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The antisaccade task is a widely used technique to measure failure of inhibition, an important cause of cognitive and clinical abnormalities found in schizophrenia. Although antisaccade performance, which reflects the ability to inhibit prepotent responses, is a putative schizophrenia endophenotype, researchers have not consistently reported the expected differences between first-degree relatives and comparison groups. Schizophrenia participants ( n=219) from the large Consortium on the Genetics of Schizophrenia (COGS) sample ( n=1078) demonstrated significant deficits on an overlap version of the antisaccade task compared to their first-degree relatives ( n=443) and community comparison subjects (CCS; n=416). Although mean antisaccade performance of first-degree relatives was intermediate between schizophrenia participants and CCS, a linear mixed-effects model adjusting for group, site, age, and gender found no significant performance differences between the first-degree relatives and CCS. However, admixture analyses showed that two components best explained the distributions in all three groups, suggesting two distinct doses of an etiological factor. Given the significant heritability of antisaccade performance, the effects of a genetic polymorphism is one possible explanation of our results. [ABSTRACT FROM AUTHOR]

Abstract: The antisaccade task is a promising schizophrenia endophenotype; it is stable over time and reflects neurophysiological deficits present in both schizophrenia subjects and their first-degree relatives. Meaningful genetic research requires large sample sizes that are best ascertained using multi-site study designs. To establish the criterion validity of the antisaccade task in a multi-site design, the Consortium on the Genetics of Schizophrenia (COGS) examined whether seven sites could detect previously reported antisaccade deficits in schizophrenia subjects. Investigators presented 3 blocks of 20 antisaccade stimuli to 143 schizophrenia subjects and 195 comparison subjects. Frequent collaborator communication, standardized training, and ongoing quality assurance optimized testing uniformity. Data were discarded from only 1.2% of subjects due to poor quality, reflecting the high fidelity of data collection and scoring methods. All sites detected a significant difference in the proportion of correct antisaccades between schizophrenia and comparison subjects (p <.02 at all sites); group differences in gain and latency were less robust. Regression analyses to adjust for the effects of group, site, age, gender, smoking, and parental education on the proportion of correct antisaccades revealed a significant effect of group, site, and age but no effect of gender, smoking, or parental education, and no group-by-site interactions. Intraclass correlations between proportion of correct antisaccades across the blocks of stimuli ranged from 0.87 to 0.93, demonstrating good within-session reliability at sites. These results confirm previous findings of antisaccade deficits in schizophrenia subjects and support the use of the antisaccade task as a potential schizophrenia endophenotype in multi-site genetic studies. [Copyright &y& Elsevier]

Background: Women with posttraumatic stress disorder (PTSD) report poor health, but associations with health care utilization are understudied.Objective: To determine associations between medical/surgical utilization and PTSD in female Veterans Affairs (VA) patients.Design: Prospective comparison of utilization rates between women screening positive or negative for PTSD on a mailed survey.Subjects: Women receiving care at an urban VA medical center between October 1996 and January 2000.Measurements: Survey responses, including a validated screen for PTSD (PCL-C), and VA utilization data through September 2002.Results: Two thousand five hundred and seventy-eight (2,578) women (78% of those eligible) completed the PCL-C; 858 (33%) of them screened positive for PTSD (PTSD+). In unadjusted models, PTSD+ women had higher rates of medical/surgical hospitalizations and surgical inpatient procedures. Among women ages 35 to 49, mean days hospitalized/100 patients/year was 43.4 (95% CI 26 to 61) for PTSD+ women versus 17.0 (16 to 18) for PTSD negative (PTSD-) women. More PTSD+ women underwent surgical procedures (P<.001). Mean annual outpatient visits were significantly higher among PTSD+ women, including: emergency department (ED) (1.1 [1.0 to 1.2] vs 0.6 [0.5 to 0.6]), primary care (3.2 [3.0 to 3.4] vs 2.2 [2.1 to 2.3]), medical/surgical subspecialists (2.1 [1.9 to 2.3] vs 1.5 [1.4 to 1.6]), ancillary services (4.1 [3.7 to 4.5] vs 2.4 [2.2 to 2.6]), and diagnostic tests (5.6 [5.1 to 6.1] vs 3.7 [3.4 to 4.0]). In multivariate models adjusted for demographics, smoking, service access, and medical comorbidities, PTSD+ women had greater likelihood of medical/surgical hospitalization (OR=1.37 [1.04 to 1.79]) and of being among the top quartile of patients for visits to the ED, primary care, ancillary services, and diagnostic testing.Conclusions: Female veterans who screen PTSD+ receive more VA medical/surgical services. Appropriateness of that care deserves further study. [ABSTRACT FROM AUTHOR]

