Depression among medical students in Tunisia: Prevalence and associated factors.

BACKGROUND: Medical school is known for its lengthy process, which is both physically and emotionally draining. Students' mental balance would shrink as they progress in their medical training. A systematic review and meta-analysis reported that the prevalence of depressive symptoms among medical students remained relatively constant at 27.2%. AIM: To assess the prevalence of depressive symptoms among Tunisian medical students and evaluate its associated factors. METHODS: This is a descriptive cross-sectional study that was carried out in the second semester of the academic year 2017/2018, between April 2018 and July 2018 among 1138 medical students. Data were collected using a socio-demographic questionnaire and the Beck Depression Inventory-II (BDI-II). RESULTS: Sixty-four percent (n = 728) of the participants had depressive symptoms, of which 266 (23.4%) met the criteria for mild, 271 (23.8%) for moderate, and 191 (16.8%) for severe depressive symptoms. Female gender, low socio-economic level, smoking habits and history of mental disorder, performing leisure and physical activities, satisfaction toward a career choice, and happiness perception were the main prognostic factors for depression among medical students. Although academic grades may not be considered a prognostic factor, final-year students appeared to be less depressive than their colleagues. CONCLUSION: These findings give insight into mental health issues and comorbidities among Tunisian medical students. It is a hopeful request for decision-makers and academic authorities to set serious measures and draw effective interventions to minimize the currency of psychological distress among this subpopulation.

Association of VEGF-A and KDR polymorphisms with the development of schizophrenia.

AIM: Several approaches indicate different blood flow disturbances in schizophrenia. VEGF-A is widely recognized as one of the key molecules involved in the angiogenesis process through mainly its receptor KDR. The current work was designed to investigate the potential association between three polymorphisms (rs699947; rs833061 and rs3025039) in VEGF-A gene and two SNPs (rs2305948 and rs1870377) within KDR gene and predisposition to schizophrenia among the Tunisian cohort. METHODS: We carried-out a case-control study composed of 200 patients with schizophrenia and 200 healthy subjects using PCR-RFLP. RESULTS: Of all analyzed polymorphisms, only rs833061, rs3025039 and rs1870377) showed a significant risk for schizophrenia (PAdjusted = 0.04, PAdjusted=<0.001, PAdjusted = 0.005 respectively). Following the stratified analysis, rs3025039 was more prevalent among undifferentiated form (PAdjusted=<0.001) and more specifically with male sex (PAdjusted=<0.001). Yet, rs1870377 was correlated with paranoid subtype (PAdjusted = 0.002) and particularly with male sex (PAdjusted = 0.005). We found also that rs699947 is associated to negative symptoms before and after treatment (P = 0.004; P = 0.001 respectively) and rs3025039 had an impact on positive and negative symptoms only after treatment (P = 0.03; P = 0.008 respectively). Haplotype analysis revealed a strong LD between rs833061 and rs3025039 only for controls and undifferentiated patients (P = 0.005). Moreover, the rs699947*C âˆ¼ rs833061*T âˆ¼ rs3025039*T haplotype, with only one mutated allele rs3025039*T, conferred a high risk to schizophrenia (P = 0.016) and, in particular, to undifferentiated and paranoid forms (P = 0.03; P = 0.02 respectively). Among the last-mentioned subgroup, we noticed another overrepresented haplotype (rs699947*A âˆ¼ rs833061*T âˆ¼ rs3025039*T; P = 0.01). Furthermore, the rs2305948*G âˆ¼ rs1870377*T haplotype carrying the minor allele rs1870377*T displayed increased frequencies in the whole group of patients and particularly among paranoid subtype (P = 0.013; P=<0.001 respectively). CONCLUSION: Our results show that all SNPs associated with the development or the severity of schizophrenia, were subsequently correlated with a decrease in the VEGF-A levels or influence KDR binding affinity. These data need to be strengthened by further independent analyses.

Clinical and genetic influencing factors on clozapine pharmacokinetics in Tunisian schizophrenic patients.

