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.

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.

Posttraumatic mental and physical health correlates of forgiveness and religious coping in military veterans.

This study assessed mental and physical health correlates of dispositional forgiveness and religious coping responses in 213 help-seeking veterans diagnosed with PTSD. Controlling for age, socioeconomic status, ethnicity, combat exposure, and hostility, the results indicated that difficulty forgiving oneself and negative religious coping were related to depression, anxiety, and PTSD symptom severity. Difficulty forgiving others was associated with depression and PTSD symptom severity, but not anxiety. Positive religious coping was associated with PTSD symptom severity in this sample. Further investigations that delineate the relevance of forgiveness and religious coping in PTSD may enhance current clinical assessment and treatment approaches.

A preliminary study of bupropion sustained-release for smoking cessation in patients with chronic posttraumatic stress disorder.

This study was conducted to evaluate the effect of bupropion sustained-release (SR) on smoking cessation in patients with chronic posttraumatic stress disorder (PTSD). Fifteen veterans with chronic PTSD who desired to stop smoking enrolled in a 12-week double-blind evaluation of bupropion SR and placebo. Patients were randomly assigned in a 2:1 ratio to receive either bupropion SR or placebo. Bupropion SR was initiated at 150 mg daily for 3 or 4 days and increased to a final dose of 150 mg twice daily (300 mg daily total). Ten patients received bupropion SR and five received placebo. Nine of the patients who received bupropion SR were already being treated with at least one other psychotropic medication. One of the ten patients did not complete the study because of medication side effects. Eighty percent of patients receiving bupropion SR successfully stopped smoking by the end of week 2, and 6 (60%) of these 10 maintained smoking cessation at the study endpoint (week 12). At the 6-month follow-up, 40% of the patients (4 of 10) who received bupropion SR maintained smoking cessation. One (20%) of the five patients who received placebo stopped smoking and maintained smoking cessation at the 6-month follow-up. Bupropion SR was generally well-tolerated in combination with other psychotropic medications. Bupropion SR may be effective in helping patients who desire to quit smoking and who also have a concomitant anxiety disorder, such as PTSD.

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.

Feigning combat-related posttraumatic stress disorder on the personality assessment inventory.

This study examined whether individuals who were instructed on the Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) criteria for posttraumatic stress disorder (PTSD) could feign PTSD on the Personality Assessment Inventory (PAI; Morey, 1991). The study also investigated whether PAI indexes of symptom exaggeration, the Negative Impression Management (NIM) scale and the Malingering index, could identify individuals feigning PTSD. The diagnostic rule for PTSD (Morey, 1991, 1996) was applied to the profiles of a group of 23 veterans with combat-related PTSD and 23 male undergraduates instructed to malinger PTSD. Seventy percent of the student malingerers produced profiles that received diagnostic consideration for PTSD. The NIM cutting score (> or = 8) was highly effective in detecting simulation of PTSD but resulted in the misclassification of a large number of true PTSD cases. There were no significant differences in the overall efficiency of the test with various validity criteria. We discuss the implications of these findings for the use of the PAI in the diagnosis of combat-related PTSD.

Lack of efficacy for fluoxetine in PTSD: a placebo controlled trial in combat veterans.

BACKGROUND: Fluoxetine and placebo were studied in a population of combat veterans with severe, chronic PTSD. METHODS: Twelve male veterans with PTSD were enrolled in a 12 week double-blind evaluation of fluoxetine and placebo. Mean fluoxetine dose at endpoint (week 12) was 48 mg/day with a range of 10 mg to 60 mg. RESULTS: One fluoxetine patient responded (17%) and two of the six placebo patients responded (33%). CONCLUSIONS: Fluoxetine patients did not show a greater response than placebo patients in this small sample of male combat veterans with severe, chronic PTSD. Fluoxetine has displayed an efficacious response in controlled studies of patients with PTSD who were predominantly female, suffered civilian (noncombat) traumas, and were overall experiencing less severe PTSD. The reasons for the low response rate to fluoxetine in our study is unknown and will await further study examining variables other than symptoms that might influence outcome, such as gender, comorbidity, prior treatment history, trauma type, severity and chronicity.

