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Objective: The Molecular Genetics of Schizophrenia (MGS2) project recruited an adult control sample of non-Hispanic European-ancestry (N=3,364) and African American (N=1,301) subjects. Method: Subjects gave consent to deposit phenotypic data and blood samples into a repository for general research use, with full anonymization of the sample. The authors compared the control sample with population census data for demographic data and with previous population surveys for anthropometrics and prevalences of psychiatric disorders as estimated by an Internet-administered questionnaire. Results: The full MGS2 control sample includes 4,665 subjects (European-ancestry: N=3,364; African American: N=1,301), of whom 3,626 were included in the MGS2 genome-wide association study (GWAS). The sample is generally demographically representative of the U.S. population, except for being older and more female, educated, and affluent, although all strata are represented. Self-reported ancestry was consistent with genotypic and census data. Lifetime prevalences for depressive, anxiety, and substance use diagnoses were higher than in previous population-based surveys, probably due to use of an abbreviated self-report instrument. However, patterns such as sex ratios, comorbidity, and demographic associations were consistent with previous reports. DNA quality for the Internet collected/evaluated control sample was comparable to that of the face-to-face case sample. Conclusions: The Internet-based methods facilitated the rapid collection of large and anonymized non-Hispanic European-ancestry and African American control samples that have been validated as being generally representative for many aspects of demography, ancestry, and morbidity. Utilization of clinical screening data shared with the scientific community may permit investigators to select appropriate controls for some studies.

Objective: The authors carried out a genetic association study of 14 schizophrenia candidate genes (RGS4, DISC1, DTNBP1, STX7, TAAR6, PPP3CC, NRG1, DRD2, HTR2A, DAOA, AKT1, CHRNA7, COMT, and ARVCF). This study tested the hypothesis of association of schizophrenia with common single nucleotide polymorphisms (SNPs) in these genes using the largest sample to date that has been collected with uniform clinical methods and the most comprehensive set of SNPs in each gene. Method: The sample included 1,870 cases (schizophrenia and schizoaffective disorder) and 2,002 screened comparison subjects (i.e. controls), all of European ancestry, with ancestral outliers excluded based on analysis of ancestry-informative markers. The authors genotyped 789 SNPs, including tags for most common SNPs in each gene, SNPs previously reported as associated, and SNPs located in functional domains of genes such as promoters, coding exons (including nonsynonymous SNPs), 3' untranslated regions, and conserved noncoding sequences. After extensive data cleaning, 648 SNPs were analyzed for association of single SNPs and of haplotypes. Results: Neither experiment-wide nor gene-wide statistical significance was observed in the primary single-SNP analyses or in secondary analyses of haplotypes or of imputed genotypes for additional common HapMap SNPs. Results in SNPs previously reported as associated with schizophrenia were consistent with chance expectation, and four functional polymorphisms in COMT, DRD2, and HTR2A did not produce nominally significant evidence to support previous evidence for association. Conclusions: It is unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects cannot be ruled out.

Objective: Systems Training for Emotional Predictability and Problem Solving (STEPPS) is a 20-week manual-based group treatment program for outpatients with borderline personality disorder that combines cognitive behavioral elements and skills training with a systems component. The authors compared STEPPS plus treatment as usual with treatment as usual alone in a randomized controlled trial. Method: Subjects with borderline personality disorder were randomly assigned to STEPPS plus treatment as usual or treatment as usual alone. Total score on the Zanarini Rating Scale for Borderline Personality Disorder was the primary outcome measure. Secondary outcomes included measures of global functioning, depression, impulsivity, and social functioning; suicide attempts and self-harm acts; and crisis utilization. Subjects were followed 1 year posttreatment. A linear mixed-effects model was used in the analysis. Results: Data pertaining to 124 subjects (STEPPS plus treatment as usual [N=65]; treatment as usual alone [N=59]) were analyzed. Subjects assigned to STEPPS plus treatment as usual experienced greater improvement in the Zanarini Rating Scale for Borderline Personality Disorder total score and subscales assessing affective, cognitive, interpersonal, and impulsive domains. STEPPS plus treatment as usual also led to greater improvements in impulsivity, negative affectivity, mood, and global functioning. These differences yielded moderate to large effect sizes. There were no differences between groups for suicide attempts, self-harm acts, or hospitalizations. Most gains attributed to STEPPS were maintained during follow-up. Fewer STEPPS plus treatment as usual subjects had emergency department visits during treatment and follow-up. The discontinuation rate was high in both groups. Conclusions: STEPPS, an adjunctive group treatment, can deliver clinically meaningful improvements in borderline personality disorder-related symptoms and behaviors, enhance global functioning, and relieve depression.