Clozapine (Clz) is an atypical antipsychotic, which its pharmacokinetics can be influenced by several factors. The CYP1A2 and CYP2C19, major enzymes implicated in Clz metabolism, present an interethnic variation on their activity caused by single nucleotide polymorphisms (SNPs). The present study investigated the influence of genetic and nongenetic factors on Clz pharmacokinetics in a southern Mediterranean population. We included adult Tunisian schizophrenic patients having received Clz and undergone a therapeutic drug monitoring (TDM) of Clz by morning C0 monitoring. The genomic DNA was extracted using a salting-out procedure. CYP1A2*1F (rs762551;-163C>A), CYP1A2*1C (rs2069514;-3860 G>A) and CYP 2C19*2 (rs4244285; 681G>A) was analyzed using PCR-RFLP. Fifty-one patients were enrolled in the study. The mutant allele (CYP1A2*1F) was the most frequently detected (58.8%). For CYP1A2*1F, Clz dose-normalized (C0/D ratio) was as high as 1.28 ± 0.37 in CC versus 0.67 ± 0.32 ng mL-1 per mg day-1 in AA group (p < 0.001). The influence of genetic (CYP1A2*1F, CYP1A2*1C and CYP2C19*2) and nongenetic parameters (age, weight, gender, tobacco, coffee, and alcohol consumption) on the variation of the Clz C0/D ratio was investigated. Only the CYP1A2*1 F polymorphism correlates significantly with the Clz C0/D variation and could explain 24% of its variability. Our data support a critical role of the CYP1A2 -163C>A on the variation of Clz exposure in Tunisian schizophrenic patients. Considering its narrow therapeutic range, CYP1A2 genotyping combined with TDM of Clz may improve efficacy and safety of this drug. Further studies are needed to investigate this issue.

Suicidal ideation and suicide attempts among Tunisian adolescents: prevalence and associated factors.

INTRODUCTION: Studies directed on suicidal behavior in North African adolescents are rare. This study was conducted to estimate the prevalence of suicidal thoughts and attempts among high school students in Tunisia and to determine factors associated with this suicidal behavior. METHODS: This is an analytical cross-sectional study composed of a population containing 821 high school students obtained through cluster sampling. The participants completed a pre-established form related to socio-demographic characteristics and anxiety symptoms, the Suicide Behavior Questionnaire-Revised, the Beck depression scale, and the Rosenberg self-esteem scale. RESULTS: The mean age of the adolescents was 17.7±0.97 years. Prevalence of suicidal behavior was 26.9% for brief passing suicidal thoughts, 9.6% for serious suicidal thoughts, and 7.3% for suicide attempts. Six determining factors of suicidal behavior were found: female gender (OR=2.56 (1.32-4.95); p= 0.005), personal history of depression (OR=2.29 (1.38-3.80); p=0.001), tobacco smoking (OR=3.59 (1.61-8.01); p=0.002), current depression symptoms (OR=5.50 (2.14-14.11); p<0.001), history of non-suicidal self-injurious behavior (OR= 3.16 (2.05-4.86); p<0.001), and low self-esteem (OR=2.74 (1.71-4.38); p<0.001). CONCLUSION: Suicidal ideation and attempts are frequent among Tunisian adolescents and represent a serious public health problem. An urgent national prevention program is required.

Lipid profile in schizophrenia: case control study.

