不同年龄双相情感性精神障碍与多巴胺D2、儿茶酚氧位甲基转移酶基因多态性的关联分析

目的　探索多巴胺D2 受体 (DRD2 )基因及儿茶酚氧位甲基转移酶 (COMT)基因在双相情感性精神障碍 (BD)发病中的作用。方法　 (1 )在临床主治医师诊断后 ,由研究者采用美国精神障碍诊断与统计手册第 3版修订本的定式检查提纲 (SCID P)对精神疾病患者进行面检 ,共选择符合标准的 1 0 5例BD患者 ,并将患者的发病年龄以≤ 2 5岁为早发组 ,>2 5岁为晚发组 ;(2 )对入组患者和对照组 (1 2 8名健康人 )按常规方法提取DNA ,然后对DRD2、COMT基因定型 ;(3)各组间构成比差异用 χ2检验进行统计学分析。结果DRD2、COMT基因多态性均与正常对照组间的差异无显著性 ,但发病年龄大于 2 5岁组与正常对照组之间DRD2基因多态性的差异有显著性 (χ2 =4 36 ,P =0 0 4 )。结论DRD2基因与发病年龄较晚的BD可能存在关联     

Lack of association between dopamine D1 and D2 receptor genes and bipolar affective disorder.

Fifty-six patients with bipolar affective disorder and 69 healthy control subjects were tested for association of restriction fragment length polymorphism alleles at the dopamine D1 and D2 receptor loci. No significant associations were found; thus, the hypothesis that a single mutant form of either receptor gene is responsible for the phenotype of patients with bipolar affective disorder was not supported.     

Association between bipolar affective disorder and multiple sclerosis

Ten patients from Monroe County, N.Y., had both multiple sclerosis and bipolar affective disorder. Epidemiologic data indicate that the expected number would be 5.4. This difference may indicate an association between these disorders.     

双相情感障碍与DRD3、DRD2和COMT基因多态性的关联分析

目的　探索多巴胺D3受体 (DRD3)、多巴胺D2受体 (DRD2 )和儿茶酚氧位甲基转移酶 (COMT)基因多态性与双相情感障碍的关系。方法　使用病例 对照的关联分析方法 ,对 10 5名双相情感障碍患者和 12 8名对照者之DRD3、DRD2和COMT的多态性进行检测 ,并进行关联分析。结果　DRD3等位基因在两组间的分布有显著性差异 (χ2 =5 77,P =0 0 2 ) ,Logistic多元回归分析发现基因型 1/ 1和 2 / 2在两组间分布的有显著性差异 (P =0 0 36 ,OR=5 72 7) ,等位基因分析也有显著性差异 (P =0 0 2 2 ,OR =6 786 ) ;DRD2和COMT基因型和等位基因的分布在两组间无显著性差异 (χ2 =1 983,P =0 37/ χ2 =1 6 7,P =0 4 1;χ2 =0 2 16 ,P >0 0 5 / χ2 =0 14 3,P >0 0 5 ) ;将DRD3和DRD2共同分析时发现OR值升高 (OR =6 6 97)。结论　DRD3基因多态性与双相情感障碍有关联 ,且与DRD2有协同作用。     

Allelic association study between phospholipase A2 genes and bipolar affective disorder

Objectives:  In vivo studies demonstrating that lithium is a powerful phospholipase A2 (PLA2) inhibitor suggest that PLA2 activation, and subsequent cell signaling overactivation by increased fatty acid release may be the primary abnormality in bipolar affective disorder (BPAD), thus making PLA2 genes attractive candidates for the susceptibility to BPAD. The present study investigates polymorphisms in cytosolic phospholipase A2 (cPLA2), calcium-independent phospholipase A2 (iPLA2), and secretory phospholipase (sPLA2) genes in a Brazilian sample.
Methods:  A cross-sectional study was performed with 181 unrelated DSM-IIIR BPAD subjects and 312 controls. A polymerase chain reaction–restriction fragment length polymorphism assay for Ban I cPLA2 and Avr II iPLA2 polymorphisms was performed, and an ATT repeat in sPLA2 was assessed using a semiautomated genetic analyzer (ALFexpress).
Results:  There was no significant difference observed in the allelic and genotypic distribution between the BPAD and control groups for cPLA2 (genotype: χ² = 0.8, 2df, p = 0.6; allele χ² = 0, 1df, p = 0.9), iPLA2 (genotype: χ² = 1.7, 2df, p = 0.4; allele: χ² = 0.3, 1df, p = 0.6), and sPLA2 (allele: χ² = 3.6, 6df, p = 0.8).
Conclusion:  Our results failed to demonstrate that the studied PLA2 polymorphisms were associated with an increased risk for BPAD in our sample.     

