[Metacognitive deficit in schizophrenia: Characteristics and links]. / Déficit métacognitif dans la schizophrénie : caractéristiques et liens.

OBJECTIVES: Research indicates that many patients with schizophrenia experience deficits in metacognitive capacity defined as the ability to form complex representations of themselves and others. The aim of the current study was to assess metacognitive deficit in patients with schizophrenia. These variables were collected together with many other sociodemographic, clinical and therapeutic data. METHODS: We conducted a descriptive and analytical cross-sectional study in the psychiatry department at the Hedi Chaker University Hospital in Sfax (Tunisia). Patients were in a non-acute phase, defined by the absence of any psychiatric symptoms during the last four weeks, also, no changes in medication during the previous month had been required. An informed written consent was obtained, following which patients completed questionnaires assessing sociodemographic and clinical data during structured interviews. Symptoms and severity of the illness were assessed using the Positive and Negative Symptoms Scale (PANSS). Insight was assessed using the Insight Scale (Q8). In addition, the Metacognition Assessment Scale-Abbreviated (MAS-A) was used to assess metacognitive capacities. The MAS-A contains four dimensions: self-reflectivity, awareness of the mind of others, decentration, and mastery. Higher scores reflect an ability to effectively respond to psychological challenges on the basis of psychological knowledge. RESULTS: We recruited 74 adults with schizophrenia disorder. The diagnosis was with DSM5. Their average age was 45 years (SD=9.84 years) with a sex ratio (M/F) of 1.552. Nineteen patients (25.5%) were married, and low educational level was present in 43% of cases. Forty patients (54%) were unemployed. Metacognitive deficit was detected in all the patients. They had low levels in all four dimensions of metacognition. The most affected dimension in our series was "Mastery". All patients had an overall insight score less than six (the average score was 2.73) with poor awareness in 62% of patients. The main factors correlated with metacognitive deficit were: occupational inactivity (P-0.015), Primary education level (P=0.045), tobacco consumption (P=0.002), low insight (P-0.001), negative symptomatology (P<10-3) and the use of first generation of antipsychotics (P=0.003). The multivariate analysis showed that three factors (occupational inactivity, low insight and the presence of negative symptomatology) were predictors of metacognitive deficits. CONCLUSION: Based on our results, occupational inactivity, negative symptomatology and low insight are predictors of metacognitive deficit in schizophrenia. Specific therapeutics should be proposed to act on these factors. A metacognitive training program, tailored to this vulnerable population, is a priority to improve their quality of life.

[Effects of continuous positive airway pressure on depression, anxiety and quality of life in obstructive sleep apnea hypopnea syndrome patients]. / Effets de la ventilation en pression positive continue sur la dépression, l'anxiété et la qualité de vie au cours du syndrome des apnées-hypopnées obstructives du sommeil.

INTRODUCTION: The obstructive sleep apnea hypopnea syndrome (OSAHS) is a chronic stressor that may alter the emotional state and quality of life (QOL) of patients suffering from it. In this work, we proposed to estimate the prevalence of depression and anxiety, to assess the QOL in a Tunisian population of apneic patients, and to assess their evolution under continuous positive airway pressure (CPAP). METHODS: We conducted a prospective study, involving 33 apneic patients followed for SAHOS with moderate or severe class disease in the pneumology department at Hedi Chaker university hospital in Sfax, Tunisia. They received CPAP treatment for three months. We used an epidemiological record. Two scales, the Hospital Anxiety and Depression Scale (HADS) and the 36-item Short-Form Health Survey (SF-36), were completed before and after treatment to evaluate the effect of three months of treatment with CPAP. RESULTS: The prevalence of depression in the study's patients, according to the HADS, was 45.5% and that of anxiety was 21.2%. After 3months of CPAP, the prevalence of depression and anxiety had become 18.2% and 6.1%, respectively. QOL was impaired in 81.8% of cases before treatment, according to the SF-36. This figure had decreased to 69.7% after 3months of treatment with CPAP. Apart from the third dimension (physical pain), all other dimensions were significantly improved after 3months of CPAP treatment. The treatment with CPAP induced a significant improvement in the average scores of depression (P<0.001), anxiety (P=0.002) and QOL (P<0.001). CONCLUSIONS: These results attest to the importance of the frequency of anxio-depressive disorders as well as an altered QOL in patients with OSAHS. CPAP treatment was shown to be effective in improving these parameters, but this efficacy was partial. Specialized care may be needed in cases of residual anxio-depressive symptoms.

