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Biomedical subjects

A Y Shalev

Publications and source records attributed to A Y Shalev.

At least 19 recordsLinked to original sources
PubMed2005

Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors.

Trauma survivors show marked differences in the severity and persistence of post-traumatic stress disorder (PTSD) symptoms. Early symptoms subside in most, but persist as acute and chronic PTSD in a significant minority. The underlying molecular mechanisms or outcome predictors determining these differences are not known. Molecular markers for identifying any mental disorder are currently lacking. Gene expression profiling during the triggering and development of PTSD may be informative of its onset and course. We used oligonucleotide microarrays to measure peripheral blood mononuclear cell (PBMC) gene expression of trauma survivors at the emergency room and 4 months later. Gene expression signatures at both time points distinguished survivors who met DSM-IV diagnostic criteria for PTSD at 1 and 4 months, from those who met no PTSD criterion. Expression signatures at both time points correlated with the severity of each of the three PTSD symptom clusters assessed 4 months following exposure among all survivors. Results demonstrate a general reduction in PBMCs' expression of transcription activators among psychologically affected trauma survivors. Several differentiating genes were previously described as having a role in stress response. These findings provide initial evidence that peripheral gene expression signatures following trauma identify an evolving neuropsychiatric disorder and are informative of its key clinical features and outcome. Replications in larger samples, as well as studies focusing on specific markers within the signatures discovered, are warranted to confirm and extend the diagnostic utility and pathogenetic implications of our results.

Adaptation, Psychological↗
PubMed2002

Association between the dopamine transporter gene and posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a chronic anxiety disorder that follows exposure to extreme events. A large twin study of Vietnam veterans had demonstrated a significant genetic contribution to chronic PTSD upon exposure to combat.(1,2) The underlying genes, however, have not been described. Given previous findings of abnormal dopamine (DA) function in PTSD, and given the putative effect of dopamine neurotransmission in shaping the responses to stress in animals, this study examined the association of the dopamine transporter (DAT) SLC6A3 3' variable number tandem repeat (VNTR) polymorphism with PTSD. The study evaluated 102 chronic PTSD patients and 104 carefully-documented trauma survivors (TS) who did not develop PTSD. Significant excess of 9 repeat allele was observed among PTSD patients (43% vs 30.5% in TS controls; chi(2) = 6.3, df = 1, P = 0.012). An excess of 9 repeat homozygous genotype was also observed in PTSD (20.43% in PTSD vs 9.47% in TS controls; chi(2) = 6.11, df = 2, P < 0.047). These findings suggest that genetically determined changes in dopaminergic reactivity may contribute to the occurrence of PTSD among trauma survivors.

Adult↗
PubMed2001

Vagal modulation of responses to mental challenge in posttraumatic stress disorder.

BACKGROUND: Studies of the autonomic nervous system in posttraumatic stress syndrome (PTSD) have focused on the sympathetic modulation of arousal and have neglected the parasympathetic contribution. This study addresses the parasympathetic control of heart rate in individuals who have survived traumatic events. METHODS: Twenty-nine survivors, 14 with current PTSD and 15 without, participated in the study. The groups were comparable with regard to age, type of trauma, time since the latest traumatic event, and lifetime exposure to traumatic events. Electrocardiograms were recorded during rest and an arithmetic task. Heart period, respiratory sinus arrhythmia (RSA), and the amplitude of the Traube-Hering-Mayer wave were quantified. RESULTS: The groups did not differ on resting measures. During the arithmetic task, the past trauma group showed a significant increase in RSA (p <.007), whereas the PTSD group did not. In the past trauma group only, RSA and heart period were highly correlated (r =.75), thereby suggesting that the response to challenge was under vagal control. CONCLUSIONS: Trauma survivors who develop PTSD differ from those who do not in the extent to which their heart rate response to challenge is controlled by vagal activity. Responses to challenge in PTSD may be mediated by nonvagal, possibly sympathetic mechanisms.

Adult↗
PubMed2001

Posttraumatic stress disorder: diagnosis and epidemiology, comorbidity and social consequences, biology and treatment.

