Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder.

BACKGROUND: The anticonvulsant, lamotrigine, may be useful for symptom management in PTSD. METHODS: Subjects enrolled in a 12-week double-blind evaluation of lamotrigine and placebo. Patients were randomized 2:1 to either lamotrigine or placebo. Lamotrigine was initiated at 25 mg/day and slowly titrated every 1 to 2 weeks over 8 weeks to a maximum dosage of 500 mg/day if tolerated. RESULTS: Fifteen subjects entered treatment, fourteen of whom returned for subsequent visits. Of 10 patients who received lamotrigine, 5 (50%) responded according to the DGRP, compared to 1 of 4 (25%) who received placebo. Lamotrigine patients showed improvement on reexperiencing and avoidance/numbing symptoms compared to placebo patients. Treatments were generally well tolerated. CONCLUSIONS: Lamotrigine may be effective as a primary psychopharmacologic treatment in both combat and civilian PTSD and could also be considered as an adjunct to antidepressant therapy used in the treatment of PTSD. These promising results warrant further large sample double-blind, placebo-controlled trials.

Health status, somatization, and severity of posttraumatic stress disorder in Vietnam combat veterans with posttraumatic stress disorder.

OBJECTIVE: A two-part study was conducted to examine the health status of Vietnam veterans with posttraumatic stress disorder (PTSD). In part 1, veterans with and without PTSD were compared on health behaviors and on self-reported and physician-rated health problems. Consistency of self-report with physician rating for health problems across the two groups was compared. In part 2, the association between health status and PTSD symptom severity, depression, somatization, and health behaviors in PTSD patients was evaluated. METHOD: In part 1, 276 combat veterans (225 with PTSD and 51 without PTSD) provided health status information, and medical records were reviewed. In part 2, 225 PTSD patients completed standardized PTSD severity, somatization, and depression measures. RESULTS: When analyses controlled for age, socioeconomic status, minority status, combat exposure, alcohol use, and pack-year history, veterans with PTSD reported and were rated as having a greater number of health problems than veterans without PTSD. Agreement between self-report and physician ratings for both groups ranged from low to moderate. Level of agreement between patient and physician was similar across groups. In the analysis of veterans with PTSD, somatization and PTSD symptom severity were significantly related to self-report of health problems, whereas only PTSD symptom severity was related to physician-rated health. Pack-year history was significantly related to self-reported health status in both groups. CONCLUSIONS: The presence and severity of PTSD in veterans were associated with greater physical health problems and conditions. Psychological variables (e.g., PTSD status, PTSD severity, somatization) and a behavioral variable (pack-year history) were related to health status.

Open trial of nefazodone for combat-related posttraumatic stress disorder.

BACKGROUND: Because of its ability to block 5-HT2 receptors postsynaptically and inhibit 5-HT reuptake presynaptically and/or its enhancement of sleep quality, nefazodone may be useful for symptom management in posttraumatic stress disorder (PTSD) patients. METHOD: Ten patients with combat-related DSM-IV posttraumatic stress disorder (PTSD) entered an open-label 12-week trial of nefazodone with a 4-week follow-up, beginning with 100 mg/day and increasing as necessary to achieve a maximal response or until reaching a maximum dosage of 600 mg/day. RESULTS: Nefazodone was well tolerated, and no significant changes in sexual function were reported. Based on Clinical Global Impressions-Improvement scores, all 10 patients were rated as much improved. All PTSD symptoms (except self-reported PTSD reexperiencing symptoms), sleep, and clinician-rated depression significantly improved at week 12. At follow-up, significant changes were maintained, and self-reported PTSD reexperiencing symptoms had also significantly improved. Effect sizes for all changed symptoms were moderate to large at week 12 and at follow-up. Self-reported and clinician-rated anger significantly improved. Self-reported depression failed to improve. Improvement in social and occupational functioning was minimal. CONCLUSION: These preliminary data suggest that nefazodone may be effective in reducing the 3 primary PTSD symptom clusters and may be particularly helpful in improving sleep and decreasing anger.

Caregiver burden in partners of Vietnam War veterans with posttraumatic stress disorder.

