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Biomedical subjects

Joseph Zohar

Publications and source records attributed to Joseph Zohar.

At least 19 recordsLinked to original sources
PubMed2006

Long-lasting behavioral effects of juvenile trauma in an animal model of PTSD associated with a failure of the autonomic nervous system to recover.

BACKGROUND: Early life exposure to potentially traumatic experiences (PTEs) significantly increases the risk of responding more severely to stressful events experienced in adulthood. The aim of this study was to assess the autonomic nervous system (ANS) response to exposure to two PTEs in youth and again in adulthood, in terms of heart rate and heart rate variability in animals that responded to the PTE dramatically as compared to those that displayed virtually no behavioral response and to control animals. METHODS: The prevalence of individuals displaying extreme anxiety-like behavioral responses to the PTE (predator urine or elevated platform) was assessed in the elevated plus-maze and startle response paradigms. Behavioral paradigms were complemented by assessment of the involvement of the ANS in relation to changes in behavior. RESULTS: Juvenile trauma increases the vulnerability for developing long-term behavioral disruptions, taken to represent post-traumatic stress symptoms, after a second exposure to the same stressor in adulthood. PTSD-like behaviors and persisting physiological abnormalities resulted from disturbed recovery from the initial stress response. CONCLUSIONS: Exposure to a PTE during youth can have significant and long-lasting effects in adulthood and predispose the individual to PTSD upon subsequent re-exposure. Monitoring of ANS parameters confirms that development of extreme long-term (PTSD-like) behavioral changes is associated with a failure of recovery from the initial ANS responses to stress exposure.

Aging↗
PubMed2006

The effect of early poststressor intervention with sertraline on behavioral responses in an animal model of post-traumatic stress disorder.

Whereas several well-controlled studies have established the selective serotonin reuptake inhibitors (SSRIs) as the recommended first-line pharmacotherapeutic agents for acute and chronic post-traumatic stress disorder (PTSD), drug interventions in the acute postexposure phase have not been studied to the same extent and tend to be largely speculative. This study employed an animal model which assesses prevalence of individual stress-response behavior patterns in order to assess the short-term effects of a brief treatment regimen with an SSRI (sertraline) administered immediately after stress-exposure, with those of an identical delayed regimen and of saline. Prevalence rates of rats displaying extreme anxiety-like behavioral responses to predator stress, compared to partial and minimal responses, were assessed in the elevated plus maze and startle response paradigms, with and without intraperitoneal administration of sertraline for 7 days immediately postexposure, or 7 days after exposure. Immediate postexposure administration of sertraline reduced anxiety-like and avoidant behavior, decreased hyperarousal responses and diminished the overall incidence of extreme (PTSD-like) behavioral responses, compared to the delayed treatment regimen and to saline controls. Brief immediate poststress exposure treatment with sertraline reduced prevalence rates of extreme behavioral disruption in the short-term. SSRI drugs are thus worthy of further investigation as agents of secondary prevention in the acute aftermath of stress-exposure.

Animals↗
PubMed2006

Anisomycin, a protein synthesis inhibitor, disrupts traumatic memory consolidation and attenuates posttraumatic stress response in rats.

BACKGROUND: Paradoxical changes in memory represent a troublesome characteristic of posttraumatic stress disorder (PTSD). Exceptionally vivid intrusive memories of some aspects of the trauma are mingled with patchy amnesia regarding other important aspects. Molecular studies of the memory process suggest that the conversion from labile short-term memory into long-term fixed traces involves protein synthesis. This study assessed the effects of administration of anisomycin, a protein synthesis inhibitor, after initial exposure, after exposure to a cue associated with triggering experience, and after reexposure to the triggering trauma in an animal model of PTSD. METHOD: Magnitude of changes in prevalence of anxiety-like behaviors on the elevated plus-maze and nonhabituated exaggerated startle reaction were compared in rats that were exposed to predator stress, with and without microinjection of anisomycin. RESULTS: Microinjection of anisomycin before and after stress exposure reduced anxiety-like and avoidant behavior, reduced the mean startle amplitude, and reversed the stress-induced habituation deficit 7 days later. The persistent anxiety-like behaviors that were seen after stress exposure do not appear to be sensitive to anisomycin after reexposure to a cue associated with the event or after reexposure to the index experience. CONCLUSIONS: Disruption of the process of traumatic memory consolidation may be useful for mitigating PTSD symptoms.

