Dopamine, a neurotransmitter, influences the immune system

Dopamine (DA) is a monoamine neurotransmitter of both central and peripheral nervous system. Its role in the neural-immune communication has been discussed in the present review. Results reveal that in vivo damage or stimulation of specific central dopaminergic system suppresses or enhances functional activities of the immune effector cells. The possible influences of other immunomodulators of the brain by altering brain DA may be the underlying mechanism. Direct effects of DA on the immune effector cells are also contradictory, it is suppressive in vitro, while in pharmacological doses, it is mostly stimulatory in vivo. The possible mechanisms have been discussed. Lastly, future areas of relevance on DA and immunity have been highlighted to advance our knowledge regarding DA as an immune regulator.     

Positive association between synapsin II and schizophrenia.

BACKGROUND: Synapsin II encodes a neuron-specific phosphoprotein that selectively binds to small synaptic vesicles in the presynaptic nerve terminal. The expressions of messenger ribonucleic acid and protein of synapsin II have been reported to be significantly reduced in the brains of schizophrenia patients. The synapsin II gene is located on 3p25, a region that has been implicated to be associated with schizophrenia by genetic linkage. All these findings suggest synapsin II as a candidate gene for schizophrenia. METHODS: In this work, we studied four markers (two single nucleotide polymorphisms (SNPs): rs308963 and rs795009; and two insertion/deletion polymorphisms: rs2307981 and rs2308169) covering 144.2 kilobase pairs (kb) with an average interval of 38 kb in synapsin II in a sample of 654 schizophrenic patients and 628 normal control subjects to explore the mechanism underlying schizophrenia. RESULTS: We found significant differences in allele frequency distribution of SNP rs795009 (p =.000018, odds ratio 1.405, 95% confidence interval 1.202-1.641) between patients and control subjects. The T allele was significantly higher in patients than in control subjects. Moreover, the overall frequency of haplotype showed significant differences between patients and control subjects (p <.000001). CONCLUSIONS: This study suggests a positive association between synapsin II and schizophrenia, implying that synapsin II is involved in the etiology of schizophrenia.     

Negative association between schizophrenia and rheumatoid arthritis.

Persuasive evidence has accumulated demonstrating a strong negative association between rheumatoid arthritis and schizophrenia at the population level. Explanations for this phenomenon have taken into consideration immunological, biochemical, and genetic factors. In this article, we examine these and other factors in closer detail. We then propose hypotheses at the molecular level that might account for the negative association between the two diseases. These hypotheses may provide clues for our colleagues in molecular biology as they search for candidate genes, "anti-genes," and molecular mechanisms relevant to schizophrenia.     

The gluten connection: the association between schizophrenia and celiac disease

OBJECTIVE: Schizophrenia affects roughly 1% of the population and is considered one of the top 10 causes of disability worldwide. Given the immense cost to society, successful treatment options are imperative. Based on initial findings, gluten withdrawal may serve as a safe and economical alternative for the reduction of symptoms in a subset of patients. METHOD: A review of the literature relevant to the association between schizophrenia and celiac disease (gluten intolerance) was conducted. RESULTS: A drastic reduction, if not full remission, of schizophrenic symptoms after initiation of gluten withdrawal has been noted in a variety of studies. However, this occurs only in a subset of schizophrenic patients. CONCLUSION: Large-scale epidemiological studies and clinical trials are needed to confirm the association between gluten and schizophrenia, and address the underlying mechanisms by which this association occurs.     

α7-烟碱样乙酰胆碱受体基因多态性与精神分裂症的关联研究

目的 研究α7-熘碱样乙酰胆碱受体基因rs1042724多态性与精神分裂症的相关性。方法运用聚合酶链反应扩增及单核苷酸多态性的分子生物学技术，对符合精神分裂症诊断标准的98个先证者及其父母组成的核心家系，测定α7-烟碱样乙酰胆碱受体基因分型，进行精神分裂症的α7-烟碱样乙酰胆碱受体基因多态性的关联分析和传递不平衡（TDT）检验。结果TDT检验结果提示α7-烟碱样乙酰胆碱受体基因等位基因与精神分裂症之间的相关性（McNemarX^2=4．21，P〈0．05），且等位基因T携带者，其精神分裂症的易患性是C携带者的1．31倍（RR=1．31,X^2（RR）=3．96，P〈0．05）。结论 提示α7-烟碱样乙酰胆碱受体基因rs1042724与精神分裂症相关联。     

The association between fluid balance and outcomes after subarachnoid hemorrhage

Background

We sought to determine the association between early fluid balance and neurological/vital outcome of patients with subarachnoid hemorrhage.

