| 1 | Exp. Mol. Med. 2012 Sep 44: 545-53 |
|---|---|
| PMID | 22809901 |
| Title | Inhibition of mouse brown adipocyte differentiation by second-generation antipsychotics. |
| Abstract | Brown adipose tissue is specialized to burn lipids for thermogenesis and energy expenditure. Second-generation antipsychotics (SGA) are the most commonly used drugs forschizophreniawith several advantages over first-line drugs, however, it can cause clinically-significant weight gain. To reveal the involvement of brown adipocytes in SGA-induced weight gain, we compared the effect of clozapine, quetiapine, and ziprasidone, SGA with different propensities to induce weight gain, on the differentiation and the expression of brown fat-specific markers, lipogenic genes and adipokines in a mouse brown preadipocyte cell line. On Oil Red-O staining, the differentiation was inhibited almost completely by clozapine (40 ?M) and partially by quetiapine (30 ?M). Clozapine significantly down-regulated the brown adipogenesis markers PRDM16, C/EBP?, PPAR?2, UCP-1, PGC-1?, and Cidea in dose- and time-dependent manners, whereas quetiapine suppressed PRDM16, PPAR? 2, and UCP-1 much weakly than clozapine. Clozapine also significantly inhibited the mRNA expressions of lipogenic genes ACC, SCD1, GLUT4, aP2, andCD36as well as adipokines such as resistin, leptin, and adiponectin. In contrast, quetiapine suppressed only resistin and leptin but not those of lipogenic genes and adiponectin. Ziprasidone (10 ?M) did not alter the differentiation as well as the gene expression patterns. Our results suggest for the first time that the inhibition of brown adipogenesis may be a possible mechanism to explain weight gain induced by clozapine and quetiapine. |
| SCZ关键字 | schizophrenia |
| 2 | Eur. J. Hum. Genet. 2015 May 23: 628-32 |
| PMID | 25074461 |
| Title | Genomic aberrations of the CACNA2D1 gene in three patients with epilepsy and intellectual disability. |
| Abstract | 电压门控钙通道在神经传递中具有重要作用。影响编码这些通道α亚基的基因的畸变与癫痫和神经精神疾病（如自闭症或自闭症或神经精神疾病）有关schizophrenia. Here we report three patients with a genomic aberration affecting the CACNA2D1 gene encoding the ?2? subunit of these voltage-gated calcium channels. All three patients present with epilepsy and intellectual disability pinpointing the CACNA2D1 gene as an interesting candidate gene for these clinical features. Besides these characteristics, patient 2 also presents with obesity with hyperinsulinism, which is very likely to be caused by deletion of theCD36gene. |
| SCZ关键字 | schizophrenia |
| 3 | Brain Behav. Immun. 2016 Feb 52: 178-86 |
| PMID | 26541453 |
| Title | Pretreatment levels of the fatty acid handling proteins H-FABP and CD36 predict response to olanzapine in recent-onset schizophrenia patients. |
| Abstract | 传统的schizophreniapharmacotherapy remains a subjective trial and error process involving administration, titration and switching of drugs multiple times until an adequate response is achieved. Despite this time-consuming and costly process, not all patients show an adequate response to treatment. As a consequence, relapse is a common occurrence and early intervention is hampered. Here, we have attempted to identify candidate blood biomarkers associated with drug response in 121 initially antipsychotic-free recent-onsetschizophreniapatients treated with widely-used antipsychotics, namely olanzapine (n=40), quetiapine (n=23), risperidone (n=30) and a mixture of these drugs (n=28). Patients were recruited and investigated as two separate cohorts to allow biomarker validation. Data analysis showed the most significant relationship between pre-treatment levels of heart-type fatty acid binding protein (H-FABP) and response to olanzapine (p=0.008, F=8.6, ?=70.4 in the discovery cohort and p=0.003, F=15.2, ?=24.4 in the validation cohort, adjusted for relevant confounding variables). In a functional follow-up analysis of this finding, we tested an independent cohort of 10 patients treated with olanzapine and found that baseline levels of plasma H-FABP and expression of the binding partner for H-FABP, fatty acid translocase (CD36),在单核细胞预测reduction of psychotic symptoms (p=0.040, F=6.0, ?=116.3 and p=0.012, F=11.9, ?=-0.0054, respectively). We also identified a set of serum molecules changed after treatment with antipsychotic medication, in particular olanzapine. These molecules are predominantly involved in cellular development and metabolism. Taken together, our findings suggest an association between biomarkers involved in fatty acid metabolism and response to olanzapine, while other proteins may serve as surrogate markers associated with drug efficacy and side effects. |
| SCZ关键字 | schizophrenia |