The Emerging Field of Psychedelic Psychotherapy.

PURPOSE OF REVIEW: Few treatments are available for patients with mood disorders or post-traumatic stress disorder (PTSD) who have already failed multiple interventions. After several decades when research into psychedelics was effectively halted by federal legislation, the past several years have shown the re-emergence of thoughtful investigations studying the utility of compounds such as 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin. RECENT FINDINGS: Several studies have coupled the safe administration of psychedelic compounds in a controlled environment after several hours of preparation of study participants and followed by multiple sessions to integrate the psychedelic experience. The improvement participants experience appear related to the often profound perspective changes experienced and seem unlike the improvements seen in the currently available care paradigms. Studies cited include treatment resistant depression, end of life despair, and PTSD. Psychedelic psychotherapy, a unique remarriage of biological therapy and psychotherapy, has the potential to transform mental health care.

Inescapable footshocks induce molecular changes in the prefrontal cortex of rats in an amyloid-beta-42 model of Alzheimer's disease.

Alzheimer's disease (AD) affects several brain areas, including the prefrontal cortex (PFC) involved in execution, working memory, and fear extinction. Despite these critical roles, the PFC is understudied in AD pathology. People with post-traumatic stress disorder (PTSD) have twice the risk of developing AD, and the underlying mechanisms linking these two diseases are less understood. Here, we investigated the effect of footshock stress on behavioural vis-a-vis molecular changes in the PFC of an amyloid-beta (Aß)-42 lesion rat model of AD. Trauma-like conditions were induced by exposing the animals to several footshocks. AD-like condition was induced via intra-hippocampal injection of Aß-42 peptide. Following Aß-42 injections, animals were tested for behavioural changes using the Open Field Test (OFT) and Y-maze test. The PFC was later harvested for neurochemical analyses. Our results showed an interactive effect of footshocks and Aß-42 lesion on: reduced percentage alternation in the Y-maze test, suggesting memory impairment; reduced number of line crosses and time spent in the centre square of the OFT, indicating anxiogenic responses. Similarly, there was an interactive effect of footshocks and Aß-42 lesion on: increased FK506 binding protein 51 (FKBP5) expression, which can be associated with stress-induced anxiogenic behaviours; and increased neuronal apoptosis in the PFC of the animals. In addition, footshocks, as well as Aß-42 lesion, reduced superoxide dismutase levels and Bridging Integrator-1 (BIN1) expression in the PFC of the animals, which can be linked to the observed memory impairment. In conclusion, our findings indicate that footshocks exaggerate PFC-associated behavioural and molecular changes induced by an AD-like pathology.

Effects of Marijuana Use in Patients with Orthopaedic Trauma.

➢: The use of cannabis and cannabis-related products has increased dramatically in the last 2 decades. As states continue to legalize cannabis products, it is important for surgeons to understand the effects they may have on patients who have sustained orthopaedic trauma. ➢: Cannabinoids have been shown to decrease the severity of certain symptoms related to traumatic brain injury as well as posttraumatic stress disorder. ➢: Cannabinoids can modulate the body's endocannabinoid system, which can play an important role in bone homeostasis. Activation of cannabinoid receptors has been shown to be bone-protective in adults. ➢: Venous thromboembolism is a major concern for trauma patients. Cannabis use has been linked to overall increased rates of venous thromboembolism events. ➢: Literature regarding human-based cannabis studies is sparse; however, the growing field is opening new opportunities for research of this topic.

Activation of NPY receptor subtype 1 by [D-His26]NPY is sufficient to prevent development of anxiety and depressive like effects in the single prolonged stress rodent model of PTSD.

The neuropeptide Y (NPY) system plays an important role in mediating resilience to the harmful effect of stress in post-traumatic stress disorder (PTSD). It can mediate its effects via several G-protein coupled receptors: Y1R, Y2R, Y4R and Y5R. To investigate the role of individual NPY receptors in the resilience effects of NPY to traumatic stress, intranasal infusion of either Y1R agonists [D-His26]NPY, [Leu31Pro34]NPY, Y2R agonist NPY (3-36) or NPY were administered to male Sprague-Dawley rats immediately following the last stressor of the single prolonged stress (SPS) protocol, a widely used PTSD animal model. After 7 or 14 days, effects of the treatments were measured on the elevated plus maze (EPM) for anxiety, in forced swim test (FST) for development of depressive-like or re-experiencing behavior, in social interaction (SI) test for impaired social behavior, and acoustic startle response (ASR) for hyperarousal. [D-His26]NPY, but not [Leu31Pro34]NPY nor NPY (3-36) Y2R, was effective in preventing the SPS-elicited development of anxiety. Y1R, but not Y2R agonists prevented development of depressive- feature on FST, with [D-His26]NPY superior to NPY. The results demonstrate that [D-His26]NPY was sufficient to prevent development of anxiety, social impairment and depressive symptoms, and has promise as an early intervention therapy following traumatic stress.