Background: The purpose of this report is to identify self-reported health problems and functional impairment associated with screening positive for posttraumatic stress disorder (PTSD) in women seen for care at a Department of Veterans Affairs (VA) medical center. Methods: A survey was mailed to all women (N = 1935) who received care at the VA Puget Sound Health Care System between October 1996 and January 1998. The survey inquired about health history and habits. It included the PTSD Checklist–Civilian Version (PCL-C) and validated screening measures for other psychiatric disorders. The veteran's version of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36-V) was included to assess health-related quality of life. Results: Of the 1259 eligible women who completed the survey, 266 women (21%) screened positive for current PTSD (PCL-C score ≥ 50). In age-adjusted bivariate analyses, women who screened positive for PTSD reported more psychiatric problems, substance abuse, and lifetime exposure to domestic violence. They were significantly more likely to endorse physical health problems including obesity, smoking, irritable bowel syndrome, fibromyalgia, chronic pelvic pain, polycystic ovary disease, asthma, cervical cancer, and stroke. In fully adjusted multivariate models, a PCL-C score of 50 or greater was independently associated with scoring in the lowest quartile on SF-36-V subscales and composite scales. Conclusions: Symptoms of PTSD are common in women treated at VA facilities. In addition, PTSD is associated with self-reported mental and physical health problems and poor health-related quality of life in these patients. These findings have implications for the design of VA primary care services for the growing population of female veterans. [ABSTRACT FROM AUTHOR]

We evaluated the screening validity of a self-report measure for post traumatic stress disorder (PTSD), the PTSD Checklist (PCL), in female Veterans Affairs (VA) patients. All women seen for care at the VA Puget Sound Health Care system from October 1996–January 1999 (n=2,545) were invited to participate in a research interview. Participants (n=282) completed the 17-item PCL, followed by a gold standard diagnostic interview for PTSD, the Clinician Administered PTSD Scale (CAPS). Thirty-six percent of the participants (n=100) met CAPS diagnostic criteria for current PTSD. Receiver Operating Characteristic (ROC) analysis was used to evaluate the screening performance of the PCL. The area under the ROC curve was 0.86 (95% CI 0.82–0.90). A PCL score of 38 optimized the performance of the PCL as a screening test (sensitivity 0.79, specificity 0.79). The PCL performed well as a screening measure for the detection of PTSD in female VA patients. [Copyright &y& Elsevier]

Although Post-traumatic Stress Disorder (PTSD) is common among patients seeking care at medical clinics, little is known about the performance of screening instruments for this disorder in these settings. Previous studies of acute trauma populations using the PTSD Checklist (PCL) have suggested that scores of 45–50 provide the best discrimination between cases and noncases. We gave the PCL to 1,225 randomly selected women enrolled in an HMO. After interviewing a sample of 261 of these women using a structured, clinician-administered PTSD interview, we compared the results of the PCL to the clinician interviews over a range of possible cut scores using Receiver Operating Characteristic analysis. The optimum balance of sensitivity and specificity for this population was a score of 30, yielding a sensitivity of .82 and specificity of .76. The positive and negative likelihood ratios for this cut score were 3.40 and 0.24, respectively. By comparison, the use of 45 as a cut score would result in very low sensitivity (.36) in this setting. The lower cut score found in this study may indicate that the use of previously published cut scores of 45–50 may not optimize the function of the PCL as a screening tool outside of acute trauma settings due to an unacceptably high number of false negative cases. [Copyright &y& Elsevier]

The impaired ability to make correct antisaccades (i.e., antisaccade performance) is well documented among schizophrenia subjects, and researchers have successfully demonstrated that antisaccade performance is a valid schizophrenia endophenotype that is useful for genetic studies. However, it is unclear how the ascertainment biases that unavoidably result from recruitment differences in schizophrenia subjects identified in family versus case–control studies may influence patient–control differences in antisaccade performance. To assess the impact of ascertainment bias, researchers from the Consortium on the Genetics of Schizophrenia (COGS) compared antisaccade performance and antisaccade metrics (latency and gain) in schizophrenia and control subjects from COGS-1, a family-based schizophrenia study, to schizophrenia and control subjects from COGS-2, a corresponding case–control study. COGS-2 schizophrenia subjects were substantially older; had lower education status, worse psychosocial function, and more severe symptoms; and were three times more likely to be a member of a multiplex family than COGS-1 schizophrenia subjects. Despite these variations, which were likely the result of ascertainment differences (as described in the introduction to this special issue), the effect sizes of the control–schizophrenia differences in antisaccade performance were similar in both studies (Cohen's d effect size of 1.06 and 1.01 in COGS-1 and COGS-2, respectively). This suggests that, in addition to the robust, state-independent schizophrenia-related deficits described in endophenotype studies, group differences in antisaccade performance do not vary based on subject ascertainment and recruitment factors. [ABSTRACT FROM AUTHOR]