Epidemiological studies clearly indicate that posttraumatic stress disorder (PTSD) is becoming a major health concern worldwide even if still poorly recognized and not well treated. PTSD commonly co-occurs with other psychiatric disorders, and several symptoms overlap with major depressive disorders, anxiety disorders and substance abuse; this may contribute to diagnostic confusion and underdiagnosis. This anxiety disorder provokes significant occupational, psychiatric, medical and psychosocial disability, and its consequences are enormously costly, not only to the survivors and their families, but also to the health care system and society. Work impairment associated with PTSD is very similar to the amount of work impairment associated with major depression. The pathophysiology of PTSD is multifactorial and involves dysregulation of the serotonergic as well as the noradrenergic system. A rational therapeutic approach should normalize the specific psychobiological alterations associated with PTSD. This can be achieved through the use of antidepressant drugs, mainly of those that potentiate serotonergic mechanisms. Recent double-blind placebo-controlled studies report the efficacy of selective serotonin reuptake inhibitors. Several cognitive-behavioral and psychosocial treatments have also been reported to be efficacious and could be considered when treating PTSD patients.

Antidepressive Agents↗
PubMed2001

Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD.

OBJECTIVE: The authors prospectively explored whether a reduction in the volume of the hippocampus occurs in recent trauma survivors who develop posttraumatic stress disorder (PTSD). METHOD: Thirty-seven survivors of traumatic events were assessed within a week of the traumatic event and 6 months later. The assessment included magnetic resonance imaging of the brain (including 124 coronal slices of 1.5-mm thickness), psychometric testing, and structured clinical interviews. The Clinician-Administered PTSD Scale conferred PTSD diagnoses at 6 months. RESULTS: Ten subjects (27%) had PTSD at 6 months. The subjects with PTSD did not differ from those without PTSD in hippocampal volume (right or left) at 1 week or 6 months. There was no reduction in hippocampal volume in the PTSD subjects between 1 week and 6 months. CONCLUSIONS: Smaller hippocampal volume is not a necessary risk factor for developing PTSD and does not occur within 6 months of expressing the disorder. This brain abnormality might occur in individuals with chronic or complicated PTSD.

Adult↗
PubMed2001

Stress-induced enhancement of auditory startle: an animal model of posttraumatic stress disorder.

An innovative animal model of posttraumatic stress disorder (PTSD) is proposed in which nonhabituation of the acoustic startle response is developed in rats subsequent to tailshock exposure. Subjects (n = 31) received 30 minutes of intermittent tail shock on 2 days followed by exposure to the tailshock apparatus on the third day. Compared to baseline startle reactions, 9 of 31 tailshock-exposed rats developed nonhabituation of startle response reactions during the subsequent 3 weeks of testing. No control rats developed nonhabituation of startle reactions over a similar time period. These data suggest that this system models useful aspects of clinical PTSD emphasizing nonhabituation of startle reactions as a dependent variable. The method consistently identifies a subgroup of rats that develop persistent nonhabituation of startle in response to a tailshock-stress paradigm.

Animals↗
PubMed2001

Triiodothyronine augmentation of selective serotonin reuptake inhibitors in posttraumatic stress disorder.

BACKGROUND: There is considerable comorbidity of major depression and posttraumatic stress disorder (PTSD), and antidepressants have been reported to be effective in treating PTSD. Addition of triiodothyronine (T3) to ongoing antidepressant treatment is considered an effective augmentation strategy in refractory depression. We report the effect of T3 augmentation of antidepressants in patients with PTSD. METHOD: T3 (25 microg/day) was added to treatment with a selective serotonin reuptake inhibitor (SSRI) (paroxetine or fluoxetine, 20 mg/day for at least 4 weeks and 40 mg/day for a further 4 weeks) of 5 patients who fulfilled DSM-IV criteria for PTSD but not for major depressive disorder (although all patients had significant depressive symptoms). The Clinician-Administered PTSD Scale, the 21-item Hamilton Rating Scale for Depression, and the Clinical Global Impressions-Severity of Illness scale were administered every 2 weeks, and self-assessments were performed with a 100 mm visual analog mood scale. RESULTS: In 4 of the 5 patients, partial clinical improvement was observed with SSRI treatment at a daily dose of 20 mg with little further improvement when the dose was raised to 40 mg/day. This improvement was substantially enhanced by the addition of T3. Improvement was most striking on the Hamilton Rating Scale for Depression. CONCLUSION: T3 augmentation of SSRI treatment may be of therapeutic benefit in patients with PTSD, particularly those with depressive symptoms. Larger samples and controlled studies are needed in order to confirm this observation.

Adult↗
PubMed2001

What is posttraumatic stress disorder?