Ketamine Administration During Hospitalization Is Not Associated With Posttraumatic Stress Disorder Outcomes in Military Combat Casualties: A Matched Cohort Study.

BACKGROUND: Ketamine is routinely used within the context of combat casualty care. Despite early concerns that ketamine administration may be associated with elevated risk of posttraumatic stress disorder (PTSD), more recent evidence suggests no relationship. Because PTSD occurs with regular frequency in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Service Members (SMs) and combat-related injuries are associated with higher likelihood of PTSD, it is important to investigate the relationship between ketamine exposure during inpatient medical and surgical care and PTSD symptoms in OIF/OEF SMs. METHODS: Medical record data from OIF/OEF SMs medically evacuated from combat (N = 1158) included demographic characteristics, injury severity, body areas injured, and PTSD Checklist (PCL) scores. The primary analysis assessed the association between ketamine versus nonketamine exposure on positive PTSD screen (logistic regression) and PCL scores (linear regression) after using 1:1 propensity score matching to adjust for available potential confounding variables. Because there were 2 primary outcomes, the binary positive PTSD screen (yes/no) and continuous PCL score, the significance level was set at P ≤ .025. In sensitivity analyses, propensity scores were used to match ketamine to nonketamine records in a 1:4 ratio, as well as to conduct inverse probability treatment weighting (IPTW). Regressions examining the relationship between ketamine exposure and outcomes were repeated for unconditional, 1:4 matching, and IPTW models. RESULTS: In the sample, 107 received ketamine and 1051 did not. In the logistic regression, the probability of a positive PTSD screen was not significantly different between ketamine versus nonketamine patients (odds ratio [OR] = 1.28; 95% confidence interval [CI], 0.48-3.47; P = .62). In the linear regression, PCL scores were not significantly different between ketamine versus nonketamine patients (mean difference = 1.98 [95% CI, -0.99 to 4.96]; P = .19). The results were consistent in the unconditional, 1:4 matching, and IPTW models. CONCLUSIONS: No differences in PTSD screening risk or symptom levels between ketamine exposed and nonexposed were found. Given the small sample size, wide CIs of the effects, and additional confounds inherent to retrospective studies, future studies are needed to examine the complex relationships between ketamine and psychological symptoms.

Long-Term Clinical and Neuronuclear Imaging Sequelae of Cancer Therapy, Trauma, and Brain Injury.

Neuronuclear imaging has been used for several decades in the study of primary neurodegenerative conditions, such as dementia and parkinsonian syndromes, both for research and for clinical purposes. There has been a relative paucity of applications of neuronuclear imaging to evaluate nonneurodegenerative conditions that can also have long-term effects on cognition and function. This article summarizes clinical and imaging aspects of 3 such conditions that have garnered considerable attention in recent years: cancer- and chemotherapy-related cognitive impairment, posttraumatic stress disorder, and traumatic brain injury. Further, we describe current research using neuroimaging tools aimed to better understand the relationships between the clinical presentations and brain structure and function in these conditions.

OX1R ANTAGONIST SB408124 ACTION AND EXTRAHYPOTHALAMIC CRF IN RATS AFTER PSYCHOTRAUMATIC EXPOSURE.