[Post-traumatic stress disorder, depression and anxiety in parents of children with epilepsy]. / Trouble stress post traumatique, dépression et anxiété chez les parents d'enfant(s) atteint(s) d'épilepsie.

INTRODUCTION: Post-traumatic Stress Disorder (PTSD), depression and anxiety are the most common psychiatric consequences among parents of children with epilepsy. OBJECTIVES: We aimed to investigate the prevalence and predictors of PTSD, depression and anxiety in a sample of parents of children with epilepsy. METHODS: A survey of 135 parents of children with epilepsy, treated in the pediatric neurology department at the Sfax Teaching Hospital in Tunisia, was conducted in the last quarter of 2019. The PTSD Checklist for DSM-5 and the Hospital Anxiety and Depression Scale (HADS) were used to assess, respectively, PTSD, depression and anxiety in parents. Associations with clinical and demographic variables with PTSD, depression and anxiety were evaluated in a logistic regression model. RESULTS: Results revealed PTSD rates of 20.7%, depression rates of 28.9% and anxiety rates of 55.6%. The main factors associated with PTSD on multivariable analysis were female gender (P=0.026, ORa=13.1), insufficient involvement of partner in disease management (P<10-3, ORa=12.1) and duration of epilepsy less than 12 months (P=0.001; ORa=0.1). Female gender (P=0.006, ORa=18.1) and restriction of social life (P=0.006, ORa=4.1) were associated with depression. Factors associated with anxiety were insufficient involvement of partner in disease management (P=0.03, ORa=4.6) and PTSD (P=0.005, ORa=9.1). CONCLUSION: These findings suggest that clinicians should pay more attention to psychological health of parents of children with epilepsy and help healthcare providers to develop preventive and intervention strategies for parents of such children.

[The handling of psychotropics in diseases of central nervous system]. / Le maniement des psychotropes dans les maladies du système nerveux central.

Psychiatric signs and symptoms occur frequently in individuals with central nervous system diseases. Inadequately treated, these comorbid conditions affect patient rehabilitation, compliance with treatment and quality of life. Their management poses a major challenge given the variable efficacy and safety profiles of available psychotropic drugs and increased risk of drug interaction. This review aims to summarize the existing literature on the prescription of psychotropic drugs for management of psychiatric disorders among persons with central nervous system's diseases.

[Alcohol use in adolescents and its association with sensation seeking and impulsivity: A survey in the city of Sfax, Tunisia]. / Enquête sur la consommation d'alcool et sa relation avec la recherche de sensations et l'impulsivité chez l'adolescent de la région de Sfax, Tunisie.

BACKGROUND: Although the increase of media interest for psychoactive substances use, especially alcohol, among young people, since the revolution, Tunisia has few epidemiological studies on this subject, which does not allow having a clear idea of the importance of the problem and its different determinants. AIMS: To assess the prevalence of alcohol consumption among adolescents in the region of Sfax (Tunisia) and to determine its relations to the two personality dimensions: sensation seeking and impulsivity. METHODS: This was a cross-sectional study involving 317 middle and high school students in Sfax (Tunisia). We used the Alcohol Use Disorders Identification Test (AUDIT) to assess risky alcohol-consumption, the Barratt Impulsiveness Scale (BIS-11) to assess the degree of impulsivity and the Sensation Seeking Scale (SSS-V) to assess the level of sensation seeking. RESULTS: The average age of students was 15.79±1.5 years with a sex-ratio of 1.07. The prevalence of experimenters (who had drunk alcohol at least once in their lifetime) was 19.6% while that of current consumers (who had drunk alcohol more than one time during the past 12 months before the survey) was 8.8%. Among those who reported alcohol use during the last year, 42.8% were alcohol-dependent, according to the AUDIT. The analysis of personality dimensions showed a significant association between current alcohol consumption and sensation seeking (P<0.001) in particular on the dimensions of disinhibition (DIS), experience seeking (ES) and boredom susceptibility (BS) (P respectively: <0.001; 0.002 and 0.001). Total impulsivity and motor and attention impulsivity were associated with current alcohol consumption (respective P: 0.001, 0.005 and 0.015). CONCLUSION: Our study of schooled Tunisian adolescents shows that sensation seeking and impulsivity are associated with the development of alcohol use. Such a behavior is worrisome because it appears to be quite frequent and often problematic.

Molecular modeling of retinoschisin with functional analysis of pathogenic mutations from human X-linked retinoschisis.

