Further evidence for genetic association of CACNA1C and schizophrenia: New risk loci in a Han Chinese population and a meta-analysis

CACNA1C (12p13.3) has been implicated as a susceptibility gene for schizophrenia by several replicated genome wide association studies. While these results have been consistent among studies in European populations, the findings in East Asian populations have varied. To test whether CACNA1C is a risk gene for schizophrenia, we conducted a case–control study in 5897 schizophrenic patients and 6323 healthy control subjects selected from Han Chinese population. Our study replicated the positive associations of rs1006737 (P = 0.0108, OR = 1.16, 95% CI: 1.03–1.29) and rs1024582 (P = 0.0062, OR = 1.18, 95% CI: 1.05–1.33), and identified a novel risk locus, rs2007044 (P = 0.0053, OR = 1.08, 95% CI: 1.02–1.14). A meta-analysis of rs1006737 combining our study and previous studies was conducted in a total of 8222 schizophrenia cases and 24,661 healthy controls. In the meta-analysis, the association between rs1006737 and schizophrenia remained significant (OR = 1.14, 95% CI: 1.07–1.22, P = 0.0001). Stratified analysis showed no heterogeneity between East Asian and European ancestries (χ²[1] = 0.07, P = 0.795), and the difference in pooled ORs between ancestries was not significant (Z = 0.25, P = 0.801). Our results provide further support for associations of rs1006737 and rs1024582 with schizophrenia, identify a new risk locus rs2007044 in a Han Chinese population, and further establish CACNA1C as an important susceptibility gene for the disease across world populations.     

Severe Systemic Reaction to the Pneumococcal Revaccination

Predictors of severe reaction to polyvalent pneumococcal vaccine (PPV) are not established. In the absence of prospective studies, revaccination within 5 years and high titer of protective antibody appear to increase the risk of a local reaction that manifests as self-limiting pain, localized erythema, and edema. A more severe systemic reaction, manifesting as fever, arthralgia, and extensive edema involving the entire upper extremity, is rare, and we report a case in a patient with myeloproliferative disease.     

条件性位置厌恶大鼠伏隔核壳区多巴胺及其代谢产物3，4二羟基苯乙酸水平变化

目的探讨伏隔核壳区（AcbSh）多巴胺（DA）及其代谢产物3,4-二羟基苯乙酸（DOPAC）在吗啡依赖戒断所致厌恶动机中的作用,揭示阿片依赖戒断的厌恶动机机制。方法40只SPF级雄性Sprage．Dawley大鼠分为实验组（吗啡＋纳洛酮,MN组）与对照组（吗啡＋生理盐水,MS组;生理盐水＋纳洛酮,sN组）,连续6．5d吗啡注射（10mg／kg,bid,IP）一次纳洛酮催瘾（0．3mg／kg,IP）,同时搭配条件性位置训练箱建立条件性位置厌恶（CPA）大鼠模型。在立体定位术后3-5d,CPA建立前、后收集AcbSh中的细胞外液,采用高效液相色谱-电化学方法对透析液中DA及DOPAC浓度进行测定。结果连续6．5d的吗啡注射与纳洛酮一次催瘾搭配,实验组大鼠表现出明显的厌恶动机,在伴药侧的时间[（230．01±24．76）S]明显缩短,与实验前[（566．04±19．80）s]相比,差异具有统计学意义（t=11．889,P〈0．01）。CPA建立后,MN组AcbSh中DA水平（1．72±0．10）明显升高,与MS组（0．95±0．05）和sN组（0．09±0．06）相比差异有统计学意义（F=42．319,P〈0．01）;MN组DOPAC水平（1．56±0．07）与MS组（1．19±0．04）、SN组（1．07±0．02）相比,明显升高,差异具有统计学意义（F=25．375,P〈0．01）。结论AcbSh中DA及DOPAC可能参与CPA的建立,中脑边缘系统的多巴胺机制可能在物质依赖厌恶动机中起到十分重要的调节作用。     

