Neurofeedback Improves Memory and Peak Alpha Frequency in Individuals with Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is a syndrome characterized by a decrease in cognitive abilities, while daily function is maintained. This condition, which is associated with an increased risk for the development of Alzheimer's disease, has no known definitive treatment at present. In this open-label pilot study we explored the possible benefits of neurofeedback for subjects with MCI. Eleven participants diagnosed with MCI were trained to increase the power of their individual upper alpha band of the electroencephalogram (EEG) signal over the central parietal region. This was achieved using an EEG-based neurofeedback training protocol. Training comprised ten 30-min sessions delivered over 5 weeks. Cognitive and electroencephalographic assessments were conducted before and after training and at 30 days following the last training session. A dose-dependent increase in peak alpha frequency was observed throughout the period of training. Memory performance also improved significantly following training, and this improvement was maintained at 30-day follow-up, while peak alpha frequency returned to baseline at this evaluation. Our findings suggest that neurofeedback may improve memory performance in subjects with mild cognitive impairment, and this benefit may be maintained beyond the training period.

Biological and Behavioral Patterns of Post-Stroke Depression in Rats.

BACKGROUND: Post-stroke depression (PSD) is the most frequent psychiatric complication following ischemic stroke. It affects up to 60% of all patients and is associated with increased morbidity and mortality following ischemic stroke. The pathophysiology of PSD remains elusive and appears to be multifactorial, rather than "purely" biological or psychosocial in origin. Thus, valid animal models of PSD would contribute to the study of the etiology (and treatment) of this disorder. METHODS: The present study depicts a rat model for PSD, using middle cerebral artery occlusion (MCAO). The two-way shuttle avoidance task, Porsolt forced-swim test, and sucrose preference test were employed to assess any depression-like behavior. Localized brain expressions of brain-derived neurotrophic factor (BDNF) protein levels were evaluated to examine the possible involvement of the brain neuronal plasticity in the observed behavioral syndrome. The raw data were subjected to unsupervised fuzzy clustering (UFC) algorithms to assess the sensitivity of bio-behavioral measures indicative of depressive symptoms post MCAO. RESULTS: About 56% of the rats developed significant depressive-like behavioral disruptions as a result of MCAO compared with 4% in the sham-operated control rats. A pattern of a depressive-like behavioral response was common to all affected MCAO animals, characterized by significantly more escape failures and reduced number of total avoidance shuttles, a significant elevation in immobility duration, and reduced sucrose preference. Significant downregulations of BDNF protein levels in the hippocampal sub-regions, frontal cortex, and hypothalamus were observed in all affected MCAO animals. CONCLUSION: The UFC analysis supports the behavioral analysis and thus, lends validity to our results.

Immediate Effects of Transcranial Direct Current Stimulation on Obsession-Induced Anxiety in Refractory Obsessive-Compulsive Disorder: A Pilot Study.

OBJECTIVE: Studies have shown that transcranial direct current stimulation (tDCS) has immediate effects on brain activity. The aim of this study was to investigate the potential use of tDCS to regulate obsession-induced anxiety immediately after symptom provocation in patients with refractory obsessive-compulsive disorder (OCD). METHODS: Twelve patients with refractory OCD received cathode, anode, and sham transcranial direct current stimulation over the medial prefrontal cortex conjugant to pharmacological treatment in a crossover design. Before and after the DC stimulation, patients graded the intensity of their anxiety after a short exposure to a provoking stimulus using the visual analogue scale. Clinical questionnaires assessing symptoms severity were also applied before each stimulation mode. RESULTS: We found a statistically significant decrease in the severity of the obsession-induced anxiety (decreased visual analogue scale) as a result of cathode tDCS in comparison with the anode and sham stimulation. Reduction in obsession-induced anxiety was consistent, yet short lasting, and was independent of symptom severity. CONCLUSIONS: Cathode tDCS could be potentially used to regulate obsession-induced anxiety in refractory OCD patients. Further studies are warranted to confirm our results as well as to determine whether tDCS can achieve prolonged benefits in OCD and be of aid in behavioral treatments based on exposure.

[NONINVASIVE BRAIN STIMULATION IN NEUROPSYCHIATRIC DISORDERS].