Gene mutations that encode retinoschisin (RS1) cause X-linked retinoschisis (XLRS), a form of juvenile macular and retinal degeneration that affects males. RS1 is an adhesive protein which is proposed to preserve the structural and functional integrity of the retina, but there is very little evidence of the mechanism by which protein changes are related to XLRS disease. Here, we report molecular modeling of the RS1 protein and consider perturbations caused by mutations found in human XLRS subjects. In 60 XLRS patients who share 27 missense mutations, we then evaluated possible correlations of the molecular modeling with retinal function as determined by the electroretinogram (ERG) a- and b-waves. The b/a-wave ratio reflects visual-signal transfer in retina. We sorted the ERG b/a-ratios by patient age and by the mutation impact on protein structure. The majority of RS1 mutations caused minimal structure perturbation and targeted the protein surface. These patients' b/a-ratios were similar across younger and older subjects. Maximum structural perturbations from either the removal or insertion of cysteine residues or changes in the hydrophobic core were associated with greater difference in the b/a-ratio with age, with a significantly smaller ratio at younger ages, analogous to the ERG changes with age observed in mice with no RS1-protein expression due to a recombinant RS1-knockout gene. The molecular modeling suggests an association between the predicted structural alteration and/or damage to retinoschisin and the severity of XLRS as measured by the ERG analogous to the RS1-knockout mouse.

The functional effect of pathogenic mutations in Rab escort protein 1.

Choroideremia (CHM) is a chorioretinal degeneration with an X-linked pattern of inheritance. Affected males experience progressive atrophy of the choroid, retinal pigment epithelium and retina leading to eventual blindness. The CHM gene encodes Rab escort protein 1 (REP-1). REP-1 is involved in trafficking of Rab proteins in the cell. To date, the majority of reported mutations in the CHM gene cause a complete loss of REP-1 function. Here we report pathogenic mutations: a novel missense mutation, L550P; a truncation c.1542T>A, STOP; and two deletions (c.525_526delAG and c.1646delC) in the CHM gene and their phenotypic effect. To analyze the effect of mutations, the 3D structure of human REP-1 and the proteins associated with REP-1 function were modeled using sequence homology with rat proteins. In silico analysis of the missense mutation L550P suggests that the proline residue at position 550 destabilizes the beta-structural elements, and the REP-1 tertiary structure. Truncation and deletion mutants are associated with a partial or total loss of the REP-1 essential activity and protein-protein interactions as predicted by the analysis of the structure and stability of these protein products. The presumptive loss of protein was confirmed by Western Blot analysis of protein from mononuclear cells and fibroblasts (FB) from CHM patients.

Structural analysis of the minisatellite present at the 3' end of the human apolipoprotein B gene: new definition of the alleles and evolutionary implications.

The internal structure of different alleles of the minisatellite present at the 3' end of the apolipoprotein B (ApoB) gene has been analysed by different approaches including sequencing. The repeat unit arrangements of the minisatellite on 570 chromosomes belonging to European and African populations were thus determined. It was possible to group the alleles using this structural criterion much more clearly than by the number of repeat units which can in some cases be misleading in case-control genetic epidemiological studies using such DNA sequences as markers. We were thus able to define five types (a to e) of alleles and their subtypes and to recognize clearly those which are, respectively, specific of the African and Caucasian populations. A phylogeny of the different alleles found in all human populations could also be deduced by this approach. The different putative mutational events leading from one type, or subtype, to the other were simply determined as point mutations, expansion/contraction and conversion events. Sequencing of one chimpanzee's allele suggested that the ApoB minisatellite was present before divergence between great apes and humans. It was determined also that a particular ApoB gene haplotype was in linkage disequilibrium with the minisatellite (a) type of alleles. This and the observation that the potential scaffold attachment regions (SAR) and topoisomerase II binding sites present in this minisatellite have a different distribution between the Caucasian and the African specific alleles suggest that the minisatellite could be involved in the epidemiology of coronary diseases.

[Association between type 1 diabetes and polymorphism of the CTLA-4 gene in a Tunisian population]. / Etude de l'association entre diabète type 1 et polymorphisme du gène CTLA-4 dans une population tunisienne.

Susceptibility to type 1 diabetes mellitus is strongly associated with particular HLA class II alleles. However, non HLA genetic factors are likely to be required for the development of disease. The candidate genes include the cytotoxic T lymphocyte associated 4 (CTLA-4) located on chromosome 2q33 and designated (IDDM12), which encodes a cell surface negative signal T molecule providing for activation. We investigated CTLA-4 exon 1 dimorphism in 74 type 1 patients and a control group of 48 healthy subjects from Tunisia using two methods PCR (polymerase chain reaction) allele specific and polymerase chain reaction restriction fragment length polymorphism (PCR RFLP). The CTLA-4/G allele was found on 68.9% in type 1 patients as compared to 51.02% in controls (p = 0.002), mostly in homozygous from 43.24% versus 22.45% (p = 0.0058). This results indicate that CTLA-4/G allele was significantly associated with predisposition to type 1 diabetes in our group from Tunisian population.

