Efficacy and Safety of Mifepristone in the Treatment of Male US Veterans With Posttraumatic Stress Disorder: A Phase 2a Randomized Clinical Trial.

Importance: To date, no psychopharmacologic treatment has been found to be uniformly effective in veterans with posttraumatic stress disorder (PTSD); novel targets and approaches are needed to treat this disabling disorder. Objective: To examine whether treatment with the glucocorticoid receptor antagonist mifepristone yields a signal for clinical efficacy in male veterans with PTSD. Design, Setting, and Participants: This phase 2a, double-blind, parallel-group randomized clinical trial was conducted from November 19, 2012 (accrual started), through November 16, 2016 (final follow-up), within the US Department of Veterans Affairs. Participants were male veterans with chronic PTSD and a screening Clinician-Administered PTSD Scale score of 50 or higher. A total of 181 veterans consented to participation. Statistical analysis was conducted between August 2014 and May 2017. Interventions: Participants were randomized in a 1:1 ratio to mifepristone (600 mg) or matched placebo taken orally for 7 days. Main Outcomes and Measures: The clinical outcome was whether a veteran achieved a clinical response status (a reduction of ≥30% of total Clinician-Administered PTSD Scale score from baseline) at 4- and 12-week follow-up. On the basis of a binary statistical selection rule, a difference in the proportion of treatment vs control group responders of 15% would be a clinically relevant difference. Self-report measures of PTSD and associated symptoms were also obtained. Neuroendocrine outcomes and plasma levels of mifepristone were measured. Safety was assessed throughout the study. The primary analysis was based on a multiple imputation technique to address missing outcome data; thus, some participant numbers may not appear as whole numbers. Results: A total of 81 veterans were enrolled and randomized. Excluding 1 participant randomized in error, 80 were included in the modified intention-to-treat analysis (41 randomized to mifepristone and 39 to placebo). The mean (SD) age was 43.1 (13.7) years. A total of 15.6 (38.1%) in the mifepristone group and 12.1 (31.1%) in the placebo group were clinical responders at 4 weeks in the analysis using the multiple imputation technique. The group difference in the proportion of clinical responders (7.0%) was less than the predefined margin of 15% indicating signal for clinical efficacy. In an exploratory analysis, the difference in response to mifepristone vs placebo in the subgroup with no lifetime history of traumatic brain injury (TBI) (7.0 [50.0%] vs 3.0 [27.3%]; difference, 22.7%) exceeded the efficacy margin at 4 weeks and was sustained at 12 weeks. In contrast, in veterans with PTSD and lifetime TBI, the response rate to mifepristone was lower than placebo at 12 weeks (7.4 [27.4%] vs 13.5 [48.3%]; difference, -20.9%). Conclusions and Relevance: This study did not detect a signal for efficacy for mifepristone at 600 mg/d for 1 week in male veterans with chronic PTSD. Thus, this study does not support a phase 3 trial in this population. Future studies of mifepristone for the treatment of PTSD may be of interest in those without a history of TBI or in samples with a low base rate of lifetime head trauma. Trial Registration: ClinicalTrials.gov Identifier: NCT01946685.

Increased Vascular Pathology in Older Veterans With a Purple Heart Commendation or Chronic Post-Traumatic Stress Disorder.

The goal of this retrospective cohort study was to determine whether stressors related to military service, determined by a diagnosis of chronic post-traumatic stress disorder (cPTSD) or receiving a Purple Heart (PH), are associated with an increased risk of vascular risk factors and disease, which are of great concern for veterans, who constitute a significant portion of the aging US population. The Veterans Integrated Service Network (VISN) 16 administrative database was searched for individuals 65 years or older between October 1, 1997 to September 30, 1999 who either received a PH but did not have cPTSD (PH+/cPTSD-; n = 1499), had cPTSD without a PH (PH-/cPTSD+; n = 3593), had neither (PH-/cPTSD-; n = 5010), or had both (PH+/cPTSD+; n = 153). In comparison to the control group (PH-/cPTSD-), the PH+/cPTSD- group had increased odds ratios for incidence and prevalence of diabetes mellitus, hypertension, and hyperlipidemia. The PH-/cPTSD+ group had increased odds ratios for prevalence of diabetes mellitus and for the incidence and prevalence of hyperlipidemia. The PH-/cPTSD+ and PH+/cPTSD- groups were associated with ischemic heart disease and cerebrovascular disease, but not independently of the other risk factors. The PH+/cPTSD+ group was associated only with an increase in the incidence and prevalence of hyperlipidemia, though this group's much smaller sample size may limit the reliability of this finding. We conclude that certain physical and psychological stressors related to military service are associated with a greater incidence of several vascular risk factors in veterans aged 65 years or older, which in turn are associated with greater rates of ischemic heart disease and cerebrovascular disease.