INTRODUCTION: Noninvasive brain stimulation is a growing field of treatment for many neuropsychiatric problems. In this review, several of the more common brain stimulation devices are presented. Specifically, we will review Transcranial Magnetic Stimulation (TMS), Transcranial Direct Current Stimulation (tDCS), Alternating Current Stimulation (ACS), Infrared Stimulation, Electroencephalography Neurofeedback (EEG-NF) and functional Magnetic Resonance Imagining Neurofeedback (fMRI-NF). We will outline some of the properties of these devices including the mechanism, side effect profile, using sham for research and major future developments.

[CAN POST-TRAUMATIC STRESS DISORDER BE PREVENTED WITH GLUCOCORTICOIDS?]

INTRODUCTION: Glucocorticoids (GCs) play a major role in orchestrating the complex physiological and behavioral reactions essential for the maintenance of homeostasis. These compounds enable the organism to prepare for, respond to and cope with the acute demands of physical and emotional stressors. The appropriate GC release, commensurate with stressor severity, enables the body to properly contain stress responses so as to promote recovery by rapidly restoring homeostasis. Indeed, inadequate GC release following stress not only delays recovery by disrupting biological homeostasis in the short run but can also interfere with the processing or interpretation of stressful information that results in long-term disruptions in memory integration. While conventional wisdom holds that people who develop post-traumatic stress disorder (PTSD) following exposure to extreme trauma might have sustained elevations in GCs, several studies have reported that lower cortisol levels in the acute aftermath of trauma are predictors for subsequent PTSD symptoms. Therefore, it is possible that the administration of exogenous cortisol immediately after exposure to a trauma might alter the trajectory of trauma exposure by promoting recovery. Our group has initiated a series of studies examining the role of GCs in susceptibility to "PTSD-like behaviors" in a well-validated animal model for PTSD. The results of these studies highlight the importance of an initial bolus of endogenous corticosteroids in the normative response to stress as a key to a return to homeostasis. Aberrations in the normative response play an equally pivotal role in determining long-term cyto-architecture, and also localized brain biomolecular and overall neuro-hormonal disruptions underlying the PTSD-like behavioral responses in animals, and may be related to the emotional and behavioral symptoms of PTSD in patients. The data provides initial evidence that a single dose of hydrocortisone administered in the acute aftermath of trauma promotes recovery while promoting enhanced synaptic plasticity and connectivity in the secondary prevention of PTSD. We suggested that exogenous hydrocortisone, if given during the 'window of opportunity' - right after the exposure and before consolidation of the traumatic memory - may promote the restoration of homeostasis by constraining central nervous system activity.

[BEHAVIORAL, PHYSIOLOGICAL AND MORPHOLOGICAL CHARACTERISTICS ASSOCIATED WITH POST-TRAUMATIC RESPONSE TO CONTINUOUS EXPOSURE VERSUS ALTERNATE EXPOSURE IN AN ANIMAL MODEL OF POST-TRAUMATIC STRESS DISORDER].

AIMS: The aim of this study was to approximate these conditions in an animal model of post-traumatic stress disorder (PTSD). More specifically, the neurobiological basis of these conditions, focusing on stress-related behavioral changes, HPA-axis and morphological were evaluated. The intention was to employ this well-validated, reproducible and reliable model for PTSD, to elicit data which will provide some guidance in the planning of a prospective study involving military personal. BACKGROUND: Combat personnel are exposed to significant stress and hardship, both physical and emotional, during their service and especially during active combat. Military forces are increasingly involved in conflicts involving nonmilitary or paramilitary adversaries in which they are exposed not to battles but to sporadic events, in what has come to be labeled "low intensity conflict". "Low intensity conflict" refers to a level of hostilities or use of military power that falls short of a full scale conventional or general war. These are characterized by brief periods of extreme stress and tangible danger interspersed by prolonged periods of siege. Whereas the potentially traumatizing effect of battle conditions is well documented, the risks of the sporadic highly stressful nature of "low intensity conflict" have not been studied. Furthermore, in recent years, soldiers commonly receive "relaxation periods" before re-engaging in battle. This new policy may possibly contradict the traditional treatment principles, focusing on "proximity" and "continuity" to the battlefield and its effects have not been studied. METHODS: Continuous and sporadic stresses, representing battlefield conditions, were induced in a validated rat animalmodel for PTSD and behavioral changes, hormonal levels and brain morphology were evaluated. RESULTS: Behavioral response, hormonal levels and brain morphological changes suggest that PTSD-like reactions were significantly higher in rats exposed to continuous stress compared to those exposed to intermittent stress and the control group. CONCLUSIONS: The results support the assumption that "refreshing" during warfare may reduce the incidence of PTSD. Since this study is based on an animal model, its conclusions should also be validated in human observation studies.

