青少年双相情感障碍患者的家庭功能探讨

目的 分析青少年双相情感障碍患者的家庭功能.方法 随机选取2018年10月～2020年12月在我院治疗的双相情感障碍青少年患者70例为观察组,选取同期在我院体检的青少年70例为对照组,采用家庭功能评定量表(FAD)、家庭亲密度与适应性量表(FACES)对两组的家庭功能进行评估.结果 与对照组相比较,观察组FAD量表中在...     

双相情感障碍患者健康状况与肠道菌群的相关性分析

探讨双相情感障碍（BD）患者健康状况与肠道菌群的相关性,为该类患者的治疗提供参考。

收集我院BD患者（BD组）和健康人群（健康对照组）的粪便样本,使用QIAamp^® DNA粪便抽提试剂盒进行粪便样本的总DNA提取,随后进行16S rRNA基因测序,使用主成分分析（PCoA）探究健康对照组和BD组患者肠道菌群多样性情况。采用BD患者自我报告健康问卷评估患者的健康状况。

BD患者肠道菌群Shannon指数（P = 0.020 5）、Chao指数（P = 0.025 1）和Simpson指数（P = 0.020 8）显著低于健康对照组（均P＜0.05）。加权的Unifrac PCoA分析表明,BD组患者肠道菌群相似性低于健康对照组。两组对象肠道菌群门水平上有差异的菌群为放线菌门和厚壁菌门;属、种水平上的差异菌群有普氏粪杆菌、梭状芽胞杆菌和瘤胃球菌属。两组对象在功能性身体健康（PCS）、心理健康（MCS）、睡眠质量（PSQI）、抑郁（PHQ-9）、焦虑（GAD-7）和狂躁（ASRM）的平均总成绩上差异均有统计学意义（均P＜0.05）。BD患者的功能性身体健康得分与肠道放线菌门、厚壁菌门、拟杆菌属、梭状芽胞杆菌呈负相关,与普氏粪杆菌以及瘤胃球菌属呈正相关。

健康对照组和BD组患者的肠道菌群结构大致相似,BD患者的肠道菌群多样性低于健康对照组,BD患者健康状况与肠道菌群存在一定的相关性。

     

BDNF、GRIN1基因与双相情感障碍的关联研究

为了探讨GRIN1和BDNF基因的遗传变异在双相情感障碍疾病中的相关作用, 从GRIN1、BDNF基因上各取2个SNP位点, 采用TaqMan法对100例双相情感障碍患者和100例健康人进行了单核苷酸多态性分析, 比较两组基因型频率的差异, 并使用软件SHEsis进行单体型分析。结果发现GRIN1基因上的rs2301363和hcv1840191与双相情感障碍发病的关联有统计学意义(P<0.05), 它们形成的单倍型T/G在两组人群中的分布差异亦有统计学意义(P<0.05)。而BDNF基因上的rs7103411和rs6265与双相情感障碍发病无统计学意义。实验结果表明GRIN1基因是双相情感障碍的易感基因之一。     