Genotypic diagnosis of familial Mediterranean fever (FMF) using new microsatellite markers: example of two extensive non-Ashkenazi Jewish pedigrees.

Familial Mediterranean fever is an autosomal recessive disease characterised by multiple attacks of serosal inflammation in the absence of treatment. In the absence of timely diagnosis, renal amyloidosis is a life threatening complication. The diagnosis is often missed because no specific test is available. Early colchicine treatment prevents attacks and renal complications. The FMF gene (MEF) has been mapped to chromosome 16p 13.3 but has not yet been identified. We compared the suitability of a series of microsatellite markers (four of them were new) and propose the routine use of seven of these markers, exhibiting alleles in strong linkage disequilibrium with the disease and informative in 100% of diagnosed patients. Moreover, the discovery of a homozygous status for the 3-3-9 (or 3-3-18) haplotype at the core loci (D16S3070, D16S3082, and D16S3275), which was found in 73% non-Ashkenazi Jewish patients, points to a diagnosis of FMF, even in sporadic cases, with a risk of error of only 2.10(-5). Two extensive pedigrees covering most indications for genetic counselling are presented, showing that it is now possible both prospectively and retrospectively to identify members likely to have MEF mutations. With the help of this accurate test, colchicine treatment can be better targeted, especially where the symptomatology is mild or atypical.

A transcriptional Map of the FMF region.

Familial Mediterranean fever (FMF) is a recessively inherited disorder characterized by attacks of fever and serositis, which affects primarily non-Ashkenazi Jews, Armenians, Turks, and Arabs. We present here a transcriptional map covering the FMF locus that we constructed in the course of the positional cloning of the gene responsible for this disease. This map was established from a contig constructed with YAC, BAC, and cosmid clones and covers about 500 kb of 16p13.3. It contains nine transcriptional units corresponding to known genes or to genes belonging to known gene families, 23 gene fragments characterized by partial sequences, and an endogenous retrovirus sequence. It thus considerably increases the number of genes in this interval and improves our knowledge concerning some of the genes or gene families present in this region. Data accumulated in this region were also used in a comparative study of different methods of exon detection.

Prenatal diagnosis of chromosome disorders in Tunisian population.

Cytogenetic prenatal diagnosis (PND) is under national health program in most developed countries, while it concerns a small part of population at risk in developing countries. Finance is common reason of absence of PND development, but socio-cultural believes play an important role in Arab Muslim countries. In this paper we report results of 3110 fetal karyotypes carried out in a Tunisian population, by cultured amniocytes analysis. It is the largest report in a Muslim Arab country in our Knowledge. Abnormal karyotypes rate was 4.18% classified in two groups: bad prognosis (3.05%) and good prognosis (1.13%). Common amniocentesis indication was maternal age. The highest predictive value was observed in balanced karyotype and fetal ultrasound findings indications. Maternal serum markers were not commonly used for trisomy 21 screening. Pregnancy termination that is permitted by legal and religious authorities was accepted by 94,74% parents. Information about PND outcomes was given by genetic counselling prior to fetal sampling, pregnancy interruption was discussed with parents at cytogenetic result announcement. The authors conclude that in order to prevent mental and physical handicap related to cytogenetic disorders we have to promote PND by education for population, genetic counselling and fetal ultrasound screening; all three methods available in Tunisia.

Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF).

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurring attacks of fever and serositis. It affects primarily North African Jews, Armenians, Turks and Arabs, in which a founder effect has been demonstrated. The marenostrin-pyrin-encoding gene has been proposed as a candidate gene for the disease ( MEFV ), on the basis of the identification of putative mutations clustered in exon 10 (M680V, M694I, M694V and V726A), each segregating with one ancestral haplotype. In a search for additional MEFV mutations in 120 apparently non-founder FMF chromosomes, we observed eight novel mutations in exon 2 (E148Q, E167D and T267I), exon 5 (F479L) and exon 10 (I692del K695R, A744S and R761H). Except for E148Q and K695R, all mutations were found in a single chromosome. Mutation E148Q was found in all ethnic groups studied and in association with a novel ancestral haplotype in non-Ashkenazi Jews (S2). Altogether, these new findings definitively establish the marenostrin/pyrin-encoding gene as the MEFV locus.