[SUPPRESSION OF A NON-TRAUMA-RELATED THREATENING THOUGHT AS AN AVOIDANCE STRATEGY IN POST-TRAUMATIC STRESS DISORDER PATIENTS].

AIMS: Our goal was to examine how suppression of nontrauma- related thoughts differs between PTSD patients and patients with non-PTSD anxiety disorder compared to a group of matched controls. BACKGROUND: Intrusive recollections of aspects of the traumatic event and its sequelae are at the core of the post-traumatic stress disorder (PTSD). People who have suffered a traumatic event may implement some form of avoidance coping strategies in order to deal with the unwanted memories that accompany them. Thought suppression refers to the conscious effort that is made in order NOT to think about a particular thought and is used to regulate affect. The effects of thought suppression on trauma survivors indicates that suppression of trauma related thoughts produces a rebound effect, increasing frequency of negative autobiographical memory recall and may result in the maintenance of PTSD symptoms. RESULTS: The results show that PTSD patients differed in their performance of purposeful suppression of non-traumarelated thoughts, and spent significantly longer time thinking about the target thought during suppression as compared to the control groups. The duration to disengage attention from any thought content was significantly longer in PTSD patients as compared to the anxiety group and controls. CONCLUSIONS: We suggest that PTSD patients demonstrated a mental control deficient in self-regulatory mechanisms involved in coping with threat. DISCUSSION: While PTSD patients used external objects in the room, the control groups used mental contents as distractors. When given suppression instructions, such as distraction thought, all groups demonstrated shorter duration to disengage attention, but the PTSD patients exhibited the significant advantage.

ß-Alanine supplemented diets enhance behavioral resilience to stress exposure in an animal model of PTSD.

This study investigated the effects of ß-alanine (BA) ingestion on the behavioral and neuroendocrine response of post-traumatic stress disorder (PTSD) in a murine model. Animals were fed a normal diet with or without (PL) BA supplementation (100 mg kg(-1)) for 30 days. Animals were then exposed to a predator-scent stress (PSS) or a sham (UNEX). Behaviors were evaluated using an elevated plus maze (EPM) and acoustic startle response (ASR) 7 days following exposure to the PSS. Corticosterone concentrations (CS), expression of brain-derived neurotrophic factor (BDNF), and brain carnosine concentrations were analyzed a day later. Animals in PSS+PL spent significantly less time in the open arms and in the number of entries in the EPM than PSS+BA, UNEX+BA, or UNEX+PL. Animals in PSS+BA had comparable scores to UNEX+BA. Anxiety index was higher (p < 0.05) in PSS+PL compared to PSS+BA or animals that were unexposed. ASR and freezing were greater (p < 0.05) in animals exposed to PSS compared to animals unexposed. CS expression was higher (p < 0.05) in animals exposed to PSS compared to unexposed animals. Brain carnosine concentrations in the hippocampus and other brain sections were significantly greater in animals supplemented with BA compared to PL. BDNF expression in the CA1 and DG subregions of the hippocampus was lower (p < 0.05) in animals exposed and fed a normal diet compared to animals exposed and supplemented with BA, or animals unexposed. In conclusion, BA supplementation in rats increased brain carnosine concentrations and resulted in a reduction in PTSD-like behavior, which may be mediated in part by maintaining BDNF expression in the hippocampus.

The influence of air-suspended particulate concentration on the incidence of suicide attempts and exacerbation of schizophrenia.