Analysis of Variance↗
PubMed2006

Blunted HPA axis response to stress influences susceptibility to posttraumatic stress response in rats.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with low levels of circulating cortisol, and recent studies suggest that cortisol administration may reduce PTSD symptoms. This study investigated the role of cortisol in the manifestation of anxiety- and fear-like symptoms in an animal model of PTSD. METHOD: Magnitude of changes in prevalence of anxiety-like behaviors on the elevated plus-maze and nonhabituated exaggerated startle reaction were compared in three strains of rats exposed to predator stress, with and without prior corticosterone treatment. Extreme behavioral changes in both paradigms implied an extreme behavioral response (EBR), representing PTSD-like symptoms. RESULTS: Lewis rats exhibited greater baseline anxiety-like behaviors and greater stress-induced increases in anxiety-like behaviors than Fischer F344 or Sprague-Dawley rats, with only minor corticosterone increases following stress. Prevalence of EBR was 50% among Lewis rats compared with 10% of Fischer F344 and 25% of Sprague-Dawley rats. Administering corticosterone 1 hour before stress exposure reduced the prevalence of EBR from 50% to 8% in the Lewis rats. CONCLUSIONS: These results suggest that a blunted HPA response to stress may play a causal role in this model of PTSD and that this susceptibility may be prevented by administration of cortisol before stress exposure.

Analysis of Variance↗
PubMed2006

Posttraumatic stress disorder, tenderness, and fibromyalgia syndrome: are they different entities?

OBJECTIVES: Many features of fibromyalgia syndrome (FMS) resemble those of posttraumatic stress disorder (PTSD). The goal of this study was to investigate the comorbidity of FMS and PTSD in a cohort of men following an intensive, initial, defined traumatic event. METHODS: One hundred twenty-four males (55 patients with PTSD, 20 patients with major depression, and 49 controls) were evaluated for the presence of FMS. The major traumatic events in all PTSD patients were combat-related. Each individual completed questionnaires characterizing his disease, disabilities, and quality of life. RESULTS: Forty-nine percent of PTSD patients, compared to 5% of major depression patients and none of normal controls, fulfilled the American College of Rheumatology criteria for FMS (P<.0001). Significant correlations were detected between tender points and measured parameters in the PTSD group. CONCLUSIONS: In male patients, PTSD is highly associated with FMS. The degree and impact of these disorders are also highly related.

Adolescent↗
PubMed2006

The contribution of an animal model toward uncovering biological risk factors for PTSD.

Clinical studies of posttraumatic stress disorder (PTSD) have elicited proposed risk factors for developing PTSD in the aftermath of stress exposure. Generally, these risk factors have arisen from retrospective analysis of premorbid characteristics of study populations. A valid animal model of PTSD can complement clinical studies and help to elucidate issues, such as the contribution of proposed risk factors, in ways which are not practicable in the clinical arena. Important qualities of animal models include the possibility to conduct controlled prospective studies, easy access to postmortem brains, and the availability of genetically manipulated subjects, which can be tailored to specific needs. When these qualities are further complemented by an approach which defines phenomenologic criteria to address the variance in individual response pattern and magnitude, enabling the animal subjects to be classified into definable groups for focused study, the model acquires added validity. This article presents an overview of a series of studies in such an animal model which examine the contribution of two proposed risk factors and the value of two early postexposure pharmacological manipulations on the prevalence rates of subjects displaying an extreme magnitude of behavioral response to a predator stress paradigm.

Animals↗
PubMed2006

Natural course of posttraumatic stress disorder: a 20-month prospective study of Turkish earthquake survivors.

OBJECTIVE: A 20-month prospective follow-up of survivors of the severe earthquake in Turkey in 1999 examined the natural course of posttraumatic stress disorder (PTSD) and the contribution of different symptom clusters to the emergence of PTSD. METHOD: Subjects were randomly sampled in a suburb of Istanbul that was severely affected by the earthquake. A total of 464 adults were assessed with a self-report instrument for PTSD symptoms on 3 consecutive surveys that were administered 1 to 3, 6 to 10, and 18 to 20 months following the earthquake. RESULTS: The prevalence of PTSD was 30.2% on the first survey and decreased to 26.9% and 10.6% on the second and third surveys, respectively. Female subjects showed initially higher (34.8%) PTSD rates compared with male subjects (19.1%). However, gender differences disappeared by the time of the third survey due to high spontaneous remission rates in female subjects. Low levels of chronic and delayed-onset PTSD were observed. A major contribution of the avoidance symptoms to PTSD diagnosis was identified by statistical analysis. CONCLUSIONS: Initial PTSD following an earthquake may be as prevalent as in other natural disasters, but high rates of spontaneous remission lead to low prevalence 1.5 years following the earthquake. Initial avoidance characteristics play a major role in the emergence of PTSD.