Objective: The authors explored the family history and psychiatric comorbidity of a group of compulsive buyers who volunteered for medication studies. Compulsive buying is characterized by inappropriate shopping and spending behavior that leads to impairment. Method: Thirty-three subjects who met the criteria of McElroy and colleagues for compulsive buying, and who scored more than two standard deviations above the mean on the Compulsive Buying Scale, were recruited. Twenty-two comparison subjects were recruited in the course of another study, and the presence of obsessive-compulsive disorder was the only reason for exclusion. Both groups were administered the Structured Clinical Interview for DSM-III-R disorders. The Family History Research Diagnostic Criteria were used to collect information about psychiatric disorders in first-degree relatives. Results: Compulsive buyers had a mean age of 40 years; two (6%) were men. Comparison subjects had a mean age of 39 years; six (27%) were men. The two groups differed in gender distribution but not in age, marital status, or educational achievement. Compulsive buyers were more likely than comparison subjects to have lifetime mood disorders (especially major depression) and to have more than one psychiatric disorder. First-degree relatives of compulsive buyers were more likely than comparison relatives to suffer from depression, alcoholism, and a drug use disorder and to suffer more psychiatric disorders in general. Conclusions: These results indicate that persons who report compulsive buying behavior, and their first-degree relatives, are more likely to have a higher prevalence of psychiatric disorder than are comparison subjects.

Objective: The goal of this study was to identify chromosomal regions likely to contain schizophrenia susceptibility genes. Method: A genomewide map of 310 microsatellite DNA markers with average spacing of 11 centimorgans was genotyped in 269 individuals - 126 of them with schizophrenia-related psychoses - from 43 pedigrees. Nonparametric linkage analysis was used to assess the pattern of allele sharing at each marker locus relative to the presence of disease. Results: Nonparametric linkage scores did not reach a genomewide level of statistical significance for any marker. There were five chromosomal regions in which empirically derived p values reached nominal levels of significance at eight marker locations. There were p values less than 0.01 at chromosomes 2q (with the peak value in this region at D2S410) and 10q (D10S1239), and there were p values less than 0.05 at chromosomes 4q (D4S2623), 9q (D9S257), and 11q (D11S2002). Conclusions.' The results do not support the hypothesis that a single gene causes a large increase in the risk of schizophrenia. The sample (like most others being studied for psychiatric disorders) has limited power to detect genes of small effect or those that are determinants of risk in a small proportion of families. All of the most positive results could be due to chance, or some could reflect weak linkage (genes of small effect). Multicenter studies may be useful in the effort to identify chromosomal regions most likely to contain schizophrenia susceptibility genes.

Background: Statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors) have been used for a decade to lower low-density lipoprotein (LDL) cholesterol levels and to improve cardiovascular disease and clinical outcomes. Objective: To evaluate the safety profile of atorvastatin (Lipitor). Methods: Data were pooled for 21 completed (2502 patients) and 23 ongoing (1769 patients) clinical trials of atorvastatin conducted in US and international community- and university-based research centers. In these trials, patients with lipid disorders received atorvastatin at dosages of 10 to 80 mg/d. The majority of patients had moderate to severe hypercholesterolemia and were treated from 4 weeks to more than 24 months. Main Outcome Measures: Transaminase and creatine phosphokinase levels and adverse events were recorded. Results: Atorvastatin was well tolerated; fewer than 2% of the atorvastatin-treated patients withdrew due to drug-attributable adverse events. The overall adverse event profile for atorvastatin was similar to that observed with other statins. The most common adverse events with atorvastatin as well as with other statins tested were constipation, flatulence, dyspepsia, and abdominal pain. Approximately 5% of atorvastatin-treated patients had serious adverse events; only 2 of these events were possibly associated with treatment. Thirty patients (0.7%) had confirmed transaminase elevations greater than 3 times the upper limit of the normal range. Most elevations occurred within 16 weeks of beginning treatment. No patients had a conclusive characterization of drug-induced myopathy. Conclusions: The safety profile of atorvastatin was consistent with that of all statins tested and was similar to that seen in all compounds of this class. Arch Intern Med. 1998;158:577-584