The main objective of this study was to evaluate the role of the concentration of solid air-suspended particles (SSP) in the incidence of mental disorders. The study is based on 1,871 cases, registered in the Beer-Sheva Mental Health Center (BS-MHC) at Ben-Gurion University (Israel) during a 16-month period from 2001 to 2002; 1,445 persons were hospitalized due to exacerbation of schizophrenia (ICD-10: F20-F29) and 426 after committing a suicide attempt using a variety of means as coded in the ICD-10 (ICD-10: X60-X84). Pearson and Spearman test correlations were used; the statistical significance was tested at p < 0.1. A significant correlation between variations of SSP number concentration (N C ) during eastern desert wind during early morning hours and number of suicide attempts, N SU , was found (ρ > 0.3, p < 0.05), whereas correlation between N C and N SU during western air streams (sea breeze) was not observed (p > 0.2). A trend towards positive correlation (ρ > 0.2, p < 0.1) between the N C and number of persons with exacerbation of schizophrenia as manifested in psychotic attack (N PS ) in periods with dominant eastern winds (4-9 am, local time) has been observed, while in the afternoon and evening hours (1-8 pm local time) with dominant western winds, N C and N PS are not correlated (p > 0.1). Obviously, concentration of SSP is not the one and only parameter of air pollution state determining meteorological-biological impact, involving incidence of mental disorders, although its role can scarcely be overstated. However, since it is one of the simplest measured parameters, it could be widely used and helpful in the daily struggle for human life comfort in semi-arid areas as well as urban and industrial surroundings, where air pollution reaches crucial values. This study may permit determination of the limits for different external factors, which do not overcome threshold values (without provoking avalanche situations), to single out the group of people at increased risk (with according degree of statistic probability), whose reactions to the weather violations can involve the outbreak of frustration points and prevent or alleviate detrimental mental effects.

[Psychiatric advance directives--medical models into psychiatric medicine].

Since the year 2005, in the field of general medicine, the legislature in Israel determined ways to implement medically advanced directives according to the power of the law. Different states in the world had implemented parallel legislation for patients who suffer from mental illness. Psychiatric Advance Directives is a legitimate document which is valid in Australia, New Zealand, Scotland, England and in 25 countries in the U.S.A. Psychiatric advance directives (PAD's) allow competent persons, through advance instructions, to state their preferences for future mental health treatment in the event of an incapacitating psychiatric crisis. Self Determination Theory, Self Care and Autonomy are dominant supportive approaches in the creation of Psychiatric Advance Directives. Research conducted on psychiatric advance directives shows positive potential benefits for mental health clients, therapists and psychiatrists. More research in that area must be conducted. Psychiatric advance directives are currently developed and implemented with the cooperation of the Tauber Foundation and the Beer Sheva Mental Health Center. This is the first step in learning of effective ways to use this intervention in Israel and change perceptions toward a positive connection between medical efficiency and client preferences.

Staff attitudes and perceptions towards the use of coercive measures in psychiatric patients.

The failure of efforts to significantly reduce the use of physical coercive measures (PCMs) in psychiatric hospitals remains a global concern. There is a gap in the understanding of staff's characteristics that may affect their attitudes and perceptions towards PCMs. This study used a cross-sectional design to examine the attitudes and perceptions of staff working at a mental health centre in Israel regarding the use of PCMs and to explore whether staff attitudes differed depending on their professional and demographic background. This study also sought to explore staff willingness to accept a policy of reducing the use of PCMs. The data were collected from 149 staff members (nurses, physicians, and auxiliary staff) working at mental health centre, using a questionnaire developed for this study. The findings indicate a low degree of support for use of PCMs among participants who were older, female, more qualified psychiatric nurses, with longer duration of employment, and those who have not participated in coercive intervention in the past year. The majority of the sample reported a low willingness to reduce the use of PCMs, and a lack of institutional support after participating in a coercive event. High hospital occupancy and insufficient staffing were perceived as contributing factors to coercive incidents. Therefore, availability of trained and experienced staff, elimination of organizational barriers, along with creating and maintaining a safe clinical environment should be a priority. Alternative non-coercive interventions should further be taught and used for managing aggressive and violent behaviour in the psychiatric clinical settings.

The influence of several changes in atmospheric states over semi-arid areas on the incidence of mental health disorders.