INTRODUCTION: Cardiovascular diseases are common co morbidities of schizophrenia and constitute the main factors of high mortality in this pathology. Cardiovascular damages are favored by some risk factors, of which one of the most important is dyslipidemia. In this context, a study of lipid profile in schizophrenia is interesting.  The aims of this study were to compare the lipid profile of patients with schizophrenia to healthy controls and to investigate the associations between lipid parameters and demographics, clinical and treatment characteristics of the patients. METHODS: We conducted a case-control study between April 2013 and March 2014 on 78 patients with schizophrenia and 68 healthy subjects who benefited from the dosage of four serum lipid parameters: total cholesterol (TC), triglycerides (TG), High-density lipoprotein Cholesterol (HDL-C) and Low-density lipoprotein cholesterol (LDL-C). For the socio-demographic and clinical assessments, we used an information sheet and the following psychometric scales: PANSS (Positive And Negative Syndrome Scale), CGI (Clinical Global Impressions), GAF (Global Assessment Functionning) and the Calgary scale for depression. RESULTS: The comparative study showed that serum concentrations of TC and LDL-C were significantly higher for patients compared to healthy controls respectively with (t=2,83 ; p=0,008) and             (t=9,35; p<0,001), the cholesterol ratio (TC / HDL-C) was also significantly higher for patients           (t=2,23; p=0,033). The patients had significantly higher prevalence of hypercholesterolemia              (OR = 2.96) and low density hyperlipoproteinemia (OR = 18.79). The analytical study in the population of patients showed that the age ≥35 year-old, male gender and alcohol consumption were associated with disturbances in lipid parameters. Cannabis consumption was associated with significantly lower concentrations in TG. Concerning clinical features, paranoid schizophrenia was associated with less dyslipidemia unlike the depressive dimension assessed by the Calgary scale. There was a negative correlation between plasmatic TG concentrations and doses of antipsychotics. CONCLUSION: The vast majority of the literature confirms that patients with schizophrenia are at greater risk of dyslipidemia. This high risk appears to be more important with the consumption of alcohol and tobacco. It seems also that age and masculine gender are dyslipidemia risk factors for schizophrenic patients. The paranoid type of schizophrenia and positive symptoms seem to be associated with less dyslipidemia while depressive symptoms worsen lipid parameters. It then follows that, clinical and regular monitoring of lipid profile, lifestyle recommendations (smoking cessation, exercise and balanced diet) and appropriate therapeutic choices could help reduce morbidity and mortality among patients with schizophrenia. A special focus should be accorded to patients with high negative and depression symptoms.

Haplotypes of TNFα/ß Genes Associated with Sex-Specific Paranoid Schizophrenic Risk in Tunisian Population.

Several medical research findings have announced a strong association between the biology of cytokines and various brain activities. Since growing evidences suggest the crucial and complex role of the tumor necrosis factor in the CNS, we have hypothesized that functional genetic variants of the LTA and TNFA genes (LTA +252A/G (rs909253) and TNFA -857C/T (rs1799724) and TNFA -238G/A (rs361525)) may be involved in the predisposition to schizophrenia. This research is based on a case-control study. The RFLP-PCR genotyping was conducted on a Tunisian population composed of 208 patients and 208 controls. We found a strong significant overrepresentation of the minor alleles (G, T, and A, respectively) in all patients compared with controls (p = 0.003, OR = 1.55; p = 0.005, OR = 1.78; and p = 0.0001, OR = 1.74, respectively). This correlation was confirmed for male but not for female patients. Interestingly, the frequencies of the minor alleles were significantly more common among patients with paranoid schizophrenia when compared with controls (p = 0.003, OR = 1.75; p = 5 · 10-6, OR = 3.04; and p = 4 · 10-6, OR = 2.35, respectively). This potential association was confirmed by a logistic binary regression analysis only for the development of the paranoid form of schizophrenia (p = 0.001/OR = 2.6; p = 0.0002/OR = 3.2; and p = 0.0004/OR = 3.1, respectively) and remained not significant for the other subtypes. Moreover, our study showed an important association between GCA haplotype and the development of this pathological form (p = 10-4, OR = 3.71). In conclusion, our results proved a significant association between the three polymorphisms and paranoid schizophrenia, at least in the Tunisian population, suggesting a substantially increased risk for paranoid schizophrenia with dominant inheritance of these three minor alleles.

Comparison of Mineral Contents in Three Different Tobacco Formulations.

We identified and quantified a variety of mineral elements in 18 tobacco samples purchased from a Tunisian market. In total, 25 mineral elements have been measured in cigarettes, water pipe tobacco, and smokeless tobacco using inductively coupled plasma-optical emission spectroscopy following microwave-assisted digestion. Statistical analyses were performed using SPSSTM, version 18.0. The lowest concentrations of all studied elements were observed in water pipe tobacco. Significantly higher concentrations of Al, Fe, Mg, Na, Ca, Cr, and Co were found in smokeless tobacco, while cigarettes brands contained the highest concentrations of K, Mn, Ni, Ba, and Sr. There was no significant difference between the mineral contents of local and foreign cigarettes and conventional and light cigarettes. Our findings demonstrated that local smokeless tobacco appears to be the most hazardous tobacco type. The concentration of minerals in light cigarettes was not significantly different from the concentration in conventional cigarettes.