一种计算疾病遗传度的简便方法

根据闭值模型和正态分布的特点,作者对Falconer公式进行了转换,借助于“正态分布表”来计算遗传度。该方法既精确又简便易行。     

基于TOPSIS模型的海南岛土地综合承载力时空变化及障碍度诊断

土地是人类一切活动的根本,是区域经济与社会发展的重要保障。为探讨海南岛土地综合承载能力,依据2009-2019年统计数据,采用TOPSIS和GM （1.1）模型从时序角度评价并预测了2020-2030年海南岛土地综合承载力,并借助ArcGIS软件和障碍度模型对各市县2015年、2019的土地综合承载力进行动态分析及障碍度诊断。结果显示,海南岛土地综合承载力主要受经济与社会子系统的影响,2009-2019年土地综合承载力水平虽有波动但整体呈缓慢升高趋势,其中水土资源与生态环境子系统贴近度值表现为下降趋势,而经济与社会子系统贴近度值明显升高。预测结果表明2020-2030年土地综合承载力呈持续上升趋势。土地综合承载力空间动态变化差异显著,总体表现为沿海市县综合承载力水平高于内陆市县,2015年与2019年处于较高水平的是海口和三亚,处于中等水平的2015年为8个市县,2019年达到11个市县,处于较低水平的2015年为8个市县,2019年只有5个市县,并且各市县子系统承载力差异显著。障碍度分析表明,2015年和2019年子系统障碍度最高的是经济子系统,2015年障碍因子主要有经济密度（X₉）、地均固定资产投资（X₁₂）、耕地有效灌溉率（X₆）及人均GDP （X₈）;2019年障碍因子主要有经济密度（X₉）、地均固定资产投资（X₁₂）、人均GDP （X₈）及复种指数（X₁₄）。经济发展水平是制约各市县土地综合承载力的主要障碍因素。研究将为海南岛自由贸易港建设中生态环境与社会经济可持续发展提供科学依据。     

含不可忽略缺失数据非线性再生散度模型参数的Bayes估计

给出协变量带有不可忽略缺失数据的非线性再生散度模型的Bayes方法,缺失数据机制由Logistic回归模型来确定.Gibbs抽样技术和Metropolis-Hastings算法(简称MH算法)用来得到模型参数、缺失数据机制中回归系数的联合Bayes估计,并用实例加以说明.     

多物种集合的种-多度关系模型研究进展

种 -多度关系是群落结构研究最基本的方面之一。Preston最早描述的物种“常见性和罕见性的分布”是群落中种 -多度关系的一般特性。自从 Motomura开创性地提出一个几何序列模型用于描述这种特性后 ,生态学家已建立了许多拟合种 -多度关系的经验模型和理论模型 ,主要包括对数序列分布、对数正态分布等统计模型 ,几何序列模型、分割线段模型等生态位模型以及反映群落动态和环境制约作用的动态模型 ,还有其中一些模型的扩展模型。近年来 ,种 -多度关系研究领域已大大拓宽 ,如“群落”的内涵已延伸为“多物种集合”,物种“多度”的测度推广到“广义多度”。尽管种 -多度关系研究已取得很大进展 ,仍有一些问题尚待解决 ,诸如多度指标选择、种 -多度分布时空变化规律及其机制以及种 -多度关系模型的选择、检验、解释与应用。     

加性-显性-母体效应及GE互作效应遗传模型的模拟比较

运用蒙特卡罗方法比较了8个亲本正反应的加性－显性－母体效应的全模型及缩减模型,当σ^2M和σ^2ME存在时,检测各项遗传方差分量的功效高达97％以上,如何存在σ^2M和σ^2ME而缩减模型未包括这两项效应时,除显性效应以外的各项方差分量都被高估。对于加性－显性模型,如果忽略了基因型与环境互作,σ^2ε和σ^2A将被高估。当母体效应和基因型与环境互作被忽略时,将显著地增加遗传效应预测值的方差。     

立体定向多靶点联合毁损术治疗情感障碍患者的疗效观察

目的:研究立体定向多靶点联合毁损术在治疗以强迫症状为核心症状情感障碍患者中的疗效及并发症.方法:在立体定向基础上,应用3.0T高场强核磁共振、神经导航系统和微电极电生理技术进行核团定位,对37例以强迫症状为核心症状情感障碍患者行立体定向杏仁核、内囊前肢、扣带回、伏隔核多靶点联合毁损术.分别在术前2天与术后2周、6个月、1年由精神科医师进行Yale-Brown强迫症量表(Y-BOCS)、汉密顿抑郁量表(HAMD)、汉密顿焦虑量表(HAMA)测评,观察手术疗效及并发症.结果:37例患者中,3例痊愈,32例显效,2例复发,且痊愈和显效患者均发现术后抗情感障碍药物敏感性提高.术后随访期6～18个月,35例显著进步.术后6个月的总有效率94.5%,术后6个月、1年的总有效率与术后2周总有效率比较无明显差异,且无明显并发症.术后各期Y-BOCS、HAMD、HAMA评分与术前比较均明显降低.结论:立体定向杏仁核、内囊前肢、扣带回、伏隔核多靶点联合毁损术可以有效缓解患者强迫症状,提高药物敏感性,明显改善患者生存质量.     