The incidence of suicide attempts [Deliberate Self Harm (DSH); ICD-10: X60-X84] and psychotic attacks (PsA; ICD-10, F20-F29) in association with atmospheric states, typical for areas close to big deserts, was analyzed. A retrospective study is based on the 4,325 cases of DSH and PsA registered in the Mental Health Center (MHC) of Ben-Gurion University (Be'er-Sheva, Israel) during 2001-2003. Pearson and Spearman test correlations were used; the statistical significance was tested at p < 0.1. The influence of temperature and humidity on suicide attempts (N(SU)) and psychotic attacks (N(PS)) was weakly pronounced (p > 0.1). Correlation coefficients between N(SU) and N(PS) and speed WS of westerly wind reaches 0.3 (p < 0.05), while their dependence on easterly WS was weaker (p > 0.09). Variations in easterly wind direction WD influence N(SU) and N(PS) values (p < 0.04), but no corresponding correlation with westerly winds was found (p > 0.3). Obviously ,in transition areas located between different regions ,the main role of air streams in meteorological-biological impact can scarcely be exaggerated. An unstable balance in the internal state of a weather-sensitive person is disturbed when the atmospheric state is changed by specific desert winds, which can provoke significant perturbations in meteorological parameters. Results indicate the importance of wind direction, defining mainly the atmospheric situation in semi-arid areas: changes in direction of the easterly wind influence N(SU) and N(PS), while changes in WS are important for mental health under westerly air streams. Obviously, N(SU) and N(PS) are more affected by the disturbance of weather from its normal state, for a given season, to which the local population is accustomed, than by absolute values of meteorological parameters.

Management of the suicidal patient in the era of defensive medicine: focus on suicide risk assessment and boundaries of responsibility.

Suicide is universal within the range of human behaviors and is not necessarily related to psychiatric morbidity, though it is considerably more prevalent among psychiatric patients. Considering the limitations of medical knowledge, psychiatrists cope with an unfounded and almost mythical perception of their ability to predict and prevent suicide. We set out to compose a position paper for the Israel Psychiatric Association (IPA) that clarifies expectations from psychiatrists when treating suicidal patients, focusing on risk assessment and boundaries of responsibility, in the era of defensive medicine. The final draft of the position paper was by consensus. The IPA Position Paper established the first standard of care concerning expectations from psychiatrists in Israel with regard to knowledge-based assessment of suicide risk, elucidation of the therapist's responsibility to the suicidal psychotic patient (defined by law) compared to patients with preserved reality testing, capacity for choice, and responsibility for their actions. Therapists will be judged for professional performance rather than outcomes and wisdom of hindsight. This paper may provide support for psychiatrists who, with clinical professionalism rather than extenuating considerations of defensive medicine, strive to save the lives of suicidal patients.

Mild Cognitive Impairment and Neurofeedback: A Randomized Controlled Trial.

Background and Objectives: Mild cognitive impairment (MCI) is often a precursor of dementia, and in particular of Alzheimer's Disease (AD) which is the most common cause of dementia. Individuals with amnestic MCI are several-fold more likely to develop AD than the general population. Therefore, MCI comprises a well-detectable, early stage time-point for therapeutic intervention and strategic prevention. Based on common electroencephalographical (EEG) pattern changes seen in individuals with MCI, we postulated that EEG-based neurofeedback could help improve the memory performance of patients with MCI. Memory performance is of particular importance in these patients, since memory decline is the most prominent symptom in most patients with MCI, and is the most predictive symptom for cognitive deterioration and the development of AD. Methods: In order to improve the memory performance of patients with MCI we used a system of EEG-based neurofeedback in an attempt to reverse alterations of the EEG that are known to be common in patients with MCI. Our protocol comprised the provision of positive feedback in order to enhance the activity level of the upper alpha band. Participants were divided to two groups receiving either neurofeedback training to enhance the upper alpha frequency (Experimental group) or random feedbacks (Sham group) Results: We witnessed a significant improvement in memory performance in subjects in the experimental group compared to those in the sham group. This improvement was maintained for at least 1 month. Conclusions: Neurofeedback may be a promising and affordable novel approach for treating the decline in memory witnessed in patients with MCI.

Significance of the orexinergic system in modulating stress-related responses in an animal model of post-traumatic stress disorder.