Our understanding of posttraumatic stress disorder (PTSD) has increased significantly over the last 2 decades. Although the cause of the condition is usually easy to determine in individual patients, the symptoms of PTSD are diverse and a mixture of psychological processes are involved. This article presents a broad overview of PTSD, including its definition according to DSM-IV and ICD-10 diagnostic criteria, and its clinical course with reference to its association with depression and other mental disorders. The article also briefly reviews the assessment of patients and considers physiologic features such as responses to startle stimuli that appear to be useful in diagnosing PTSD and in differentiating it from other anxiety disorders and depression. Finally, a brief overview of the treatment of PTSD is given, including psychological and biological treatment options.

Acoustic Stimulation↗
PubMed2000

Psychophysiologic assessment of aversive conditioning in posttraumatic stress disorder.

BACKGROUND: The objective of this study was to evaluate the acquisition, generalization, and extinction of conditioned physiologic responses to aversive stimuli in posttraumatic stress disorder (PTSD). METHODS: Thirty-six PTSD patients, 20 individuals with past trauma and no current PTSD, and 30 mentally healthy individuals without exposure to major trauma underwent a differential aversive conditioning experiment. Bursts of 105 dB white noise were used as unconditioned stimuli (UCSs), and 35x24 mm slides of different colors served as either CS+ (paired) or CS- (unpaired) stimuli. Heart rate (HR) and nondominant palm skin conductance (SC) were measured at rest and between 1 and 4 sec following each CS presentation. RESULTS: The PTSD group showed higher levels of resting SC and resting HR, larger SC responses to the initial presentation of unpaired CSs, larger HR responses following paired CS+ stimuli, larger SC responses to unpaired CS- during acquisition and extinction, and larger SC and HR responses to CS+ during extinction. The group differences in responses to CS+ during extinction remained statistically significant after controlling for age, resting physiologic levels, and initial responsivity. CONCLUSIONS: PTSD is associated with elevated autonomic responses to both innocuous and aversive stimuli, with larger responses to unpaired cues and with reduced extinction of conditioned responses.

Adult↗
PubMed2000

Biological responses to disasters.

The pathogenic effect of extreme events has been equated with their immediate stressfulness, and thereby with the biology of stress. This article extends this classical view to include, among other pathogenic factors the biological dimensions of learning, social interaction, territorial behavior, and a top-down brain process that links personal and cultural meanings with emotional and bodily responses. The paper depicts the way in which mechanisms related to stress and aversive learning trigger an initial response and those related to separation, loss and sensitization shape its long-term consequences. Traumatic events are followed by a critical period of increased brain plasticity, during which irreversible neuronal changes may occur in those who develop traumatic stress disorders.

Arousal↗
PubMed2000

Auditory startle response in trauma survivors with posttraumatic stress disorder: a prospective study.

OBJECTIVE: Previous studies have shown elevated autonomic responses to startling tones in trauma survivors with chronic posttraumatic stress disorder (PTSD). The origin of these abnormal responses is obscure. The present study attempted to clarify this issue by prospectively evaluating responses to sudden, loud tones in individuals who arrived at a hospital emergency room after psychologically traumatic events. METHOD: By using a previously established protocol, autonomic and muscular responses to the tones were evaluated at 1 week, 1 month, and 4 months after the traumatic event. Structured diagnostic interviews performed at 4 months classified subjects into groups with (N=36) and without (N=182) PTSD, which were further subdivided according to the presence or absence of major depressive disorder as follows: neither PTSD nor depression (N=166), depression alone (N=16), PTSD alone (N=21), and both PTSD and depression (N=15). RESULTS: The groups showed comparable physiological responses to the tones at 1 week posttrauma. However, at 1 and 4 months posttrauma, the subjects with PTSD showed a greater heart rate response and required more stimulus trials to reach the criteria of skin conductance and orbicularis oculi electromyogram nonresponse. These findings were not significantly influenced by comorbid depression and were not explained by the severity of the traumatic event or by the intensity of the initial symptoms. CONCLUSIONS: Differences in physiological response to startling tones develop along with PTSD in the months that follow a traumatic event. This pattern supports the theories that associate PTSD with progressive neuronal sensitization.

Accidents, Traffic↗
PubMed2000

Measuring outcome in posttraumatic stress disorder.

