Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium.

BACKGROUND: Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. METHODS: This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). RESULTS: Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (ß std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. CONCLUSIONS: Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

Metacognitive beliefs mediate the effect of emotional abuse on depressive and psychotic symptoms in severe mental disorders.

BACKGROUND: Early trauma is linked to higher symptom levels in bipolar and psychotic disorders, but the translating mechanisms are not well understood. This study examines whether the relationship between early emotional abuse and depressive symptoms is mediated by metacognitive beliefs about thoughts being uncontrollable/dangerous, and whether this pathway extends to influence positive symptoms. METHOD: Patients (N = 261) with psychotic or bipolar disorders were assessed for early trauma experiences, metacognitive beliefs, and current depression/anxiety and positive symptoms. Mediation path analyses using ordinary least-squares regressions tested if the effect of early emotional abuse on depression/anxiety was mediated by metacognitive beliefs, and if the effect of early emotional abuse on positive symptoms was mediated by metacognitive beliefs and depression/anxiety. RESULTS: Metacognitive beliefs about thoughts being uncontrollable/dangerous significantly mediated the relationship between early emotional abuse and depression/anxiety. Metacognitive beliefs and depression/anxiety significantly mediated the relationship between early emotional abuse and positive symptoms. The models explained a moderate amount of the variance in symptoms (R 2 = 0.21-0.29). CONCLUSION: Our results indicate that early emotional abuse is relevant to depression/anxiety and positive symptoms in bipolar and psychotic disorders, and suggest that metacognitive beliefs could play a role in an affective pathway to psychosis. Metacognitive beliefs could be relevant treatment targets with regards to depression/anxiety and positive symptoms in bipolar and psychotic disorders.

Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium.

OBJECTIVE: Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia. METHOD: This prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness. RESULTS: Positive symptom severity was negatively related to STG thickness in both hemispheres (left: ßstd = -0.052; P = 0.021; right: ßstd = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness. CONCLUSION: Our findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia.

Modelling difficulties in abstract thinking in psychosis: the importance of socio-developmental background.

INTRODUCTION: Abstract thinking is important in modern understanding of neurocognitive abilities, and a symptom of thought disorder in psychosis. In patients with psychosis, we assessed if socio-developmental background influences abstract thinking, and the association with executive functioning and clinical psychosis symptoms. METHODS: Participants (n = 174) had a diagnosis of psychotic or bipolar disorder, were 17-65 years, intelligence quotient (IQ) > 70, fluent in a Scandinavian language, and their full primary education in Norway. Immigrants (N = 58) were matched (1:2) with participants without a history of migration (N = 116). All participants completed a neurocognitive and clinical assessment. Socio-developmental background was operationalised as human developmental index (HDI) of country of birth, at year of birth. Structural equation modelling was used to assess the model with best fit. RESULTS: The model with best fit, χ2 = 96.591, df = 33, p < .001, confirmed a significant indirect effect of HDI scores on abstract thinking through executive functioning, but not through clinical psychosis symptoms. CONCLUSIONS: This study found that socio-developmental background influences abstract thinking in psychosis by indirect effect through executive functioning. We should take into account socio-developmental background in the interpretation of neurocognitive performance in patients with psychosis, and prioritise cognitive remediation in treatment of immigrant patients.

Childhood trauma mediates the association between ethnic minority status and more severe hallucinations in psychotic disorder.

