Contribution of ethical reasoning learning sessions on medical training.

INTRODUCTION: Ethical reasoning is an important skill for all physicians who often face complex ethical dilemmas in their daily practice. Therefore, medical training should include methods for learning ethical theories and concepts, as well as how to apply them in practical situations. AIM: Assess the contribution of an Ethical Reasoning Learning session to fifth medical students' training through a comparison of results of the same objective and structured clinical examination (OSCE) in the form of simulated interview before and after sessions. METHODS: Four 45- minutes' sessions of Ethical Reasoning Learning (ERL) were implemented during a psychiatry internship for four groups of 5th-year students of the faculty of medicine of Monastir (Tunisia). Each session was divided into 7 parts: introduction, reading of a clinical vignette, brainstorming concerning the problems posed by this clinical situation, classification of the problems, identification of the principles of medical ethics, construction of the ethical matrix, and a conclusion. RESULTS: Fifty-seven students participated in the study divided into 4 groups. We found a significant difference in the means of the OSCE scores before and after the ERL session and a significant difference between the probability of respecting medical secrecy during pre and post-ethical reasoning learning sessions (p <0.001). We have found an effect of ERL sessions on the acquisition of this ethical competence by medical students. CONCLUSION: We learned that an ERL session has improved medical training in ethics applied to psychiatry. Other sessions dealing with other ethical skills are necessary to confirm these results.

Exploring clozapine pharmacokinetics in Tunisian schizophrenic patients: A population-based modelling approach investigating the impact of genetic and non-genetic variables.

Clozapine is characterized by a large within- and between-patient variability in its pharmacokinetics, attributed to non-genetic and genetic factors. A cross-sectional analysis of clozapine trough concentration (Clz C0) issued from Tunisian schizophrenic patients was collected and analysed using a nonparametric modelling approach. We assessed the impact of demographic covariates (age, weight and sex), patient's habits (smoking status, alcohol and caffeine intake) and the genetic factors (CYP1A2*1C, CYP1A2*1F and CYP2C19*2 polymorphisms) on each pharmacokinetic parameter. An external validation of this pharmacokinetic model using an independent data set was performed. Fit goodness between observed- and individual-predicted data was evaluated using the mean prediction error (% MPE), the mean absolute prediction error (% MAPE) as a measure of bias, and the root mean squared error (% RMSE) as a measure of precision. Sixty-three CLz C0 values issued from 51 schizophrenic patients were assessed in this study and divided into building and validation groups. CYP1A2*1F polymorphism and smoking status were the only covariates significantly associated with clozapine clearance. Precision parameters were as follows: 1.02%, 0.95% and 22.4%, respectively, for % MPE, % MAPE and % RMSE. We developed and validated an accurate pharmacokinetic model able to predict Clz C0 in Tunisian schizophrenic patients using the two parameters CYP1A2*1F polymorphism and smoking.

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.

An international research agenda for clozapine-resistant schizophrenia.

Treatment-resistant symptoms occur in about a third of patients with schizophrenia and are associated with a substantial reduction in their quality of life. The development of new treatment options for clozapine-resistant schizophrenia constitutes a crucial, unmet need in psychiatry. Additionally, an overview of past and possible future research avenues to optimise the early detection, diagnosis, and management of clozapine-resistant schizophrenia is unavailable. In this Health Policy, we discuss the ongoing challenges associated with clozapine-resistant schizophrenia faced by patients and health-care providers worldwide to improve the understanding of this condition. We then revisit several clozapine guidelines, the diagnostic tests and treatment options for clozapine-resistant schizophrenia, and currently applied research approaches in clozapine-resistant schizophrenia. We also suggest methodologies and targets for future research, divided into innovative nosology-oriented field trials (eg, examining dimensional symptom staging), translational approaches (eg, genetics), epidemiological research (eg, real-world studies), and interventional studies (eg, non-traditional trial designs incorporating lived experiences and caregivers' perspectives). Finally, we note that low-income and middle-income countries are under-represented in studies on clozapine-resistant schizophrenia and propose an agenda to guide multinational research on the cause and treatment of clozapine-resistant schizophrenia. We hope that this research agenda will empower better global representation of patients living with clozapine-resistant schizophrenia and ultimately improve their functional outcomes and quality of life.

