Ferid Zaafrane

Les récidives suicidaires : étude comparative des caractéristiques des suicidants à répétition et des primosuicidants admis aux urgences d’un hôpital général tunisien

Resume Les objectifs de ce travail etaient d’estimer la frequence des suicidants a repetition parmi l’ensemble des suicidants admis aux urgences et de comparer les caracteristiques des suicidants a repetition et des primosuicidants afin de degager les facteurs associes a la recidive suicidaire. Il s’agit d’une etude transversale portant sur l’ensemble des suicidants admis aux urgences du Centre hospitalo-universitaire de Monastir (Tunisie), durant le deuxieme semestre de l’annee 1999. Parmi les 90 suicidants recrutes, 38 (42,2 %) avaient effectue au moins une tentative de suicide anterieure. Les caracteristiques de ce groupe des suicidants ont ete comparees a celles du groupe des primosuicidants (n = 52). Les suicidants a repetition avaient des taux significativement plus eleves de chomage : 60,5 % versus 34,6 % (p = 0,01), de separation conjugale ou de divorce : 21,1 % versus 5,8 % (p = 0,05) et d’appartenance a une famille nombreuse (fratrie ≥ 4) : 73,7 % versus 46,2 % (p = 0,01). Ils avaient des antecedents psychiatriques familiaux et personnels plus frequents, des symptomes depressifs plus marques avec des scores eleves (> 14) a l’echelle de depression de Montgomery et Asberg : 71,1 % versus 48,1 % (p = 0,01) et une intensite elevee des facteurs de stress vecus au cours du dernier semestre selon l’echelle de Holmes et Rahe : 68,4 % versus 42,3 % (p = 0,04). L’analyse de ces resultats, en fonction des donnees de la litterature, devrait deboucher sur des actions preventives afin de faire face a l’augmentation des recidives suicidaires.

Toxoplasma gondii infection in schizophrenia and associated clinical features

The belief that latent toxoplasmosis is asymptomatic has been questioned, in particular due to the repeated highlighted link between the Toxoplasma gondii infection and an increased incidence of schizophrenia. However, to understand this relationship, the effect of infection with Toxoplasma gondii on the severity of schizophrenia has been poorly studied. Our work focused on comparing the prevalence of Toxoplasma infection between schizophrenic patients and healthy controls, as well as comparing the clinical features and the demographic characteristics between Toxoplasma-seronegative and Toxoplasma-seropositive patients with schizophrenia. The rate of IgG antibody in the schizophrenia patients was 74.8% compared 53.8% in controls. Patients with schizophrenia had a significantly higher mean of serum IgG antibodies to T. gondii compared to controls. The seropositive male patients had a higher age of disease onset, a higher BPRS score, a greater negative PANSS score and a lower GAF score than the seronegative male patients. These results suggest a higher severity of clinical symptoms in the male patients with schizophrenia. This study provides further evidence to the hypothesis that exposure to Toxoplasma may be a risk factor for schizophrenia. Moreover, toxoplasmosis in men with schizophrenia may lead to more severe negative and cognitive symptoms and a less favorable course of schizophrenia.

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.

Use of Clozapine for Borderline Personality Disorder: A Case Report.

Patients with borderline personality disorder (BPD) show significant impairment in functioning, particularly in the interpersonal and social domains. Prior reports suggest that clozapine may be effective in the management of BPD. We present the case of a patient with BPD who experienced persistent suicidal ideation and was treated with clozapine at a state psychiatric hospital. After treatment failure with other psychotropic medications, clozapine medication was initiated; not only did suicidal ideation cease, but social and professional functioning also greatly improved to the point of no longer requiring intensive levels of observation or restrictive procedures. Clozapine appears to be efficacious in the management of suicide attempts and self-injurious behavior. Moreover, it appears to be promising as a therapeutic measure for ameliorating the global functioning of patients with severe BPD. Larger, randomized, blinded, and controlled prospective studies are needed to confirm these findings and to determine optimal dosage.

A gender-specific association of interleukin 1 receptor antagonist polymorphism with schizophrenia susceptibility.

Objective Recent genetic studies have revealed that the interleukin (IL) 1 gene complex is associated with schizophrenia in the Caucasian population; however, data from the North African population are limited. To further assess the role of interleukin 1 receptor antagonist protein (IL1Ra) in schizophrenia, we examined a functional multiallelic polymorphism localised in intron 2 of this receptor gene associated with an altered level of IL1Ra. Methods In the present case–control study, we have analysed the (86 bp)n polymorphism of the interleukin 1 receptor antagonist (IL1RN) gene (RS 1794068) by polymerase chain reaction genotyping in 259 patients with schizophrenia and 178 healthy controls from the Tunisian population. Results We showed that the frequencies of the IL1RN*2/2 genotype and allele 2 were higher in the patient group compared with the control group, and the difference was statistically significant [13.5% vs. 5.6%, p = 10−3, odds ratio (OR) = 3.2% and 32.8% vs. 21.9%, p = 3 × 10−4, OR = 1.76, respectively). When we evaluated the association between this genetic polymorphism and the clinical variables of schizophrenia, we found that the frequencies of the 2/2 genotype and allele 2 were significantly higher in the male patient group (p = 10−4 and 10−5, respectively) compared with the male control group, indicating a substantially increased risk for sex-onset schizophrenia with inheritance of the IL1RN2 allele. When the association between the genotypes and outcome was evaluated by multiple logistic regression analysis, the adjusted OR for the IL1RN genotypes remained statistically significant [1.39; 95% confidence interval (CI) = 1.11–1.73; p = 0.003]. Conclusion The intron 2 polymorphism in IL1RN or a genetic polymorphism at proximity seems to be associated specifically with schizophrenia in the Tunisian male population.

