SNAP-25 gene polymorphisms and weight gain in schizophrenic patients

Drug induced weight gain is a serious side effect of several atypical antipsychotics. As genetic factors play an important role in the homeostasis of hunger/satiety we tried to replicate a preliminary previous finding about an impact of three polymorphisms in the synaptosomal-associated protein of 25kDa (SNAP-25; sites MnlI, TaiI and DdelI in the 3(')-UTR) on clinical response and antipsychotic induced weight gain. We genotyped 162 schizophrenic patients being treated in monotherapy with atypical antipsychotics and 312 healthy control subjects for the three polymorphisms in the SNAP-25 gene using PCR. PANSS scores and weight were measured weekly for a minimum of five weeks. We found significant associations between the TaiI and MnlI polymorphisms and serum triglyceride levels at baseline and for the DdelI polymorphism and weight gain. In conclusion our study can at least partly replicate the previous findings concerning the impact of SNAP-25 gene polymorphisms on weight gain during antipsychotic treatment.     

CD4 memory T cells survive and proliferate but fail to differentiate in the absence of CD40

Secondary T cell responses are enhanced because of an expansion in numbers of antigen-specific (memory) cells. Using major histocompatibility complex class II tetramers we have tracked peptide-specific endogenous (non-T cell receptor transgenic) CD4 memory T cells in normal and in costimulation-deficient mice. CD4 memory T cells were detectable after immunization for more than 200 days, although decay was apparent. Memory cells generated in CD40 knockout mice by immunization with peptide-pulsed wild-type dendritic cells survived in the absence of CD40 and proliferated when boosted with peptide (plus adjuvant) in a CD40-independent fashion. However, differentiation of the memory cells into cytokine-producing effector cells did not occur in the absence of CD40. The data indicate that memory cells can be generated without passing through the effector cell stage.     

Polymorphisms in the apolipoprotein E (APOE) gene in gerontopsychiatric patients

Two recently described polymorphisms in the promoter region of the apolipoprotein E (APOE), the −491A7T and Th1/E47csT/G polymorphism, have been suggested to be associated with an increased risk for Alzheimer's disease (AD) independent from the APOE ɛ4 carrier status. We studied the association between the APOE ɛ4 polymorphism and the −491A/T and Th1E47csT/G polymorphisms in a sample of 118 healthy, non-demented controls and 239 consecutively recruited gerontopsychiatric patients diagnosed as: Alzheimer's disease (N = 89), age mild cognitive impairment (N = 32), memory complainers without any congitive deficit (N = 54) and depression/other psychiatric disorders (N = 64), to test whether the investigated polymorphisms have a high enough selectivity and specificity to distinguish between the different gerontopsychiatric disorders to differentiate AD genetically from other forms of dementia, respectively. Also a possible association with the APOE ɛ4 polymorphism was examined. We found a statistically significant association between the APOE ɛ4 allele and Alzheimer's disease (p = 0.0001) and age associated memory impairment (p = 0.006). Our study failed to show an association between the promoter polymorphisms −491A/T and Th1E47csT/G in the APOE gene and gerontopsychiatric disorders either alone or in relationship to the APOE ɛ4 polymorphism. However, if we combine our results with three previous published positive reports there seems to be an association between the −491A/T polymorphism and AD, though its size is less than found in the original publication. Accepted: 3 February 2001     

Factors associated with health-related quality of life (HRQoL) deterioration in glioma patients during the progression-free survival period

BackgroundMaintenance of functioning and well-being during the progression-free survival (PFS) period is important for glioma patients. This study aimed to determine whether health-related quality of life (HRQoL) can be maintained during progression-free time, and factors associated with HRQoL deterioration in this period.MethodsWe included longitudinal HRQoL data from previously published clinical trials in glioma. The percentage of patients with stable HRQoL until progression was determined per scale and at the individual patient level (i.e. considering all scales simultaneously). We assessed time to a clinically relevant deterioration in HRQoL, expressed in deterioration-free survival and time-to-deterioration (the first including progression as an event). We also determined the association between sociodemographic and clinical factors and HRQoL deterioration in the progression-free period.ResultsFive thousand five hundred and thirty-nine patients with at least baseline HRQoL scores had a median time from randomization to progression of 7.6 months. Between 9–29% of the patients deteriorated before disease progression on the evaluated HRQoL scales. When considering all scales simultaneously, 47% of patients deteriorated on ≥1 scale. Median deterioration-free survival period ranged between 3.8–5.4 months, and median time-to-deterioration between 8.2–11.9 months. For most scales, only poor performance status was independently associated with clinically relevant HRQoL deterioration in the progression-free period.ConclusionsHRQoL was maintained in only 53% of patients in their progression-free period, and treatment was not independently associated with this deterioration in HRQoL. Routine monitoring of the patients’ functioning and well-being during the entire disease course is therefore important, so that interventions can be initiated when problems are signaled.