Caregiver burden in 58 partners of Vietnam veterans with posttraumatic stress disorder (PTSD) was examined. The relationship between patient PTSD severity and caregiver burden, as well as the effect of several caregiver and patient variables on caregiver psychological status, was evaluated twice, an average of 8 months apart. Patient symptom severity was positively correlated with caregiver burden. Time 1 cross-sectional analysis indicated that greater caregiver burden was associated with greater caregiver psychological distress, dysphoria, and anxiety. Patient symptom severity also contributed to caregiver psychological distress; financial stress contributed to caregiver dysphoria and trait anxiety. Time 2 cross-sectional analyses essentially replicated the Time 1 findings. A third set of analyses examining change scores indicated that changes in caregiver burden for individuals in the sample positively predicted individual changes in caregiver psychological distress, dysphoria, and state anxiety.

Measures of neuroticism and disease status in coronary angiography patients.

A high percentage of patients who undergo diagnostic angiography because they have chest pain are found to be free of significant coronary artery disease. To examine the psychological characteristics of these patients, we used several Minnesota Multiphasic Personality Inventory (MMPI; Hathaway & McKinley, 1943) measures to assess the relationships between different aspects of neuroticism and coronary artery disease severity (CADSEV) in a sample of 1,462 angiography patients. The Conversion V profile was inversely and most strongly related to CADSEV. Single high scores on hypochondriasis or hysteria were also inversely related to CADSEV, but psychasthenia and Taylor Manifest Anxiety Scale (TMA; Taylor, 1953) scores were not. Using measures derived by a factor analysis of the MMPI, items relating somatic complaints were inversely related to CADSEV, but a measure of general neuroticism was not. These results support the hypothesis that the association between neuroticism and angiographic findings may be specific to a particular aspect of neuroticism, somatic preoccupation. The implications for neuroticism measurement and clinical practice are discussed.

Drug use and validity of substance use self-reports in veterans seeking help for posttraumatic stress disorder.

The present study assessed drug use and the validity of self-reports of substance use among help-seeking veterans referred to a specialty clinic for the assessment of posttraumatic stress disorder (PTSD). Patients (n = 341) were asked to provide a urine sample for use in drug screening as part of an evaluation of PTSD. Self-reports of substance use were compared with same-day supervised urine samples for 317 patients who volunteered to participate in a drug screening. Results suggested that self-reports were generally quite valid. Only 8% of the cases involved patients not reporting substance use detected by urine screens. A total of 42% of the participants were identified as using drugs of abuse (excluding alcohol) through self-report and urine drug screens. Among participants using drugs, PTSD diagnosis was significantly associated with greater marijuana and depressant use as compared with stimulant (cocaine and amphetamines) use.

Ambulatory cardiovascular activity in Vietnam combat veterans with and without posttraumatic stress disorder.

The present study investigated the relationship between daily diary affect ratings and ambulatory cardiovascular activity in 117 male Vietnam combat veterans (61 with posttraumatic stress disorder [PTSD] and 56 without PTSD). Participants completed 12-14 hr of ambulatory monitoring and daily diary affect ratings. Compared with veterans without PTSD, veterans with PTSD reported higher negative affect and lower positive affect in daily diary ratings. No differences were detected for mean laboratory initial recordings or mean ambulatory heart rate (HR), systolic blood pressure (SBP), or diastolic blood pressure (DBP). However, compared with veterans without PTSD, veterans with PTSD demonstrated higher SBP and DBP variability and a higher proportion of HR activity (compared with initial recording values) during daily activity. There was a significant Time of Day x Group interaction for mean HR, with a trend for PTSD participants to maintain HR levels during evening hours.

Age differences in hostility among middle-aged and older adults.

Multiple measures of hostility were administered to middle-aged and older volunteers. There was a positive association between age and self-report measures reflecting hostile beliefs about others, including cynicism and suspiciousness. There was a weak inverse relationship between age and self-report measures of the overt expression of anger and aggression, but no association between age and measures of covert hostility was found. There was a positive relationship between age and an assessment of hostile behavior that was based on the respondent's interaction style during an interview. The magnitude of these age trends did not differ between men (n = 50) and women (n = 75). These findings illustrate the multidimensional nature of hostility. They also have practical implications for older people because hostility is associated with psychological well-being and has been shown to have consequences for health and longevity.