Association analysis of genes in serotonin pathway with attention and executive function in patients with bipolar affective disorder

Background

The reason why it is difficult to identify susceptibility genes attributed to bipolar disorder (BPD) is the phenotypic heterogeneity. The use of endophenotypes has been advocated as one possible strategy to discovery cause variants of BPD.

Methods

A total of 164 patients with BPD and 164 matched controls were employed in the present research. Fifty-two single nucleotide polymorphisms (SNPs) within the genes in serotonin pathway were selected for genotyping using the GoldenGate genotyping assay. All participants completed three neurocognitive tests including the tower of Hanoi (TOH), the Wisconsin card sorting test (WCST) and Trail making tests (TMTA and TMTB-M).

Results

Patients with BPD demonstrated a wide range of deficits in mental activities of attention and speed of information processing, and executive function. Significant interactions between rs2760347 in 5HTR2A gene and diagnosis were found for the executive time of TOH, with β = 11.82 and P = 0.002 (adjusted P = 0.03 after Bonferroni correction).

Conclusions

Cognitive impairments existing in BPD may be particularly notable in certain domains of attention and executive function, and 5HTR2A gene may be involved in modulating executive function of BP-I patients.     

Association of the dysbindin gene with bipolar affective disorder

OBJECTIVE: In the study of bipolar affective disorder and schizophrenia, there is some evidence suggesting a phenotypic and genetic overlap between the two disorders. A possible link between bipolar affective disorder and schizophrenia remains arguable, however. The authors hypothesized that dysbindin, which is a probable susceptibility gene for schizophrenia, was associated with bipolar affective disorder and tested this hypothesis using a case-control design study. METHOD: Participants included 213 patients with bipolar I disorder and 197 comparison subjects. In each subject, 10 polymorphisms in the dysbindin gene were genotyped and assessed. RESULTS: Two polymorphisms showed individual genotypic association with bipolar I disorder. Multiple marker haplotypes were more strongly associated, with the rarer of the two common haplotypes being overrepresented in the patients with bipolar affective disorder. A similar finding was reported in patients with schizophrenia in a previous study. CONCLUSIONS: Findings suggest that the human dysbindin gene may play a role in the susceptibility to bipolar affective disorder, which underscores a potentially important area of etiological overlap with schizophrenia. The existence of shared genetic risk factors will, in time, lead to changes in the current nosology of major psychoses.     

Association analysis of monoamine oxidase A gene and bipolar affective disorder in Han Chinese

Background  

Monoamine oxidase A (MAOA) is a mitochondrial enzyme involved in degrading several different biological amines, including serotonin. Although several pieces of evidence suggested that MAOA is important in the etiology of bipolar affective disorder (BPD), associations for markers of the MAOA gene with BPD were not conclusive and the association has not been investigated in Taiwanese population. This study was designed to illustrate the role of MAOA in the etiology of BPD in Han Chinese.     

Rapid cycling bipolar affective disorder. I. Association with grade I hypothyroidism

Thirty patients with rapid cycling bipolar affective disorder were studied prospectively to assess presence and severity of thyroid hypofunction. Seven (23%) were classified as having grade I hypothyroidism, while 8 (27%) had grade II and 3 (10%) had grade III abnormalities. This prevalence of grade I hypothyroidism is significantly greater than that reported in studies of unselected bipolar patients during long-term treatment with lithium carbonate, although only 63% of this sample of rapid cycling patients was taking lithium carbonate or carbamazepine. The association of rapid cycling with grade I hypothyroidism cannot be accounted for by lithium carbonate use or by the preponderance of women among rapid cycling patients. These findings (1) indicate that hypothyroidism during bipolar illness is a risk factor for the development of rapid cycling, and (2) leads to the hypothesis that a relative central thyroid hormone deficit occurring in bipolar patients predisposes to a rapid cycling course.     

