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OBJECTIVE: The authors compared the efficacy and tolerability of low and moderate dosages of extended-release quetiapine in adults with borderline personality disorder. METHOD: Ninety-five participants with DSM-IV borderline personality disorder were randomly assigned to receive 150 mg/day of quetiapine (the low-dosage group; N=33), 300 mg/day of quetiapine (the moderate-dosage group; N=33), or placebo (N=29). Total score over time on the clinician-rated Zanarini Rating Scale for Borderline Personality Disorder ('Zanarini scale') was analyzed in a mixed-effects model accounting for informative dropout. RESULTS: Participants in the low-dosage quetiapine group had significant improvement on the Zanarini scale compared with those in the placebo group. Time to response (defined as a reduction of 50% or more on the Zanarini scale total score) was significantly shorter for both the low-dosage quetiapine group (hazard ratio=2.54, p=0.007) and the moderate-dosage quetiapine group (hazard ratio=2.37, p=0.011) than for the placebo group. Among participants who completed the study, 82% in the low-dosage quetiapine group were rated as 'responders,' compared with 74% in the moderate-dosage group and 48% in the placebo group. Treatment-emergent adverse events included sedation, change in appetite, and dry mouth. The overall completion rate for the 8-week double-blind treatment phase was 67% (67% for the low-dosage quetiapine group, 58% for the moderate-dosage quetiapine group, and 79% for the placebo group). Participants who experienced sedation were more likely to drop out. CONCLUSIONS: Participants treated with 150 mg/day of quetiapine had a significant reduction in the severity of borderline personality disorder symptoms compared with those who received placebo. Adverse events were more likely in participants taking 300 mg/day of quetiapine. [ABSTRACT FROM AUTHOR]

Objective: Multiple sources of evidence suggest that genetic factors influence variation in clinical features of schizophrenia. The authors present the first genome-wide association study (GWAS) of dimensional symptom scores among individuals with schizophrenia. Method: Based on the Lifetime Dimensions of Psychosis Scale ratings of 2,454 case subjects of European ancestry from the Molecular Genetics of Schizophrenia (MGS) sample, three symptom factors (positive, negative/disorganized, andmood) were identified with exploratory factor analysis. Quantitative scores for each factor from a confirmatory factor analysis were analyzed for association with 696,491 single-nucleotide polymorphisms (SNPs) using linear regression, with correction for age, sex, clinical site, and ancestry. Polygenic score analysis was carried out to determine whether case and comparison subjects in 16 Psychiatric GWAS Consortium (PGC) schizophrenia samples (excluding MGS samples) differed in scores computed by weighting their genotypes by MGS association test results for each symptom factor. Results: No genome-wide significant associations were observed between SNPs and factor scores. Most of the SNPs producing the strongest evidence for association were in or near genes involved in neurodevelopment, neuroprotection, or neurotransmission, including genes playing a role in Mendelian CNS diseases, but no statistically significant effect was observed for any defined gene pathway. Finally, polygenic scores based on MGS GWAS results for the negative/disorganized factor were significantly different between case and comparison subjects in the PGC data set; for MGS subjects, negative/ disorganized factor scores were correlated with polygenic scores generated using case-control GWAS results from the other PGC samples. Conclusions: The polygenic signal that has been observed in cross-sample analyses of schizophrenia GWAS data sets could be in part related to genetic effects on negative and disorganized symptoms (i.e., core features of chronic schizophrenia). [ABSTRACT FROM AUTHOR]