Heart Rate Variability and Cognitive Bias Feedback Interventions to Prevent Post-deployment PTSD: Results from a Randomized Controlled Trial.

Introduction: There is a long history of pre-deployment PTSD prevention efforts in the military and effective pre-deployment strategies to prevent post-deployment PTSD are still needed. Materials and Methods: This randomized controlled trial included three arms: heart rate variability biofeedback (HRVB), cognitive bias modification for interpretation (CBM-I), and control. The hypothesis was that pre-deployment resilience training would result in lower post-deployment PTSD symptoms compared with control. Army National Guard soldiers (n = 342) were enrolled in the Warriors Achieving Resilience (WAR) study and analyzed. The outcome was PTSD symptom severity using the PTSD Checklist - Military version (PCL) measured at pre-deployment, 3- and 12-month post-deployment. Due to the repeated measures for each participant and cluster randomization at the company level, generalized linear mixed models were used for the analysis. This study was approved by the Army Human Research Protection Office, Central Arkansas Veterans Healthcare System Institutional Review Board (IRB), and Southeast Louisiana Veterans Health Care System IRB. Results: Overall, there was no significant intervention effect. However, there were significant intervention effects for subgroups of soldiers. For example, at 3-months post-deployment, the HRVB arm had significantly lower PCL scores than the control arm for soldiers with no previous combat zone exposure who were age 30 and older and for soldiers with previous combat zone exposure who were 45 and older (unadjusted effect size -0.97 and -1.03, respectively). A significant difference between the CBM-I and control arms was found for soldiers without previous combat zone exposure between ages 23 and 42 (unadjusted effect size -0.41). Similarly, at 12-months post-deployment, the HRVB arm had significantly lower PCL scores in older soldiers. Conclusion: Pre-deployment resilience training was acceptable and feasible and resulted in lower post-deployment PTSD symptom scores in subgroups of older soldiers compared with controls. Strengths of the study included cluster randomization at the company level, use of iPod device to deliver the resilience intervention throughout the deployment cycle, and minimal disruption of pre-deployment training by using self-paced resilience training. Weaknesses included self-report app use, study personnel not able to contact soldiers during deployment, and in general a low level of PTSD symptom severity throughout the study. In future studies, it would important for the study team and/or military personnel implementing the resilience training to be in frequent contact with participants to ensure proper use of the resilience training apps.

Heart rate variability: Pre-deployment predictor of post-deployment PTSD symptoms.

Heart rate variability is a physiological measure associated with autonomic nervous system activity. This study hypothesized that lower pre-deployment HRV would be associated with higher post-deployment post-traumatic stress disorder (PTSD) symptoms. Three-hundred-forty-three Army National Guard soldiers enrolled in the Warriors Achieving Resilience (WAR) study were analyzed. The primary outcome was PTSD symptom severity using the PTSD Checklist - Military version (PCL) measured at baseline, 3- and 12-month post-deployment. Heart rate variability predictor variables included: high frequency power (HF) and standard deviation of the normal cardiac inter-beat interval (SDNN). Generalized linear mixed models revealed that the pre-deployment PCL*ln(HF) interaction term was significant (p<0.0001). Pre-deployment SDNN was not a significant predictor of post-deployment PCL. Covariates included age, pre-deployment PCL, race/ethnicity, marital status, tobacco use, childhood abuse, pre-deployment traumatic brain injury, and previous combat zone deployment. Pre-deployment heart rate variability predicts post-deployment PTSD symptoms in the context of higher pre-deployment PCL scores.

Differentiating between appraisal process and product in cognitive theories of posttraumatic stress.