Backward masking in bipolar affective disorder.

1. When an informational stimulus, the target, is followed closely in time by a non-informational stimulus, the mask, the visual system's processing of the informational stimulus is disturbed. This disturbance is known as backward visual masking. 2. Transient and sustained visual pathways detect different characteristics of a visual stimulus, at different times in early visual information processing, and have unique anatomic distribution with regard to retinal origin, thalamic and cortical projections. 3. Backward masking occurs by two mechanisms. Interruption occurs when activity in the transient channels of the mask disrupt activity in the sustained channels of the target. Integration occurs when activity in the sustained channels of the mask disrupt activity of the sustained channels of the target. 4. Characteristics of the mask--energy, location, or the time presented after the target--can be altered to enhance interruption or integration. Interruption is a bell-shaped function of, and integration is an exponential function of, visual performance and interstimulus interval. 5. An impairment in backward masking is present in bipolar subjects during manic episodes, is not related to the presence of psychotic symptoms, and persists when mania resolves. Lithium appears to have a detrimental effect on backward masking.     

Linkage disequilibrium between dopamine D1 receptor gene (DRD1) and bipolar disorder.

BACKGROUND: Based on the dopamine hypothesis, the dopamine D1 receptor gene (DRD1) is considered to be a good candidate gene for bipolar disorder (BP). METHODS: In our study, three polymorphisms of the DRD1 gene, -800T/C, -48A/G, and 1403T/C, were analyzed in 286 BP trios. Both the transmission disequilibrium test (TDT) and haplotype TDT were performed on the genotype data to test for the presence of linkage disequilibrium between DRD1 and bipolar disorder. With the extended transmission disequilibrium test (ETDT), we also calculated the maternal transmission and paternal transmission for each allele. RESULTS: Although no association was found for each individual polymorphism, there is a significant association between DRD1 and BP for haplotype TDT analysis (chi(2) = 16.068, df = 3, p =.0011). CONCLUSIONS: These results indicate that DRD1 may play a role in the etiology of bipolar disorder.     

甲状腺功能水平与双相情感障碍相关性的对照研究

目的 探索甲状腺功能与双相情感障碍的相关性.方法 以符合美国精神疾病分类与诊断标准第4版修订本(DSM-Ⅳ-TR)的双相情感障碍诊断标准的患者59例为研究对象,并选取41名健康人作为对照,应用酶联免疫吸附法(ELISA)分别测定所有研究对象的血清甲状腺激素水平,包括TT3、FT3、TT4、FT4及TSH.选用HAMD、HAMA及Bech-Rafaelsen躁狂量表评估患者组临床症状.结果 双相躁狂组中TT4、FT4水平明显高于对照组,FT3水平明显高于抑郁组,差异有统计学意义(P<0.01).双相抑郁组中TT3、FT3水平明显低于对照组,FT4水平则明显高于对照组,差异有统计学意义(P<0.01).按性别分层比较,女性双相躁狂组FT4水平与对照组相比明显升高,差异有统计学意义(P<0.05);女性双相抑郁组TT3明显低于对照组或双相躁狂组,FT4明显高于对照组,FT3则明显低于对照组,差异均有统计学意义(P<0.05),而男性躁狂组中仅TT4水平显著高于对照组(P<0.05).在双相抑郁患者中,HAMD总分与FT4呈负相关(r=-0.34,P=0.03).结论 双相情感障碍患者的甲状腺功能存在一定的改变,不同临床相甲状腺功能改变亦不相同,且这种变化以女性患者明显.     

Association study between the corticotropin-releasing hormone receptor 2 gene and suicidality in bipolar disorder.