Eating disorder and anxiety during Covid19 pandemic: the Maghrebian experience.

The coronavirus pandemic is considered the worst-hit that the world had witnessed in the current century. The impact of the pandemic, especially during the lockdown, was not only diverse but also worldwide. The African continent, including the Maghreb, was no exception. The aim of this study was to assess the levels of anxiety and eating behaviors and their correlations in three Maghrebian countries following the official outbreak of the COVID19 pandemic. It is a cross-sectional study of 754 participants from Tunisia, Algeria and Morocco. It took place between 30 April and 2 July 2020. The survey showed that eating disorders represented 45.9% of the sample while 26.8% (202 participants) matched the anxiety criteria. Statistical significant factors for eating disorders were gender (p = 0.002; OR = 1.760), underweight (p = 0.021; OR = 0.306), anxiety (p = 0.001; OR = 0.470), bulimia (p = 0.000; OR = 0.794) and body dissatisfaction (p = 0.000; OR = 0.920). This rise goes along with other surveys in different parts of the world. These results can be explained by multiple reasons such as the 'food insecurity' mechanism, the excessive feeling of boredom and loneliness resulting from social distancing and the overwhelming overthinking about the onset of a serious economic crisis.

Attitudes toward mental illness among medical students and impact of temperament.

BACKGROUND: Mental health-related stigma is a serious problem that has undesirable consequences for individuals with mental disorders including physical health disparities, increasing mortality, and social dysfunction. Besides, these individuals frequently report feeling 'devalued, dismissed, and dehumanized' when encountering health professionals who are also perpetrators of stigmatizing attitudes and discriminatory behaviors. AIMS: The present study concentrates on attitudes, and behavioral responses of medical students and junior doctors toward individuals with a mental illness and explores factors associated with stigma including temperament. METHODS: A cross-sectional study was conducted among medical students and junior doctors from medical schools of universities in Tunisia. All participants were invited to complete a brief anonymous electronic survey administered on the google forms online platform. Data were collected using self-administered questionnaires, Stigma Measurement, Mental Illness: Clinicians' Attitudes (MICA), Assessment of Affective Temperament, TEMPS-A scale. RESULTS: A total of 1,028 medical students and junior doctors were recruited. The completion of a psychiatry clerkship for medical students didn't improve significantly the level of stigma toward people with a mental illness. Students in the fourth year had significantly the lowest MICA scores comparing to other students. Psychiatrists had significantly lower scores of explicit stigma attitudes than the other groups (Mean score = 0.42). As for other specialties, surgical residents had more stigmatizing attitudes than those who had medical specialties. 70% of participants believed that people with a mental illness are more dangerous than the other patients. Hyperthymic temperament was significantly associated with decreased stigma attitudes toward patients with mental illness. CONCLUSION: A combination of medical school experiences of psychiatry's theoretical learning and clerkship and wider societal beliefs are important factors that shape students. Awareness of this will enable educators to develop locally relevant anti-stigma teaching resources throughout the psychiatry curriculum to improve students' attitudes toward mental illnesses.

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.

Hashimoto's Encephalopathy Revealed by Hypochondriacal Delusion: A Case Report Involving a Male Patient.

Hashimoto's encephalopathy (HE) is a rare autoimmune disorder. It associates encephalopathy with autoimmune thyroiditis, presenting abnormal elevations of thyroid antibodies. It is more common in females. It can present with various symptoms, including seizures, myoclonus, psychosis, hallucinations, and mood disturbances. Hypochondriacal delusion is an unusual clinical presentation of this disorder. The authors report a case of HE in a male patient whose clinical presentation was dominated by hypochondriacal delusion. The absence of response to antipsychotics, high serum antithyroid peroxidase antibodiesof about 199 UI/ml, the normality of magnetic resonance imaging, and improvement with corticosteroids confirmed the diagnosis. This neuroendocrine disorder is often misdiagnosed and it represents a diagnostic challenge for clinicians. It should be considered in patients presenting a refractory or an atypical neuropsychiatric disorder and having a family history of autoimmune disease.

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.

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.

ADHD in Tunisian Adolescents: Prevalence and Associated Factors.