Converging evidence indicates that orexins (ORXs), the regulatory neuropeptides, are implicated in anxiety- and depression-related behaviors via the modulation of neuroendocrine, serotonergic, and noradrenergic systems. This study evaluated the role of the orexinergic system in stress-associated physiological responses in a controlled prospective animal model. The pattern and time course of activation of hypothalamic ORX neurons in response to predator-scent stress (PSS) were examined using c-Fos as a marker for neuronal activity. The relationship between the behavioral response pattern 7 days post-exposure and expressions of ORXs was evaluated. We also investigated the effects of intracerebroventricular microinfusion of ORX-A or almorexant (ORX-A/B receptor antagonist) on behavioral responses 7 days following PSS exposure. Hypothalamic levels of ORX-A, neuropeptide Y (NPY), and brain-derived neurotrophic factor (BDNF) were assessed. Compared with rats whose behaviors were extremely disrupted (post-traumatic stress disorder [PTSD]-phenotype), those whose behaviors were minimally selectively disrupted displayed significantly upregulated ORX-A and ORX-B levels in the hypothalamic nuclei. Intracerebroventricular microinfusion of ORX-A before PSS reduced the prevalence of the PTSD phenotype compared with that of artificial cerebrospinal fluid or almorexant, and rats treated with almorexant displayed a higher prevalence of the PTSD phenotype than did untreated rats. Activated ORX neurons led to upregulated expressions of BDNF and NPY, which might provide an additional regulatory mechanism for the modulation of adaptive stress responses. The study indicates that the activated ORX system might promote adaptive responses to PSS probably via stimulation of BDNF and NPY secretion, and early intervention with ORX-A reduces the prevalence of the PTSD phenotype and increases the prevalence of adaptive phenotypes. The findings provide some insights into the mechanisms underlying the involvement of the ORX system in stress-related disorders.

Role of Endogenous and Exogenous Corticosterone on Behavioral and Cognitive Responses to Low-Pressure Blast Wave Exposure.

The complex interactions and overlapping symptoms of comorbid post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) induced by an explosive blast wave have become a focus of attention in recent years, making clinical distinction and effective intervention difficult. Because dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is thought to underlie trauma-related (psycho)pathology, we evaluated both the endogenous corticosterone response and the efficacy of exogenous hydrocortisone treatment provided shortly after blast exposure. We employed a controlled experimental blast-wave paradigm in which unanesthetized animals were exposed to visual, auditory, olfactory, and tactile effects of an explosive blast wave produced by exploding a thin copper wire. Endogenous corticosterone concentrations were evaluated at different time points (before, and 3 h, 5 h and 17 days) after blast exposure. Subsequently, the efficacy of exogenous hydrocortisone (25 mg/kg-1 or 125 mg/kg-1) injected intraperitoneally 1 h after exposure was compared with that of a similarly timed saline injection. Validated cognitive and behavioral tests were used to assess both PTSD and mTBI phenotypes on days 7-14 following the blast. Retrospective analysis revealed that animals demonstrating the PTSD phenotype exhibited a significantly blunted endogenous corticosterone response to the blast compared with all other groups. Moreover, a single 125 mg/kg-1 dose of hydrocortisone administered 1 h after exposure significantly reduced the occurrence of the PTSD phenotype. Hydrocortisone treatment did not have a similar effect on the mTBI phenotype. Results of this study indicate that an inadequate corticosteroid response following blast exposure increases risk for PTSD phenotype, and corticosteroid treatment is a potential clinical intervention for attenuating PTSD. The differences in patterns of physiological and therapeutic response between PTSD and mTBI phenotypes lend credence to the retrospective behavioral and cognitive classification criteria we designed, and is in keeping with the assumption that mTBI and PTSD phenotypes may reflect distinct underlying biological and clinical profiles.

The immediate early gene Arc is associated with behavioral resilience to stress exposure in an animal model of posttraumatic stress disorder.