Adult↗
PubMed2005

Unsupervised fuzzy clustering analysis supports behavioral cutoff criteria in an animal model of posttraumatic stress disorder.

BACKGROUND: Unsupervised fuzzy clustering (UFC) analysis is a mathematical technique that groups together objects in the multidimensional feature space according to a specified similarity measurement, thereby yielding clusters of similar data points that can be represented by a set of prototypes or centroids. METHODS: Since clinical studies of mental disorders distinguish between affected and unaffected individuals, we designed an inclusion/exclusion criteria (cutoff behavioral criteria [CBC]) approach for animal behavioral studies. The effect of classifying the study population into clearly affected versus clearly unaffected individuals according to behaviors on two behavioral paradigms was statistically significant. RESULTS: Here the raw data from previous studies were subjected to UFC algorithms as a means of objectively testing the validity of the concept of the CBC for our experimental model. The first UFC algorithm yielded two clearly discrete clusters, found to consist almost exclusively of the exposed animals in the one and unexposed animals in the other. The second algorithm yielded three clusters corresponding to animals designated as clearly affected, partially affected, and clearly unaffected. The algorithm for physiological data in addition to behavioral data failed to elicit discrete clusters. CONCLUSIONS: The UFC analysis yielded data that support the conceptual contention of the CBC and lends additional validity to our previous behavioral studies.

Acoustic Stimulation↗
PubMed2005

Posttraumatic obsessive-compulsive disorder: a case series.

This report documents emerging posttraumatic obsessive-compulsive disorder in 13 Israeli military veterans diagnosed with both obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD), for whom the onset of OCD was clearly associated with the trauma. Data presented include four detailed case reports that delineate relations between symptomatology in the two disorders. Clinical and theoretical implications of these data are discussed.

Adult↗
PubMed2005

Anxiogenic effects of Sumatriptan in panic disorder: a double-blind, placebo-controlled study.

BACKGROUND: Several lines of evidence point to serotonergic abnormalities in patients with panic disorder (PD). Our goal was to further examine central serotonergic function in panic patients using autonomic and subjective responses to the postsynaptic serotonin 5-HT1D receptor agonist Sumatriptan. METHOD: Using a double-blind, randomized, placebo-controlled design, we assessed autonomic and subjective responses to oral Sumatriptan (100 mg) and placebo in 15 patients with PD, free of medication. Subjective responses were measured using the Hamilton Anxiety Rating Scale (HAM-A), National Institute of Mental Health Anxiety Scale (NIMHA), a modified version of the Panic Symptom Inventory (PI), Hamilton Depression Rating Scale (HAM-D), and Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: PD patients exhibited significantly enhanced autonomic and subjective responses following challenge with Sumatriptan. We observed an increased pulse rate and augmentation of various parameters measured on different anxiety scales. A constant inclination of aggravation of the measured parameters was detected during the hour post challenge. CONCLUSION: Oral administration of Sumatriptan, a 5-HT1D agonist, has been associated with an anxiogenic effect in PD patients.

Adolescent↗
PubMed2005

Pathological responses to terrorism.

Many important gains have been made in understanding PTSD and other responses to trauma as a result of neuroscience-based observations. Yet there are many gaps in our knowledge that currently impede our ability to predict those who will develop pathologic responses. Such knowledge is essential for developing appropriate strategies for mounting a mental health response in the aftermath of terrorism and for facilitating the recovery of individuals and society. This paper reviews clinical and biological studies that have led to an identification of pathologic responses following psychological trauma, including terrorism, and highlights areas of future-research. It is important to not only determine risk factors for the development of short- and long-term mental health responses to terrorism, but also apply these risk factors to the prediction of such responses on an individual level. It is also critical to consider the full spectrum of responses to terrorism, as well as the interplay between biological and psychological variables that contribute to these responses. Finally, it is essential to remove the barriers to collecting data in the aftermath of trauma by creating a culture of education in which the academic community can communicate to the public what is and is not known so that survivors of trauma and terrorism will understand the value of their participation in research to the generation of useful knowledge, and by maintaining the acquisition of knowledge as a priority for the government and those involved in the immediate delivery of services in the aftermath of large-scale disaster or trauma.

Adaptation, Psychological↗
PubMed2004

The serotonin-dopamine interaction is critical for fast-onset action of antidepressant treatment: in vivo studies in an animal model of depression.