BACKGROUND: To assess the lipid-lowering effects and safety of atorvastatin and niacin in patients with combined hyperlipidemia or isolated hypertriglyceridemia. METHODS: We performed a randomized, open-label, parallel-design, active-controlled, study in eight centers in the United States. We enrolled 108 patients with total cholesterol (TC) of [is greater than or equal to] 200 mg/dL, serum triglycerides (TG) [is greater than or equal to] 200 and [is less than or equal to] 800 mg/dL, and apolipoprotein B (apo B) [is greater than or equal to] 110 mg/dL. Patients were randomly assigned to receive atorvastatin 10 mg once daily (n = 55) or immediate-release niacin 1 g three times daily for 12 weeks (n = 53). Patients were stratified based on low-density lipoprotein cholesterol (LDL-C): Patients with LDL-C [is greater than or equal to] 135 mg/dL were considered to have combined hyperlipidemia and patients with LDL-C [is less than] 135 mg/dL were considered to have isolated hypertriglyceridemia. The primary outcome measure was percent change from baseline in LDL-C. Other lipid levels were evaluated as secondary parameters. RESULTS: Atorvastatin reduced LDL-C 30% and TC 26% from baseline, and increased high-density lipoprotein cholesterol (FIDL-C) 4%. Total TG were reduced 17%. Niacin reduced LDL-C 2%, TC 7%, increased HDL-C 25%, and reduced total TG 29% from baseline. There was a significant difference in LDL-C reduction, the primary efficacy parameter, between the two treatment groups (P [is less than] 0.05, favoring atorvastatin), as well as a significant difference in the improvement in HDL-C (P [is less than] 0.05, favoring niacin). The effect of atorvastatin was relatively consistent between patients with combined hyperlipidemia and isolated hypertriglyceridemia, whereas there was more variability between these strata in the niacin treatment group. Atorvastatin was better tolerated than niacin. CONCLUSION: Atorvastatin may allow patients with combined hyperlipidemia to be treated with monotherapy and offers an efficacious and well-tolerated alternative to niacin for the treatment of patients with isolated hypertriglyceridemia. Am J Med. 1998;104:137-143. [C] 1998 by Excerpta. Medica, Inc.

Objective: The authors describe the sociodemographic features, phenomenology, and psychiatric comorbidity of 36 subjects reporting compulsive sexual behavior. Method: Twenty-eight men and eight women who responded to advertisements for 'persons ... who have a problem with compulsive sexual behavior' completed structured and semistructured assessments, including the Diagnostic Interview Schedule for DSM-III-R disorders (axis I) and the Structured Interview for DSM-III-R Personality Disorders, Revised (axis II). Results: The typical subject was a 27-year-old man who reported experiencing compulsive sexual behavior for nearly 9 years. Sexual behavior was described as excessive and poorly controlled and was associated with either subjective distress or impairment in interpersonal or occupational functioning or as overly time-consuming. Fourteen subjects (39%) reported a history of major depression or dysthymia, 15 (42%) a history of phobic disorder, and 23 (64%) a history of substance use disorder. Personality disorders were quite frequent, particularly the paranoid, histrionic, obsessive-compulsive, and passive-aggressive subtypes. The compulsive sexual behavior was quite varied and included both paraphilic (e.g., cross-dressing) and nonparaphilic (e.g., compulsive masturbation) types. Conclusions: Compulsive sexual behavior may be a clinically useful concept, but it describes a heterogeneous group of individuals with substantial psychiatric comorbidity and diverse behavioral problems.