抑郁症患者脑源性神经营养因子蛋白及基因表达水平与自杀行为的关联分析

目的:探讨抑郁症患者外周血脑源性神经营养因子(BDNF)蛋白和mRNA表达水平与自杀行为、抑郁症状的关联。方法:共纳入符合中国精神障碍分类与诊断标准第3版诊断标准的抑郁症患者65例,按有无自杀未遂行为分为自杀未遂组(n=31)、无自杀行为组(n=34),健康对照30名。采用汉密顿抑郁量表(HAMD)、Beck绝望量表(BHS)、自杀意念自评量表(SIOSS)评估病例组的抑郁、绝望与自杀意念;采用酶联免疫吸附法测定血清BDNF蛋白浓度,实时荧光定量聚合酶链式反应(PCR)法测定BDNF mRNA相对表达量。结果:自杀未遂组与无自杀行为组的BDNF蛋白浓度[(57.3±9.2)ng/mL,(76.0±25.7)ng/mL vs.(113.8±44.4)ng/mL,均P0.05]与BDNF mRNA相对表达量[(0.2±0.0),(0.5±0.0)vs.(1.0±0.1),均P0.05]均低于正常对照组,自杀未遂组的血清BDNF蛋白浓度和mRNA相对表达量低于无自杀组(P0.05)。病例组(n=65)血清BDNF蛋白浓度与SIOSS总分(r=-0.24,P0.01)呈负相关,与BDNF mRNA相对表达量(r=0.28,P0.01)呈正相关;BDNF mR-NA相对表达量与HAM D总分(r=-0.46,P0.01)、BHS总分(r=-0.42,P0.01)、SIOSS总分(r=-0.43,P0.01)呈负相关,与病程(r=0.19,P0.05)呈正相关。结论:研究提示外周血BDNF蛋白和mRNA水平低可能是抑郁发作患者出现自杀行为的危险因素之一。     

Unusual clinical description of adult with Timothy syndrome,carrier of a new heterozygote mutation of CACNA1C

CANAC1C encodes for the main cardiac L-type calcium channel and mutations on it lead to a prolonged QT interval in Timothy Syndrome (TS). We provide a new de novo constitutional heterozygote missense variation in CACNA1C in a living adult woman, also carrier of the known c.2146-1G>C heterozygous variation of PKP2 inherited from her father. To our knowledge, this patient is the first to have the two variations in these genes. Theses clinical and molecular findings expand the clinical and molecular spectrum of TS and show the interest of next generation sequencing or whole exome sequencing in rare disorders, atypical or novel phenotype.     

Association between cerebral dopamine neurotrophic factor (<Emphasis Type="Italic">CDNF</Emphasis>) 2 polymorphisms and schizophrenia susceptibility and symptoms in the Han Chinese population

Background

Schizophrenia (SZ) is a complex polygenic psychiatric disorder caused in part by abnormal dopamine levels. Cerebral dopamine neurotrophic factor (CDNF) 2 is known to protect and repair the dopaminergic system. Dopamine dysfunction is one of the pathogenesis of SZ. However, the relationship between CDNF2 and SZ has not been previously investigated. We speculated that CDNF2 may be a susceptibility factor for SZ.

Methods

To address this issue, we carried out a study to investigate the association between CDNF2 and SZ in the total sample 1371 (670 SZ patients and 701 healthy controls) Han Chinese population. Stage 1 included 528 SZ patients and 528 healthy controls; and stage 2 included 142 SZ patients and 173 healthy controls. The allele and genotype frequencies of five single nucleotide polymorphisms (rs2577074, rs2577075, rs2249810, rs6506891, and rs2118343) of CDNF2 were compared between patients and controls.

Results

We found a significant association in allele and genotype frequencies between the two groups at rs2249810 (χ² = 4.38 and 6.45, respectively; P = 0.03 and 0.04, respectively). An association was also observed in males at rs2249810 (χ² = 8.76; P = 0.03). Haplotype TGATC differed between SZ and controls in stage 2 samples (χ² = 6.38; P = 0.01), and rs2118343 genotypes were associated with negative factor scores (F = 4.396; P = 0.01).

Conclusions

These results suggest that rs2249810 and haplotype TGATC of CDNF2 are an SZ susceptibility locus and factor, respectively, and that rs2118343 genotypes are associated with negative symptoms of SZ in the Han Chinese population.

     

Oral contraception

An orally administered formulation intended to prevent pregnancy. Oral contraception in women is available in two formulations: products containing both oestrogen and progestogen – combined oral contraceptives (COCs, The Pill) and those containing progestogen alone – progestogen-only pills (POPs, The Mini-Pill).COCs first became available in the UK in 1961 and have become an extremely safe, effective and popular method of reversible contraception. They also benefit from having non-contraceptive health benefits.This article aims to outline the advantages and disadvantages of taking oral contraception and important aspects of safe prescribing.Initially the article will focus on the COC pill, with the differences arising with the progestogen-only pill outlined later.