In the last decade, many new antidepressants have been developed that display a more rapid onset to clinical effects than classical antidepressants. However, the mechanism that enables some drugs to have a faster onset of action than others is poorly understood. The aim of the present study was to determine neural alterations that are specific to fast-acting antidepressant action using Flinders Sensitive Line (FSL) rats, an animal model of depression. Because of the central role of accumbal dopamine in the mediation of motivation and reward, our measurements were focused on dopaminergic neurotransmission in the nucleus accumbens (NAC). The authors found that 7-day treatment with nefazodone (a putative fast-onset antidepressant) but not with desipramine (a classical antidepressant) normalized immobility time in the swim test in FSL rats. Serotonin (5-HT)-induced dopamine release but not basal dopamine levels correlated with the improvement of depressive-like behavior. The authors conclude that the 5-HT-dopamine interaction is critical to the fast-onset action of antidepressant treatment.

Adrenergic Uptake Inhibitors↗
PubMed2004

Setting apart the affected: the use of behavioral criteria in animal models of post traumatic stress disorder.

Post-traumatic stress disorder (PTSD) affects about 20-30% of exposed individuals. Clinical studies of PTSD generally employ stringent criteria for inclusion in study populations, and yet in animal studies the data collection and analysis are generally expressed as a function of exposed vs nonexposed populations, regardless of individual variation in response. Prior data support an approach to animal models analogous to inclusion criteria in clinical studies. This series of studies sought to assess prevalence rates of maladaptive vs adaptive responses determined according to a more stringent approach to the concept of inclusion/exclusion criteria (cutoff behavioral criteria-CBC), consisting of two successive behavioral tests (elevated plus maze and acoustic startle response tests). The rats were exposed to stressors in two different paradigms; exposure to a predator and underwater trauma. The prevalence rates of maladaptive responses to stress in these two distinct models dropped over time from 90% in the acute phase to 25% enduring/maladaptive response at 7 days, to remain constant over 30 days. As setting the affected individuals apart from the unaffected approximates clinical studies, it might also help to clarify some of the pending issues in PTSD research.

Acoustic Stimulation↗
PubMed2004

Serotonergic dissection of obsessive compulsive symptoms: a challenge study with m-chlorophenylpiperazine and sumatriptan.

We have conducted a pharmacological challenge experiment in 10 medication-free obsessive compulsive (OC) disorder (OCD) patients. We used a placebo-controlled paradigm for m-chlorophenylpiperazine (mCPP) and sumatriptan challenges. Endocrine, physiological and behavioral variables were assessed at baseline and over a 3-hour period after the challenge. Both cortisol and prolactin were significantly elevated in OCD patients following mCPP administration. Both mCPP and sumatriptan caused significant OC symptom exacerbation with the response to sumatriptan being more robust. We conclude that the 5-HT(1Dbeta) receptor may play a role in the pathophysiology of OCD.

Adult↗
PubMed2004

An animal model of posttraumatic stress disorder: the use of cut-off behavioral criteria.

Considerable heterogeneity exists in the response of human subjects exposed to extreme traumatizing events. Posttraumatic stress disorder (PTSD) is diagnosed in 20-30% of those exposed. Clinical studies of this population employ stringent inclusion/exclusion criteria, yet animal studies have routinely included the entire exposed population as the study population. We examined the effect of grouping stressed rats according to the magnitude of their response on the statistical analysis of behavioral models. Exposure to a predator stimulus was used as the stress paradigm. Response magnitude was assessed in two consecutive behavioral tests measuring anxiety- and stress-related behaviors and was used to divide the animals into groups. The two extremes were studied, that is, those clearly "maladapted" and those clearly "well-adapted," using arbitrarily selected severity-measures, the "cut-off behavioral criteria" (CBC). Data for the partially affected middle group were discarded for reasons of clarity. The hypothalamic-pituitary-adrenal axis and heart rate variability were analyzed for the entire exposed population and then reexamined according to the CBCs. When the CBCs were applied, we found PTSD-like symptoms in only 22.0% of exposed rats. Compared to controls and to well-adapted exposed rats, the behaviorally maladapted rats displayed disordered physiological measures. They had significantly higher plasma corticosterone and ACTH levels, increased sympathetic activity, diminished vagal tone, and increased sympathovagal balance. These differences surfaced only when data were analyzed according to the CBCs. Animals respond to stress heterogeneously, resembling humans. Overlooking heterogeneity in responses obscures the results of biobehavioral data analysis. We submit that animals exposed to trauma should be divided into groups according to the magnitude of their response and be studied accordingly.

Adaptation, Psychological↗