Byline: Neal D. Hillman, Jon N. Meliones, Donald R. Black, Damian M. Craig, Ira M. Cheifetz, Peter K. Smith Abstract: Acute respiratory distress syndrome continues to be associated with significant morbidity and mortality related to ventilation-perfusion mismatch, pulmonary hypertension, and right ventricular failure. It has been suggested that inhaled nitric oxide, which is a selective pulmonary vasodilator, may be effective in the treatment of acute respiratory distress syndrome; however, the effects of nitric oxide on cardiopulmonary interactions are poorly understood. We therefore developed a model of acute lung injury that mimics the clinical syndrome of acute respiratory distress syndrome. In our model, inhaled nitric oxide significantly reduced pulmonary artery pressure, pulmonary vascular resistance, and pulmonary vascular impedance. In addition, inhaled nitric oxide improved transpulmonary vascular efficiency and ventilation-perfusion matching, which resulted in increased arterial oxygen tension. Although arterial oxygen tension increased, oxygen delivery did not improve significantly. These data suggest that by improving ventilation-perfusion matching and arterial oxygen tension while lowering pulmonary vascular resistance and impedance, nitric oxide may be beneficial in patients with acute respiratory distress syndrome. However, additional measures to enhance cardiac performance may be required. (J THORAC CARDIOVASC SURG 1995;110: 593-600) Author Affiliation: Durham, N.C Article Note: (footnote) [star] From the Departments of Pediatricsa and Surgery,b Duke University Medical Center, Durham, N.C., [star][star] Supported in part by a grant from the Duke Children's Hospital Miracle Network Telethon., a Read at the Twentieth Annual Meeting of The Western Thoracic Surgical Association, Olympic Valley, Calif., June 22-25, 1994., aa Address for reprints: Jon Meliones, MD, Duke University Medical Center, Box 3442, Durham NC 27710, acents 12/6/65893

Background: Fluvastatin sodium is a new, entirely synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor that may be an effective lipid-lowering agent in patients whose hyperlipidemia does not respond to dietary therapy. We conducted a study to evaluate the effects of fluvastatin on lipoprotein levels in subjects with primary hypercholesterolemia and to compare the efficacy and safety of two fluvastatin sodium dosing regimens: 20 mg once daily vs 10 mg twice daily. Design: We conducted a double-blind, placebo-controlled, multicenter trial involving 207 patients with low-density lipoprotein cholesterol levels of 4.15 mmol/L (160 mg/dL) or higher despite dietary intervention and with triglyceride levels of 3.38 mmol/L or lower. Three parallel treatment groups received 6 weeks of treatment with 20 mg of fluvastatin sodium once daily, 10 mg of fluvastatin sodium twice daily, or a placebo. Results: Total cholesterol and low-density lipoprotein cholesterol levels were reduced from baseline by 16% and 22%, respectively, with 20 mg of fluvastatin sodium once daily (P

Objective: The authors sought to determine the frequency of DSM-III personality disorders in subjects with obsessive-compulsive disorder, well comparison subjects, and their first-degree relatives. Method: Thirty-two subjects with obsessive-compulsive disorder and 33 age- (within 5 years) and gender-matched well comparison subjects were assessed with the Structured Interview for DSM-III Personality Disorder and several self-report instruments. Their first-degree relatives were assessed in a blind manner with the same instruments. Results: Subjects with obsessive-compulsive disorder were more likely than well comparison subjects to have a personality disorder, but compulsive personality was not the most frequent. No significant differences were found in the prevalence of personality disorders among first-degree relatives, including compulsive personality, or in obsessional, hysterical, or oral character traits. Conclusions: Personality disorders are highly prevalent among patients with obsessive-compulsive disorder, but the data do not support a relationship between obsessive-compulsive disorder and compulsive personality.

Objectives: The authors sought to determine the association between mental disorder and morbid obesity, defined as weight at least 100% or 100 lb over ideal body weight. Method: Eighty-eight morbidly obese subjects who had come to a tertiary care center surgery clinic requesting vertical banded gastroplasty were systematically interviewed with the National Institute of Mental Health Diagnostic Interview Schedule (DIS) and the Structured Interview for DSM-III Personality Disorders. A comparison group of 76 psychiatrically normal subjects who were matched in age (within 5 years) and gender to the morbidly obese subjects were also interviewed. Results: Most of the morbidly obese subjects were women, were of low socioeconomic status as indicated by method of payment for medical care, weighed more than 300 lb, and had been obese for more than 14 years. The morbidly obese subjects were more likely than the comparison group to have a lifetime history of mood disorders, anxiety disorders, bulimia, and tobacco dependence. The morbidly obese subjects were also more likely to meet diagnostic criteria for one or more personality disorders. Conclusions: Substantial psychopathology exists in morbidly obese individuals requesting gastroplasty, a finding that has important clinical implications.