Biased appraisal is central to cognitive theories of posttraumatic stress, but little research has examined the potentially distinct meanings of the term. The ongoing process of appraising social information and the beliefs that emerge as products of that process can be distinguished conceptually. This study sought to examine whether these 2 meanings are empirically distinct as well, and if so, to begin exploring potential relations between these appraisal constructs and posttraumatic stress symptoms. Soldiers (N = 424) preparing for deployment to Iraq or Afghanistan were administered measures of each construct. Results of confirmatory factor analysis suggest that the appraisal process and the products of that process (i.e., beliefs) are indeed distinct. Structural equation models are consistent with cognitive bias and social information processing literatures, which posit that a biased appraisal process may contribute to the development of dysfunctional beliefs and posttraumatic stress symptoms following trauma. The potential utility of distinctly conceptualizing and measuring the appraisal process in both clinical and research settings is discussed.

Effect of Symptom Over-Reporting on Heart Rate Variability in Veterans With Posttraumatic Stress Disorder.

Physiological assessment of posttraumatic stress disorder (PTSD) presents an additional avenue for evaluating the severity of PTSD symptoms. We investigated whether the presence of a high number of uncommon symptoms attenuated the relation between self-reported PTSD symptoms and heart rate variability (HRV). Participants were 115 veterans from Operation Iraqi Freedom and Operation Enduring Freedom with or without PTSD. Symptom over-report was assessed using the Miller Forensic Assessment of Symptoms Test (M-FAST). Participants completed the Clinician-Administered PTSD Scale and M-FAST and underwent physiological assessment to determine HRV. These data were then entered into a hierarchical linear regression equation to test the moderating effect of over-reporting on the relation between PTSD symptom severity and HRV. The result of this analysis failed to demonstrate a significant moderating effect of over-reporting on the PTSD and HRV relation. HRV was a significant predictor of PTSD symptom severity, and this relation did not differ across levels of over-reporting. These findings did not support the hypothesis that over-reporting would attenuate the relation between PTSD and HRV. Clinical and research implications and directions for future investigation are discussed.

Telemedicine-based collaborative care for posttraumatic stress disorder: a randomized clinical trial.

IMPORTANCE: Posttraumatic stress disorder (PTSD) is prevalent, persistent, and disabling. Although psychotherapy and pharmacotherapy have proven efficacious in randomized clinical trials, geographic barriers impede rural veterans from engaging in these evidence-based treatments. OBJECTIVE: To test a telemedicine-based collaborative care model designed to improve engagement in evidence-based treatment of PTSD. DESIGN, SETTING, AND PARTICIPANTS: The Telemedicine Outreach for PTSD (TOP) study used a pragmatic randomized effectiveness trial design with intention-to-treat analyses. Outpatients were recruited from 11 Department of Veterans Affairs (VA) community-based outpatient clinics serving predominantly rural veterans. Inclusion required meeting diagnostic criteria for current PTSD according to the Clinician-Administered PTSD Scale. Exclusion criteria included receiving PTSD treatment at a VA medical center or a current diagnosis of schizophrenia, bipolar disorder, or substance dependence. Two hundred sixty-five veterans were enrolled from November 23, 2009, through September 28, 2011, randomized to usual care (UC) or the TOP intervention, and followed up for 12 months. INTERVENTIONS: Off-site PTSD care teams located at VA medical centers supported on-site community-based outpatient clinic providers. Off-site PTSD care teams included telephone nurse care managers, telephone pharmacists, telepsychologists, and telepsychiatrists. Nurses conducted care management activities. Pharmacists reviewed medication histories. Psychologists delivered cognitive processing therapy via interactive video. Psychiatrists supervised the team and conducted interactive video psychiatric consultations. MAIN OUTCOMES AND MEASURES: The primary outcome was PTSD severity as measured by the Posttraumatic Diagnostic Scale. Process-of-care outcomes included medication prescribing and regimen adherence and initiation of and adherence to cognitive processing therapy. RESULTS: During the 12-month follow-up period, 73 of the 133 patients randomized to TOP (54.9%) received cognitive processing therapy compared with 16 of 132 randomized to UC (12.1%) (odds ratio, 18.08 [95% CI, 7.96-41.06]; P < .001). Patients in the TOP arm had significantly larger decreases in Posttraumatic Diagnostic Scale scores (from 35.0 to 29.1) compared with those in the UC arm (from 33.5 to 32.1) at 6 months (ß = -3.81; P = .002). Patients in the TOP arm also had significantly larger decreases in Posttraumatic Diagnostic Scale scores (from 35.0 to 30.1) compared with those in the UC arm (from 33.5 to 31.7) at 12 months (ß = -2.49; P=.04). There were no significant group differences in the number of PTSD medications prescribed and adherence to medication regimens were not significant. Attendance at 8 or more sessions of cognitive processing therapy significantly predicted improvement in Posttraumatic Diagnostic Scale scores (ß = -3.86 [95% CI, -7.19 to -0.54]; P = .02) and fully mediated the intervention effect at 12 months. CONCLUSIONS AND RELEVANCE: Telemedicine-based collaborative care can successfully engage rural veterans in evidence-based psychotherapy to improve PTSD outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00821678.