Objective: To evaluate previously reported associations of copy number variants (CNVs) with schizophrenia and to identify additional associations, the authors analyzed CNVs in the Molecular Genetics of Schizophrenia study (MGS) and additional available data. Method: After quality control, MGS data for 3,945 subjects with schizophrenia or schizoaffective disorder and 3,611 screened comparison subjects were available for analysis of rare CNVs (<1% frequency). CNV detection thresholds were chosen that maximized concordance in 151 duplicate assays. Pointwise and gene-wise analyses were carried out, as well as analyses of previously reported regions. Selected regions were visually inspected and confirmed with quantitative polymerase chain reaction. Results: In analyses of MGS data combined with other available data sets, odds ratios of 7.5 or greater were observed for previously reported deletions in chromosomes 1q21.1, 15q13.3, and 22q11.21, duplications in 16p11.2, and exon-disrupting. deletions in NRXN1. The most consistently supported candidate associations across data sets included a 1.6-Mb deletion in chromosome 3q29 (21 genes, TFRC to BDH1) that was previously described in a mild-moderate mental retardation syndrome, exonic duplications in the gene for vasoactive intestinal peptide receptor 2 (VIPR2), and exonic duplications in C16orf72. The case subjects had a modestly higher genome-wide number of gene-containing deletions (>100 kb and >1 Mb) but not duplications. Conclusions: The data strongly confirm the association of schizophrenia with 1q21.1, 15q13.3, and 22q11.21 deletions, 16p11.2 duplications, and exonic NRXN1 deletions. These CNVs, as well as 3q29 deletions, are also associated with mental retardation, autism spectrum disorders, and epilepsy. Additional candidate genes and regions, including VIPR2, were identified. Study of the mechanisms underlying these associations should shed light on the pathophysiology of schizophrenia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 1870 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Presents a case of a patient with problematic use of the Internet, a new category of psychopathology. Patient's history that raises questions about the relationship of his excessive use of the Internet for viewing pornography and the return of a depressed mood; Issue of how best to diagnose the patient's problematic sexual behavior.

Investigates the family history and psychiatric comorbidity of compulsive buyers. Detailed overview of compulsive buying; Characteristics of compulsive buying; Analysis of statistical data on lifetime psychiatric diagnoses of compulsive buyers; conclusions of this investigation.

Describes the sociodemographic features, phenomenology, and psychiatric comorbidity of 36 subjects reporting compulsive sexual behavior. Description of sexual behavior as poorly controlled with subjective distress or impairment in interpersonal functioning; Application of comorbid psychiatric diagnosis; Possible occurrence of compulsive sexual behavior in heterogenous group.

Determines the frequency of DSM-III personality disorders in subjects with obsessive-compulsive disorder, well-comparison subjects, and their first-degree relatives. No significant differences findings in the prevalence of personality disorders among first-degree relatives; High prevalence of personality disorder among patients with obsessive-compulsive disorder.

Objective: Sociodemographic features, phenomenology, and psychiatric comorbidity of 30 subjects reporting pathological gambling behavior were examined. Methods: Twenty-three men and seven women were recruited by advertisement and word-of-mouth. They all scored higher than 5 points on the South Oaks Gambling Screen, indicating problematic gambling behaviors. They completed structured and semistructured assessments, including the Diagnostic Interview Schedule for DSM-III-R disorders (DIS), the Personality Diagnostic Questionnaire, Fourth Revision (PDQ-IV), and the Minnesota Impulsive Disorders Interview. Results: The typical subject was a 44-year-old white married man with a mean income of $34,250 who visited a casino once or more weekly. All 30 subjects reported gambling more money than they intended to. Twenty subjects (67 percent) reported gambling as a current problem, and nine (30 percent) reported it as a past problem. Twentyone subjects (70 percent) wanted to stop gambling but did not feel they could. According to DIS results, 18 subjects (60 percent) had a lifetime mood disorder, 19 (64 percent) a lifetime substance use disorder, and 12 (40 percent) a lifetime anxiety disorder. Based on the PDQ-IV, 26 subjects (87 percent) had a personality disorder, the most common being obsessive-compulsive, avoidant, schizotypal, and paranoid personality disorders. The sample also had a relatively high rate of antisocial personality disorder. Impulse control disorders were common, especially compulsive buying and compulsive sexual behavior. Conclusions: The results confirm that individuals with pathological gambling suffer substantial psychiatric comorbidity. They support continued inclusion of pathological gambling in the diagnostic category of impulse control disorders. [ABSTRACT FROM AUTHOR]

Focuses on a study pertaining to psychiatry, which identifies the chromosomal regions which contain genes of schizphrenia susceptibility. Reference to the performance of nonparametric linkage; Limitations of the study; Conclusion and discussion of the study.