青少年双生子体型指征相关指标的遗传度研究(英文)

目的:用经典的双生子设计探讨遗传因素对青少年身高、体重、体质指数(BMI)等体型指征的影响程度。方法:从青岛市双生子库中选择自愿参加本研究的362对11-19岁双生子,测量身高、体重。同性别的双生子通过16个多态标记进行卵型鉴定,在此基础上,应用Mx软件构建结构方程模型分析计算遗传度。结果:对362对有效双生子数据进行分析,其中同卵双生子194对,异卵双生子168对,身高的最佳拟合模型ACE模型,体重和BMI的最佳拟合模型为AE模型。调整年龄性别后,身高的遗传度为66%,体重的遗传度为84%,体质指数的遗传度为75%。结论:在青少年体型指征的相关指标中,身高、体重、BMI受遗传因素影响都较大。     

Molecular genetics of bipolar disorder

Bipolar disorder (BPD) is an often devastating illness characterized by extreme mood dysregulation. Although family, twin and adoption studies consistently indicate a strong genetic component, specific genes that contribute to the illness remain unclear. This study gives an overview of linkage studies of BPD, concluding that the regions with the best evidence for linkage include areas on chromosomes 2p, 4p, 4q, 6q, 8q, 11p, 12q, 13q, 16p, 16q, 18p, 18q, 21q, 22q and Xq. Association studies are summarized, which support a possible role for numerous candidate genes in BPD including COMT, DAT, HTR4, DRD4, DRD2, HTR2A, 5-HTT, the G72/G30 complex, DISC1, P2RX7, MAOA and BDNF. Animal models related to bipolar illness are also reviewed, with special attention paid to those with clear genetic implications. We conclude with suggestions for strategies that may help clarify the genetic bases of this complex illness.     

Broadening the diagnosis of bipolar disorder: benefits vs. risks

There is considerable debate over whether bipolar and related disorders that share common signs and symptoms, but are currently defined as distinct clinical entities in DSM-IV and ICD-10, may be better characterized as falling within a more broadly defined "bipolar spectrum". With a spectrum view in mind, the possibility of broadening the diagnosis of bipolar disorder has been proposed. This paper discusses some of the rationale for an expanded diagnostic scheme from both clinical and research perspectives in light of potential drawbacks. The ultimate goal of broadening the diagnosis of bipolar disorder is to help identify a common etiopathogenesis for these conditions to better guide treatment. To help achieve this goal, bipolar researchers have increasingly expanded their patient populations to identify objective biological or endophenotypic markers that transcend phenomenological observation. Although this approach has and will likely continue to produce beneficial results, the upcoming DSM-IV and ICD-10 revisions will place increasing scrutiny on psychiatry's diagnostic classification systems and pressure to re-evaluate our conceptions of bipolar disorder. However, until research findings can provide consistent and converging evidence as to the validity of a broader diagnostic conception, clinical expansion to a dimensional bipolar spectrum should be considered with caution.     