Objective: Involvement of genetic factors in the pathogenesis of schizophrenia spectrum disorders has been indicated in twin, adoption, and familial aggregation studies; the pivotal role played by the dopamine transporter in dopaminergic neurotransmission makes it a candidate gene for these disorders. Detection of close linkage between a dopamine transporter marker and schizophrenia spectrum disorders would strongly support the existence of causal relationships between genetic mutations at the dopamine transporter locus and the disease phenotype. Method: The authors assessed the linkage between this gene and schizophrenia spectrum disorders by using polymorphic dopamine transporter gene markers in 156 subjects from 16 multiplex pedigrees with schizophrenia as well as schizophreniform, schizoaffective, and schizotypal disorders and mood-incongruent psychotic depression. Results: Complete ([Theta]=0.0) linkage to the schizophrenia spectrum was excluded under both dominant and recessive models. Conclusions: These results indicate that allelic variants at the dopamine transporter locus do not provide major genetic contributions to the etiology of schizophrenia and related disorders in these pedigrees.

Objective: To assess the prevalence of and risk factors for self-reported symptoms suggestive of multiple chemical sensitivities/idiopathic environmental intolerance (MCS/IEI) in Persian Gulf War (PGW) veterans from Iowa and a comparison group of PGW-era military personnel. Methods: A population-based sample of Iowa military personnel was surveyed using a cross-sectional telephone interview. Study participants were randomly drawn from 1 of 4 domains: PGW active duty, PGW National Guard/Reserve, non-PGW active duty, and non-PGW National Guard/Reserve. A complex sample survey design was used selecting participants from the following substrata: age, sex, race, rank, and military branch. The criteria for MCS/IEI were developed using expert consensus and the medical literature. Results: A total of 3695 study participants (76% of those eligible) completed the telephone survey. The prevalence of symptoms suggestive of MCS/IEI in all participants was 3.4%. Veterans of the PGW reported a significantly higher prevalence of symptoms suggestive of MCS/IEI than did non-PGW military personnel (5.4% vs 2.6%); greater sensitivity to organic chemicals, vehicle exhaust, cosmetics, and smog; and more lifestyle changes. The following risk factors for MCS/IEI were identified with univariate analysis: deployment to the Persian Gulf, age ([is greater than] 25 years), female sex, receiving a physician diagnosis of MCS, previous professional psychiatric treatment, previous psychotropic medication use, current psychiatric illness, and a low level of preparedness. Multiple logistic regression analysis identified several independent risk factors for MCS/IEI, including deployment to the Persian Gulf, age, sex, rank, branch of service, previous professional psychiatric treatment, and current mental illness. Conclusions: Self-reported symptoms suggestive of MCS/IEI are relatively frequent in a military population and are more common among PGW veterans than comparable controls. Reported chemical sensitivities and accompanying behavioral changes were also frequent. After adjusting for age, sex, and training preparedness, previous professional psychiatric treatment and previous psychotropic medication use (before deployment) showed a robust association with symptoms suggestive of MCS. Arch Intern Med. 2000;160:1169-1176

In the recently published revision of the Diagnostic and Statistical Manual of Mental Disorders, third edition - a reference book for the classification and diagnosis of psychiatric disorders - the term 'simple schizophrenia' has been omitted as a diagnostic category and it has been replaced by the term 'schizotypal personality'. Although usage of the earlier term has generally been discontinued in the United States, it remains in ICD-9 (International Classification of Diseases, ninth edition), a text which is used internationally. The authors believe the deletion is premature and simple schizophrenia should be reinstated as a diagnostic category in the forthcoming DSM-IV, as the nature of this disorder is not adequately described elsewhere. This condition was originally documented in the late nineteenth century by psychiatrists who classified it as a simple primary dementia syndrome. Subsequent investigators, Otto Diem and Eugen Bleuler, further described the condition and Kraepelin characterized simple schizophrenia, which he initially termed 'dementia praecox', as a specific disease. The scope and definition of this disorder have frequently changed over that last several decades. As a result the term 'schizophrenia' has become quite broad and the term 'simple schizophrenia' has been thought to be somewhat vague. However, further research is recommended before this classification be eliminated. The authors have enclosed an appendix entitled 'Proposed Criteria for Simple Schizophrenia (Simple Deteriorated State)' to assist in clarifying and defining simple schizophrenia. Included in the appendix are the description and duration of symptoms, criteria for the elimination of other possibilities such as organic causes, and the consideration of patient's history.