Mechanisms involved in adaptative and maladaptive changes in neural plasticity and synaptic efficacy in various brain areas are pivotal to understanding the physiology of the response to stress and the pathophysiology of posttraumatic stress disorder (PTSD). Activity-regulated cytoskeletal-associated protein (Arc) is an effector immediate early gene (IEG) which has direct effects on intracellular homeostatic functions. Increased expression of Arc has been associated with increased neuronal activity and with consolidation of long-term memory. It may thus play an important role in mediating experience-induced reorganization and/or development of synaptic connections. This study sought to characterize the pattern of expression of mRNA for the Arc gene in selected brain areas of test subjects classified according to their individual pattern of behavioral response to a stressor, correlated with circulating levels of corticosterone (as a physiological marker of stress response). The hippocampal CA1 and CA3 subregions of individuals whose behavior was minimally or partially disrupted in response to predator scent stress demonstrated significantly increased levels of mRNA for Arc, compared to unexposed controls. The group whose behavior was severely disrupted demonstrated no such upregulation. Consistent with the hypothesis that the Arc gene has a promoting effect on neuronal function and/or structural changes, the lack of Arc expression in the behaviorally and physiologically more severely affected individuals raises the possibility that Arc may be associated with resilience and/or recovery after stress exposure.

Brief post-stressor treatment with pregabalin in an animal model for PTSD: short-term anxiolytic effects without long-term anxiogenic effect.

BACKGROUND: The short- and long-term behavioral effects of a brief course of pregabalin, an antiepileptic structural analogue of alpha-aminobyturic acid with analgesic and anxiolytic effects, were assessed in an animal model of post-traumatic stress disorder (PTSD). METHOD: Two-hundred thirty-three adult male Sprague-Dawley rats were employed. Behavioral responses to traumatic stress exposure (predator urine scent) were assessed immediately after (1 h) and 30 days after treatment with saline or pregabalin (at doses of 30, 100 and 300 mg/kg) in terms of behavior in the elevated plus maze (EPM) and the acoustic startle response (ASR) paradigms. At day 31 the freezing response to a trauma cue (clean cat litter) was assessed. The same treatment regimen initiated at day 7 was assessed at day 30 and in response to the trauma cue on day 31 in a separate experiment. RESULTS: In the short term, doses of 100 mg/kg and 300 mg/kg of pregabalin effectively attenuated anxiety-like behaviors. In the longer-term, pregabalin did not attenuate the onset of PTSD-like behaviors or the prevalence rates of severe cue-responses, for either the immediate or the delayed treatment regimens. CONCLUSION: Pregabalin may present an alternative compound for acute anxiolytic treatment after exposure to trauma, but has no long-term protective/preventive effects.

Protein synthesis inhibition before or after stress exposure results in divergent endocrine and BDNF responses disassociated from behavioral responses.

This study aimed to assess the effects of anisomycin, a protein synthesis inhibitor, on behavioral responses, brain-derived neurotrophic factor (BDNF) and TrkB mRNA levels, and circulating corticosterone in rats-when administered before or after initial exposure to a predator scent stress stimulus. Magnitude of changes in prevalence of anxiety-like behaviors on the elevated plus-maze and exaggerated startle reaction as well as corticosterone levels and mRNA BDNF and TrkB were compared in rats exposed to predator stress, microinjected with anisomycin before or after stress exposure. Administration of anisomycin before or after stress exposure reduced anxiety-like behavior in the elevated plus-maze and reduced the mean startle amplitude 7 days postexposure. Although the behavioral responses were similar when anisomycin was microinjected before or after stress exposure, the levels of mRNAs for BDNF and TrkB, which play a role in modulation of synaptic plasticity and the consolidation process, showed varying responses.

Elevated serum homocysteine levels in male patients with PTSD.

It has been suggested that an elevated serum or plasma homocysteine level may be a risk factor for neuropsychiatric conditions such as Alzheimer's disease, schizophrenia, and depression. Because depression is closely related to anxiety disorders, and because it has been suggested that stress may be associated with an elevated homocysteine level, we studied whether serum homocysteine levels are elevated in patients with posttraumatic stress disorder (PTSD). Total serum homocysteine levels in 28 male patients with PTSD were compared to those of 223 healthy controls. The effect of PTSD on the serum homocysteine level was significant (F=42.96, P<.0001). In a regression model for the PTSD patients, the duration of PTSD was found to predict serum homocysteine levels (t=2.228, P=.035). Our results suggest that elevated levels of homocysteine in male patients with PTSD may be related to pathophysiological aspects associated with the chronicity of this disorder.