Multimorbidity and the Etiology of Schizophrenia.

PURPOSE OF REVIEW: A global study of multimorbidity in schizophrenia, especially of the association with physical conditions, might offer much needed etiological insights. RECENT FINDINGS: Our review suggests that life-style factors and medication related to schizophrenia are only part of the explanation of the increase in risk for cardiovascular, metabolic, pulmonary disorders, and some cancers. Positive associations with autoimmune disorders (with the exception of rheumatoid arthritis) and epilepsy are promising avenues of research but to date have not been fully exploited. The same holds for the negative comorbidity seen for rheumatoid arthritis and some cancers (e.g., prostate). As a whole, our review suggests that most of the explored conditions have a different prevalence in schizophrenia than in the general population. Several hypotheses emerged from this review such as the role of immune and genetic factors, of sex hormones, and of more general variability factors.

Tobacco use in first-episode psychosis, a multinational EU-GEI study.

BACKGROUND: Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis. METHODS: The sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use. RESULTS: After controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1-3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2-2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (ß = -2.3; p ⩽ 0.001; 95% CI [-3.7 to -0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0-1.8]); however, these results were no longer significant after controlling for cannabis use. CONCLUSIONS: Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.

Schizotypal dimensions are associated with current but not former tobacco consumption.

OBJECTIVES: We aimed to study the relationship between tobacco smoking and attenuated psychosis measures taking into account several aspects of tobacco consumption that to date have not been explored and that could help understand this association, such as age of onset, the influence of former consumption and the duration of abstinence. METHODS: We investigated, in a sample of 580 students, the relationship between schizotypy (using the schizotypal personality questionnaire-brief in a Likert format) and smoking status, nicotine dependence (measured with the Fagerström test for nicotine dependence), age of onset of smoking and in former smokers, duration of smoking abstinence. RESULTS: 35.2% of the students were current smokers and 13.4% were former smokers. We found that current but not former smokers had higher scores of schizotypy (total, positive and disorganized) than non-smokers. We found no association between schizotypy scores and nicotine dependence or earlier age of onset of smoking. The duration of smoking abstinence, in former smokers, was inversely correlated to the score of positive and total schizotypy. CONCLUSIONS: Our results suggest that tobacco has a reversible effect on schizotypy, but more studies with a different design (controlled, longitudinal) and a more thorough exploration of potential confounders (e.g. cannabis) are needed before a firm conclusion can be reached.

Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study.

AIMS: Gene x environment (G×E) interactions, i.e. genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression, have not been reliably established regarding aetiology of psychotic disorders. Moreover, recent studies have shown associations between the polygenic risk scores for schizophrenia (PRS-SZ) and some risk factors of psychotic disorders, challenging the traditional gene v. environment dichotomy. In the present article, we studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the PRS-SZ on subclinical psychosis in a population-based sample. METHODS: Data were drawn from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (n = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. Associations between the PRS-SZ and the psychosocial stressors were tested. For each dimension, the interactions between genes and environment were assessed using linear models and comparing explained variances of 'Genetic' models (solely fitted with PRS-SZ), 'Environmental' models (solely fitted with each environmental stressor), 'Independent' models (with PRS-SZ and each environmental factor), and 'Interaction' models (Independent models plus an interaction term between the PRS-SZ and each environmental factor). Likelihood ration tests (LRT) compared the fit of the different models. RESULTS: There were no genes-environment associations. PRS-SZ was associated with positive dimensions (ß = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension. CONCLUSIONS: This study in subjects without psychotic disorders suggests that (i) the aetiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, (ii) genetic and environmental factors have independent effects on the level of this positive dimension, (iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.

Schizotypal Personality Questionnaire-Brief: Effect of invalid responding on factor structure analysis and scores of schizotypy.

OBJECTIVES: We assessed the effect of invalid responding on factor structure and on scores of schizotypy through the factor analysis of the Schizotypal Personality Questionnaire-Brief (SPQ-B) in a sample of 580 Romanian students using 3 validity items and 5 social desirability items. METHODS: We examined the factor structure of the SPQ-B, we compared the mean SPQ-B scores between reliable and unreliable responders and between high vs. low social desirability responders, and we re-run the factor analysis restricting the sample to the reliable or low social desirability responders. RESULTS: Factor analysis resulted in a 3-factor solution: Cognitive-perceptual, Interpersonal and Disorganized dimensions. Unreliable responders had lower scores of positive, negative and total schizotypy. Subjects with high social desirability scores had lower scores of disorganized schizotypy. Factor analyses in the samples of "good" responders showed minor differences in reliable responders, whereas, after taking into account the effect of social desirability, 2 items correctly loaded on expected dimensions. CONCLUSIONS: Random responding and social desirability could influence scores of schizotypy and factor structure. Simple methods could be used to identify invalid responses. The effect of social desirability could be linked to the phrasing of items.

