Association of Disrupted in Schizophrenia 1 (DISC1) missense variants with ultra-resistant schizophrenia.

Three common missense variants of the Disrupted in Schizophrenia 1 (DISC1) gene, rs3738401 (Q264R), rs6675281 (L607F) and rs821616 (S704C), have been variably associated with the risk of schizophrenia. In a case-control study, we examine whether these gene variants are associated with schizophrenia and ultra-resistant schizophrenia (URS) in a population of French Caucasian patients. The URS phenotype is characterized according to stringent criteria as patients who experience no clinical, social and/or occupational remission in spite of treatment with clozapine and at least two periods of treatment with distinct conventional or atypical antipsychotic drugs. We find a significant association between DISC1 missense variants and URS. The association with rs3738401 remains significant after appropriate correction for multiple testing. These results suggest that the DISC1 rs3738401 missense variant is statistically linked with ultra-resistance to antipsychotic treatment.

[Validation of the French version of the expanded Brief Psychiatric Rating Scale with anchor BPRS-E(A)]. / Validation de la version française de l'échelle abrégée d'appréciation psychiatrique étendue avec ancrage, BPRS-E(A).

INTRODUCTION: The Brief Psychiatric Rating Scale was initially developed as a rapid method to assess symptom change in psychiatric inpatients of various diagnoses. The original version was expanded to an 18-item version and thereafter to a 24-item version to increase sensitivity to a broader range of psychotic and affective symptoms. The latest version of the expanded 24- item BPRS provides probe questions and detailed anchor points for the ratings for each item. LITERATURE FINDINGS: Studies have shown the expanded and anchored 24-item BPRS to be a sensitive and effective measure of psychiatric symptoms with good interrater reliability that can be maintained over time. To our knowledge, there are eight published papers including factor analyses of the BPRS-E(A). While many similarities are evident between these studies, inconsistencies are apparent that may have been due to sample size, characteristics and / or methodological differences in the factor analysis computation. Among these studies, six provided a four-factor solution. There was no French version of this scale available. METHODS: After its translation into French and back translation, we investigated the validity of the French BPRS-E(A) version. We carried out a component analysis on the data of 111 participants of various diagnoses, mostly hospitalised for a first psychotic episode, yielding to a three-factor solution (positive symptoms--disorganisation; depression-anxiety and negative symptoms). RESULTS: A good internal consistency and interrater reliability were found. These results confirm the psychometric value of the BPRS-E(A) in its French version. We compared those findings to earlier reports; similarities and differences are discussed.

New evidences of gene and environment interactions affecting prenatal neurodevelopment in schizophrenia-spectrum disorders: a family dermatoglyphic study.

BACKGROUND: Several studies have reported an increase of dermatoglyphic anomalies in schizophrenic patients compared to controls. However, the recognition of specific dermatoglyphic variables related to this disorder and their genetic and/or environmental component are still controversial. METHOD: We conducted a dermatoglyphic analysis in a new sample of 617 individuals: 205 patients with schizophrenia-spectrum disorders, 224 healthy first degree relatives and 188 healthy controls. The dermatoglyphic variables studied were: the total a-b ridge count (TABRC) and its fluctuating asymmetry (FAABRC), and the presence of ridge dissociations (RD) and abnormal palmar flexion creases (APFC). RESULTS: Patients, relatives and controls did not differ in TABRC. However, within the patients group those with a low birth weight or absence of psychiatric family history showed lower TABRC than the others. The frequency of ectodermic derivates abnormalities (RD and/or APFC) appeared to be higher in patients and relatives than in controls, while first degree relatives did not differ from patients. Males showed an increased rate of ectodermic derivates abnormalities compared to females in all groups and male patients also presented higher FAABRC than female patients. CONCLUSIONS: Our results suggest a different relative weight of genetic and environmental factors on each dermatoglyphic variable analyzed: i) TABRC may be a sensitive marker to environmental factors in schizophrenia, ii) ectodermal derivates abnormalities appear to be influenced by genetic risk factors, which could be involved both in the disrupted development of ectodermic derivates like dermatoglyphics and central nervous system and in the vulnerability for schizophrenia.

Onset of intolerance symptoms during exercise testing is a reproducible threshold for evaluation of cardiac function.

Twenty-one male patients with a history of myocardial infarction underwent bicycle cardiopulmonary exercise testing. The onset of leg pain or dyspnea, which reflects anaerobic metabolism, was termed anaerobic exercise symptom threshold (AEST). Our aims were (1) to evaluate the temporal relationship between AEST and the ventilatory anaerobic threshold (VAT) and (2) to determine whether heart rate, rate-pressure product, exercise time, and the ventilatory parameters at AEST are reproducible and correlate with the same parameters at VAT. AEST overlapped VAT in 4 patients and lagged behind VAT in 15. AEST never preceded VAT. The mean exercise time at VAT was 4.1 +/- 1.2 min and at AEST 5.6 +/- 1.6 min (p < 0.0001); the mean heart rate was 97 +/- 10 and 107 +/- 12, respectively (p < 0.001). The mean values of the rate-pressure product and the oxygen consumption at AEST were significantly higher than at VAT. The correlation coefficient ranged from r = 0.74 to r = 0.93. Fifteen patients were examined twice within 1 month; the above parameters were reproducible at AEST, VAT, and peak exercise. In conclusion, AEST, which is easily recorded during bicycle exercise testing, is useful as a reference point for evaluation and follow-up of the cardiac aerobic function.