BACKGROUND: Ethnic minority status and childhood trauma are established risk factors for psychotic disorders. Both are found to be associated with increased level of positive symptoms, in particular auditory hallucinations. Our main aim was to investigate the experience and effect of childhood trauma in patients with psychosis from ethnic minorities, hypothesizing that they would report more childhood trauma than the majority and that this would be associated with more current and lifetime hallucinations. METHOD: In this cross-sectional study we included 454 patients with a SCID-I DSM-IV diagnosis of non-affective or affective psychotic disorder. Current hallucinations were measured with the Positive and Negative Syndrome Scale (P3; Hallucinatory Behaviour). Lifetime hallucinations were assessed with the SCID-I items: auditory hallucinations, voices commenting and two or more voices conversing. Childhood trauma was assessed with the Childhood Trauma Questionnaire, self-report version. RESULTS: Patients from ethnic minority groups (n = 69) reported significantly more childhood trauma, specifically physical abuse/neglect, and sexual abuse. They had significantly more current hallucinatory behaviour and lifetime symptoms of hearing two or more voices conversing. Regression analyses revealed that the presence of childhood trauma mediated the association between ethnic minorities and hallucinations. CONCLUSIONS: More childhood trauma in ethnic minorities with psychosis may partially explain findings of more positive symptoms, especially hallucinations, in this group. The association between childhood trauma and these first-rank symptoms may in part explain this group's higher risk of being diagnosed with a schizophrenia-spectrum diagnosis. The findings show the importance of childhood trauma in symptom development in psychosis.

Allocating medical resources in rural America: alternative perceptions of justice.

In national debates concerning the allocation of medical resources rural America is a neglected topic, and the voices of rural health professionals are seldom heard. This paper highlights the special problems encountered in allocating medical resources within the rural setting and indicates the strategies that rural residents compose for dealing with them. Our findings are based on a study consisting of in-depth open-ended interviews with family physicians in the rural northwest United States. We contrast the approach to justice expressed by these rural physicians with the conception of justice that dominates Western philosophy and bioethics. In the course of our discussion, the diversity within Western culture becomes apparent. We discuss strategies for incorporating different perspectives into local and national allocation debates, clarify the reasons why a more encompassing approach to justice is necessary, and review the implications of our work for future research.

Evaluation of a physician education intervention to improve primary care for low-back pain. II. Impact on patients.

A physician education intervention was previously found to have significantly improved perceived physician knowledge, confidence, and patient-reassuring behavior in the treatment of low-back pain. This study examined whether this intervention, presented in a health maintenance organization clinic, had an effect on patient outcomes. Outcomes of care for 148 patients seen for low-back pain before the intervention were compared with outcomes of care for 157 patients seen after the intervention. Patients were telephoned 2-4 weeks after their back-pain visit and were asked about symptom improvement, amount of disability, and satisfaction with care. Satisfaction was measured with a three-dimensional instrument for low-back pain developed specifically for this study, which was found to be valid and reliable. The preintervention and postintervention patient cohorts were similar in terms of key baseline variables. Despite its apparent benefit to physicians, the intervention did not result in significant improvements in any patient outcomes, even for the subset of patients whose physicians had perceived the greatest benefit.

Evaluation of a physician education intervention to improve primary care for low-back pain. I. Impact on physicians.

In an effort to improve the cost-effectiveness of primary care for low-back pain, we developed, implemented, and evaluated a physician education intervention. The program was designed to provide family physicians with specific information, tools, and techniques that our previous studies and the literature suggested should be associated with more satisfying and cost-effective care for low-back pain. The in-clinic educational intervention included feedback of the findings of our previous studies of care for back pain (comparing family physicians and chiropractors), an up-to-date summary of scientific knowledge relevant to the management of back pain in primary care, a videotape contrasting ineffective and effective patient encounters, and a clinical assessment form for low-back pain. The back pain-related beliefs, attitudes, and behaviors of 15 primary care providers in a large health maintenance organization clinic and of 14 family physicians in six group practices were assessed before and after the intervention. Significant increases were noted in the proportions of providers who felt confident they knew how to manage low-back pain, who believed their patients were satisfied, and who claimed they reassured patients that they did not have serious disease. The intervention, however, had little impact on the prevalence of negative feelings about patients with back pain or frustration with patients who wanted their doctor to "fix" their problem. The intervention had a similar impact on health maintenance organization and fee-for-service physicians.

Misconduct in science: does family medicine have a problem?

Through several recent and widely publicized cases, misconduct in science has caught the public's attention and reached the agenda of Congress. After a brief historical overview, this article presents a number of cases from family medicine raising issues of duplicate publication, plagiarism, inappropriate authorship, citation errors, inappropriate attribution, and data manipulation and fabrication. Misconduct policies from national organizations are noted, and specific recommendations are made that would limit growth of misconduct in the family medicine research community.