Over-reporting bias and the modified Stroop effect in Operation Enduring and Iraqi Freedom veterans with and without PTSD.

The current study investigated in a sample of Operation Enduring and Iraqi Freedom (OEF/OIF) veterans how a symptom overreporting response style might influence the association between PTSD diagnostic status and color-naming response latency for trauma-related stimuli during the Modified Stroop Task (i.e., the Modified Stroop Task effect, MST effect). It was hypothesized that, if an overreporting response style reflected feigning or exaggerating PTSD symptoms, an attenuated MST effect would be expected in overreporters with PTSD as compared with PTSD-diagnosed veterans without an overreporting style. If, however, overreporting stemmed from high levels of distress, the MST effect might be greater in overreporters compared with those with a neutral response style. The results showed that veterans with PTSD and an overreporting response style demonstrated an augmented MST effect in comparison with those with a more neutral style of response. Overreporters also reported greater levels of psychopathology, including markedly elevated reports of dissociative experiences. We suggest that dissociation-prone overreporters may misattribute emotional distress to combat experiences leading to the enhanced MST effect. Other possible explanations for these results are also discussed.

Recruitment and Retention of Smokers Versus Nonsmokers in an rTMS Study.

Repetitive transcranial magnetic stimulation (rTMS) is a new frontier in the examination of addictive behaviors and perhaps the development of new interventions. This study examined differences in recruitment, eligibility, and retention among smokers and nonsmokers in an rTMS study. We modeled participant eligibility and study completion among eligible participants accounting for demographic differences between smokers and nonsmokers. Nonsmokers were more likely than smokers to remain eligible for the study after the in-person screen (84.2% versus 57.4%; OR 4.0 CI: 1.0, 15.4, p=0.05) and to complete the study (87.5% versus 59.3%; OR=43.9 CI: 2.8, 687.2, p=0.007). The preliminary findings suggest that careful screening for drugs of abuse and brain abnormalities among smokers prior to administering rTMS is warranted. More research is needed concerning the prevalence of brain abnormalities in smokers. Smokers might need to be informed about a higher risk of incidental MRI findings.

Focal electrical stimulation as an effective sham control for active rTMS and biofeedback treatments.

A valid sham control is important for determining the efficacy and effectiveness of repetitive transcranial magnetic stimulation (rTMS) as an experimental and clinical tool. Given the manner in which rTMS is applied, separately or in combination with self-regulatory approaches, and its intended impact on brain states, a valid sham control of this type may well serve as a meaningful control for biofeedback studies, where efforts to develop a credible control have often been less than ideal. This study examined the effectiveness of focal electrical stimulation of the frontalis muscle as a sham technique for blinding participants to high-frequency rTMS over the dorso-lateral prefrontal cortex (DLPFC) at durations, intensities, and schedules of stimulation similar to many clinical applications. In this within-subjects single blind design, 19 participants made guesses immediately after receiving 54 counterbalanced rTMS sessions (sham, 10 Hz, 20 Hz); 7 (13 %) of the guesses were made for sham, 31 (57 %) were made for 10 Hz, and 16 (30 %) were made for 20 Hz. Participants correctly guessed the sham condition 6 % (CI 1, 32 %) of the time, which is less than the odds of chance (i.e., of guessing at random, 33 %); correctly guessed the 10 Hz condition 66 % (CI 43, 84 %) of the time, which was greater than chance; and correctly guessed the 20 Hz condition 41 % (CI 21, 65 %) of the time, which was no different than chance. Focal electrical stimulation therefore can be an effective sham control for high-frequency rTMS of the DLPFC, as well as for active biofeedback interventions. Participants were unaware that electrical stimulation was, in fact, sham rTMS.