OBJECTIVE: The aims of the study were to determine the prevalence of ADHD in a population of high school students and to explore the factors associated with this disorder. METHOD: This was a cross-sectional study that had included 447 high school students. The diagnosis of ADHD was made by the Adult ADHD Self-Report Scale translated in Arabic language. The sociodemographic and clinical characteristics were evaluated by a preestablished questionnaire. The self-esteem was assessed by the Rosenberg Self-Esteem Scale. RESULTS: The prevalence of ADHD was 18.1%. The logistic regression analysis showed an association between the diagnosis of ADHD and the bad relationships with parents (odds ratio [OR] = 16.43; p < 10-3), the presence of personal psychiatric antecedents (OR = 12.16; p < 10-3), internet misuse (OR = 2.39; p = .014), and maltreatment antecedents (OR = 3.16; p = .009). CONCLUSION: The prevalence of ADHD in this study was one of the highest prevalence reported. The factors associated with ADHD may have diagnostic and therapeutic implications.

Neurological soft signs in Tunisian patients with first-episode psychosis and relation with cannabis use.

BACKGROUND: Neurological soft signs (NSS) are minor non-localizing neurological abnormalities that are conceptualized as neurodevelopmental markers that mediate the biological risk for psychosis. We aimed to explore the relationship between NSS and cannabis use, an environmental risk factor of psychosis. METHODS: This was a cross-sectional study in consecutively admitted patients hospitalized for first-episode psychosis. NSS were assessed by the NSS scale (23 items exploring motor coordination, motor integrative function, sensory integration, involuntary movements or posture, quality of lateralization). Presence of NSS was defined as a NSS scale total score ≥9.5. Cannabis use was ascertained with the cannabis subsection in the Composite International Diagnostic Interview. RESULTS: Among 61 first-episode psychosis patients (mean age = 28.9 ± 9.4 years; male = 86.9%, antipsychotic-naïve = 75.4%), the prevalence of current cannabis use was 14.8% (heavy use = 8.2%, occasional use = 6.6%). NSS were present in 83.6% of the sample (cannabis users = 66.7% versus cannabis non-users = 85.5%, p = 0.16). The mean total NSS score was 15.3 ± 6.7, with a significant lower total NSS score in cannabis users (11.2 ± 5.6 versus 16.0 ± 6.7, p = 0.048). Differences were strongest for the "motor coordination" (p = 0.06) and "involuntary movements" (p = 0.07) sub-scores. CONCLUSIONS: This study demonstrated a negative association between cannabis use and NSS, especially regarding motor discoordination. This finding supports the hypothesis that a strong environmental risk factor, such as cannabis, may contribute to the onset of psychosis even in the presence of lower biological and genetic vulnerability, as reflected indirectly by lower NSS scores. Nevertheless, additional studies are needed that explore this interaction further in larger samples and considering additional neurobiological and environmental risk factors.

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.

Decreased glutathione levels and impaired antioxidant enzyme activities in drug-naive first-episode schizophrenic patients.

BACKGROUND: The aim of this study was to determine glutathione levels and antioxidant enzyme activities in the drug-naive first-episode patients with schizophrenia in comparison with healthy control subjects. METHODS: It was a case-controlled study carried on twenty-three patients (20 men and 3 women, mean age = 29.3 ± 7.5 years) recruited in their first-episode of schizophrenia and 40 healthy control subjects (36 men and 9 women, mean age = 29.6 ± 6.2 years). In patients, the blood samples were obtained prior to the initiation of neuroleptic treatments. Glutathione levels: total glutathione (GSHt), reduced glutathione (GSHr) and oxidized glutathione (GSSG) and antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) were determined by spectrophotometry. RESULTS: GSHt and reduced GSHr were significantly lower in patients than in controls, whereas GSSG was significantly higher in patients. GPx activity was significantly higher in patients compared to control subjects. CAT activity was significantly lower in patients, whereas the SOD activity was comparable to that of controls. CONCLUSION: This is a report of decreased plasma levels of GSHt and GSHr, and impaired antioxidant enzyme activities in drug-naive first-episode patients with schizophrenia. The GSH deficit seems to be implicated in psychosis, and may be an important indirect biomarker of oxidative stress in schizophrenia early in the course of illness. Finally, our results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies for schizophrenia from early stages.