Paraoxonase 1 activity and lipid profile in schizophrenic patients.

OBJECTIVE: This study aimed to investigate the variations of paraoxonase 1 (PON1) activity and lipid profile in patients with schizophrenia and the association of this activity with the sociodemographic, clinical and therapeutical characteristics of this population. PATIENTS AND METHODS: Our cross-sectional study included 140 schizophrenic patients and 119 control subjects aged respectively 37.3±10.4 and 41.4±10 years. PON1 activity was determined using Konelab 30™ equipment (Thermo Electron Corporation). Plasma total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (c-HDL) and low-density lipoprotein cholesterol (c-LDL) concentrations were determined using Cobas 6000™ (Roche Diagnostics), apolipoproteins (ApoA1, ApoB) and lipoprotein (a) (Lp(a)) were determined using Integra 400 plus (Roche Diagnostics). RESULTS: Compared to controls, patients had no significant decrease of PON1 activity and significantly lower ApoA1, c-HDL levels, and significantly higher levels of TG, ApoB, Lp(a) and TC/c-HDL and ApoB/ApoA1 ratios. Furthermore, PON1 activity was correlated with TG/c-HDL ratio. The lowest PON1 activity was noted in obese patients, in paranoid sub-type and in patients treated with combination of typical and atypical antipsychotics without significant difference. Moreover, it was associated with gender and cigarette smoking but not with alcohol consumption status. CONCLUSION: Schizophrenic patients had a decrease in PON1 activity and perturbations in their lipid profiles that contribute to increase the risk of cardiovascular diseases. In addition, our results revealed that there was no association between the decrease of PON1 activity and any demographic or clinical characteristics. Therefore, such patients require specific care, particularly with regard to their lipid profile.

[Study of sexuality among Tunisian women in remission from non-metastatic breast cancer, about 100 women]. / Étude de la sexualité chez les femmes Tunisiennes en rémission complète d'un cancer du sein non métastatique, à propos de 100 femmes.

The prognosis of breast cancer has significantly improved during the last years due to progress of the treatment options. It is a public health problem because of its frequency, severity, physical and psychological consequences. Quality of life appears increasingly as fundamental criteria in the assessment of treatment outcomes. This underlines the specific impact on sexuality. Aim. To evaluate the frequency and type of sexual dysfunction in 100 patients treated for non-metastatic breast cancer in post-treatment monitoring in external consultation of the Department of Oncological Medicine, CHU Farhat Hached, Sousse. Then, to identify predictive factors of these disorders. Procedure. Sexuality and body image were evaluated respectively using two scales: Relationship and Sexuality (RSS) and Body-Esteem Scale for Adolescents and Adults (BESAA). Results. Sexual desire has been affected by the disease and its treatment for 47 women. The capacity to achieve orgasm was reduced in 61 patients. Twenty felt less sexually attractive. Fifty-three women had reported a decrease in the frequency of sexual intercourse. Sixteen patients had reported a fear of sex. Dyspareunia and vaginal dryness were present in 45 women. The analytic study had found that sexual problems are related to the rural origin, the profession of the husband, the premenopausal period, lack of breast reconstruction, the CMF chemotherapy protocol (cyclophosphamide, methotrexate, 5-fluorouracil) and number of cycles of chemotherapy. Body image was significantly altered in patients with sexual dysfunction. In addition, psychosocial factors that best predicted sexual difficulties are the perception by the wife of an emotional distance in the relationship with her partner and fear of sex. Conclusion. The support for these sexual difficulties requires a joint and collaborative approach between oncologists, gynecologists, psychiatrists and sexologists.

Interference of tobacco smoke with immunochromatography assay for urinary drug detection.