Methods

Hospital admission, imaging, ICU and outcome data were retrospectively collected from the medical records of adult patients with aneurysmal SAH admitted to a level-1 trauma and stroke referral center during a 5-year period. Two groups were identified based on cumulative fluid balance by ICU day 3: (i) patients with a positive fluid balance (n?=?221) and (ii) patients with even or negative fluid balance (n?=?135). Multivariable logistic regression was used to adjust for age, Hunt-Hess and Fisher scores, mechanical ventilation and troponin elevation (>0.40?ng/ml) at ICU admission. The primary outcome was a composite of hospital mortality or new stroke.

Results

Patients with positive fluid balance had worse admission GCS and Hunt-Hess score, and by ICU day 3 had cumulatively received more IV fluids, but had less urine output when compared with the negative fluid balance group. There was no difference in the odds of hospital death or new stroke (adjusted OR: 1.47, 95%CI: 0.85, 2.54) between patients with positive and negative fluid balance. However, positive fluid balance was associated with increased odds of TCD vasospasm (adjusted OR 2.25, 95%CI: 1.37, 3.71) and prolonged hospital length of stay.

Conclusions

Although handling of IV fluid administration was not an independent predictor of mortality or new stroke, patients with early positive fluid balance had worse clinical presentation and had greater resource use during the hospital course.     

Analysis of the association between Apolipoprotein D and schizophrenia

Schizophrenia is a severe, chronic and common complex debilitating mental illness with a large genetic component. Evidence to date suggests that apolipoprotein D protein may be closely related to schizophrenia. To investigate the role of the APOD gene in the etiology of schizophrenia, we genotyped three genetic polymorphisms (rs7659, rs2280520 and rs4677695) in a case-control study using subjects from the Chinese population, and altogether 425 cases and 473 controls were analyzed in the study. However, we found no significant discrepancies in allele and genotype frequencies of the three polymorphisms nor in the haplotype distribution between the cases and the controls. Our data indicate no direct evidence of association between schizophrenia and the APOD gene, and the results suggest that the three genetic polymorphisms within the APOD gene are unlikely to confer increased susceptibility to the illness in the Chinese population.     

Associations between Chlamydophila infections, schizophrenia and risk of HLA-A10

Several microbes have been suspected as pathogenetic factors in schizophrenia. We have previously observed increased frequencies of chlamydial infections and of human lymphocyte antigen (HLA)-A10 in independent studies of schizophrenia. Our aim here was to analyze frequencies of three types of Chlamydiaceae in schizophrenic patients (n=72), random controls (n=225) and hospital-patient controls (n=36), together with HLA-A genotypes. Patients were diagnosed with schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders-IV. Blood samples were collected at the beginning of hospitalization and analyzed with Chlamydiaceae species-specific polymerase chain reaction (PCR). Control panels consisted of randomly selected volunteers and hospitalized, non-schizophrenic patients. We found chlamydial infection in 40.3% of the schizophrenic patients compared to 6.7% in the controls. The association of schizophrenia with Chlamydiaceae infections was highly significant (P=1.39 x 10(-10), odds ratio (OR)=9.43), especially with Chlamydophila psittaci (P=2.81 x 10(-7), OR=24.39). Schizophrenic carriers of the HLA-A10 genotype were clearly most often infected with Chlamydophila, especially C. psittaci (P=8.03 x 10(-5), OR=50.00). Chlamydophila infections represent the highest risk factor yet found to be associated with schizophrenia. This risk is even further enhanced in carriers of the HLA-A10 genotype.     

A population-based register study of the association between schizophrenia and rheumatoid arthritis.

