoms as “episodes of repeated

PTSD symptoms are currently obsessive-compulsive disorder or postulated to reflect the pathological depressive episode) is plausible. In changes in neurobiological stress- addition to evidence of trauma, there response systems, or failure of must be a repetitive, intrusive neurobiological systems to recover recollection or re-enactment of the from, or adapt to extreme stressors event in memories, daytime imagery, [33]. Some of neurobiological or dreams. Conspicuous emotional investigations in PTSD have detachment, numbing of feeling and concentrating on stress-regulating avoidance of stimuli that might arouse neuroendocrine systems, such as for recollection of the trauma are often instance the hypothalamic-pituitary- present but are not essential for the adrenal (HPA) and hypothalamic- diagnosis. The autonomic disturbances, pituitary- thyroid axes (HPT) [34, 35]. mood disorder, and behavioral Other studies have focusing on the abnormalities all contribute to the neurotransmitters and neuropeptides diagnosis but are not of prime that connect and regulate brain regions importance.” involved in fear and stress response Pathogenesis of PTSD [36]. (Figure 1).

Figure 1 Neurotransmitters and HPA Axis in Stress/Fear Response. [37].

Norepinephrine is one of the principle Acute stressors activate the mediators of the stress response in the HPA. Neurons in the hypothalamic central nerve system (CNS), and may paraventricular nucleus (PVN) secrete play a role in the development of corticotrophic-releasing hormone specific PTSD symptoms [36]. (CRH) that stimulates the production Noradrenergic cell bodies of the locus of adrenocorticotropic hormone ceruleus are responsible for production (ACTH) in the pituitary gland, and the of the majority of CNS norepinephrine release of glucocorticoids such as and through extensive branching cortisol from the adrenal cortex. The project to the major brain regions hippocampus and prefrontal cortex involved in the stress response inhibit the HPA axis, whereas the including the prefrontal cortex, amygdala and brainstem monoamines amygdala, hypothalamus, periaque- stimulate the PVN to start this flow. ductal gray, and thalamus [37]. Although acute stressors activate the Converging evidence from animal HPA, the bulk of studies in combat models of fear conditioning and veterans, refugees, and holocaust neuromolecular and neuroimaging survivors with PTSD have found techniques propose that norepinephrine decreased blood concentrations of interacts with CRH to initiate the fight cortisol [37-39]. Studies show that or flight response involving increased hypocortisolism in PTSD occurs in the heart rate, blood pressure, and skin context of sustained increases in CRH conductance in the peripheral nervous levels, suggesting increased sensitivity system and also enhanced arousal and of the HPA axis to negative feedback vigilance and facilitated encoding of from cortisol [40, 41]. The majority of fear-related memories in the CNS. PTSD studies have also demonstrated Glucocorticoids appear to inhibit this reduced volume of the hippocampus, response [43]. In the peripheral the brain region responsible for nervous system, adrenal activation inhibition of the HPA [42]. Together, during exposure to stressors results in these findings propose that PTSD may release of norepinephrine and reflect chronic sensitization of the epinephrine from the adrenal medulla HPA axis to the stressors effects [38]. and from sympathetic nerve endings. Recent studies have proven that low This hyperactivity may contribute to cortisol levels during exposure to the core autonomic hyperarousal and traumatic stressors predict PTSD re-experiencing symptoms [1]. development. Since glucocorticoids Hyperactivity of the sympathetic also interfere with the retrieval of branch of the autonomic nervous traumatic memories, they may system has been proved in various ultimately prove to be effective PTSD specimens and is similarly treatment for PTSD. CRH may exhibited by patients with PTSD in similarly play a role in conditioned fear response to reminders of traumatic response, increased startle, and experiences [44, 45]. hyperarousal; consequently, Serotonin or 5- antagonism of CRF receptors may hydroxytryptamine (5-HT) of neurons prove to be an effective approach to originating in the dorsal and median PTSD treatment [37]. raphe nuclei also project to the Catecholaminergic activity amygdala, the hippocampus, and the increases during stress, and research prefrontal cortex, and mediate findings propose that anxiogenic responses via 5-HT2 catecholaminergic dysfunction, receptors, whereas neurons from the especially in norepinephrine [1].

7 مجلة بابل الطبية- المجلد الحادي عشر - العدد ال ول - Medical Journal of Babylon-Vol. 11 - No. 1 -201 4 201 4 protective role or contribute to median raphe facilitate extinction recovery from PTSD [51]. learning (i.e., the suppression of Dopamine is involved in responses associated with fear control of locomotion, cognition, memories) via 5-HT1A receptors [46]. affect, and neuroendocrine secretion. Similarly, γ-Aminobutyric acid Preclinical studies reveal that the (GABA) inhibits the CRF/ norepinep- mesocortical/mesoprefrontal and hrine circuits, mediating fear and stress mesolimbic systems appear to be the responses through the inhibitory dopaminergic neuronal systems most actions of the GABAA (an ionotropic vulnerable to the effects of stress [52, receptor and ligand-gated ion 53]. Clinical results that support a role channel)/benzodiazepine (BZ) receptor for dopamine in the stress response and complex. Decreased BZ receptor in PTSD involve the high rates of density or affinity may contribute to psychotic symptoms observed among the pathophysiology of PTSD in a non- individuals with PTSD [54] and the specific manner [47, 48]. abnormally high levels of urinary Glutamate is the primary dopamine (in addition to cortisol and excitatory neurotransmitter in the norepinephrine) in children with PTSD brain. Glutamate binds to a number of after years of severe maltreatment [55]. excitatory amino acid receptors Exposure to trauma can result including the N-methyl-D-aspartate in immune dysregulation, implicating (NMDA) receptor. The the immune system in PTSD glutamate/NMDA receptor system is pathophysiology. Cytokine profiles in thought to be critical to the process of PTSD are similar to those observed in long-term potentiation and memory clinical chronic psychological stress consolidation (including traumatic models, although differences are noted memories). The partial NMDA in other immune parameters [56]. The receptor antagonist d-cycloserine has pathophysiology of PTSD also may been shown to facilitate extinction of involve dysfunction of the innate fear in animal models and in phobic immune inflammatory system. PTSD human subjects receiving exposure patients have been found to exhibit therapy. Its role in facilitating high levels of circulating inflammatory exposure-based therapies for patients markers such as C-reactive protein and with PTSD is an area of active study interleukin-6 (IL-6), suggesting [49]. dysfunction of the innate immune Other neuropeptides implicated inflammatory system [57]. Similarly, in the pathophysiology of PTSD women with PTSD also show involve neuropeptide Y (NPY) and the increased nuclear factor-κB (NF-κB) endogenous opioids, where opioid pathway activity compared to controls system dysfunction is seen in the and was positively correlated with avoidance/numbing and hyperarousal PTSD severity. These findings suggest symptoms of PTSD [1]. Elevated that enhanced inflammatory system levels of NPY have been demonstrated activity in participants with PTSD is in combat veterans without PTSD observable at the level of NF-κB, and compared with veterans with PTSD that in general decreased immune cell [50]. Due to the fact that NPY reduces glucocorticoid sensitivity may the release of norepinephrine from contribute to increased NF-κB pathway sympathetic nerve cells and inhibits activity [58]. CRF/norepinephrine circuits involved Neuroimaging studies on brain in the fear response, it has been structure and function indicated that proposed that NPY may play a

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