BACKGROUND: This study aimed to evaluate the interference of tobacco smoke on immunochromatography assay of urinary drug detection. METHODS: Our study included 256 voluntary subjects (143 passive smokers and 113 current smokers). Cotinine was measured by immunoenzymatic method and thiocyanates (SCN(-)) by selective electrode. Urinary drug was detected by immunochromatography assay. A positive result is completed by an analytical method with an immunometric assay. RESULTS: False positive results for benzodiazepines are significantly more frequent in smokers compared with passive smokers (90.2% Vs 22.4%; χ(2) = 116.62, p < 10(-3)). For smokers, the number of cigarettes was significantly higher in subjects with falsely positive results for benzodiazepines compared with subjects with negative results (32 ± 11 Vs 20 ± 10; p = 0.04). Between these two groups, we established a significant difference for urinary cotinine (345 ± 211 Vs 117 ± 54 µg/µmol; p < 10(-3)) and for plasma SCN(-) (101.6 ± 3.4 Vs 98.8 ± 2.1 µmol/L; p = 10(-3)). Urinary cotinine and consumption duration present the highest values of areas under curves (AUC) of the receiver-operating-characteristic (ROC) curves. The cut-off of 167.6 µg/µmol and 10.5 years were found as predictive factors of false positive results. CONCLUSION: Tobacco smoke interferes with immunochromatography assay of urinary drug detection; therefore, all subjects must be questioned about their smoking status to avoid such false results during results interpretation.

[Risk of hyperthyroidism in a Tunisian population of smokers]. / Risque d'hyperthyroïdie dans une population de fumeurs tunisiens.

OBJECTIVES: This study aimed to examine the effect of cigarette smoking on thyroid function especially TSH and FT4 levels and to determine the correlation between these parameters and the biological tobacco markers: plasma thiocyanate and cotininuria. METHODS: The initial study was conducted on 300 voluntary subjects, 162 current smokers, 27 former smokers and 111 nonsmokers aged respectively 35.4±16.1, 31.6±1.8 and 38.0±14.6 years. TSH and FT4 levels were determined using electrochemiluminescence, cotinine by homogenous enzymes immunoassay and thiocyanate by selective electrode. RESULTS: Before and after adjustment for potentials confounder factors, we found a significant decrease of TSH and a significant increase of FT4 levels according to smoking status. In current and former smokers, we found significant decrease in TSH and increase in FT4 levels compared to nonsmokers. Moreover, we noted a significant decrease of TSH levels in subjects smoking more than 40 cigarettes/day compared to those smoking less than 20 cigarettes/day. Additionally, TSH levels were significantly reduced in subjects smoking more than 5 years compared to those who smoked < 5 years. In smokers, cotininuria and plasma thiocyanates presented a negative correlation with TSH and a positive correlation with FT4 levels. CONCLUSION: cigarette smoking is associated to perturbations in FT4 and TSH levels, these perturbations were strongly correlated with smoking status parameters. The associations with smoking cessation suggest that smoking may have reversible effects on thyroid function. Therefore, it is recommended to stop or reduce smoking and to introduce testing of thyroid estimation as a routine test, especially in subjects at risk.

Effect of cigarette smoking on paraoxonase 1 activity according to PON1 L55M and PON1 Q192R gene polymorphisms.

OBJECTIVE: This study aims to investigate the effect of cigarette smoking on paraoxonase 1 (PON1) activity according to PON1 L55M and PON1 Q192R gene polymorphisms. MATERIALS AND METHODS: Our sample included 300 voluntary subjects: 138 nonsmokers and 162 current smokers aged 38.47 ± 21.91 and 35.55 ± 16.03 years, respectively. PON1 activity was determined by kinetic methods. L55M and Q192R gene polymorphisms of PON1 were determined by multiplex polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). RESULTS: We found in smokers a significant decrease of PON1 activity before and after adjustment. We noted a significant association between smoking status and lower PON1 activity [odds ratio (OR) = 3.03, confidence interval 95% = 1.5-5.9, p = 0.001]. In smokers, there was significant association between PON1 activity and PON1 L55M polymorphisms (p = 0.01). Also, the 55MM genotype presented the lowest paraoxonase activity, while the 55LL genotype showed the highest one. After adjustment for confounding variables, smokers with PON1 L55M polymorphism had the highest risk for lower PON1 activity; however, PON1 Q192R genotype might protect smokers from decrease in PON1 activity. We found significant interaction between the effect of cigarette smoking and both PON1 L55M and PON1 Q192R polymorphisms on lower PON1 activity. CONCLUSIONS: Cigarette smoking was significantly associated with decrease in PON1 activity. Moreover, PON1 L55M polymorphism predisposes smokers to decreased PON1 activity in contrast to PON1 Q192R genotype.