Corticoliberin (CRF) isn't only regulates hypothalamic-pituitary-adrenal axis activity, but also functions as a neurotransmitter in extrahypothalamic brain regions like amygdala, implicated in the emotional responses to stress. The CRF system provides an input to orexin neurons and can modulate the activity of orexinergic neurons in stress response. Some data showed the role of orexin-A in extinction of aversive memory. The orexin system was shown to participate in stress-induced behavior connected with the extended amygdala structures, like central nucleus of the amygdala. The objective was to study the effects of orexin-A antagonist SB-408124 in rats after predator-induced stress using behavioral tests and its effects on CRF level in amygdala. In this study 30 male Wistar rats were used. The animals received an intranasally selective antagonist of Orexin receptor 1 type SB-408124. Posttraumatic stress disorder was modelled by single predator exposure. A group of 10-12 rats were placed in a terrarium with an indian python. 7 days after exposure to the predator, the behavior of animals was tested in the Open Field and Elevated Cross-Maze tests. Free motor activity of animals was studied in the "open field" test. To assess stress, we used the "elevated cross-maze " test. CRF concentrations in brain structures were measured by solid-phase ELISA using the Corticotropin Releasing Factor (CRF) test system. In the group of stressed rats receiving intranasally SB-408124, the time of stay in the light arm was restored, but did not reach the control values, the number of runs was restored to the control level, and the number of grooming acts increased in comparison with both the control group and the stressed animals. In the "open field" in the group of stressed rats receiving saline solution, the number of sniffs and rearing were decreased, but the number of peeks into holes was increased. In the group of stressed rats receiving SB-408124 20 µg intranasally, the number of sniffs was increased and the number of hole peeking decreased in comparison with the stressed rats receiving saline solution. The CRF level in the homogenates of amygdala in stressed rats was lower (0.44±0.07 ng/mg protein vs. 0.61±0.01 ng/mg in the control group). In the intranasal administration of SB408124 group this decrease was not recorded and the CRF level in the amygdala was 0.57±0.01 pg/mg protein. Orexin A antagonist SB-408124 reduced anxiety after psychotraumatic exposure. Predator induced acute psychotraumatic exposure decrease CRF level in the rat's amygdala. Intranasal administration of selective orexin 1 receptor antagonist SB408124 restored it closely to normal and has an anxiolytic effect on animal behaviour.

Cannabis and mental illness: a review.

With the increasing push to legalize cannabis in Western nations, there is a need to gage the potential impact of this policy change on vulnerable populations, such as those with mental illness, including schizophrenia, mood, and anxiety disorders. This is particularly important as there are strong motives in these individuals to seek short-term reward (e.g., "getting high"). Nonetheless, data to support the beneficial effects of cannabis use in psychiatric populations are limited, and potential harms in patients with psychotic and mood disorders have been increasingly documented. This article reviews the effects of cannabis in people with mental illness. Then, we provide a reconciliation of the addiction vulnerability and allostatic hypotheses to explain co-morbidity addiction in mentally ill cannabis users, as well as to further aid in developing a rational framework for the assessment and treatment of problematic cannabis use in these patients.

A Review of the Neurobiological Basis of Trauma-Related Dissociation and Its Relation to Cannabinoid- and Opioid-Mediated Stress Response: a Transdiagnostic, Translational Approach.

Dissociative experiences have been associated with increased disease severity, chronicity, and, in some cases, reduced treatment response across trauma-related and other psychiatric disorders. A better understanding of the neurobiological mechanisms through which dissociative experiences occur may assist in identifying novel pharmacological and non-pharmacological treatment approaches. Here, we review emerging work on the dissociative subtype of posttraumatic stress disorder (PTSD), and other trauma-related disorders providing evidence for two related overarching neurobiological models of dissociation, the defense cascade model of dissociation and Mobb's threat detection model. In particular, we review neuroimaging studies highlighting alterations in functional connectivity of key brain regions associated with these models, including connectivity between the prefrontal cortex, the amygdala and its complexes, the insula, and the periaqueductal gray. Work implicating the kappa-opioid and endocannabinoid systems in trauma-related dissociative experiences is also reviewed. Finally, we hypothesize mechanisms by which pharmacological modulation of these neurochemical systems may serve as promising transdiagnostic treatment modalities for individuals experiencing clinically significant levels of dissociation. Specifically, whereas kappa-opioid receptor antagonists may serve as a pharmacological vehicle for the selective targeting of dissociative symptoms and associated emotion overmodulation in the dissociative subtype of posttraumatic stress disorder and transdiagnostically, modulation of the endocannabinoid system may reduce symptoms associated with emotional undermodulation of the fight or flight components of the defense cascade model.

Benzodiazepine Use and Neuropsychiatric Outcomes in the ICU: A Systematic Review.

