Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study
Chen J, Yang P, Zhang Q, Chen R, Wang P, Liu B, Sun W, Jian X, Xiang S, Zhou J, Li N, Wang K, Gao C, Wen Y, Wu C, Zhang J, Zhao Y, Yang Q, Li M, Stewart R, Sun Y, Pan D, Niu Y, Wang Z, Xu Y, Li X, He L, Li Z, Shi Y. Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study. Transl Psychiatry. 2021 Jun 3;11(1):343. doi: 10.1038/s41398-021-01470-z. PMID: 34083506.
- “Clozapine is considered to be the most effective antipsychotic medication for schizophrenia. However, it is associated with several adverse effects such as leukopenia, and the underlying mechanism has not yet been fully elucidated.”
- “The authors performed a genome-wide association study (GWAS) in a Chinese population to identify genetic markers for clozapine-induced leukopenia (CIL) and clozapine-induced neutropenia (CIN).”
- “A total of 1879 patients (225 CIL cases, including 43 CIN cases, and 1,654 controls) of Chinese descent were included.“
- “The authors also performed a trans-ancestry meta-analysis with GWAS results of European individuals from the Clozapine-Induced Agranulocytosis Consortium (CIAC).”
- “The authors identified several novel loci reaching the threshold of genome-wide significance level (P < 5 × 10-8). Three novel loci were associated with CIL while six were associated with CIN, and two T cell related genes (TRAC and TRAT1) were implicated. The authors also observed that one locus with evidence close to genome-wide significance (P = 5.08 × 10-8) was near the HLA-B gene in the major histocompatibility complex region in the trans-ancestry meta-analysis.”
Memory changes following adjuvant temporo-parietal repetitive transcranial magnetic stimulation in schizophrenia
Gupta P, Sahu A, Prasad S, Sinha VK, Bakhla AK. Memory changes following adjuvant temporo-parietal repetitive transcranial magnetic stimulation in schizophrenia. Indian J Psychiatry. 2021 Jan-Feb;63(1):66-69. doi: 10.4103/psychiatry.IndianJPsychiatry_532_20. Epub 2021 Feb 15. PMID: 34083822; PMCID: PMC8106430.
- “ The use of repetitive transcranial magnetic stimulation (rTMS) in schizophrenia has shown improvement as well as deficits in memory. Though most studies had focused on dorsolateral prefrontal cortex only, but impact of rTMS on cognitive functions remain inconclusive. The need of the study is to assess the impact of rTMS on memory in schizophrenia.”
- “Forty right-handed male patients with schizophrenia were included by purposive sampling and rated on Positive and Negative Syndrome Scale (PANSS) before starting the rTMS treatment with the experimental group. Low frequency 1 Hz rTMS including 1200 stimulations were given over temporo-parietal cortex for 20 min as add on to medications. At the end of 10 session treatment (5 days a week for 2 weeks), the patients were re-evaluated.”
- “Results: A total of 39 patients (20 for experimental group and 19 for control group) with mean age of 29.70 ± 9.05 and 31.26 ± 7.78 years, respectively, shows significant difference to pre- and post-treatment mean PANSS score in positive, negative and general psychopathology domains. The pre- and post-treatment mean Postgraduate Institute Memory Scale Scores with multivariate repeated measures analysis of variance revealed significant improvements in all memory domains (P < 0.01) except remote memory in both experimental and control groups.”
Brain capillary structures of schizophrenia cases and controls show a correlation with their neuron structures
Saiga R, Uesugi M, Takeuchi A, Uesugi K, Suzuki Y, Takekoshi S, Inomoto C, Nakamura N, Torii Y, Kushima I, Iritani S, Ozaki N, Oshima K, Itokawa M, Arai M, Mizutani R. Brain capillary structures of schizophrenia cases and controls show a correlation with their neuron structures. Sci Rep. 2021 Jun 3;11(1):11768. doi: 10.1038/s41598-021-91233-z. PMID: 34083657.
- “Brain blood vessels constitute a micrometer-scale vascular network responsible for supply of oxygen and nutrition. In this study, we analyzed cerebral tissues of the anterior cingulate cortex and superior temporal gyrus of schizophrenia cases and age/gender-matched controls by using synchrotron radiation microtomography or micro-CT in order to examine the three-dimensional structure of cerebral vessels.”
- “Over 1 m of cerebral blood vessels was traced to build Cartesian-coordinate models, which were then used for calculating structural parameters including the diameter and curvature of the vessels. The distribution of vessel outer diameters showed a peak at 7-9 μm, corresponding to the diameter of the capillaries. Mean curvatures of the capillary vessels showed a significant correlation to the mean curvatures of neurites, while the mean capillary diameter was almost constant, independent of the cases.”
- “Our previous studies indicated that the neurites of schizophrenia cases are thin and tortuous compared to controls. The curved capillaries with a constant diameter should occupy a nearly constant volume, while neurons suffering from neurite thinning should have reduced volumes, resulting in a volumetric imbalance between the neurons and the vessels. We suggest that the observed structural correlation between neurons and blood vessels is related to neurovascular abnormalities in schizophrenia.”
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