Chronic posttraumatic stress disorder and chronic pain in Vietnam combat veterans.

A study was conducted to investigate chronic pain patterns in Vietnam veterans with posttraumatic stress disorder (PTSD). Combat veterans with PTSD completed standardized PTSD severity, pain, somatization, and depression measures. Of 129 consecutive out-patient combat veterans with PTSD, 80% reported chronic pain. In descending order were limb pain (83%), back pain (77%), torso pain (50%), and headache pain (32%). Compared to PTSD combat veterans without chronic pain, PTSD veterans who reported chronic pain reported significantly higher somatization as measured by the Minnesota Multiphasic Inventory 2 hypochondriasis and hysteria subscales. In the sample of 103 combat veterans with PTSD and chronic pain, MMPI 2 hypochondriasis scores and B PTSD symptoms (reexperiencing symptoms) were significantly related to pain disability, overall pain index, and current pain level MMPI 2 hypochondriasis and depression scores were also significantly related to percent body pain. These results are discussed in the context of current conceptualizations of PTSD.

Prevalence and correlates of heavy smoking in Vietnam veterans with chronic posttraumatic stress disorder.

A study was conducted to investigate smoking patterns in 445 Vietnam veterans with and without posttraumatic stress disorder (PTSD). Combat veterans with PTSD reported similar occurrence of smoking (53%) compared to combat veterans without PTSD (45%). For those who smoked, combat veterans with PTSD reported a significantly higher rate of heavy smoking (> or = 25 cigarettes daily): 28% of combat veterans without PTSD were heavy smokers and 48% of combat veterans with PTSD were heavy smokers. PTSD diagnosis and heavy smoking status were independently and differentially related to motives for smoking. In combat veterans with PTSD, heavy smoking status was positively related to total health complaints, lifetime health complaints, health complaints in the past year, negative health behaviors, total PTSD symptoms, DSM-IV C cluster (avoidance and numbing) and D cluster (hyperarousal) PTSD symptoms. Heavy smoking status was also associated with fewer positive health behaviors.

Smoking withdrawal symptoms in response to a trauma-related stressor among Vietnam combat veterans with posttraumatic stress disorder.

This study investigated the relationship between a trauma-related stressor and smoking withdrawal symptoms in 25 male Vietnam combat veterans with posttraumatic stress disorder (PTSD) using a within-subjects design. All subjects were smokers. The stressor involved a modified Stroop task, in which the veterans color-named either anxiety-related or neutral control words. Anxiety-related words produced more withdrawal symptoms than neutral control words, including increased craving, negative affect symptoms, somatic symptoms, and lack of alertness.

Emotional processing and fear measurement synchrony as indicators of treatment outcome in fear of flying.

Minimal-therapist-involvement stress inoculation training was used to treat flying phobics. Relative to no-treatment controls, treatment subjects reported more fear reduction, were more likely to participate in an exposure session, and flew more during a two-month follow-up period. Subjects who exhibited synchronous changes in heart rate and report of anxiety during exposure had greater fear reduction than subjects showing less synchrony. Subjects who voluntarily took plane flights in the two months following treatment showed greater indications of emotional processing during in vivo exposure. Relative to flight avoiders, fliers had higher mean heart rate in the plane, a greater reduction in heart rate from the beginning to the end of the flight, and greater reported fear reduction from pre- to post-flight.

Patient predictors of caregiver burden, optimism, and pessimism in rheumatoid arthritis.

