Clozapine is a potent atypical antipsychotic which binds to a variety of neurotransmitter receptors including serotonin (5-HT) receptors. However, the precise neurochemical site of clozapine's therapeutic action is unknown. We hypothesize that genetic variation in the neurotransmitter receptors to which the drug binds may influence clozapine response. To test this hypothesis we genotyped a novel −1438-G/A polymorphism detected in the promoter region, and a His452Tyr polymorphism described in the coding region of the 5-HT 2A receptor gene in two independent samples of clozapine-treated patients including responders and nonresponders. Although the strong association between these polymorphisms and clozapine response observed in the first sample (sample I) was not statistically significant in the second sample (sample II), the results in both samples were in the same direction. Homozygosity for the allele G-1438 was higher among non-responders (56% in sample I, 43% in sample II) than in responders (28% in sample I and 32% in sample II) in both samples. Similarly, the frequency of allele Tyr452 was higher in non-responders (11% in sample I, 16% in sample II) than in responders (6% in sample I and 10% in sample II). A combined analysis of both samples showed association between both polymorphisms and clozapine response. These results provide further evidence suggesting that genetic variation at 5-HT 2A receptors may influence clozapine response and strengthen the candidacy of these receptors as important therapeutic targets.

A highly flexible resistive switching (RS) memory was fabricated in the Al/TiO/Al/polyimide structure using a simple and cost-effective method. An electronic-resistive-switching-based flexible memory with high performance that can withstand a bending strain of up to 3.6% was obtained. The RS properties showed no obvious degradation even after the bending tests that were conducted up to 10 000 times, and over 4000 writing/erasing cycles were confirmed at the maximally bent state. The superior electrical properties against the mechanical stress of the device can be ascribed to the electronic RS mechanism related to electron trapping/detrapping, which can prevent the inevitable degradation in the case of the RS related with the ionic defects.

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