Laboratory evolution of adenylyl cyclase independent learning in Drosophila and missing heritability

Gene interactions are acknowledged to be a likely source of missing heritability in large‐scale genetic studies of complex neurological phenotypes. However, involvement of rare variants, de novo mutations, genetic lesions that are not easily detected with commonly used methods and epigenetic factors also are possible explanations. We used a laboratory evolution study to investigate the modulatory effects of background genetic variation on the phenotypic effect size of a null mutation with known impact on olfactory learning. To accomplish this, we first established a population that contained variation at just 23 loci and used selection to evolve suppression of the learning defect seen with null mutations in the rutabaga adenylyl cyclase. We thus biased the system to favor relatively simplified outcomes by choosing a Mendelian trait and by restricting the genetic variation segregating in the population. This experimental design also assures that the causal effects are among the known 23 segregating loci. We observe a robust response to selection that requires the presence of the 23 variants. Analyses of the underlying genotypes showed that interactions between more than two loci are likely to be involved in explaining the selection response, with implications for the missing heritability problem.     

Mood and disruptive behavior disorders and symptoms in the offspring of patients with bipolar I disorder

The study aimed to ascertain the prevalence of mood and disruptive behavior disorders and symptoms in 35 children of 29 adult outpatients with a DSM-IV diagnosis of bipolar I disorder, compared with 33 children of 29 healthy adults, matched with patients on age, socioeconomic status and education. The offspring of bipolar patients had a 9.48 fold higher risk of receiving a psychiatric diagnosis. While only two children of patients with bipolar disorder were diagnosed with a mood disorder, 30.9% displayed mild depressed mood, compared with 8.8% of the controls, a statistically significant difference. The bipolar offspring also scored significantly higher on the hyperactivity and conduct problems subscales as well as the ADHD index of the Conners’ Teacher Rating Scale. The disruptive behavior and mood symptoms observed in early life in the offspring of bipolar patients may indicate the need for early psychosocial intervention.     

Association study of eight circadian genes with bipolar I disorder, schizoaffective disorder and schizophrenia

We hypothesize that circadian dysfunction could underlie, at least partially, the liability for bipolar 1 disorder (BD1). Our hypothesis motivated tests for the association between the polymorphisms of genes that mediate circadian function and liability for BD1. The US Caucasian patients with BD1 (DSM-IV criteria) and available parents were recruited from Pittsburgh and surrounding areas (n = 138 cases, 196 parents) and also selected from the NIMH Genetics Collaborative Initiative (n = 96 cases, 192 parents). We assayed 44 informative single-nucleotide polymorphisms (SNPs) from eight circadian genes in the BD1 samples. A population-based sample, specifically cord blood samples from local live births, served as community-based controls (n = 180). It was used as a contrast for genotype and haplotype distributions with those of patients. US patients with schizophrenia/schizoaffective disorder (SZ/SZA, n = 331) and available parents from Pittsburgh (n = 344) were assayed for a smaller set of SNPs based on the results from the BD1 samples. Modest associations with SNPs at ARNTL (BmaL1) and TIMELESS genes were observed in the BD1 samples. The associations were detected using family-based and case-control analyses, albeit with different SNPs. Associations with TIMELESS and PERIOD3 were also detected in the Pittsburgh SZ/SZA group. Thus far, evidence for association between specific SNPs at the circadian gene loci and BD1 is tentative. Additional studies using larger samples are required to evaluate the associations reported here.     

The clinical characterization of the adult patient with bipolar disorder aimed at personalization of management

