The International Mood Network (IMN) Nosology Project: differentiating borderline personality from bipolar illness.

OBJECTIVE: The differential diagnosis of bipolar illness vs. borderline personality is controversial. Both conditions manifest impulsive behavior, unstable interpersonal relationships, and mood symptoms. This study examines whether and which mood clinical features can differentiate between both conditions. METHOD: A total of 260 patients (mean ± standard deviation age 41 ± 13 years, 68% female) attending to a mood clinic were examined for diagnosis of bipolar illness and borderline personality disorder using SCID-I, SCID-II, and clinical mood criteria extracted from Mood Disorder Questionnaire (MDQ). They were analyzed using diagnoses as dependent variables. Predictors of bipolar and borderline diagnoses were identified by multivariable logistic regressions, and predictive validity of models was assessed using ROC curve analysis. RESULTS: Bipolar illness was strongly predicted by elevated mood (OR = 4.02, 95% CI: 1.80-9.15), increased goal-directed activities (OR = 3.90, 95% CI: 1.73-8.96), and episodicity of mood symptoms (OR = 3.48, 95% CI 1.49-8.39). This triad model predicted bipolar illness with 88.7% sensitivity, 81.4% specificity, and obtained an auROC of 0.91 (95% CI: 0.76-0.96) and a positive predictive value of 85.1%. For borderline personality disorder, only female gender was a statistically significant predictor (OR = 3.41, 95% CI: 1.29-13.7), and the predictive model obtained an auROC of 0.67 (95% CI: 0.53-0.74). CONCLUSION: In a mood disorder clinic setting, manic criteria and episodic mood course distinguished bipolar illness from borderline personality disorder.

A clinical predictive score for mood disorder risk in low-income primary care settings.

BACKGROUND: Despite availability of validated screening tests for mood disorders, busy general practitioners (GPs) often lack the time to use them routinely. This study aimed to develop a simplified clinical predictive score to help screen for presence of current mood disorder in low-income primary care settings. METHODS: In a cross-sectional study, 197 patients seen at 10 primary care centers in Santiago, Chile completed self-administered screening tools for mood disorders: the Patient Health questionnaire (PHQ-9) and the Mood Disorder Questionnaire (MDQ). To determine participants' current-point mood disorder status, trained clinicians applied a gold-standard diagnostic interview (SCID-I). A simplified clinical predictive model (CM) was developed based on clinical features and selected questions from the screening tools. Using CM, a clinical predictive score (PS) was developed. Full PHQ-9 and GP assessment were compared with PS. RESULTS: Using multivariate logistic regression, clinical and demographic variables predictive of current mood disorder were identified for a simplified 8-point predictive score (PS). PS had better discrimination than GP assessment (auROC-statistic=0.80 [95% CI 0.72, 0.85] vs. 0.58 [95% CI 0.52, 0.62] p-value <0.0001), but not as good as the full PHQ-9 (0.89 [95% CI 0.85, 0.93], p-value=0.03). Compared with GP assessment, PS increased sensitivity by 50% at a fixed specificity of 90%. Administered in a typical primary care clinical population, it correctly predicted almost 80% of cases. LIMITATIONS: Further research must verify external validity of the PS. CONCLUSION: An easily administered clinical predictive score determined, with reasonable accuracy, the current risk of mood disorders in low-income primary care settings.

Predictors of response to ziprasidone: results from a 6-week randomized double-blind, placebo-controlled trial for acute depressive mixed state.

INTRODUCTION: The present study is aimed at investigating possible predictors of response to ziprasidone in a sample of patients with mixed depressive state. METHODS: 72 patients were randomized to either ziprasidone or placebo and treated prospectively for 6 weeks. The clinical response and remission were defined with various clinical variables including Montgomery Asberg Depression Rating Scale. Further outcome measures included predictors of remission and other clinical variables over time. RESULTS: None of the variables under investigation were significantly associated with response or remission at 6 weeks (all p-values>0.003, respectively). CONCLUSIONS: Further investigations are warranted due to clear limitations, mostly small sample size and use of concomitant medications.

Affective temperaments in clinical practice: a validation study in mood disorders.

BACKGROUND: We sought to examine correlations between clinical validators and temperaments in clinical practice. METHODS: We provided the self-report TEMPS-A (50 item long) to 123 consecutive patients seen in the Mood Disorders Program of Tufts Medical Center. Temperament was assessed as cyclothymia, dysthymia, irritable or hyperthymia. Cut-offs were tested using (50%) and (75%) thresholds of affirmative responses, as well as highest percent for dominant temperament. We reported no dominant temperament at 75% cut-off . Multivariate regression modeling was conducted to assess confounding bias. RESULTS: Using clinical and demographic validators, cyclothymia was the most strongly validated temperament, followed by dysthymia and hyperthymia. Irritable temperament did not appear to be valid in this sample. A 75% item endorsement cut-off appeared to identify clinically important temperaments in slightly less than half of this sample. Those without any temperament at 75% cut-off had better prognostic features. 50% cut-off was highly nonspecific, and poorly correlated with diagnostic validators. CONCLUSIONS: Affective temperaments correlate with clinical validators, most robustly for cyclothymia. 75% cut-off on the TEMPS may provide a useful categorical definition of abnormal affective temperaments in mood disorders. With that definition, slightly less than one-half of patients with mood disorders have affective temperaments. Those without abnormal affective temperaments have better prognostic features.