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.

Hostility and functional health status in women veterans with and without posttraumatic stress disorder: a preliminary study.

This study investigated hostility and functional health status in 90 women veterans with and without PTSD. Compared to women without PTSD, women veterans with PTSD reported significantly higher levels of hostility. Minority status was associated with increased hostility. Compared to a national sample, hostility scores for women with PTSD were greater by a factor of 1.5 PTSD diagnosis was also associated with poorer functioning on all SF-36 Health Survey scales. Controlling for age and education, hostility was related to all SF-36 Health Survey scales in the women with PTSD.

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.

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.

Atrocities exposure in Vietnam combat veterans with chronic posttraumatic stress disorder: relationship to combat exposure, symptom severity, guilt, and interpersonal violence.

Vietnam combat veterans (N = 151) with chronic posttraumatic stress disorder (PTSD) completed measures of atrocities exposure, combat exposure, PTSD symptom severity, guilt and interpersonal violence. PTSD symptom severity, guilt and interpersonal violence rates were similar to previously reported studies that examined treatment seeking combat veterans with PTSD. Controlling for combat exposure, endorsement of atrocities exposure was related to PTSD symptom severity, PTSD B (reexperiencing) symptoms, Global Guilt, Guilt Cognitions, and cognitive subscales of Hindsight-Bias/Responsibility and Wrongdoing. These results are discussed in the context of previous research conducted regarding atrocities exposure and PTSD.

Trail making test performance in Vietnam combat veterans with and without posttraumatic stress disorder.

The present study investigated variables associated with performance on the Trail Making Test from the Halstead-Reitan neuropsychological test battery in Vietnam combat veterans. There was a significant difference in performance between veterans with and without PTSD on both parts of the Trail Making Test. In subgroup analyses excluding participants on medications (antianxiety, antidepressant, and cardiac), comorbid diagnoses (history of alcohol or substance abuse, history of major depression and comorbid anxiety disorder) and compensation-seeking status, the group difference on Trails B remained significant. However, subgroup analyses suggested that poorer performance on Trails A was influenced by antianxiety and cardiac medications, as well as heavy combat exposure status.

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.

Trust, health, and longevity.

Scores on the Rotter Interpersonal Trust Scale were evaluated as predictors of psychological well-being, functional health, and longevity in a sample of 100 men and women who were between 55 and 80 years old at baseline (mean age 66.8). Cross-sectionally, high levels of trust were associated with better self-rated health and more life satisfaction. Follow-up over approximately 8 years found baseline levels of trust to be positively related to subsequent functional health, but not to subsequent life satisfaction. Mortality follow-up after 14 years demonstrated that those with high levels of trust had longer survival (p = .03), a finding that was somewhat weakened by controlling for baseline health ratings. These findings illustrate the health protective effects of high levels of trust and suggest the potential usefulness of the trust concept for understanding successful aging.

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.

Minnesota Multiphasic Personality Inventory profiles of Vietnam combat veterans with posttraumatic stress disorder and their children.

Forty children of 28 fathers who are Vietnam veterans with posttraumatic stress disorder (PTSD) completed the Minnesota Multiphasic Personality Inventory. Each of the fathers had at least one elevated clinical scale. Fathers averaged eight elevated clinical scales, and compared to more recent norms, fathers averaged seven elevated clinical scales. Seventy-eight percent of the children had at least one clinically elevated scale (averaging three elevated clinical scales). Compared to contemporary normal adolescents and adults, 65% of children had at least one clinically elevated scale (still averaging three elevated clinical scales). No consistent MMPI profile patterns emerged within or across the two groups. No gender differences were detected among child MMPI profiles. Forty percent of the children reported illegal drug use, and 35% reported behavior problems. Fifteen percent of children reported previous violent behavior. Eighty-three percent of the children reported elevated Cook-Medley hostility scores as compared to an age-matched national normative sample. Children with higher PK scores were also significantly more likely to report higher Cook-Medley hostility scores. Forty-five percent of children reported significant elevations on the PTSD/PK subscales.