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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.

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.

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.