Asking fathers: a study of psychosocial adaptation.

Although few contemporary studies specifically address paternal adaptation, the theme of paternal estrangement from medical care and from family relationships is pervasive in the psychosocial literature on haemophilia. This estrangement has been shown to have a negative effect on fathers' psychological well-being, marital relationships and the adaptive outcome of their sons who have haemophilia. The goals of this study were to provide contemporary data on the psychosocial adaptation of fathers of boys with haemophilia and to examine specific variables that might influence their adjustment. Eighty-three eligible fathers returned a survey instrument that collected demographic and medical information, as well as scores on self-measures of adaptation in marital and parenting roles. Statistically significant direct correlations (P < 0.01) were found between fathers' scores on the Marital Adjustment Test and the Parenting Sense of Competence subscales (parenting efficacy and satisfaction). Variables specific to rearing a son with haemophilia that negatively affected fathers' marital adjustment scores included: feeling left out of medical decision making by their wives or partners, worry about their sons' having limited activity, and the presence of a secondary diagnosis in the affected child. Scores on the parenting efficacy subscale of the PSOC were statistically significantly reduced (i.e. fathers felt less effective in the parenting role) in men who 'rarely' or 'never' infused their sons (42/80, 53%). Variables that negatively affected scores on the parenting satisfaction subscale included frustrating interactions with medical staff and concern about their sons' potential to contract an infection or secondary diagnosis. This paper presents a model to examine the interrelationships among the data and discusses the clinical implications.

Genetics and social class.

OBJECTIVE: To assess claims that genes are a major determinant of social class. DESIGN: Using genetic epidemiological principles, five claims on the role of genes in determining social class are examined: (1) traits that run in families are usually inherited; (2) complex traits can be explained by alleles at a single gene locus; (3) complex traits are transmitted intact from one generation to the next; (4) natural selection explains social advantage. (5) Heritability estimates provide a valid estimate of the importance of genes in explaining complex human traits or behaviour. RESULTS: (1) Traits that run in families can result from environmental exposures that differ by social class. (2) The protein encoded by any single gene has too narrow a range of biological activity to explain traits as complex as social status. (3) Because alleles at different gene loci are transmitted independently, genetic inheritance cannot explain why offspring display the same complex traits as their parents. (4) The propagation of mutations that might result in a selective advantage takes much longer than the time for which any social class has achieved or maintained dominance. (5) Heritability measures are accurate only when environment is maintained constant. This is impossible in evaluating human traits. CONCLUSIONS: The roots of social class differences do not lie in our genes. Consequently, genetics cannot be used as a justification for maintaining a ruling class, limiting procreation among the poor, or minimising social support programmes.

Carrier screening for cystic fibrosis among Maryland obstetricians before and after the 1997 NIH Consensus Conference.

The 1997 National Institutes of Health (NIH) Consensus Conference on Cystic Fibrosis (CF) testing recommended that carrier screening be offered to all pregnant women and couples planning a pregnancy. We surveyed 492 Maryland Ob-Gyns before and after the consensus conference to: (1) assess whether obstetricians changed their practice regarding CF carrier testing, and (2) identify the factors associated with changing practice patterns, including awareness of the statement, and knowledge about CF. Fifty-six percent (275) responded to the first mail questionnaire and 107 obstetricians responded to both questionnaires. In 1998, only 18% of respondents to the second questionnaire were familiar with the NIH statement, but 43% reported discussing testing with patients with no family history, a significant increase from 1997, when only 20% reported discussing testing. Less than one-third correctly answered six multiple-choice knowledge questions about CF and carrier testing. In multivariate analysis, knowledge and familiarity with the NIH consensus statement were not associated with beginning to discuss CF carrier testing after the CF conference with their patients without a family history.

Putting the search for genes in perspective.

The sequencing of the human genome has been heralded by both the mass media and scientists as a breakthrough that will allow the detection of individuals at increased risk for common diseases and the tailoring of drugs to an individual's genetic profile in order to prevent disease. Sequencing is likely to benefit those at risk of developing rare diseases in which inherited mutations in a single gene play a major causal role. In the vast majority of people with common diseases, however, genotypes at many different loci, as well as environmental exposures, must be simultaneously present before disease appears. Elucidating the genes involved will prove elusive. In addition to the large number, different combinations account for a particular disease. Most of the genotypes that contribute to the constellation of necessary genes are uncommon and will be difficult to find. Common genotypes may confer susceptibility but will be weak predictors of disease. Because of the difficulty of discovering genes for common diseases, designing therapies will also prove difficult. More attention to environmental risk factors for particular diseases will have greater yield than a genetic search, but this too will be difficult because of environmental-genetic and other interactions. The search for risk factors for particular diseases neglects the political and social milieu in which individuals swim or sink and in which all diseases occur.