Bipolar disorder is heterogeneous in phenomenology, illness trajectory, and response to treatment. Despite evidence for the efficacy of multimodal­ity interventions, the majority of persons affected by this disorder do not achieve and sustain full syndromal recovery. It is eagerly anticipated that combining datasets across various information sources (e.g., hierarchical “multi‐omic” measures, electronic health records), analyzed using advanced computational methods (e.g., machine learning), will inform future diagnosis and treatment selection. In the interim, identifying clinically meaningful subgroups of persons with the disorder having differential response to specific treatments at point‐of‐care is an empirical priority. This paper endeavours to synthesize salient domains in the clinical characterization of the adult patient with bipolar disorder, with the overarching aim to improve health outcomes by informing patient management and treatment considerations. Extant data indicate that characterizing select domains in bipolar disorder provides actionable information and guides shared decision making. For example, it is robustly established that the presence of mixed features – especially during depressive episodes – and of physical and psychiatric comorbidities informs illness trajectory, response to treatment, and suicide risk. In addition, early environmental exposures (e.g., sexual and physical abuse, emotional neglect) are highly associated with more complicated illness presentations, inviting the need for developmentally‐oriented and integrated treatment approaches. There have been significant advances in validating subtypes of bipolar disorder (e.g., bipolar I vs. II disorder), particularly in regard to pharmacological interventions. As with other severe mental disorders, social functioning, interpersonal/family relationships and internalized stigma are domains highly relevant to relapse risk, health outcomes, and quality of life. The elevated standardized mortality ratio for completed suicide and suicidal behaviour in bipolar disorder invites the need for characterization of this domain in all patients. The framework of this paper is to describe all the above salient domains, providing a synthesis of extant literature and recommendations for decision support tools and clinical metrics that can be implemented at point‐of‐care.     

Association and linkage analysis of RGS4 polymorphisms with schizophrenia and bipolar disorder in Brazil

Linkage and association studies in five independently ascertained samples have suggested that polymorphisms of the regulator of G-protein signaling 4 (RGS4) may confer risk for schizophrenia (SCZ). Suggestive evidence for association with bipolar disorder (BD) has also been presented. However, the associated alleles and haplotypes have differed among the samples. Data from other independent samples may clarify the putative associations. Hence, we investigated an independent, ethnically diverse Brazilian population comprising patients with SCZ (n=271) or BD1 (n=306), who were contrasted with 576 community-based controls. Parents of 49 SCZ cases and 44 BD cases were available for transmission disequilibrium tests (TDTs). Four RGS4 single-nucleotide polymorphisms (SNPs) 1, 4, 7 and 18 putatively associated with SCZ were investigated. In the SCZ samples, significant case-control differences were not observed for individual SNPs or haplotypes, though the TDT suggested transmission distortion similar to that observed in the initial report. For the BD sample, case-control comparisons revealed no significant differences for individual SNPs, but an omnibus test suggested differences in the overall distribution of haplotypes bearing all four SNPs (SNP-EM Omnibus likelihood ratio test; P=0.003). The TDT revealed over-transmission of allele A at SNP7 (P=0.016), as well as haplotypes incorporating this allele. However, global tests incorporating all haplotypes yielded only suggestive trends for association (P=0.19). In conclusion, association with SCZ was not detected in the present analyses. The failure to detect an association may be related to inadequate power or to confounds related to ethnic admixture. Suggestive associations with BD detected here require further investigation in a larger sample.     

A genome‐wide association study of bipolar disorder and comorbid migraine

Both migraine and bipolar affective disorder (BPAD) are complex phenotypes with significant genetic and nongenetic components. Epidemiological and clinical studies have showed a high degree of comorbidity between migraine and BPAD, and overlapping regions of linkage have been shown in numerous genome‐wide linkage studies. To identify susceptibility factors for the BPAD/migraine phenotype, we conducted a genome‐wide association study (GWAS) in 1001 cases with bipolar disorder collected through the NIMH Genetics Initiative for Bipolar Disorder and genotyped at 1 m single‐nucleotide polymorphisms (SNPs) as part of the Genetic Association Information Network (GAIN). We compared BPAD patients without any headache (n = 699) with BPAD patients with doctor diagnosed migraine (n = 56). The strongest evidence for association was found for several SNPs in a 317‐kb region encompassing the uncharacterized geneKIAA0564 {e.g. rs9566845 [OR = 4.98 (95% CI: 2.6–9.48), P = 7.7 × 10^?8] and rs9566867 (P = 8.2 × 10^?8)}. Although the level of signficance was significantly reduced when using the Fisher's exact test (as a result of the low count of cases with migraine), rs9566845 P = 1.4 × 10^?5 and rs9566867 P = 1.5 × 10^?5, this region remained the most prominent finding. Furthermore, marker rs9566845 was genotyped and found associated with migraine in an independent Norwegian sample of adult attention deficit hyperactivity disorder (ADHD) patients with and without comorbid migraine (n = 131 and n = 324, respectively), OR = 2.42 (1.18–4.97), P = 0.013. This is the first GWAS examining patients with bipolar disorder and comorbid migraine. These data suggest that genetic variants in the KIAA0564 gene region may predispose to migraine headaches in subgroups of patients with both BPAD and ADHD.     