Veteran perceptions of virtual reality to assess and treat posttraumatic stress disorder.

Implementation of evidence-based treatments (EBT) is necessary to address posttraumatic stress disorder (PTSD) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) military service personnel. Because virtual reality (VR) offers a promising tool for delivery of one type of EBT--exposure therapy--this study explored veterans' perceptions of VR as an assessment tool and treatment adjunct. We conducted semi-structured interviews with 14 OEF/OIF veterans being treated for PTSD after viewing two 3 minute VR scenarios as part of a larger research study. Veterans reported a capacity for immersion in VR in both combat and civilian environments, characterized by self-reported physiological reactivity, thoughts/behaviors similar to those experienced in Iraq, and triggered memories. Although participants were generally positive about VR, they expressed concerns about the possibility of negative reactions after viewing VR. Findings are discussed in the context of further development of VR aided interventions in veteran healthcare systems.

Neuromodulation of delay discounting, the reflection effect, and cigarette consumption.

Cigarette smokers and substance users discount the value of delayed outcomes more steeply than non-users. Higher discounting rates are associated with relapse and poorer treatment outcomes. The left dorsolateral prefontal cortex (DLPFC) exerts an inhibitory influence on impulsive or seductive choices. Greater activity in the prefrontal cortex is associated with lower discounting rates. We hypothesized that increasing activity in the left DLPFC with high frequency repetitive transcranial magnetic stimulation (HF rTMS) would decrease delay discounting and decrease impulsive decision-making in a gambling task as well as decrease cigarette consumption, similar to other studies. In this single-blind, within-subjects design, smokers with no intention to quit (n = 47) and nonsmokers (n = 19) underwent three counterbalanced sessions of HF rTMS (20 Hz, 10 Hz, sham) delivered over the left DLPFC. Tasks were administered at baseline and after each stimulation session. Stimulation decreased discounting of monetary gains (F([3,250]) = 4.46, p < .01), but increased discounting of monetary losses (F([3,246]) = 4.30, p < .01), producing a reflection effect, normally absent in delay discounting. Stimulation had no effect on cigarette consumption. These findings provide new insights into cognitive processes involved with decision-making and cigarette consumption and suggest that like all medications for substance dependence, HF rTMS is likely to be most effective when paired with cognitive-behavioral interventions.

Does PTSD impair cognition beyond the effect of trauma?

This systematic review analyzed data from studies examining memory and cognitive function in subjects with posttraumatic stress disorder (PTSD), compared with subjects exposed to trauma (but without PTSD). Based on analysis of 21 articles published in English from 1968 to 2009, the conclusion is that individuals with PTSD, particularly veterans, show signs of cognitive impairment when tested with neuropsychological instruments, more so than individuals exposed to trauma who do not have PTSD.

Repetitive transcranial magnetic stimulation and threat memory: selective reduction of combat threat memory p300 response after right frontal-lobe stimulation.

Using the event-related potential P3a component as a marker, the authors tested the efficacy of repetitive transcranial magnetic stimulation (rTMS) for reducing hyperarousability to specific threat stimuli in one Vietnam veteran with chronic posttraumatic stress disorder (PTSD), who exhibited an exaggerated P3a response to combat-related pictures. Twenty minutes of 1-Hz rTMS to the right prefrontal area effected a reduction in the P3a amplitude, whereas similar rTMS to the left prefrontal area did not. In addition to providing evidence for the effectiveness of right frontal rTMS for an exaggerated response to trauma-related stimuli, this study provides electrophysiological corroboration of subjective reports of PTSD symptoms.

Variable changes in PET activity before and after rTMS treatment for tinnitus.