This article summarizes the features of posttraumatic stress disorder (PTSD) that may affect treatment outcome and discusses the areas in which treatment outcome can be productively evaluated. PTSD is a complex psychiatric condition that tends to run a chronic course. Measurement of treatment outcome in PTSD is confounded by multiple factors, including a high prevalence of comorbid disorders, reactivation of the syndrome by ongoing environmental stressors, spontaneous recovery of the early disorder, and a fluctuating course of the chronic disorder. Four principal domains of treatment outcome may be evaluated in PTSD: core symptom severity, comorbid conditions (particularly depression), adverse practices (e.g., violence or alcohol consumption), and social/vocational disability. To gain an accurate assessment of these domains, a comprehensive assessment battery is needed. The relevant instruments and their yield in studies of PTSD are reviewed.

Anxiety Disorders↗
PubMed2000

Consensus statement on posttraumatic stress disorder from the International Consensus Group on Depression and Anxiety.

OBJECTIVE: To provide primary care clinicians with a better understanding of management issues in posttraumatic stress disorder (PTSD) and guide clinical practice with recommendations on the appropriate management strategy. PARTICIPANTS: The 4 members of the International Consensus Group on Depression and Anxiety were James C. Ballenger (chair), Jonathan R. T. Davidson, Yves Lecrubier, and David J. Nutt. Other faculty invited by the chair were Edna B. Foa, Ronald C. Kessler, Alexander C. McFarlane, and Arieh Y. Shalev. EVIDENCE: The consensus statement is based on the 6 review articles that are published in this supplement and the scientific literature relevant to the issues reviewed in these articles. CONSENSUS PROCESS: Group meetings were held over a 2-day period. On day 1, the group discussed the review articles and the chair identified key issues for further debate. On day 2, the group discussed these issues to arrive at a consensus view. After the group meetings, the consensus statement was drafted by the chair and approved by all attendees. CONCLUSION: PTSD is often a chronic and recurring condition associated with an increased risk of developing secondary comorbid disorders, such as depression. Selective serotonin reuptake inhibitors are generally the most appropriate choice of first-line medication for PTSD, and effective therapy should be continued for 12 months or longer. The most appropriate psychotherapy is exposure therapy, and it should be continued for 6 months, with follow-up therapy as needed.

Cost of Illness↗
PubMed1999

Psychophysiological alterations in post-traumatic stress disorder.

Psychophysiological research in trauma-exposed populations has provided objective data supporting the validity of the post-traumatic stress disorder (PTSD) diagnostic concept. Consistent with a conditioning model, PTSD patients show specific increased peripheral physiological responding to audio-visually and imaginally presented stimuli symbolizing or resembling the etiologic traumatic event. PTSD patients respond to startling stimuli with larger autonomic and electromyographic responses, especially under threat conditions. Electroencephalographic event-related potential (ERP) response abnormalities in PTSD include reduced P2 amplitude at high stimulus intensities, impaired P1 habituation, and attenuated P3 amplitude to target auditory stimuli. However, larger P3 and N1 amplitude responses and shorter P3 and N1 latencies have been reported in PTSD subjects in response to trauma-related stimuli. These ERP findings suggest sensory, cognitive, and affective processing abnormalities in PTSD. Polysomnographic sleep studies have revealed increased awakenings, reduced sleep time, and increased motor activity, or in some cases, paradoxical deepening of sleep. There is also evidence for increased phasic eye movement activity during rapid eye movement (REM) sleep and disrupted REM continuity in PTSD. Psychophysiological studies are offering valuable insights into the pathophysiology of this important neuropsychiatric condition.

Electroencephalography↗
PubMed1998

Predicting the development of posttraumatic stress disorder from the acute response to a traumatic event.

Posttraumatic stress disorder (PTSD) is a psychiatric condition that is directly precipitated by an event that threatens a person's life or physical integrity and that invokes a response of fear, helplessness, or horror. In recent years it has become clear that only a proportion of those exposed to fear-producing events develop or sustain PTSD. Thus, it seems that an important challenge is to elucidate aberrations in the normal fear response that might precipitate trauma-related psychiatric disorder. This paper summarizes the findings from recent studies that examined the acute and longer term biological response to traumatic stress in people appearing to the emergency room immediately following trauma exposure. In the aggregate, these studies have demonstrated increased heart rate and lower cortisol levels at the time of the traumatic event in those who have PTSD at a follow-up time compared to those who do not. In contrast, certain features associated with PTSD, such as intrusive symptoms and exaggerated startle responses, are only manifest weeks after the trauma. The findings suggest that the development of PTSD may be facilitated by an atypical biological response in the immediate aftermath of a traumatic event, which in turn leads to a maladaptive psychological state.

Animals↗