[Butyrylcholinesterase activity in schizophrenic patients]. / Étude de l'activité butyrylcholinestérase chez des patients schizophrènes.

Butyrylcholinesterase (BChE) is an enzyme that has been investigated for its putative role in neurodegenerative and neuropsychiatric disorders. The aim of our work was to study BChE activity variations in schizophrenic patients and to investigate the involvement of this enzyme in schizophrenia and the importance of determining its activity in this disease. This cross-sectional study was carried out 131 (104 males and 27 females, mean age  = 38.0  ±â€Š 11.4 years) patients with chronic schizophrenia according DSM-IV criteria and 90 (64 males and 26 females, mean age  = 37.1  ±  15.9 years) healthy controls. Plasma BChE activity was determined by a kinetic method on Integra 400plus(TM) (Roche Diagnostics). Patients with schizophrenia had higher plasma BChE activity than controls (P < 0.0001). Female patients had higher BChE activity and smokers had lower BChE activity than non-smokers either in patients and controls. In patients with schizophrenia, BChE activity was not differed with age, alcohol status and clinical sub-types, and was not correlated to duration of illness. Concerning therapeutic features, BChE activity was higher in patients treated with antipsychotics monotherapy than those treated with an association of antipsychotic and anticholinergic drugs, without significant difference (P  = 0.196). Schizophrenic patients showed an increase BChE activity, which could be related to the pathophysiology of schizophrenia.

Effect of cigarette smoking on plasma uric acid concentrations.

OBJECTIVES: The purpose of this study was to examine the effect of cigarette smoking on plasma uric acid concentration and to determine the correlation between this parameter and the biological tobacco markers, plasma thiocyanate and urinary cotinine. METHODS: The initial study was conducted on 300 subjects; 138 of them were nonsmokers (62 men and 76 women) aged 14-72 years and 162 were current smokers (145 men and 17 women) aged 16-85 years. Uric acid, creatinine, and urinary cotinine were determined by the enzymatic colorimetric method and plasma thiocyanate by selective electrode. RESULTS: Plasma uric acid concentration was significantly lower in smokers than in nonsmokers. A statistically significant negative correlation was noted between the smoking status parameters, including both the number of cigarettes smoked/day (F (3-161) = 12.063; r = -0.9968; p = 0.0001) and the duration of smoking (F (3-161) = 1.305; r = -0.9406; p = 0.0274), and the plasma uric acid. Among smokers, we noted a negative correlation between uric acid and both plasma thiocyanates (r = -0.437; p < 0.05) and urinary cotinine (r = -0.580; p < 0.05). CONCLUSION: After excluding the other factors affecting the uric acid levels, the significant low plasma uric acid in smokers was attributed to a reduction of the endogenous production as a result of the chronic exposure to cigarette smoke that is a significant source of oxidative stress. Therefore, it is recommended to stop or reduce smoking and to introduce plasma uric acid estimation as a routine test, since it is cheap and simple to reflect the antioxidant level.

Association of the Met-196-Arg variation of human tumor necrosis factor receptor 2 (TNFR2) with paranoid schizophrenia.

Research has provided strong evidence for oligodendrocyte and myelin-related genes dysfunction in schizophrenia. Several studies have suggested abnormalities in the expression of myelin-related genes including tumor necrosis factor receptor 2 (TNFR2) involved in the neurodegeneration and remyelination. In order to further assess the role of TNFR2 in schizophrenia, we examined a functional bi-allelic polymorphism associated with an impaired NF-KB signaling and cell survival. In the present case/control study, 220 patients with schizophrenia and 176 healthy controls were genotyped by RFLP-PCR for the T/G polymorphism at the position 676 in exon 6 of the TNFR2 gene. We found a trend towards over-representation of TNFR2 676G in the patients compared to the controls (p=0.19 and 0.09 respectively). Interestingly, when we evaluated the association between this genetic polymorphism and the clinical variables of schizophrenia, our findings indicated that the frequencies of the G/G genotype and the G allele were significantly higher in paranoid (p=0.014 and p=0.012 respectively) and adult-onset paranoid (p=0.004 and p=0.004 respectively) schizophrenia patient group compared to the controls. The potential association was confirmed by a logistic regression model only for development of the paranoid form of schizophrenia (p=0.022) indicating a substantially increased risk for paranoid schizophrenia with inheritance of the TNFR2(G) allele. In conclusion, this polymorphism in TNFR2 or a gene in proximity seems to be associated specifically with paranoid schizophrenia, at least in the Tunisian population. A replication of our findings in other and larger populations could be of particular importance to establish TNFR2 as one of the susceptibility genes of paranoid schizophrenia.