OBJECTIVES/HYPOTHESIS: The objective was to determine whether low-frequency repetitive transcranial magnetic stimulation (rTMS) improves tinnitus by decreasing neural activity in auditory processing regions of the temporal cortex and the utility of positron emission tomography (PET) for targeting treatment. STUDY DESIGN: Randomized, sham-controlled crossover. METHODS: Patients received a five-day course of active and sham 1-Hz rTMS (1800 pulses at 110% of motor threshold) to the temporal cortex, with a week separating active and sham treatment. Visual analogue ratings of tinnitus loudness (VARL) were assessed at baseline and the end of each treatment week; regional brain blood flow (rBBF) and glucose metabolism (via PET) were measured before and after treatment in regions of interest (ROI) beneath the stimulating coil and control sites. RESULTS: The VARL for both ears significantly decreased after active but not sham treatment. Responders comprised 43% of patients, experiencing at least a 33% drop in tinnitus loudness. The site most consistently associated with a positive response was the secondary auditory cortex (Brodmann Area 22) in either hemisphere. PET asymmetries were variable across patients and not always accessible to rTMS. Whereas PET activity decreased significantly beneath the stimulating coil following active treatment, similar changes occurred at control sites and after sham stimulation. Change in tinnitus perception did not correlate significantly with change in PET activity at the treatment site ROI. CONCLUSIONS: Active TMS led to a significant reduction in tinnitus loudness, but PET scans failed to support the hypothesis that low-frequency rTMS improves tinnitus by reducing cortical activation at the stimulation site, questioning the utility of PET for targeting rTMS.

Clinician perceptions of virtual reality to assess and treat returning veterans.

OBJECTIVE: Implementation of evidence-based, innovative treatments is necessary to address posttraumatic stress disorder (PTSD) and related mental health problems of Operation Enduring Freedom and Operation Iraqi Freedom (OEF-OIF) military service personnel. The purpose of this study was to characterize mental health clinicians' perceptions of virtual reality as an assessment tool or adjunct to exposure therapy. METHODS: Focus groups were conducted with 18 prescribing and nonprescribing mental health clinicians within the Veterans Health Administration. Group discussion was digitally recorded, downloaded into Ethnograph software, and coded to arrive at primary, secondary, and tertiary themes. RESULTS: Most frequently mentioned barriers pertained to aspects of virtual reality, followed by veteran characteristics. Organizational barriers were more relevant when implementing virtual reality as a treatment adjunct. CONCLUSIONS: Although the study demonstrated that use of virtual reality as a therapy was feasible and acceptable to clinicians, successful implementation of the technology as an assessment and treatment tool will depend on consideration of the facilitators and barriers that were identified.

Greater prevalence and incidence of dementia in older veterans with posttraumatic stress disorder.

UNLABELLED: To explore the association between posttraumatic stress disorder (PTSD) and dementia in older veterans. DESIGN: Administrative database study of individuals seen within one regional division of the Veterans Affairs healthcare network. SETTING: Veterans Integrated Service Network 16. PARTICIPANTS: Veterans aged 65 and older who had a diagnosis of PTSD or who were recipients of a Purple Heart (PH) and a comparison group of the same age with no PTSD diagnosis or PH were divided into four groups: those with PTSD and no PH (PTSD+/PH-, n=3,660), those with PH and no PTSD (PTSD-/PH+, n=1,503), those with PTSD and a PH (PTSD+/PH+, n=153), and those without PTSD or a PH (PTSD-/PH-, n=5,165). MEASUREMENTS: Incidence and prevalence of dementia after controlling for confounding factors in multivariate logistic regression. RESULTS: The PTSD+/PH- group had a significantly higher incidence and prevalence of dementia than the groups without PTSD with or without a PH. The prevalence and incidence of a dementia diagnosis remained two times as high in the PTSD+/PH- group as in the PTSD-/PH+ or PTSD-/PH- group after adjusting for the confounding factors. There were no statistically significant differences between the other groups. CONCLUSION: The incidence and prevalence of dementia is greater in veterans with PTSD. It is unclear whether this is due to a common risk factor underlying PTSD and dementia or to PTSD being a risk factor for dementia. Regardless, this study suggests that veterans with PTSD should be screened more closely for dementia. Because PTSD is so common in veterans, this association has important implications for veteran care.

Cognitive dysfunctions associated with PTSD: evidence from World War II prisoners of war.