The authors investigated the association between schizophrenia and rheumatoid arthritis. The design is a population-based case-control and follow-up study. The cases were 20495 patients admitted for schizophrenia and registered in the Danish Psychiatric Case Register. A total of 204912 persons matched on age and gender and chosen from the general population served as controls. Admissions for rheumatoid arthritis and other non-autoimmune, musculoskeletal disorders were checked in the Danish National Patient Register. Odds ratios and relative risks were estimated by the Mantel-Haenszel estimator and Poisson regression. The same analyses were carried out for 10242 patients with bipolar affective disorder and 102420 controls for comparison. Individuals with schizophrenia had a reduced risk for being admitted with rheumatoid arthritis [odds ratio 0.44 (CI 0.24-0.81)] in the case-control study. A similar result was found in the follow-up study, but the incidence of the degenerative disorders in the musculoskeletal system was equally significantly lower in both studies. The incidence of rheumatoid arthritis among the bipolar patients was the same as in the control population. The negative association between schizophrenia and rheumatoid arthritis may thus be the result of ascertainment bias and selection due to under reporting and treatment of the medical illness. Clinicians are reminded of the difficulties in detecting medical illness among individuals with schizophrenia.     

The association between schizophrenia and cancer: a population-based mortality study

BACKGROUND: For most of this century there has been speculation that persons diagnosed with schizophrenia have a reduced incidence of cancer. OBJECTIVE: To determine if a history of cancer was more common in persons diagnosed with schizophrenia when compared with the general population, controlling for known risk and demographic factors. DESIGN: We used the 1986 National Mortality Followback Survey (NMFS) which sampled 1% of all deaths in the US from that year. Data were obtained from death certificates and records of hospitalizations in the last year of life. Additional health and demographic data were obtained through interviews with decedents' families and other informants. We compared persons diagnosed with schizophrenia (n=130) to individuals without schizophrenia (n=18,603) and used logistic regression to determine the odds ratio for the occurrence of cancer in persons diagnosed with schizophrenia. Adjustment for age at death was done to correct for the fact that persons diagnosed with schizophrenia die on average 10 years younger than the general population. MAIN OUTCOME MEASURE: A diagnosis of cancer on a hospital record or the death certificate. RESULTS: The unadjusted odds ratio for cancer among individuals with schizophrenia was 0.62 (95% confidence interval (CI) 0.40-0.96). After controlling for age, race, gender, marital status, education, net worth, smoking, and hospitalization in the year before death, we determined that the odds ratio for the diagnosis of cancer in persons with schizophrenia was 0.59 (95% CI 0.38-0.93). CONCLUSION: In this population-based study, we demonstrated a reduced risk of cancer among persons diagnosed with schizophrenia.     

The association between verbal memory, processing speed, negative symptoms and functional capacity in schizophrenia

The aim of this paper is to explore the links among verbal memory, processing speed, negative symptoms, and functional capacity, using structural equation modeling techniques. Model A is a multiple regression model with cognitive and symptom variables as predictors and functional capacity as the latent outcome variable. Model B consists of three two mediator models that assess the ability of each variable to mediate the effect of the other variable on outcome conditional on the inclusion of the other mediator in the model. Ninety-eight community-dwelling patients with schizophrenia (mean age = 35.8 years, S.D. = 10.1) participated in the study. Results indicate that verbal memory, processing speed and negative symptoms significantly contributed to functional status. Verbal memory was at least partially mediated by processing speed in its effect on outcome, while the impact of processing speed on outcome was mediated by both verbal memory and negative symptoms. The influence of negative symptoms on functional capacity was partially mediated by processing speed. These findings enrich our understanding of the direct and indirect effects of these three interrelated variables and provide a basis for the development of intervention strategies.     

奥氮平对精神分裂症患者血清神经递质白介素及微量元素的影响

目的探讨奥氮平对精神分裂症患者血清神经递质、白介素及微量元素的影响程度。方法选取于本院进行治疗的64例精神分裂症患者为研究对象,以随机分配方式分为对照组(氯氮平治疗组)32例和观察组(奥氮平治疗组)32例,比较2组治疗前与治疗后2周及8周的血清神经递质、白介素及微量元素水平。结果治疗后2周及8周时观察组血清NO、IL-2、Zn及Mg均高于对照组,而其他血清神经递质、白介素及微量元素水平则均低于对照组,2组治疗后血清指标比较差异有统计学意义(P0.05)。结论奥氮平对精神分裂症患者血清神经递质、白介素及微量元素的影响明显大于氯氮平,具有良好的改善作用。     

Membrane phospholipid composition, alterations in neurotransmitter systems and schizophrenia