OBJECTIVES: A systematic assessment of the role of benzodiazepine use during ICU stay as a risk factor for neuropsychiatric outcomes during and after ICU admission. DATA SOURCES: PubMed/Medline, EMBASE, The Cochrane Library, CINAHL, and PsychINFO. STUDY SELECTION: Databases were searched independently by two reviewers for studies in adult (former) ICU patients, reporting benzodiazepine use, and neuropsychiatric outcomes of delirium, posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction. DATA EXTRACTION: Data were extracted using a piloted extraction form; methodological quality of eligible studies was assessed by applying the Quality Index checklist. DATA SYNTHESIS: Forty-nine of 3,066 unique studies identified were included. Thirty-five studies reported on neuropsychiatric outcome during hospitalization, 12 after discharge, and two at both time points. Twenty-four studies identified benzodiazepine use as a risk factor for delirium, whereas seven studies on delirium or related outcomes did not; six studies reported mixed findings. Studies with high methodological quality generally found benzodiazepine use to be a risk factor for the development of delirium. Five studies reported an association between benzodiazepine use and symptoms of posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction after ICU admission; five studies reported mixed findings, and in four studies, no association was found. No association was found with methodological quality and sample size for these findings. Meta-analysis was not feasible due to major differences in study methods. CONCLUSIONS: The majority of included studies indicated that benzodiazepine use in the ICU is associated with delirium, symptoms of posttraumatic stress disorder, anxiety, depression, and cognitive dysfunction. Future well-designed studies and randomized controlled trials are necessary to rule out confounding by indication.

Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA).

RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD, particularly in treatment-resistant patients. However, given MDMA's broad pharmacological profile, further investigation is warranted before moving to a complex clinical population. OBJECTIVES: We aimed to inform clinical research by providing a translational model of MDMA's effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction. METHODS: We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training. RESULTS: MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA's effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA's effect by 5-HTT inhibition also downregulated 5-HT2A-mediated behavior, and 5-HT2A antagonism disrupted MDMA's effect on extinction. CONCLUSIONS: We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.

Predator odor evokes sex-independent stress responses in male and female Wistar rats and reduces phosphorylation of cyclic-adenosine monophosphate response element binding protein in the male, but not the female hippocampus.

Post-traumatic stress disorder (PTSD) is characterized by memory disturbances following trauma. Acute predator threat has emerged as an ethological model of PTSD, yet the effects of predator odor on signaling cascades associated with long-term memory remain poorly understood. In this study, we exposed male and female Wistar rats to the synthetic predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to assess behavioral and physiological responses as well as rapid modulation of signal transduction cascades associated with learning and memory in the male and female hippocampus. During exposure to TMT in the homecage, both male and female animals displayed robust immobility, avoidance, and altered activity as a function of time. Physiologically, TMT exposure increased circulating corticosterone and blood glucose in both male and female rodents, suggesting that TMT evokes sex-independent behavioral and physiological responses. With respect to signal transduction, TMT exposure rapidly reduced phosphorylation of cyclic-adenosine monophosphate response element binding protein (CREB) in the male, but not the female hippocampus. Furthermore, TMT exposure reduced phosphorylation of extracellular signal-regulated kinase 1/2 and increased nuclear expression of the synapto-nuclear messenger protein Jacob in the male hippocampus, consistent with activation of the CREB shut-off pathway. In a follow-up behavioral experiment, post-training exposure to TMT did not affect spatial water maze performance of male rats. However, male rats re-introduced to the context in which TMT had previously been presented displayed avoidance and hyperactivity, but not freezing behavior or elevated corticosterone responses, suggesting that TMT exposure supports a form of contextual conditioning which is not characterized by immobility. Taken together, our findings suggest that TMT evokes similar behavioral and physiological responses in male and female Wistar rats, but affects distinct signaling cascades in the male and female hippocampus which may contribute to behavioral disruptions associated with predator exposure.

Predictors of severe psychological distress trajectory after nuclear disaster: evidence from the Fukushima Health Management Survey.

OBJECTIVES: The Fukushima Daiichi Nuclear Power Plant accident, which occurred after the Great East Japan Earthquake and Tsunami in March 2011, may have a considerable long-term impact on the lives of area residents. The aims of this study were to determine the trajectories of psychological distress using 3-year consecutive data, and to find predictive factors of severe distress that may also prove useful for public health intervention. METHODS: Data were obtained on 12 371 residents who were registered in the municipalities categorised as complete evacuation areas for 3 years after the disaster and who completed an assessment in each of the 3 years. RESULTS: Using group-based trajectory modelling, we identified four trajectory patterns distinguished by the levels of psychological distress, which gradually improved over time in all trajectories. Subjective sleep insufficiency, problem drinking, poor social support and perception of radiation risk 3 years after the accident were associated with the severity of psychological distress, according to the multivariate analysis. CONCLUSIONS: The identified factors may be useful for community-based mental healthcare over the long term following a nuclear disaster.