Case-control diagnosis and Bayesian inference in common viral infections.

The predictive values of symptoms and signs for given diseases are often unknown. The fact that a high proportion of individuals with a certain disease may have a specific group of symptoms (the case-control approach) does not necessarily mean that the specific group of symptoms will allow one reliably to diagnose the disease. This study, utilizing a population based data set for common acute infections, shows that descriptions of common viral illnesses found in medical textbooks that associate illnesses with symptoms do not allow one to predict reliably isolation of the supposed causal organism. Positive predictive value of groups of symptoms for specific viral infections did not exceed 11 percent in this study. However, the data closely fitted the Bayesian statistical model often proposed for such decision making by physicians.

Does continuing medical education improve the quality of medical care? A look at the evidence.

Although continuing education has a long tradition within the medical profession, mandated continuing medical education is of very recent origin. The conceptual framework used to justify continuing medical education is that it exposes physicians to new knowledge, changes physician behavior, and favorably alters patient outcomes. Considerable evidence exists that physician knowledge can be increased, and that behavior can be changed, but there is very little to show an effect on patient outcomes. The effectiveness of continuing medical education is further clouded by such issues as consumerism, licensure politics, and professional standards review organization legislation. Family physicians should have a role in determining the outcome of the continuing medical education debate, as participants, as policy-setters, and as informed critics.

Some non-random views of statistical significance.

Although research in family medicine is growing rapidly, few family physicians have had experience or training in statistical methods. Statistical significance and P values are often misunderstood and frequently misapplied. "Significance" is arbitrary; the actual P value is of greater interest than a significant/not significant statement; P values do not measure the strength of an association; statistical significance is not equivalent to "actual" significance; P values are largely dependent on sample size; and data "dredging" is guaranteed to yield spurious results. Competent statistical consultation, careful study planning, and recognition of statistical pitfalls are important to anyone who does research, and knowledge of these areas is useful as well to anyone reading the medical literature.

Placebos: a brief review for family physicians.

Placebos are as old as the practice of medicine and for thousands of years represented nearly the totality of medical therapeutics. Positive and negative placebo effects occur in about 35 percent and 10 percent of individuals, respectively. Without exception, all medical therapeutics may be assumed to have significant placebo components. Factors contributing to the success of placebos are many, but include the expectations of physician and patient, the doctor-patient relationship, and societal norms. Ethical issues regarding the use of placebos are not clear-cut but, in general, the use of placebos is contraindicated except as an adjunct to specific therapy, or as a research tool with informed consent.

The placebo effect reconsidered.

Usage of the terms placebo and placebo effect has changed dramatically within medical history. Although placebos are still useful within research, the placebo effect has become a large and ill-defined concept threatening to obscure rather than to clarify whatever phenomenon is being described. Placebos and placebo effects should be fundamentally reconsidered if they are to be of continued use in medical practice.

Lower genitourinary infections in women.

Vaginitis, cystitis, urethritis, and cervicitis are common diagnoses made in women attending family physicians' offices. Recent research has fundamentally altered available information on the diagnosis and management of these common genitourinary infections. This clinical review discusses presenting symptoms, physical findings, laboratory diagnostic aids, treatment, and follow-up for each lower genitourinary syndrome in women concluding with a summary flow chart illustrating an overall recommended approach.

Preventing and managing pelvic inflammatory disease: key questions, practices, and evidence.

Clinicians play a pivotal role in protecting women from pelvic inflammatory disease (PID), one of the most prevalent and serious diseases affecting women of reproductive age. This article examines PID prevention and management by critically addressing five questions: (1) What are the key risk factors for PID? (2) What are the principal microorganisms involved in PID? (3) What are the appropriate diagnostic criteria for PID? (4) What are the best treatment regimens for PID? and (5) What are the effective strategies for preventing PID? In addressing each of these questions, the quality of available evidence and recommended practice is discussed and gaps in the evidence are highlighted.

The Journal of Family Practice 1974-1988. Window to an evolving academic discipline.