Risk of metabolic syndrome and its components in people with schizophrenia and related psychotic disorders,bipolar disorder and major depressive disorder: a systematic review and meta‐analysis

Metabolic syndrome (MetS) and its components are highly predictive of cardiovascular diseases. The primary aim of this systematic review and meta‐analysis was to assess the prevalence of MetS and its components in people with schizophrenia and related psychotic disorders, bipolar disorder and major depressive disorder, comparing subjects with different disorders and taking into account demographic variables and psychotropic medication use. The secondary aim was to compare the MetS prevalence in persons with any of the selected disorders versus matched general population controls. The pooled MetS prevalence in people with severe mental illness was 32.6% (95% CI: 30.8%‐34.4%; N = 198; n = 52,678). Relative risk meta‐analyses established that there was no significant difference in MetS prevalence in studies directly comparing schizophrenia versus bipolar disorder, and in those directly comparing bipolar disorder versus major depressive disorder. Only two studies directly compared people with schizophrenia and major depressive disorder, precluding meta‐analytic calculations. Older age and a higher body mass index were significant moderators in the final demographic regression model (z = ?3.6, p = 0.0003, r² = 0.19). People treated with all individual antipsychotic medications had a significantly (p<0.001) higher MetS risk compared to antipsychotic‐naïve participants. MetS risk was significantly higher with clozapine and olanzapine (except vs. clozapine) than other antipsychotics, and significantly lower with aripiprazole than other antipsychotics (except vs. amisulpride). Compared with matched general population controls, people with severe mental illness had a significantly increased risk for MetS (RR = 1.58; 95% CI: 1.35‐1.86; p<0.001) and all its components, except for hypertension (p = 0.07). These data suggest that the risk for MetS is similarly elevated in the diagnostic subgroups of severe mental illness. Routine screening and multidisciplinary management of medical and behavioral conditions is needed in these patients. Risks of individual antipsychotics should be considered when making treatment choices.     

Reconsideration of bipolar disorder as a developmental disorder: Importance of the time of onset

Bipolar disorder is a multifactorial psychiatric disorder with developmental and progressive neurophysiological alterations. This disorder is typically characterized by cyclical and recurrent episodes of mania and depression but is heterogeneous in its clinical presentation and outcome. Although the DSM-IV-TR criteria identify several features that are of phenomenological relevance, these are of less utility for defining homogeneous subgroups, for analyses of correlations with biomarkers or for directing focused medication strategies. We provide a comprehensive review of existing evidence regarding to age at onset in bipolar disorder. Eight admixture studies demonstrate three homogeneous subgroups of patients with bipolar disorder identified according to age at onset (early, intermediate and late age at onset), with two cutoff points, at 21 and 34 years. It is suggested that the early-onset subgroup has specific clinical features and outcomes different from those of the other subgroups. Early-onset subgroup may be considered a more suitable clinical phenotype for the identification of susceptibility genes with recent data demonstrating associations with genetic variants specifically in this subgroup. The use of age at onset as a specifier may also facilitate the identification of other biological markers for use in brain imaging, circadian, inflammatory and cognitive research. A key challenge is posed by the use of age at onset in treatment decision algorithms, although further research is required to increase the evidence-base. We discuss three potential benefits of specifying age at onset, namely: focused medication strategies, the targeted prevention of specific comorbid conditions and decreasing the duration of untreated illness. We argue that age at onset should be included as a specifier for bipolar disorders.