[Schizotypal Personality Questionnaire-Brief - Likert format: Factor structure analysis in general population in France]. / Analyse de la structure factorielle de la version brève du questionnaire de personnalité schizotypique (SPQ-B) ­ format Likert ­ en population générale en France.

INTRODUCTION: The main objective of the study was to explore the factorial structure of the French version of the Schizotypal Personality Questionnaire-Brief (SPQ-B) in a Likert format, in a representative sample of the general population. In addition, differences in the dimensional scores of schizotypy according to gender and age were analyzed. As the study in the general population of schizotypal traits and its determinants has been recently proposed as a way toward the understanding of aetiology and pathophysiology of schizophrenia, consistent self-report tools are crucial to measure psychometric schizotypy. A shorter version of the widely used Schizotypal Personality Questionnaire (SPQ-Brief) has been extensively investigated in different countries, particularly in samples of students or clinical adolescents, and more recently, a few studies used a Likert-type scale format which allows partial endorsement of items and reduces the risk of defensive answers. METHOD: A sample of 233 subjects representative of the adult population from an urban area near Paris (Créteil) was recruited using the "itinerary method". They completed the French version of the SPQ-B with a 5-point Likert-type response format (1=completely disagree; 5=completely agree). We examined the dimensional structure of the French version of the SPQ-B with a Principal Components Analysis (PCA) followed by a promax rotation. Factor selection was based on Eigenvalues over 1.0 (Kaiser's criterion), Cattell's Scree-plot test, and interpretability of the factors. Items with loadings greater than 0.4 were retained for each dimension. The internal consistency estimate of the dimensions was calculated with Cronbach's α. In order to study the influence of age and gender, we carried out a simple linear regression with the subscales as dependent variables. RESULTS: Our sample was composed of 131 women (mean age=52.5±18.2 years) and 102 men (mean age=53±18.1 years). SPQ-B Likert total scores ranged from 22 to 84 points (mean=43.6±13). Factor analysis resulted in a 3-factor solution that explained 47.7% of the variance. Factor 1 (disorganized; 10 items) included items related to "odd behavior", "odd speech", as well as "social anxiety", one item of "constricted affect" and one item of "ideas of reference". Factor 2 (interpersonal; 7 items) included items related to "no close friends", "constricted affect", and three of the items of "suspiciousness". Factor 3 (cognitive-perceptual; 5 items) included items related to "ideas of reference", "magical thinking", "unusual perceptual experiences" and one item of "suspiciousness". Coefficient α for the three subscales and total scale were respectively 0.81, 0.81, 0.77 and 0.88. We found no differences in total schizotypy and the three dimensions scores according to age and sex. CONCLUSION: Factor analysis of the French version of the SPQ-B in a Likert format confirmed the three-factor structure of schizotypy. We found a pure cognitive perceptual dimension including the most representative positive features. As expected, "Suspiciousness" subscale is included in both positive and negative dimensions, but mainly in the negative dimension. Surprisingly, "social anxiety" subscale is included in the disorganized dimension in our analysis. The SPQ-B in a Likert format demonstrated good internal reliability for both total and subscales scores. Unlike previous published results, we did not find any influence of age or gender on schizotypal dimensions.

Functional defects of peripheral regulatory T lymphocytes in patients with progressive vitiligo.

Auto-reactive cytotoxic T lymphocytes play a key role in the progressive loss or destruction of melanocytes in vitiligo but the mechanism underlying the loss of self-tolerance is unknown. A deregulation of regulatory T-cell biology has recently been suggested. The analysis of the suppressive effects of peripheral T regulatory cells in vitiligo patients revealed a functional defect in seven of 15 cases. This defect was strongly correlated with disease activity. The evaluation of the percentage of peripheral regulatory T lymphocytes did not reveal any intrinsic quantitative defect. Yet, a decrease in the percentage of such cells was noted in patients with progressive forms, suggesting a recruitment of regulatory T cells from the peripheral blood to the site of injury. This was further corroborated by the significant increase of Forkhead box P3 expression in the vitiliginous skin of patients. Our data support the involvement of a functional defect of peripheral regulatory T cells in the pathogenesis of vitiligo and open new possibilities to advance therapeutic approaches.

[Source monitoring: general presentation and review of literature in schizophrenia]. / Mémoire de source--présentation générale et revue des études dans la schizophrénie.