Background Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures. Methods The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS. Results Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms. Conclusions Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs. [ABSTRACT FROM AUTHOR]

Summary: Genes disrupted in schizophrenia may be revealed by de novo mutations in affected persons from otherwise healthy families. Furthermore, during normal brain development, genes are expressed in patterns specific to developmental stage and neuroanatomical structure. We identified de novo mutations in persons with schizophrenia and then mapped the responsible genes onto transcriptome profiles of normal human brain tissues from age 13 weeks gestation to adulthood. In the dorsolateral and ventrolateral prefrontal cortex during fetal development, genes harboring damaging de novo mutations in schizophrenia formed a network significantly enriched for transcriptional coexpression and protein interaction. The 50 genes in the network function in neuronal migration, synaptic transmission, signaling, transcriptional regulation, and transport. These results suggest that disruptions of fetal prefrontal cortical neurogenesis are critical to the pathophysiology of schizophrenia. These results also support the feasibility of integrating genomic and transcriptome analyses to map critical neurodevelopmental processes in time and space in the brain. [ABSTRACT FROM AUTHOR]

Objective: The Consortium on the Genetics of Schizophrenia has undertaken a large multisite study to characterize 12 neurophysiological and neurocognitive endophenotypic measures as a step toward understanding the complex genetic basis of schizophrenia. The authors previously demonstrated the heritability of these endophenotypes; in the present study, genetic linkage was evaluated. Method: Each family consisted of a proband with schizophrenia, at least one unaffected sibling, and both parents. A total of 1,286 participants from 296 families were genotyped in two phases, and 1,004 individuals were also assessed for the endophenotypes. Linkage analyses of the 6,055 singlenucleotide polymorphisms that were successfully assayed, 5,760 of which were common to both phases, were conducted using both variance components and pedigreewide regression methods. Results: Linkage analyses of the 12 endophenotypes collectively identified one region meeting genome-wide significance criteria, with a LOD (log of odds) score of 4.0 on chromosome 3p14 for the antisaccade task, and another region on 1p36 nearly meeting genome-wide significance, with a LOD score of 3.5 for emotion recognition. Chromosomal regions meeting genome-wide suggestive criteria with LOD scores >2.2 were identified for spatial processing (2p25 and 16q23), sensorimotor dexterity (2q24 and 2q32), prepulse inhibition (5p15), the California Verbal Learning Test (8q24), the degradedstimulus Continuous Performance Test (10q26), face memory (10q26 and 12p12), and the Letter-Number Span (14q23). Conclusions: Twelve regions meeting genome-wide significant and suggestive criteria for previously identified heritable, schizophrenia-related endophenotypes were observed, and several genes of potential neurobiological interest were identified. Replication and further genomic studies are needed to assess the biological significance of these results. [ABSTRACT FROM AUTHOR]

Abstract: Genetic studies of schizophrenia focus increasingly on putative endophenotypes because their genetic etiology may be simpler than clinical diagnosis. The Consortium on the Genetics of Schizophrenia (COGS), a multisite family study, aims to identify the genetic basis of several endophenotypes including verbal declarative memory (VDM), a neurocognitive function that shows robust impairment in schizophrenia. We present data on one type of measure of VDM, the California Verbal Learning Test, Second Edition (CVLT-II), in schizophrenia probands (n=305), their full biological siblings (n=449) and parents (n=232), and in community comparison subjects (CCS; n=509) across seven sites. Probands performed more poorly on each of five CVLT-II measures compared to related sibling and parent groups and CCS. Siblings and parents performed significantly worse than CCS on one measure (Discriminability), but with smaller effect sizes and less impairment than observed previously. The results raise questions about the homogeneity of VDM as an endophenotype, about methodological issues related to sampling, and about psychometric issues that impact the utility of the CVLT for detecting VDM deficits in nonpsychotic relatives of persons with schizophrenia. [Copyright &y& Elsevier]