This review addresses the relationship between modifications in membrane phospholipid composition (MPC) and alterations in dopaminergic, serotonergic and cholinergic neurotransmitter systems in schizophrenia. The main evidence in support of the MPC hypothesis of schizophrenia comes from post-mortem and platelet studies, which show that in schizophrenia, certain omega-3 and omega-6 polyunsaturated fatty acid (PUFA) levels are reduced. Furthermore, examination of several biochemical markers suggests abnormal fatty acid metabolism may be present in schizophrenia. Dietary manipulation of MPC with polyunsaturated fatty acid diets has been shown to affect densities of dopamine, serotonin and muscarinic receptors in rats. Also, supplementation with omega-3 fatty acids has been shown to improve mental health rating scores, and there is evidence that the mechanism behind this involves the serotonin receptor complex. This suggests that a tight relationship exists between essential fatty acid status and normal neurotransmission, and that altered PUFA levels may contribute to the abnormalities in neurotransmission seen in schizophrenia.     

交感神经-免疫系统调节网络的研究进展

淋巴器官受交感神经支配,这些神经支配淋巴器官中的血管平滑肌和实质区域,与血管平滑肌细胞和淋巴细胞呈非经典的突触联系,即交感神经末梢的曲张体非突触性地释放去甲肾上腺素(norepinephrine,NE),NE以旁分泌的方式扩散出去,作用于较大距离范围的血管平滑肌细胞和淋巴细胞,调节淋巴器官的血流、淋巴细胞的运输和淋巴细胞的功能.在免疫应答过程中,免疫细胞释放细胞因子,影响外周感觉神经的传入活动,继而改变交感神经的NE释放,从而影响免疫功能.T细胞上存在电压门控K+通道,K+通道代表了T细胞上主要的离子通道,T细胞激活后上调K+通道的表达和增加K+通道的通透性,交感神经可能通过减小K+通道的通透性从而抑制T细胞的功能.     

交感神经-免疫系统调节网络的研究进展

淋巴器官受交感神经支配，这些神经支配淋巴器官中的血管平滑肌和实质区域，与血管平滑肌细胞和淋巴细胞呈非经典的突触联系，即交感神经末梢的曲张体非突触性地释放去甲肾上腺紊(norepinephrine，NE)，NE以旁分泌的方式扩散出去,作用于较大距离范围的血管平滑肌细胞和淋巴细胞，调节淋巴器官的血流、淋巴细胞的运输和淋巴细胞的功能。在免疫应答过程中，免疫细胞释放细胞因子，影响外周感觉神经的传人活动，继而改变交感神经的NE释放，从而影响免疫功能。T细胞上存在电压门控K 通道，K 通道代表了T细胞上主要的离子通道，T细胞激活后上调K 通道的表达和增加K 通道的通透性，交感神经可能通过减小K 通道的通透性从而抑制T细胞的功能。     

No association between glutathione-synthesis-related genes and Japanese schizophrenia

Aims: Schizophrenia is a major psychiatric disorder with complex genetic, environmental, and psychological causes, and oxidative stress may be involved in the pathogenesis of the disease. Glutathione (GSH), one of the main cellular non‐protein antioxidants and redox regulators, and altered GSH levels have been reported in various regions in patients with schizophrenia. Three enzymes are responsible for GSH synthesis: glutamate cysteine ligase modifier (GCLM), glutamate cysteine ligase catalytic subunit (GCLC), and glutathione synthetase (GSS). Previously, positive associations between GCLM and schizophrenia were reported in Europeans, but not in the Japanese population. Thus, in this study, we investigated the association between the GSH synthesis genes (GCLM, GCLC, and GSS) and schizophrenia in Japanese individuals. Methods: Seventeen single‐nucleotide polymorphisms (SNP) in GCLM, GCLC, and GSS were genotyped in 358 patients with schizophrenia and in 359 controls. Results: No SNP showed a significant association between their allelic or genotypic frequencies and schizophrenia. Case–control haplotype association analysis using windows of two or three SNP showed no significant associations with schizophrenia. The case–control haplotype analyses based on the ascertained linkage disequilibrium blocks also showed no significant associations in any genes with schizophrenia. Conclusions: The three primary GSH synthesis genes do not have an apparent degree of association with schizophrenia in the Japanese population.