IFNGR2 genetic polymorphism associated with sex-specific paranoid schizophrenia risk

Abstract Background: Considering current scientific evidence about the significant role of chronic low grade inflammation in the physiopathology of schizophrenia, it has been hypothesized that changes in pro-inflammatory cytokines such as interferon gamma may have a significant role in the predisposition to schizophrenia. Aim: This study focuses on identifying whether the functional polymorphism of interferon gamma receptor 2 (IFNGR2) is a risk factor for the development of schizophrenia. Methods: This study was conducted by the RFLP-PCR on a Tunisian population composed of 225 patients with different sub-types of schizophrenia and 166 controls. Results: The IFNGR2 (Q64R) polymorphism analysis showed higher frequencies of minor homozygous genotype (RR) and allele (R) in all patients compared to controls (21.8% vs 10.2%; p = .006, OR = 2.54) and (44% vs 34.9%; p = .01; OR = 1.46), respectively. This correlation was confirmed only for males. This study also noted a significant increase of the mutated homozygous (RR) genotype and (R) allele frequencies of IFNGR2 in paranoid schizophrenics compared to controls (31.4% vs 10.2%; p = .001; OR = 3.34 and 47.2% vs 34.9%; p = .009; OR = 1.66, respectively). This increase remains significant after using binary logistic regression to eliminate confounding factors such as age and sex. Additionally, carriers of RR genotype have significant lower scores on the Scale of Assessment of Positive (SAPS) and negative (SANS) symptoms comparatively to the carrier of the QQ + QR genotypes, suggesting that the R recessive allele carriers could have milder symptoms. Conclusion: The IFNGR2Q64R polymorphism is correlated with male sex and paranoid schizophrenia. It is suggested that a chronic neuroinflammation may predispose to the paranoid schizophrenia development in men.

Association of the IFN-γ (+874A/T) Genetic Polymorphism with Paranoid Schizophrenia in Tunisian Population

ABSTRACT Since growing evidence suggests a significant role of chronic low-grade inflammation in the physiopathology of schizophrenia, we have hypothesized that functional genetic variant of the IFN gamma (IFN-γ; +874A/T; rs2430561) gene may be involved in the predisposition to schizophrenia. This research is based on a case–control study which aims to identify whether polymorphism of the IFN-γ gene is a risk factor for the development of schizophrenia. The RFLP-PCR genotyping of the IFN-γ gene was conducted on a Tunisian population composed of 218 patients and 162 controls. The IFN-γ (+874A/T) polymorphism analysis showed higher frequencies of minor homozygous genotype (TT) and allele (T) in all patients compared with controls (11.5 vs. 4.9%; p = 0.03, OR = 2.64 and 30.7 vs. 24.1%, p = 0.04, OR = 1.4, respectively). This correlation was confirmed for male but not for female patients. Also, the T allele was significantly more common among patients with paranoid schizophrenia when compared with controls (25.8 vs. 4.9%, p = 0.0001; OR = 6.7). Using the binary regression analysis to eliminate confounding factors as age and sex, only this last association remained significant (p = 0.03; OR = 1.76, CI = 1.05–2.93). In conclusion, our results showed a significant association between +874A/T polymorphism of IFN-γ and paranoid schizophrenia, suggesting that this single nucleotide polymorphism (SNP) or another at proximity could predispose to paranoid schizophrenia. Since the minor allele of this polymorphism was correlated with an increased expression of their product, our study validates the hypothesis of excessive pro-inflammatory cytokine in the physiopathology of paranoid schizophrenia.

Unipolar Mania: A Particular Aspect of Bipolar Disorder in Tunisia

Objective Unipolar mania is a clinical reality in our daily practice. Many authors suggested that bipolar patients can have only manic episodes without depressions. These findings lead us to explore more this particularity. Methods We conduct a retrospective, descriptive and comparative study including 173 patients, followed for bipolar disorder type I, according to the Diagnostic and Statistical Manual of Mental Disorders fifth edition criteria, during the period between January 2008 and December 2015. Two groups were identified. The first one was composed of 98 patients who had presented only manic episodes. The second group contained the rest of the sample. Unipolar mania was defined as the presence of three or more manic states without a depressive episode during the period of the study. Results One hundred seventy three patients were included in the study. The average age of the sample was 43 years old. The first episode was manic in 129 patients (74.6%). The dominant polarity was manic in 90.8% of the cases. Seasonal characteristic and psychotic symptoms were observed in respectively 11.0% and 53.2% of the sample. Rapid cycling evolution was observed among 2.3% of patients. The unipolar manic profile accounted for 56.6% of the population. This result is equivalent to an annual incidence of 8%. Comparing the two groups, we did not find a significant difference concerning the sociodemographic and clinical variables except for the number of suicide attempts (p=0.014). Conclusion Our study shows that unipolar mania is clinical evidence. More studies should be conducted in order to understand its nosological and psychopathological foundations.