This paper examines the spontaneous evolution of original work in family practice as published in The Journal of Family Practice over the 15-year period since it began publication in 1974. An analysis was carried out by principal content and type of paper for the last five years in a manner comparable to an earlier analysis of the journal's first ten years of publication. Trends that emerge from this reanalysis provide a window to observe the further development of family medicine as a scientific and academic discipline. The last five years have seen a marked increase in clinical content of papers (from approximately 60 to 80 percent of published papers) together with continued emphasis on health services subjects. There has been a concurrent sharp increase in research papers, continued strong representation of case studies, and some decrease in both reviews and methods papers. Descriptive research continues to predominate among research papers. Although experimental research still represents only 5 percent of published papers, this percentage has more than doubled over the last five years. The reanalysis also revealed a substantial decline in the proportion of educational papers, as other journals in the field have assumed the primary role for this content area. It appears that the manuscript supply represented by original work in the field is still limited and that there is at present adequate or even surplus journal capacity for publication of work carried out in family practice settings. The quality and type of work continue to mature consistent with the needs of family medicine as a scientific and academic discipline.

The Journal of Family Practice--1974-1983: analysis of an evolving literature base.

This paper examines the spontaneous evolution of original work in the field of family practice as published in this journal over the past ten years. An analysis was carried out by principal content, by type, and by source of the more than 1,700 papers published during that period. More than one half (currently 60 percent) of published papers have dealt with biomedical subjects; a majority of the remaining papers have dealt with health services and educational subjects. The most common type of paper has been observational research, with case studies, reviews, methods, opinion, and experimental research following in that order. The last five years have seen a continuing increase in the proportion of observational research papers, a slight decrease in reviews and opinion, and a marked decrease in methods papers. Sixty percent of published papers have been contributed by family physicians or others working in family practice settings. About three fourths of papers have been contributed from university or medical school settings, with one fourth from various community settings. All parts of the country have contributed to the publication of original work in the field. The trends that have been identified over the first ten years in terms of focus and content of the literature of record seem quite appropriate for the current and next stages of development of family practice as a clinical specialty.

Evaluation of fatigue in a family practice.

A retrospective chart review describing the rates of occurrence, methods of evaluation, and diagnoses of patients complaining of fatigue in a university family medicine teaching practice was performed. After excluding patients in whom an unequivocal explanation for the fatigue was reached at the initial encounter, 118 patients aged 15 years and over were identified during a two-year study in a practice with about 6,000 active adult patients (9.9/1,000 patients per year). The age and sex distributions of the cases were identical to those of the active patient population. The average laboratory examination cost approximately $48. An average of 2.7 laboratory tests per patient were ordered. Although 12 percent of laboratory tests were abnormal, laboratory tests were important in securing a diagnosis in only 9 of the 118 patients. Clinical diagnoses were classified as either primarily biomedical or primarily psychosocial. Psychosocial diagnoses were identified in 50 percent of patients, while primarily biomedical diagnoses were found in 22 percent. No diagnosis was made in 28 percent of patients. Sixty-eight percent of patients had at least one follow-up visit. Failure to follow up was uncommon in patients with depression or biomedical diagnoses other than viral syndromes but was common with other primarily psychosocial diagnoses.

How useful are symptoms in the diagnosis of Candida vaginitis?

Two hundred four female subjects symptomatic and asymptomatic for genitourinary disease were evaluated for Candida vaginitis. All were questioned regarding the presence or absence of a variety of symptoms related to the genitourinary system, including vaginal discharge, its color, if present, pruritus, dysuria, and the like. Additionally, all subjects were cultured for Candida by use of Sabouraud agar. Thirty-six subjects demonstrated cultures positive for Candida. Of 36 totally asymptomatic subjects, 4 had positive cultures, yielding a prevalence (18 percent) and asymptomatic positive rate (11 percent) consistent with those reported in the literature. All genitourinary symptoms individually and in combinations proved to be very poor predictors of the presence of Candida on culture. The study concludes that the diagnosis of Candida vaginitis cannot be made based on symptoms alone. A suggestion describing the office workup of Candida vaginitis is presented.