Specified diagnostic criteria have been credited, in part, with improving diagnostic reliability. The authors hypothesize that nonuniform application of these criteria across different research centers has been one factor responsible for the failure to replicate research findings. For example, researchers using a narrow interpretation of the Research Diagnostic Criteria (RD C) have found a highly significant association between endogenous depression and a positive dexamethasone suppression test result, whereas researchers using a broad interpretation have failed to find the predicted relationship. The authors used two interpretations of the RDC and DSM-III endogenous/melancholia criteria to diagnose 60 depressed patients and found significant differences in rates of diagnoses and symptoms. [ABSTRACT FROM AUTHOR]

The diagnostic category called simple schizophrenia has disappeared from official American nosology but has been retained in ICD-9. The diagnosis has a long history, was one of the traditional schizophrenic subtypes identified by Bleuler, and was later accepted by Kraepelin. The authors provide a historical overview of the concept, review its modern successors, and provide recommendations for its inclusion in DSM-IV as a proposed diagnostic category needing further study. [ABSTRACT FROM AUTHOR]

The authors studied 401 patients with depressions secondary to psychiatric illnesses (substance abuse disorders or somatoform, anxiety, or personality disorders) or depressions secondary to medical illnesses. They found that the patients with depressions secondary to psychiatric illnesses had an earlier age at onset, were more likely to have suicidal thoughts or to have made suicide attempts, were less likely to have memory problems, were less improved with treatment and more likely to relapse on follow-up, and had more alcoholism in their families than patients with depressions secondary to medical illnesses. Depressions secondary to medical illnesses seem to fit the category of reactive depression, and depressions secondary to psychiatric illnesses fit the definition of neurotic depression. [ABSTRACT FROM AUTHOR]

On the basis of a case-control study, the authors conclude that former psychiatric inpatients are more likely than control subjects to die of both natural and unnatural causes within 2 years of discharge. Patients who committed suicide were more likely to have had a diagnosis of affective disorder (unipolar depression) or alcoholism. Those who died of natural causes were more likely to have been admitted with medical diagnoses; no specific psychiatric diagnoses were associated with these deaths. It is doubtful that medical illnesses caused psychiatric syndromes such as depression in these inpatients. Psychiatric and medical illnesses combined may increase a patient's likelihood of seeking psychiatric help and entering the hospital. [ABSTRACT FROM AUTHOR]

The authors report suicide risk among 1,593 patients with major depression or bipolar disorder, 443 (27.8%) of whom were psychotic (260 bipolar and 183 unipolar). The subjects were followed for 0–14 years, and their suicide experience was compared with that of the state population. Eight (19.5%) of the 41 suicide victims were from the psychotic group. The psychotic and nonpsychotic subjects in each diagnostic group had similar risks for suicide. A higher risk for suicide was not found in the bipolar subjects. The authors conclude that among patients with major affective disorder psychosis per se does not predispose to suicide. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Effectiveness of Adjunctive Systems Training for Emotional Predictability and Problem Solving (STEPPS) Group Treatment in Borderline Personality disorder patients," by Nancee Blum in the April 2008 issue.

A letter to the editor is presented about the link between extreme haircutting and psychosis.

Presents a letter to the editor on suicide and psychotic depression.

A response by Donald W. Black to a letter to the editor about his article "Simple Schizophrenia: Past, Present, and Future" in a previous issue is presented.

A response to a letter to the editor about his article on depressions as secondary to psychiatric and other illnesses in the 1988 issue is presented.