Abstract: Inhibition of the P50 evoked electroencephalographic response to the second of paired auditory stimuli has been frequently examined as a neurophysiological deficit in schizophrenia. The Consortium on the Genetics of Schizophrenia (COGS), a 7-site study funded by the National Institute of Mental Health, examined this endophenotype in recordings from 181 probands with schizophrenia, 429 of their first degree relatives, and 333 community comparison control subjects. Most probands were treated with second generation antipsychotic medications. Highly significant differences in P50 inhibition, measured as either the ratio of amplitudes or their difference in response to the two stimuli, were found between the probands and the community comparison sample. There were no differences between the COGS sites for these findings. For the ratio parameter, an admixture analysis found that nearly 40% of the relatives demonstrated deficiencies in P50 inhibition that are comparable to the deficit found in the probands. These results indicate that P50 auditory evoked potentials can be recorded across multiple sites and reliably demonstrate a physiological abnormality in schizophrenia. The appearance of the physiological abnormality in a substantial proportion of clinically unaffected first degree relatives is consistent with the hypothesis that deficits in cerebral inhibition are a familial neurobiological risk factor for the illness. [Copyright &y& Elsevier]

Background: N100 evoked potential amplitude and gating abnormalities have been widely observed in schizophrenia patients. However, previous studies have been inconclusive as to whether similar deficits are present in unaffected family members. The Consortium on the Genetics of Schizophrenia (COGS) is a multisite National Institute of Mental Health (NIMH) initiative examining neurocognitive and neurophysiological measures as endophenotypes for genetic studies of schizophrenia. We report initial results from the COGS dataset of auditory N100 amplitude and gating as candidate endophenotypes. Methods: Evoked potential data were acquired from 142 schizophrenia probands, 373 unaffected first-degree relatives, and 221 community comparison subjects (CCS), using an auditory paired-click stimulation paradigm. Amplitude of the N100 response to each click and the click 2/click 1 ratio were dependent variables. Heritability was estimated based on kinships using Solar v.2.1.2. Group differences were examined after subjects were categorized as either “broad” or “narrow,” based on the presence (broad) or absence (narrow) of nonpsychotic psychiatric comorbidity. Results: Heritability estimates were .40 and .29 for click1 and click2 amplitudes and .22 for the ratio. Broad and narrow patients both had impaired click 1 amplitudes. Broad relatives, but not narrow relatives, exhibited similar impairments. There were no group differences for either click 2 amplitude or the gating ratio. Conclusions: N100 amplitude is a heritable measure that is abnormal in patients and a subset of relatives for whom psychiatric comorbidity may be a genetically associated phenotype. Auditory N100 gating, although heritable, is less viable as a schizophrenia endophenotype. [Copyright &y& Elsevier]

Abstract: Working memory (WM) impairment is a promising candidate endophenotype for schizophrenia that could facilitate the identification of susceptibility genes for this disorder. The validity of this putative endophenotype was assessed by determining whether 149 probands with schizophrenia and 337 of their first-degree relatives demonstrated WM impairment as compared to 190 unaffected community comparison subjects. Subjects were participants in the Consortium on the Genetics of Schizophrenia (COGS) project, a seven-site research network that was established to investigate the genetic architecture of endophenotypes for schizophrenia. Participants received comprehensive clinical assessments and completed two verbal WM tasks, one requiring transient on-line storage and another requiring maintenance plus complex manipulation of information by reordering the stimuli. Schizophrenia probands performed worse than the other groups on both tasks, with larger deficits found for the more challenging reordering WM task. The probands'' relatives performed more poorly than community comparison subjects on both tasks, but the difference was significant only for the more challenging maintenance plus complex manipulation WM task. This WM impairment was not attributable to diagnoses of schizophrenia spectrum disorder, mood disorders, or substance use disorders in the relatives. In conjunction with evidence that WM abilities are substantially heritable, the current results support the validity and usefulness of verbal WM impairments in manipulation of information as endophenotypes for schizophrenia in large-scale genetic linkage and association studies. [Copyright &y& Elsevier]