The authors of the present study investigated the relationship between rheumatoid arthritis (RA) patients' demographic, medical, and functional status and caregivers' burden, optimism, and pessimism. Subjects were 65 RA patients and their caregivers who were recruited from an outpatient rheumatology clinic. Each caregiver completed the Burden Interview to measure caregiver burden and the Life Orientation Test to measure optimism and pessimism. Each RA patient completed the Arthritis Impact Measurement Scale to measure pain and physical disability as well as a number of cognitive measures to assess two summary psychological cognitive factors labeled self-efficacy expectations and distorted cognitions. These cognitive factors were based on the following commonly used measures in RA research: the Cognitive Errors Questionnaire, the Arthritis Self-Efficacy Scale, the Coping Strategies Questionnaire, and the Pain Beliefs and Perceptions Inventory. Correlational analyses indicated that patients' functional and psychological measures (including poor self-efficacy expectations regarding symptoms) were related to caregiver burden, that patient self-efficacy expectations were related to caregiver optimism, and that patient physical disability was related to caregiver pessimism. Regression analyses revealed that, when competing with other demographic and disease severity variables, the relationships between patient self-efficacy expectations and caregiver burden and caregiver optimism, and patient physical function and caregiver pessimism remained significant. Taken together, these findings suggest that patient expectancies about control over arthritis-related symptoms (including pain) are strongly related to caregiver burden and caregiver optimism and that patient physical status is strongly related to caregiver pessimism.

Self-efficacy and adjustment in cancer patients: a preliminary report.

The relation between cancer self-efficacy and patient cancer adjustment, depression, psychological distress, and behavioral dysfunction in 42 cancer patients was studied in a preliminary investigation. Participants were male cancer outpatients recruited from a Veterans Administration Medical Center who completed a Cancer Self-Efficacy Scale, the Center for Epidemiological Studies-Depression Scale, the Affect Balance Scale, and the Sickness Impact Profile. Correlational analyses indicated that self-efficacy was related to all adjustment measures. Regression analyses revealed that when age, education, time since initial diagnosis, and current disease status were controlled, the relationships between patient self-efficacy expectations and cancer adjustment, psychological distress, negative affect, positive affect, and behavioral dysfunction remained statistically significant. Taken together, the results of the analyses suggested that patient expectancies about control over cancer-related symptoms were related to several important aspects of patient functioning. The results underscored the need for further investigation of this construct in cancer patients.

Smoking and anxiety in combat veterans with chronic posttraumatic stress disorder: a review.

There is growing evidence that smoking, and in particular heavy smoking, is prevalent in Vietnam combat veterans with posttraumatic stress disorder. However, the pathways responsible for development and perpetuation of smoking in this clinical population have not been identified. Relevant smoking, substance abuse, and anxiety disorder research is reviewed. Although an association between smoking and PTSD has not been directly tested, there is evidence that such research is warranted. Suggestions for future research are offered.

Behavioral assessment of chronic orofacial pain.

Orofacial pain is usually evaluated and treated from a biomedical perspective. There is no question that the large majority of individuals having acute orofacial pain benefit from timely and appropriate medical intervention. When orofacial pain persists, however, the likelihood that this pain can influence and be influenced by behavioral factors increases. While some individuals are able to adapt and cope with chronic orofacial pain, others develop significant behavioral problems. These problems may include an overly sedentary lifestyle, dependence on habit-forming narcotic medications, or severe depression or anxiety. The hallmark of the behavioral perspective on chronic pain is the insistence that a careful assessment and treatment of such behavioral problems is just as important as appropriate biomedical intervention.(1)

Smoking in help-seeking veterans with PTSD returning from Afghanistan and Iraq.

Past research has shown that veterans and individuals with posttraumatic stress disorder (PTSD) have increased rates of smoking. However, the rates of smoking in younger help-seeking veterans returning from Afghanistan and Iraq, and possible correlates of smoking among this population are unknown. In this study, we evaluated the rate of lifetime and current smoking among a sample of 90 returning male veterans diagnosed with PTSD. Fifty-nine percent reported a lifetime history of smoking including 32% that were current smokers. Current smokers were significantly younger than non-smokers. Current smokers (mean age=31) reported a mean age of smoking onset as 15.86 with a pack year history of 8.89. These smokers reported on average five previous quit attempts. According to a stages of change model, one-half of the smokers were in the contemplation phase of stopping smoking (50%), 29% were in the pre-contemplation phase and 21% were in the preparation phase. The results are placed in the context of non-psychiatric and psychiatric smokers.