[Cannabis use in a central region of Tunisia]. / Consommation de cannabis dans une région du centre tunisien.

OBJECTIVE: The objective of this study was to determine the sociodemographic characteristics of cannabis users, their consumption patterns, and effects. METHODS: Our cross-sectional, descriptive study included 205 subjects (191 men, 14 women, mean age = 25.9 ± 7.9 years). The consumption of psychotropic drugs and/or cannabis was confirmed by toxicological analysis. RESULTS: In our study population, 61% were cannabis users. Consumption was significantly higher in males (94.4%) than in females. Consumers were young adults, aged 25.8 ± 8.8 years, single (81.6%), had primary school educations (62.4%), were employed (72%) and lived in urban areas (77.6%); 28.8% had a personal history of psychiatric disorders. The mean age of first cannabis use was 20 years. Cannabis use was frequently associated with consumption of alcohol and tobacco (72%). Forty percent of consumers used cannabis daily. Most of those who had used drugs had done so with friends. In most cases, cannabis was regarded as a means of escape from problems (29.3%), relaxation (20.2%), experimentation (18.2%) and a source of pleasure (16.7%). CONCLUSION: These data suggest the importance of primary prevention of early use and rapid treatment of young users.

Lower paraoxonase 1 activity in Tunisian bipolar I patients.

BACKGROUND: The purpose of this study was to investigate the variations of paraoxonase activity and lipid profile in bipolar I patients, and the association of this activity with the sociodemographic, clinical and therapeutic characteristics of this population. PATIENTS AND METHODS: Our study included 66 patients with bipolar I disorder and 64 controls aged 37.9 ± 12.6 and 36.3 ± 18.2 years, respectively. Paraoxonase activity was determined by kinetic methods; high-density lipoprotein cholesterol (c-HDL), low-density lipoprotein cholesterol (c-LDL), triglycerides and total cholesterol were determined by enzymatic methods; apolipoprotein (Apo)A1, ApoB and lipoprotein (a) (Lp(a)) were determined by immunoturbidimetry using Konelab 30 equipment (Thermo Scientific). RESULTS: Compared with controls, patients had a significantly lower paraoxonase activity and ApoA1 level, and significantly higher total cholesterol, c-LDL and Lp(a) level and ApoB/ApoA1 ratio. Furthermore, paraoxonase activity was significantly correlated with c-HDL values (r = 0.5612; P < 0.001). The lowest paraoxonase activity was noted in relation to age and body mass index (BMI). Moreover, it was associated with gender but not with smoking and alcohol consumption status. In patients, there was no significant change in paraoxonase activity in relation to illness episodes, whereas the lowest values of this activity were seen in manic patients. In contrast, paraoxonase activity was significantly associated with treatment. Indeed, patients taking lithium had the lowest levels. CONCLUSIONS: Bipolar patients had a significant decrease in paraoxonase activity and perturbations in their lipid profile that contribute to increased risk of cardiovascular diseases. Decrease in this activity was significantly associated with treatment with lithium but not with sociodemographic and clinical characteristics. Therefore, such patients require specific care, particularly with regard to their lipid profile.

[Obesity and dyslipidemia in Tunisian bipolar subjects]. / Obésité et dyslipidémie chez des patients bipolaires tunisiens.