Abstract: Background: Startle and its inhibition by weak lead stimuli (“prepulse inhibition”: PPI) are studied to understand the neurobiology of information processing in patients and community comparison subjects (CCS). PPI has a strong genetic basis in infrahumans, and there is evidence for its heritability, stability and reliability in humans. PPI has gained increasing use as an endophenotype to identify vulnerability genes for brain disorders, including schizophrenia. Genetic studies now often employ multiple, geographically dispersed test sites to accommodate the need for large and complex study samples. Here, we assessed the feasibility of using PPI in multi-site studies. Methods: Within a 7-site investigation with multiple measures, the Consortium on the Genetics of Schizophrenia conducted a methodological study of acoustic startle and PPI in CCS. Methods were manualized, videotaped and standardized across sites with intensive in-person training sessions. Equipment was acquired and programmed at the “PPI site” (UCSD), and stringent quality assurance (QA) procedures were used. Testing was completed on 196 CCS over 2.5 years, with 5 primary startle dependent measures: eyeblink startle magnitude, habituation, peak latency, latency facilitation and PPI. Results: Analyses identified significant variability across sites in some but not all primary measures, and determined factors both within the testing process and subject characteristics that influenced a number of test measures. QA procedures also identified non-standardized practices with respect to testing methods and procedural “drift”, which may be particularly relevant to multi-site studies using these measures. Conclusion: With thorough oversight and QA procedures, measures of acoustic startle PPI can be acquired reliably across multiple testing sites. Nonetheless, even among sites with substantial expertise in utilizing psychophysiological measures, multi-site studies using startle and PPI as dependent measures require careful attention to methodological procedures. [Copyright &y& Elsevier]

Objective: To determine the prevalence and frequency of mastalgia and its association with psychiatric conditions and unexplained pain syndromes.Design, Setting, and Participants: Cross-sectional mailed survey completed by 1,219 female veterans enrolled at the VA Puget Sound Health Care System in 1998.Measurements: Breast pain in the past year, unrelated to pregnancy, was categorized as infrequent (< or =monthly) or frequent (> or =weekly) mastalgia. Surveys assessed posttraumatic stress disorder (PTSD), depression, panic disorder, and alcohol misuse with validated screening tests, as well as self-reported past-year chronic pelvic pain, fibromyalgia, and irritable bowel syndrome.Results: The response rate was 63%. Fifty-five percent of the respondents reported past-year mastalgia. Of these, 15% reported frequent mastalgia. Compared to women without mastalgia, women reporting frequent mastalgia were more likely to screen positive for PTSD (odds ratio [OR] 5.2, 95% confidence interval [CI] 3.2 to 8.4), major depression (OR 4.2, 2.6 to 6.9), panic disorder (OR 7.1, 3.9 to 12.8), eating disorder (OR 2.6, 1.5 to 4.7), alcohol misuse (OR 1.8, 1.1 to 2.8), or domestic violence (OR 3.1, 1.9 to 5.0), and to report fibromyalgia (OR 3.9, 2.1 to 7.4), chronic pelvic pain (OR 5.4, 2.7 to 10.5), or irritable bowel syndrome (OR 2.8, 1.6 to 4.8). Women with infrequent mastalgia were also more likely than women without mastalgia to screen positive for PTSD, depression, or panic disorder, or report pelvic pain or irritable bowel syndrome, although associations were weaker than with frequent mastalgia.Conclusions: Like other unexplained pain syndromes, frequent mastalgia is strongly associated with PTSD and other psychiatric conditions. Clinicians seeing patients with frequent mastalgia should inquire about anxiety, depression, alcohol misuse, and trauma history. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the prevalence and frequency of mastalgia and its association with psychiatric conditions and unexplained pain syndromes. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional mailed survey completed by 1,219 female veterans enrolled at the VA Puget Sound Health Care System in 1998. MEASUREMENTS: Breast pain in the past year, unrelated to pregnancy, was categorized as infrequent (▶ monthly) or frequent (≥ weekly) mastalgia. Surveys assessed posttraumatic stress disorder (PTSD), depression, panic disorder, and alcohol misuse with validated screening tests, as well as self-reported past-year chronic pelvic pain, fibromyalgia, and irritable bowel syndrome. RESULTS: The response rate was 63%. Fifty-five percent of the respondents reported past-year mastalgia. Of these, 15% reported frequent mastalgia. Compared to women without mastalgia, women reporting frequent mastalgia were more likely to screen positive for PTSD (odds ratio [OR] 5.2, 95% confidence interval [CI] 3.2 to 8.4), major depression (OR 4.2, 2.6 to 6.9), panic disorder (OR 7.1, 3.9 to 12.8), eating disorder (OR 2.6, 1.5 to 4.7), alcohol misuse (OR 1.8, 1.1 to 2.8), or domestic violence (OR 3.1, 1.9 to 5.0), and to report fibromyalgia (OR 3.9, 2.1 to 7.4), chronic pelvic pain (OR 5.4, 2.7 to 10.5), or irritable bowel syndrome (OR 2.8, 1.6 to 4.8). Women with infrequent mastalgia were also more likely than women without mastalgia to screen positive for PTSD, depression, or panic disorder, or report pelvic pain or irritable bowel syndrome, although associations were weaker than with frequent mastalgia. CONCLUSIONS: Like other unexplained pain syndromes, frequent mastalgia is strongly associated with PTSD and other psychiatric conditions. Clinicians seeing patients with frequent mastalgia should inquire about anxiety, depression, alcohol misuse, and trauma history. [ABSTRACT FROM AUTHOR]