Benzodiazepine use associated with co-morbid post-traumatic stress syndrome and depression in older adults seeking services in general medical settings.

BACKGROUND: Benzodiazepines (BZD) should be limited in older adults. This study aimed to determine the association between BZD use and the presence of a probable post-traumatic stress syndrome (PTSS) and whether this association is dependent on gender and co-morbid physical and mental conditions. METHODS: Data were retained from the Étude sur la Santé des Aînés (ESA) - Services study (2011-2013) and included 1,453 older adults (≥65 years) who completed a face to face at-home interview, who were covered under Quebec's public drug insurance plan, and had given permission to access their Régie de l'Assurance Maladie du Québec (RAMQ) medical and pharmaceutical services data. The presence of a PTSS was measured using the Impact of Event Scale-Revised (IES-R). The use of BZD and antidepressants in the year prior to interview was ascertained from data reported in the RAMQ drug registry. The presence of depression and an anxiety disorder was assessed with the ESA-Questionnaire which was based on DSM-5 criteria. The interaction between PTSS and gender, depression, anxiety, and multi-morbidity was also assessed. RESULTS: The prevalence of PTSS and BZD use reached 4.5% and 31.2%. Participants with PTSS were 1.9 (95% CI = 1.1-3.2) times more likely to use BZD. The presence of depression had a negative impact on the association between BZD use and PTSS (p = 0.04). CONCLUSION: The use of BZD in older adults with PTSS is still prevalent today. Differences in benzodiazepine prescribing practices for more complex co-morbid psychiatric cases needs to be further studied.

Impact of Sedation on Cognitive Function in Mechanically Ventilated Patients.

The practice of sedation dosing strategy in mechanically ventilated patient has a profound effect on cognitive function. We conducted a comprehensive review of outcome of sedation on mental health function in critically ill patients on mechanical ventilation in the intensive care unit (ICU). We specifically evaluated current sedative dosing strategy and the development of delirium, post-traumatic stress disorders (PTSDs) and agitation. Based on this review, heavy dosing sedation strategy with benzodiazepines contributes to cognitive dysfunction. However, outcome for mental health dysfunction is mixed in regard to newer sedatives agents such as dexmedetomidine and propofol. Moreover, studies that examine the impact of sedatives for persistence of PTSD/delirium and its long-term cognitive and functional outcomes for post-ICU patients are frequently underpowered. Most studies suffer from low sample sizes and methodological variations. Therefore, larger randomized controlled trials are needed to properly assess the impact of sedation dosing strategy on cognitive function.

Prescription Stimulants and PTSD Among U.S. Military Service Members.

Posttraumatic stress disorder (PTSD) is a prevalent condition among military service members and civilians who have experienced traumatic events. Stimulant use has been postulated to increase the risk of incident PTSD; however, research in this area is lacking. In this study, the association between receipt of prescription stimulants and PTSD was examined in a secondary analysis among active duty U.S. military members (n = 25,971), participating in the Millennium Cohort Study, who completed a baseline (2001-2003) and two follow-up surveys (between 2004-2008). Prescription stimulant data were obtained from the military Pharmacy Data Transaction Service. PTSD was assessed using the PTSD Checklist-Civilian Version and incident PTSD was defined as meeting the criteria at follow-up among those who did not have a history of PTSD at baseline. Overall, 1,215 (4.7%) persons developed new-onset PTSD during follow-up. Receipt of prescription stimulants were significantly associated with incident PTSD, hazard ratio = 5.09, 95% confidence interval [3.05, 8.50], after adjusting for sociodemographic factors, military characteristics, attention-deficit/hyperactivity disorder, baseline mental and physical health status, deployment experiences, and physical/sexual trauma. Findings suggested that prescription stimulants are associated with incident PTSD among military personnel; these data may inform the underlying pathogenesis of and preventive strategies for PTSD.

Methamphetamine-induced behavioral sensitization in a rodent model of posttraumatic stress disorder.