Primary care physicians' perceptions of barriers to genetic testing and their willingness to participate in research.

Our objective was to explore the barriers and motivations to: 1) appropriate diffusion of genetic services into primary care practice; and 2) primary care physicians' (PCPs) willingness to participate in clinical studies to assess the safety and effectiveness of emerging genetic technologies. A random sample (n = 994) of PCPs was invited to be interviewed. Of the 80 who agreed, 60 were interviewed, 52 by telephone. A semi-structured guide was used. A questionnaire mailed to 752 of the PCPs was used to elicit information from physicians who did not want to be interviewed. Among interviewees, uncertainty as to the clinical utility and clinical validity of predictive genetic testing were the leading barriers to incorporation of this technology into practice, being mentioned by 60 and 43% of subjects, respectively. Of the 100 (13. 3%) physicians returning the questionnaire who declined to be interviewed, 30% said they would be willing to participate in research on the safety and effectiveness of predictive genetic tests. Of those who were interviewed, 92% were willing to participate in such research. Most physicians do not see genetics as important in their practice today; many anticipate greater importance in the future. The proportion of physicians interested in participating in research to assess the safety and effectiveness of genetic tests is sufficient to make large scale, collaborative, practice-based evaluation feasible. Additionally, participation in research may serve as an effective medium for physician education in genetics.

Factors influencing health insurers' decisions to cover new genetic technologies.

OBJECTIVE: To examine the relative importance of factors influencing health insurers' coverage of new genetic technologies. METHODS: A national survey in which the decision makers for private health insurers were asked whether they would cover cystic fibrosis (CF) carrier screening, testing for genetic susceptibility to breast cancer (BRCA test), and medical costs of a clinical trial of gene therapy for CF under a variety of conditions. RESULTS: Respondents' coverage of the two tests and of medical costs of clinical trials was low at the time of the study (4%-15.5% of insurers). Their coverage of CF carrier screening and BRCA testing would be increased significantly if the group tested was restricted to those at high risk, if detection rates were higher and costs lower, and if testing was endorsed by a national professional group or consensus conference. Coverage of the medical costs of a trial of CF gene therapy would be significantly more likely if the trial was restricted to children or adults with severe CF, safety and effectiveness was proven, and therapy could be administered in a regional hospital or an outpatient setting rather than in a research hospital. CONCLUSIONS: Health insurers play a critical role in the diffusion of new genetic technologies. The validity of genetic tests and the safety and effectiveness of new therapies are primary factors influencing health insurers' coverage. Lower costs and approval of professional groups are other factors associated with increased coverage.

Should women at increased risk for breast and ovarian cancer be randomized to prophylactic surgery? An ethical and empirical assessment.

More information is needed about the relative effectiveness of prophylactic surgery, chemoprevention, and surveillance in reducing breast and ovarian cancer risk in women with an inherited susceptibility mutation. We assessed practical and ethical barriers to conducting randomized clinical trials (RCTs) to compare preventive interventions for breast and ovarian cancer. Eighty-seven at-risk women who attended an education and counseling session about BRCA1/2 testing were asked about their willingness to participate in hypothetical research studies for breast and ovarian cancer risk reduction. In addition, 247 Maryland physicians from five specialties completed a mail survey including a question about their likelihood of recommending RCT participation to an at-risk woman. Nineteen percent of at-risk women reported willingness to participate in a hypothetical RCT for breast cancer risk reduction and 17% for ovarian cancer risk reduction. Women with children and women likely to have a prophylactic mastectomy if found to have a susceptibility mutation were significantly more willing to participate in an RCT. A majority of women would be willing to participate in nonrandomized trials or registries. Fifty-two percent of physicians responded that they would be likely to recommend RCT participation to a woman carrying a breast cancer susceptibility mutation. Oncologists were the most likely to recommend an RCT. Although the results of nonrandomized trials may be difficult to interpret because of such issues as selection bias. Greater feasibility combined with fewer ethical concerns make nonrandomized trials a more viable alternative to randomized trials for evaluation of preventive interventions for breast and ovarian cancer when prophylactic surgery is one of the treatments being evaluated.

Promoting safe and effective genetic tests in the United States: work of the task force on genetic testing.

The Task Force on Genetic Testing was created to review genetic testing in the United States and, when necessary, to make recommendations to ensure the development of safe and effective genetic tests. A survey to explore the state of genetic testing was undertaken for the Task Force and completed in early 1995. The survey, as well as literature reports and other information collected for the Task Force, showed problems affecting safety and effectiveness, as defined by the Task Force: validity and utility of predictive tests, laboratory quality, and appropriate use by healthcare providers and consumers. On the basis of these findings, the Task Force made several recommendations to ensure safe and effective genetic testing. The Secretary of Health and Human Services followed up one recommendation by creating the Secretary's Advisory Committee on Genetic Testing. One of its functions will be to implement other recommendations of the Task Force.