SOURCE MONITORING FRAMEWORK: Source monitoring refers to the ability to remember the origin of information. Three source monitoring processes can be distinguished: external source monitoring, internal or self-monitoring and reality monitoring (i.e. discrimination between internal and external sources of information). Source monitoring decisions are based on memory characteristics recorded such as perceptions, contextual information or emotional reactions and heuristic or more controlled judgement processes. BRAIN STRUCTURES: Several studies suggested that specific structures in the prefrontal and the mediotemporal lobes are the main areas implicated in source monitoring. ASSESSMENT: A typical source monitoring paradigm includes an items generation stage and a second stage of recognition of items (old versus new) and identification of their sources: external (usually the examiner) or internal (the subject). Several indices can be calculated based on the raw data such as the number of false alarms, attribution biases or discrimination indexes. To date, there is no standardized source monitoring task and differences in the type of items used (words, pictures), in the cognitive or emotional effort involved or in the delay between the two test stages, contribute to the heterogeneity of results. FACTORS INFLUENCING SOURCE MONITORING: Factors such as age (either very young or very old) and emotions influence source monitoring performances. Influence of gender was not properly explored, whereas the role of IQ and selective attention is still debated. SOURCE MONITORING DEFICITS IN NEUROLOGICAL DISORDERS: Source monitoring deficits are observed mainly in disorders affecting frontotemporal areas, such as frontal trauma, Alzheimer's disease or frontotemporal dementia. SOURCE MONITORING AND SCHIZOPHRENIA: Source monitoring errors (e.g. external misattribution of self-generated information) are observed in schizophrenia and seem to correlate with positive symptomatology, in particular auditory hallucinations, thought intrusion and alien control symptoms. These results are of particular interest in clinical research because source monitoring is one of the rare cognitive tests showing a correlation with the positive dimension. Source monitoring deficits have been proposed as a potential explanation for the positive symptoms and some, but not all studies lent support to this hypothesis. Heterogeneity of studied samples, in particular different criteria to define hallucinating subjects (e.g. currently versus anytime during their lives), could explain the discordant results. SOURCE MONITORING IN PSYCHIATRIC DISORDERS WITHIN THE SCHIZOPHRENIC SPECTRUM: Source monitoring impairments were observed in pharmacological models of psychosis, in first degree relatives of schizophrenic patients, and also in the general population associated with schizotypal dimensions. These results support a relationship between source monitoring deficits and some of the symptomatic dimensions of the schizophrenic spectrum but still await replication. SOURCE MONITORING AND OTHER PSYCHIATRIC DISORDERS: Some studies found source monitoring deficits in other psychiatric conditions such as mania or obsessive-compulsive disorder. Thus, those studies suggest that source monitoring deficits may be not specific to schizophrenia. CONCLUSION: Source monitoring competencies are critical for good (i.e. adapted) everyday functioning. Source monitoring deficits have been suggested as a potential explanation for some (or all) positive psychotic symptoms. However, to date, methodological inconsistencies (especially with regard to test design and choice of subjects' samples) have precluded firm, definite conclusions.

[Association of Recklinghausen's disease, dental dystrophy and myopia in a Tunisian family]. / Association maladie de Recklinghausen, dystrophie dentaire et myopie dans une famille tunisienne.

The authors describe a tunisian family including ten patients with neurofibromatosis. Four case reports present dental anomalies (amelogenesis imperfecta) and three have myopia. The authors believe there is no clinical or genetical relation between neurofibromatosis and this dental dystrophia; but myopia may be a clinical expression of Recklinghausen disease.

[Genetic study of eight cases of spondylo-epiphyseal dysplasia tarda and its autosomal recessive transmission]. / Etude génétique de huit observations de dysplasie spondylo-épiphysaire d'apparition tardive et de transmission autosomique récessive.

Spondylo-epiphyseal dysplasia tarda is an hereditary disease of bone first described by Maroteaux in 1957. The disease affects only boys, then is transmitted on X-linked recessive pattern. The authors describe two tunisians families with 8 patients presenting clinical and radiologic symptoms resembling spondylo-epiphyseal dysplasia tarda but affecting both sexes. Autosomal recessive inheritance is probable in these families. Conclusion is that genetic heterogeneity of the disease must be precise.

[Glomerulonephritis and blindness. Apropos of 3 cases]. / Glomérulonéphrite et cécité. A propos de trois cas.

Blindness is a rare complication of acute glomerulonephritis. During three years (1980-82) 32 cases of acute glomerulonephritis are admitted in a Pediatric Department. Five children had neurologic complications among whom three developed complete, bilateral and transient blindness. In all cases blindness is associated with hypertension and intracranial pressure. The mechanism suggested in this kind of amaurosis is cerebral oedema, and the adequate treatment of this oedema permit a complete recovery of the vision.