BACKGROUND: Single prolonged stress (SPS) is a rodent model of posttraumatic stress disorder (PTSD)-like characteristics. Given that PTSD is frequently comorbid with substance abuse and dependence, including methamphetamine (METH), the current study sought to investigate the effects of SPS on METH-induced behavioral sensitization. METHODS: In experiment 1, Sprague-Dawley rats were subject to SPS or control treatment and subsequently tested across four sessions of an escalating METH dosing paradigm. METH was injected (i.p.) in escalating doses (0, 0.032, 0.1, 0.32, 1.0, and 3.2mg/kg; dissolved in saline) every 15min and ambulatory activity was recorded. In experiment 2, SPS and control treated rats were injected (i.p.) with either saline or METH (5mg/kg) for five consecutive daily sessions and tested for stereotypy as well as ambulatory activity. Two days later, all animals were injected with a challenge dose of METH (2.5mg/kg) and again tested for activity. RESULTS: No differences in the acute response to METH were observed between SPS and controls. SPS enhanced METH induced ambulatory activity across sessions, compared to controls. METH-induced stereotypy increased across sessions, indicative of behavioral sensitization; however, SPS attenuated, not enhanced, this effect suggesting that SPS may prevent the development of stereotypy sensitization. CONCLUSIONS: Collectively, results show that SPS increases repeated METH-induced ambulatory activity while preventing the transition across sessions from ambulatory activity to stereotypy. These findings suggest that SPS alters drug-induced neuroplasticity associated with behavioral sensitization to METH, which may reflect an effect on the shared neurocircuitry underlying PTSD and substance dependence.

Competing interests declared: early interventions and long-term psychological outcomes.

Survivors of motor vehicle accidents and/or survivors of critical care unit admission are at increased risk of developing post-traumatic reactions such as post-traumatic stress disorder, depression and anxiety. Examining the possible risk factors for the development of these disorders must consider pre-traumatic, peri-traumatic and post-traumatic factors and must do so across domains relating to the trauma, the person and their circumstances. The present study has found propofol administration in the first 72 hours post motor vehicle accident to confer a higher risk for full or partial post-traumatic stress disorder at 6 months. This study highlights concerns that treatment needed acutely post injury may impact adversely on long-term outcome, albeit in a different domain-the psychological.

Potential impact of propofol immediately after motor vehicle accident on later symptoms of posttraumatic stress disorder at 6-month follow up: a retrospective cohort study.

INTRODUCTION: Critically injured patients are at risk of developing posttraumatic stress disorder (PTSD). Propofol was recently reported to enhance fear memory consolidation retrospectively. Thus, we investigated here whether administration of propofol within 72 h of a motor vehicle accident (MVA) affects the subsequent development of PTSD symptoms. METHODS: We examined data obtained from a prospective cohort study of MVA-related injured patients, admitted to the intensive care unit of a general hospital. We investigated the effect of propofol administration within 72 h of MVA on outcome. Primary outcome was diagnosis of full or partial PTSD as determined by the Clinician-Administered PTSD Scale (CAPS) at 6 months. Secondary outcomes were diagnosis of full or partial PTSD at 1 month and CAPS score indicating PTSD at 1 and 6 months. Multivariate analysis was conducted adjusting for being female, age, injury severity score (ISS), and administration of ketamine or midazolam within 72 h of MVA. RESULTS: Among 300 patients recruited (mean ISS, 8.0; median Glasgow Coma Scale (GCS) score, 15.0; age, 18 to 69 years), propofol administration showed a higher risk for full or partial PTSD as determined by CAPS at 6 months (odds ratio = 6.13, 95% confidence interval (CI): 1.57 to 23.85, P = 0.009) and at 1 month (odds ratio = 1.31, 95% CI: 0.41 to 4.23, P = 0.647) in the multivariate logistic regression. Multivariate regression analysis showed a trend toward adverse effects of propofol on PTSD symptom development at 6 months after MVA (ß = 4.08, 95% CI: -0.49 to 8.64, P = 0.080), but not at 1 month after MVA (ß = -0.42, 95% CI: -6.34 to 5.51, P = 0.890). CONCLUSIONS: These findings suggest that using propofol in the acute phase after MVA might be associated with the development of PTSD symptoms 6 months later. However, since the design of this study was retrospective, these findings should be interpreted cautiously and further study is warranted.