Family, adoption and twin studies show that genetics influences suicidal behavior, but does not indicate specific susceptibility variants. Stress response is thought to be mediated by the corticotrophin-releasing hormone (CRH), which is known to be a regulator of the hypothalamic-pituitary-adrenal pathway (HPA). Alterations in HPA system have been related to impulsivity, aggression and suicidal behaviour, that are common features in Bipolar Disorder (BD). CRH is a hypothalamic factor that stimulates the pituitary gland. Two CRH receptors are known, CRHR1 and CRHR2. To search for markers conferring genetic susceptibility to suicide, we typed three polymorphisms of the CRHR2 gene, CRHR2(CA), CRHR2(GT), and CRHR2(GAT), in 312 families where at least one subject had DSM-IV bipolar disorder. Family based association analyses in the suicide attempters using FBAT yielded no difference in the distribution of the alleles for all three markers. HBAT analysis for quantitative measures on suicide-related traits showed association between haplotype 5-2-3 and higher severity. The current results show that haplotype variation at the CRHR2 locus is associated with suicidal behaviour. This is to our knowledge the first investigation on suicidal behavior and genetic variation at the CRHR2 locus, an important regulator of the HPA axis.     

情感性精神障碍与儿茶酚邻位甲基转移酶基因的关联性研究

目的：探讨单相、双相情感性精神障碍（以下简称情感障碍）患者儿茶酚邻位甲基转移酶（COMT）基因val 108 met多态的分布，以及COMT基因与情感障碍的关联性，方法：应用聚合酶链反应－限制性片段长度多态的方法。检测203例情感障碍患者及209例正常人的COMT基因多态性，按照Hardy-Weinberg平衡法则进行吻合度检验，并采用Z检验分析COMT各基因型及等痊基因在不同组间分布的差异，结果：（1）经吻合度检验，单相抑郁症组（98例）、双相情感障碍组（104例）及正常对照组COMT各基因型的分布均符合Hardy-Weinberg平衡法则(X^2值分别为2．205，0．913，3．425，均v＝1，均P＞0．05）；（2）与正常对照组比较，单相、双相情感障碍组中COMT基因型及等位基因分布的差异均无显著性（经Z检验，均v＝1，均P＞0．05）；COMT基因各基因型及等位基因分布在不同性别的组间及组内差异亦均无显著性（P＞0．05）。结论：COMT基因val 108 met多态所在的第4外量子附近可能不存在情感障碍的易感基因。     

Genetics of bipolar affective disorder

Bipolar affective disorder is a highly heritable condition, as demonstrated in twin, family, and adoption studies. Morbid risk in first degree relatives is four to six times higher than the population prevalence of about 1%. However, the mode of inheritance is complex, and linkage findings have been difficult to replicate. Despite these limitations, consistent linkage findings have emerged on several chromosomes, notably 18p, 18q, 21q, 12q, 4p, and Xq. Two additional areas, 10p and 13q, have shown linkage in regions that appear to overlap with significant linkage findings in schizophrenia. Separate linkage studies in schizophrenia also have targeted the replicated bipolar linkages on 18p and 22q. New methods are being developed for fine mapping and candidate identification. Recent candidate gene studies include some positive results for the serotonin transporter gene on 17q and the catechol-o-methyltransferase gene on 22q. No other candidate gene studies are yet showing replicated results. A convincing demonstration for a susceptibility gene will probably require a mixture of casecontrol studies, family-based association methods, and pathophysiologic studies.     

Climatic factors and bipolar affective disorder

In bipolar disorder, the factors provoking a new episode are unknown. As a seasonal variation has been noticed, it has been suggested that weather conditions may play a role. The aim of the study was to elucidate whether meteorological parameters influence the development of new bipolar phases. A group of patients with at least three previous hospitalizations for bipolar disorder was examined every 3 months for up to 3 years. At each examination an evaluation of the affective phase was made according to the Hamilton Depression Scale (HAM-D(17)), and the Bech-Rafaelsen Mania Rating Scale (MAS). In the same period, daily recordings from the Danish Meteorological Institute were received. We found no correlations between onset of bipolar episodes [defined as MAS score of 11 or more (mania) and as HAM-D(17) score of 12 or more (depression)] and any meteorological parameters. We found a statistical significant correlation between mean HAM-D(17) scores and change in mean and maximum temperature, and non-statistical significant correlations between mean MAS scores and rainfall plus atmospheric pressure, and non-statistical significant correlations between mean HAM-D(17) scores and hours of sunshine and cloudiness. Though meteorological factors may have an impact on triggering new episodes in bipolar patients, they do not constitute a dominant cause.