Brief primary care interventions for alcohol use should be tailored to patients'' readiness to change; however, validated measures of readiness to change are too lengthy to be practical in most primary care settings. We compared a readiness to change drinking algorithm (RTC Algorithm) based on three standardized questions to a validated 12-item readiness to change questionnaire (Rollnick RTCQ) in 85 hazardous drinking female Veterans Affairs (VA) patients. Results from comparisons of mean Rollnick RTCQ scale scores across RTC Algorithm categories suggest good concurrent validity. Regular assessment using the RTC Algorithm questions may help primary care providers tailor alcohol-related discussions with hazardous drinking patients. [Copyright &y& Elsevier]

Background: Primary care physicians need a brief alcohol questionnaire that identifies hazardous drinking and alcohol use disorders. The Alcohol Use Disorders Identification Test (AUDIT) questions 1 through 3 (AUDIT-C), and AUDIT question 3 alone are effective alcohol-screening tests in male Veterans Affairs (VA) patients, but have not been validated in women. Methods: Female VA patients (n=393) completed self-administered questionnaires, including the 10-item AUDIT and a previously proposed modification to AUDIT question 3 with a sex-specific threshold for binge drinking (≥4 drinks/occasion), and in-person interviews with the Alcohol Use Disorder and Associated Disabilities Interview Schedule. The AUDIT-C, AUDIT question 3 alone, and the 10-item AUDIT were each evaluated with and without the sex-specific binge question and compared with past-year hazardous drinking (>7 drinks/week or &ge:4 drinks/occasion) and/or active Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol abuse or dependence, based on interviews. Results: Eighty-nine women (22.6%) met interview criteria for past-year hazardous drinking and/or active alcohol abuse or dependence. Standard and sex-specific AUDIT-Cs were sensitive (0.81 and 0.84, respectively) and specific (0.86 and 0.85, respectively). Their areas under the receiver operating characteristic curves were equivalent (0.91, and 0.92, respectively) and slightly higher than for the standard 10-item AUDIT (0.87). A single, sex-specific question about binge drinking (modified AUDIT question 3) had a sensitivity of 0.69 and specificity of 0.94, whereas the standard AUDIT question 3 was specific (0.96) but relatively insensitive (0.45). Conclusions: The standard and sex-specific AUDIT-Cs are effective screening tests for past-year hazardous drinking and/or active alcohol abuse or dependence in female patients in a VA study. [ABSTRACT FROM AUTHOR]

Objective: Prazosin is a centrally active α[sub 1] adrenergic antagonist. The authors' goal was to evaluate prazosin efficacy for nightmares, sleep disturbance, and overall posttraumatic stress disorder (PTSD) in combat veterans. Method: Ten Vietnam combat veterans with chronic PTSD and severe trauma-related nightmares each received prazosin and placebo in a 20-week double-blind crossover protocol. Results: Prazosin (mean dose=9.5 mg/day at bedtime, SD=0.5) was superior to placebo for the three primary outcome measures: scores on the 1) recurrent distressing dreams item and the 2) difficulty falling/staying asleep item of the Clinician-Administered PTSD Scale and 3) change in overall PTSD severity and functional status according to the Clinica Global Impression of change. Total score and symptom cluster scores for reexperiencing, avoidance/numbing, and hyperarousal on the Clinician-Administered PTSD Scale also were significantly more improved in the prazosin condition, and prazosin was well tolerated. Conclusions: These data support the efficacy of prazosin for nightmares, sleep disturbance, and other PTSD symptoms. [ABSTRACT FROM AUTHOR]