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.

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.

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.

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.

Assessment of social anxiety in first episode psychosis using the Liebowitz Social Anxiety scale as a self-report measure.

OBJECTIVE: Social anxiety is a common problem in psychotic disorders. The Liebowitz Social Anxiety Scale, Self-Rating version (LSAS-SR) is a widely used instrument to capture different aspects of social anxiety, but its psychometric properties have not been tested in this patient group. The aims of the present study were to evaluate the psychometric properties of the LSAS-SR in patients with first episode psychosis, to investigate whether it differentiated between active and passive social withdrawal and to test which clinical factors contributed to current level of social anxiety. METHOD: A total of 144 first episode psychosis patients from the ongoing Thematically Organized Psychosis (TOP) study were included at the time of first treatment. Diagnoses were set according to the Structured Clinical Interview (SCID-1) for DSM-IV. A factor analysis was carried out and the relationship of social anxiety to psychotic and general symptomatology measured by the Positive and Negative Syndrome Scale (PANSS) was evaluated. Possible contributors to social anxiety were analyzed using multiple hierarchic regression analysis. RESULTS: The factor analysis identified three subscales: public performance, social interaction and observation. All three subscales showed satisfactory psychometric properties, acceptable convergent and discriminate properties, and confirmed previous findings in social anxiety samples. Self-esteem explained a significant amount of the variance in social anxiety, even after adjusting for the effects of delusions, suspiciousness and depression. CONCLUSION: The study shows that the LSAS-SR can be used in this patient group, that social anxiety is strongly related to both behavioral social avoidance and to self-esteem. The results support the use of this measure in assessment of social anxiety in both clinical settings and in research.

U.S. Preventive Services Task Force: highlights of the 1996 report.

The recent report of the U.S. Preventive Services Task Force is a compendium of the scientific evidence supporting clinical preventive services that might be offered by primary care physicians. Pediatric recommendations include height, weight and blood pressure measurements, neonatal screening for hemoglobinopathies and counseling about injury prevention, diet and exercise, sexual behavior, substance abuse and dental health. Lead screening is recommended in communities with a high prevalence of elevated lead levels. Adult recommendations include measurement of blood pressure and weight, selective screening for elevated total cholesterol level, screening persons over age 50 for colorectal cancer, screening women for cervical cancer at least every three years, and screening women 50 to 69 years of age for breast cancer with mammography every one to two years. Counseling patients about substance abuse, diet and exercise, injury prevention, sexual behavior and dental health is recommended. Women of childbearing age should receive folic acid supplementation to prevent neural tube defects if they should become pregnant. Multiple marker testing is recommended for women over age 35 to screen for Down syndrome. Immunization recommendations are similar to those of other national groups.

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 effectiveness of four interventions for the prevention of low back pain.

OBJECTIVE: Low back pain affects 60% to 80% of US adults at some time during their lives. This review evaluates the effectiveness of four strategies to prevent low back pain for asymptomatic individuals: back and aerobic exercises, education, mechanical supports (corsets), and risk factor modification. DATA SOURCES: The MEDLINE database was searched for all relevant articles published in English between 1966 and 1993. Bibliographies of identified articles were searched to ensure that all pertinent articles had been gathered and back pain specialists reviewed our final bibliography for completeness. STUDY SELECTION AND DATA EXTRACTION: A total of 190 articles were identified, and the 64 that contained original data about preventing low back pain were reviewed. Studies were graded according to strength of study design. DATA SYNTHESIS: There is limited evidence based on randomized trials and epidemiological studies that exercises to strengthen back or abdominal muscles and to improve overall fitness can decrease the incidence and duration of low back pain episodes. There is minimal evidence to support the use of educational strategies to prevent low back pain and insufficient evidence to recommend about the use of mechanical supports. Although there is no evidence supporting risk factor modification for preventing low back pain (smoking cessation and weight loss), there are other reasons to recommend the interventions. CONCLUSION: There is limited evidence to recommend exercise to prevent low back pain in asymptomatic individuals, but there is insufficient evidence to recommend other prevention strategies. These conclusions should be viewed cautiously since they are primarily based on studies conducted in the workplace rather than in clinical settings.