The authors aim to delineate cognitive dysfunction associated with posttraumatic stress disorder (PTSD) by evaluating a well-defined cohort of former World War II prisoners of war (POWs) with documented trauma and minimal comorbidities. The authors studied a cross-sectional assessment of neuropsychological performance in former POWs with PTSD, PTSD with other psychiatric comorbidities, and those with no PTSD or psychiatric diagnoses. Participants who developed PTSD had average IQ, while those who did not develop PTSD after similar traumatic experiences had higher IQs than average (approximately 116). Those with PTSD performed significantly less well in tests of selective frontal lobe functions and psychomotor speed. In addition, PTSD patients with co-occurring psychiatric conditions experienced impairment in recognition memory for faces. Higher IQ appears to protect individuals who undergo a traumatic experience from developing long-term PTSD, while cognitive dysfunctions appear to develop with or subsequent to PTSD. These distinctions were supported by the negative and positive correlations of these cognitive dysfunctions with quantitative markers of trauma, respectively. There is a suggestion that some cognitive decrements occur in PTSD patients only when they have comorbid psychiatric diagnoses.

Maintenance repetitive transcranial magnetic stimulation can inhibit the return of tinnitus.

OBJECTIVES/HYPOTHESIS: A single patient was tested to examine the safety and feasibility of using maintenance sessions of low-frequency repetitive transcranial magnetic stimulation (1 Hz rTMS) to reduce tinnitus loudness and prevent its return over time. STUDY DESIGN: Interrupted time series with multiple replications. METHODS: Tinnitus loudness was assessed using a visual analogue rating (VAR) with 0 = no tinnitus, and 100 = loudest tinnitus experienced; 1,800 TMS pulses delivered at 1 Hz and 110% of motor threshold were administered over the posterior, superior lateral temporal gyrus of the subject's right hemisphere until subjective tinnitus fell to a VAR of 25. TMS was reapplied as tinnitus returned to a VAR of 25 or higher. Cerebral metabolism was measured using positron emission tomography before and after treatment. RESULTS: In this patient, tinnitus could be reduced to a VAR of 6 or lower each time it reoccurred using one to three maintenance sessions of rTMS. Tinnitus loudness remained at or below a VAR of 25 and was reported to be unobtrusive in daily life when last assessed 4 months after the third and final round of maintenance treatment. Asymmetric increased cerebral metabolism in the right hemisphere reduced following treatment and as tinnitus improved. Maintenance treatment was well tolerated with no side effects. CONCLUSIONS: Although a case study cannot establish treatment efficacy, this study demonstrates for the first time that it is feasible to use maintenance rTMS to manage chronic tinnitus. Maintenance rTMS might impede cortical expansion of the tinnitus frequency into adjacent cortical areas, but group studies are necessary to confirm this speculation.

Repetitive transcranial magnetic stimulation for tinnitus: a pilot study.

OBJECTIVES/HYPOTHESIS: Low-frequency repetitive transcranial magnetic stimulation (rTMS) has been shown to alleviate tinnitus perception, presumably by inhibiting cortical activity associated with tinnitus. We conducted a pilot study to assess effectiveness of neuronavigated rTMS and its effects on attentional deficits and cortical asymmetry in four patients with chronic tinnitus using objective and subjective measures and employing an optimization technique refined in our laboratory. STUDY DESIGN: Randomized, placebo-controlled (sham stimulation) crossover study. METHODS: Patients received 5 consecutive days of active, low-frequency rTMS or sham treatment (using a 45-degree coil-tilt method) before crossing over. Subjective tinnitus was assessed at baseline, after each treatment, and 4 weeks later. Positron emission tomography/computed tomography (PET/CT) scans were obtained at baseline and immediately after active treatment to examine change in cortical asymmetry. Attentional vigilance was assessed at baseline and after each treatment using a simple reaction time test. RESULTS: All patients had a response to active (but not sham) rTMS, as indicated by their best tinnitus ratings; however, tinnitus returned in all patients by 4 weeks after active treatment. All patients had reduced cortical activity visualized on PET immediately after active rTMS. Mean reaction time improved (P < .05) after active but not sham rTMS. CONCLUSIONS: rTMS is a promising treatment modality that can transiently diminish tinnitus in some individuals, but further trials are needed to determine the optimal techniques required to achieve a lasting response. It is unclear whether the improved reaction times were caused by tinnitus reduction or a general effect of rTMS. PET/CT scans immediately after treatment suggest that improvement may be related to reduction of cortical asymmetry associated with tinnitus.