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.

Cognitive Impairment Among Tunisian Bipolar Patients: a Case-Control Study.

Studies exploring the cognitive performance of bipolar patients have mainly been conducted in Western countries. To our knowledge, no surveys have been reported to date in Tunisia. The present work aimed to evaluate the cognitive functions, in the three domains of memory, attention and executive functions, among a sample of Tunisian individuals with bipolar disorder, during the remission period, compared to healthy control subjects. We found that Cognitive functions in euthymic patients with bipolar disorder were significantly more impaired than in controls, apart from the working memory that did not show a significant difference between the two groups. Our findings confirm cognitive deficits associated with bipolar disorder, even at a distance from the symptomatic phases of the disease. Thus, these anomalies may be considered as a trait marker of the disease. A better understanding of cognitive decline certainly allows for better management of psychiatric pathologies, thus improving patients' social skills and quality of life.

High-Sensitive c-Reactive Protein Levels in Euthymic Bipolar Patients: Case-Control Study.

Bipolar disorder is a chronic, disabling disease that is characterized by the recurrence of thymic episodes. The role of the immune-inflammatory system in the etiopathogenesis of this affection arouses the interest of research. The aim of this work was to determine the plasma levels of the high sensitivity C reactive protein (hs-CRP) in patients with bipolar disorder in remission phase by comparing them to a control group.A case-control cross-sectional study was conducted from 56 subjects with bipolar disorder in clinical remission, and 56 volunteers and healthy control subjects.Mean plasma hs-CRP was significantly higher in patients with bipolar disorder than control subjects. In bipolar patients, a hs-CRP elevation was significantly associated with the disease severity item mean score.Through this study, bipolar disorder appears to be associated with a state of chronic inflammation. This should lead to randomized controlled trials evaluating the value of anti-inflammatory drugs in the management of bipolar disorder.

Catatonia in patients with dementia: a case report.

Catatonia occurring as part of a clinical picture of dementia has been reported with almost all types of dementia. It remains under-diagnosed in older adults and those with dementia. We review a case of a young patient admitted in our psychiatric department for catatonia and after efficient treatment with Lorazepam, assessment revealed a dementia. Catatonia is a severe neuropsychiatric syndrome with an excellent prognosis if recognized and treated without delay.

Psychiatric disorders in the acoustic neuroma: about a case.

Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder characterized by formation of central nervous system tumors. They are associated to significant morbidity due to multiple problems such as hearing loss that can lead to many psychiatric disorders.