This study aims to investigate the prevalence of obesity and overweight and their association with lipid parameters in bipolar patients. Our study included 130 patients with bipolar disorder and 130 control subjects aged respectively 37.9 +/- 12.1 and 37.2 +/- 13.1 years. Obesity was evaluated by body mass index (BMI). Concentrations of total cholesterol, triglycerides, cLDL and cHDL were determined by enzymatic methods and ApoA1, ApoB and Lp(a) by techniques immunoturbidimetric. The prevalence of obesity in patients is 30.1% vs 12.3% in controls. A significant increase in BMI was noted in patients compared with controls regardless of sex and tobacco status and in patients aged less than 35 years and those consumers of alcohol. The majority of obese and overweight patients are treated with valproic acid. We found increase in cholesterol (4.41 +/- 1.02 vs 3.90 +/- 0.98 mmol/L), in cLDL (2.13 +/- 1.09 vs 1.29 +/- 0.56 mmol/L) and in Lp(a) (236 +/- 207 vs 163 +/- 150 mg/L) and decrease in HDLc (0.98 +/- 0.28 vs 1.09 +/- 0.36 mmol/L), more frequent at the obese patients and those presenting an overweight. In conclusion, in bipolar patients, obesity and overweight are frequent and associated with perturbations in lipid profile particularly an increase in total cholesterol, cLDL and Lp(a) and decrease in cHDL that increase the risk of cardiovascular disease.

Decreased glutathione levels and antioxidant enzyme activities in untreated and treated schizophrenic patients.

There is substantial evidence found in the literature that supports the fact that the presence of oxidative stress may play an important role in the physiopathology of schizophrenia. Previous studies have reported the occurrence of impairments in the glutathione levels and the activities of the antioxidant enzymes in patients suffering from schizophrenia. However, most of these studies were performed on treated patients. The present study evaluated treated schizophrenic patients (n=52) along with neuroleptic-free or untreated schizophrenic patients (n=36) and healthy controls (n=46). The blood glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr), and oxidized glutathione (GSSG) as well as the activities of the antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were measured. The psychopathology of the patients was assessed through the Clinical Global Impressions-severity (CGI-severity). The tests revealed that in comparison with the healthy controls, the schizophrenic patients showed significantly lower levels of GSHr, SOD, and CAT. Among the schizophrenic patients, the activities of the antioxidant enzymes SOD and CAT were recorded to be significantly lower in untreated patients than in the treated ones. In addition, the levels of both GSHt and GSHr were found to be inversely correlated with the obtained CGI-severity score. These results evidently suggest that a decrease in the glutathione levels and the activities of the antioxidant enzymes in patients diagnosed with schizophrenia is not related to neuroleptic treatment and could be considered as a biological indicator of the degree of severity of the symptoms of schizophrenia.

Altered antioxidant defense system in clinically stable patients with schizophrenia and their unaffected siblings.

OBJECTIVE: To determine Red Blood Cell (RBC) antioxidant enzyme activities and plasma Thiobarbituric Acid Reactive Substances (TBARS) in clinically stable patients with schizophrenia and their unaffected siblings. METHODS: A case-control study carried out on three groups: 60 schizophrenic patients treated with neuroleptics, 33 of their unaffected siblings and 30 healthy controls with no family psychiatric history. Biological markers were measured on fasting patients after a period of tobacco abstinence: RBC antioxidant enzyme activities - superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) - by spectrophotometry and plasma levels of TBARS by spectrofluorimetry. RESULTS: RBC SOD and CAT activities were significantly lower in schizophrenic patients and their unaffected siblings compared to the control group (P<0.001). Schizophrenic patients also had significantly lower RBC GSH-Px activity than controls (P=0.03), whereas their unaffected siblings had significantly higher RBC GSH-Px activity than controls (P=0.04). Plasma TBARS were higher in schizophrenic patients than their unaffected siblings: 2.1+/-0.8 micromol/l vs. 1.7+/-0.6 micromol/l (P=0.06). CONCLUSIONS: Our results showed a decrease in antioxidant enzyme activities and an increase in lipid peroxidation confirming the existence of oxidative stress in schizophrenic patients treated with neuroleptics. Additionally, this suggests that the increase in GSH-Px activity in unaffected siblings would be a protective mechanism against oxidative stress and damage. Other studies are necessary to confirm these findings.