Serum soluble triggering receptor expressed on myeloid cells-2 was not altered by rTMS in patients with treatment-resistant depression.

AIM: Repetitive transcranial magnetic stimulation (rTMS) is one of the most effective and minimally invasive treatments for treatment-resistant depression (TRD). However, the mechanism underlying the therapeutic effects of rTMS in patients with TRD remains unclear. In recent years, the pathogenesis of depression has been closely associated with chronic inflammation and microglia are believed to play an important role in chronic inflammation. Triggering receptor expressed on myeloid cells-2 (TREM2) plays an important role in microglial neuroinflammatory regulation. In this study, we investigated the changes in peripheral soluble TREM2 (sTREM2) before and after rTMS treatment in patients with TRD. METHODS: Twenty-six patients with TRD were enrolled in this frequency (10 Hz) rTMS study. Depressive symptoms, cognitive function, and serum sTREM2 concentrations were measured at baseline and the end of the 6-week rTMS treatment. RESULTS: This study showed that rTMS ameliorated depressive symptoms and partially improved cognitive dysfunction in TRD. However, rTMS treatment did not alter serum sTREM2 levels. CONCLUSIONS: This is the first sTREM2 study in patients with TRD who underwent rTMS treatment. These results suggest that serum sTREM2 may not be relevant for the mechanism underlying the therapeutic effect of rTMS in patients with TRD. Future studies should confirm the present findings using a larger patient sample and a sham rTMS procedure, as well as CSF sTREM2. Furthermore, a longitudinal study should be conducted to clarify the effects of rTMS on sTREM2 levels.

Changes in the metabolites of cerebrospinal fluid induced by rTMS in treatment-resistant depression: A pilot study.

Repetitive transcranial magnetic stimulation (rTMS) improves depressive symptoms in treatment-resistant depression (TRD). This study aimed to analyze changes in cerebrospinal fluid (CSF) metabolites in patients with TRD after rTMS. Five patients with TRD were enrolled in a high frequency (10-Hz) rTMS study. The concentration of 72 CSF metabolites were measured at baseline and at the end of the 6-week rTMS treatment. rTMS significantly increased CSF niacinamide, kynurenine, and creatinine levels and significantly decreased CSF cystine levels, but not the levels of the other 68 CSF metabolites. This is the first CSF metabolomics study on patients with TRD who underwent rTMS.

Changes in interleukin-1 beta induced by rTMS are significantly correlated with partial improvement of cognitive dysfunction in treatment-resistant depression: a pilot study.

The impairment experienced by many individuals with depression is closely related to the cognitive symptoms of the disorder. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation method that provides a promising technique for improving cognitive symptoms in treatment-resistant depression (TRD). It has recently been demonstrated that TRD is associated with increased inflammatory process. In the present study, we investigated whether a relationship exists between changes in cognitive function and those in inflammatory cytokines before and after rTMS treatment. Eleven patients with TRD were enrolled in a high-frequency (10 Hz) rTMS study. Cognitive function, depressive symptoms and serum concentration of inflammatory cytokines (interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α) were measured at baseline and at the endpoint of rTMS treatment. rTMS treatment significantly improved depressive symptom scores and some subscales of cognitive dysfunction. The present study has demonstrated that partial changes in cognitive function and changes in IL-1ß were significantly correlated. The partial improvement of cognitive dysfunction by rTMS in the present study might be attributable to the reduction of peripheral IL-1ß levels. The present results should be replicated for verification in future studies.

Risk factors for development of systemic lupus erythematosus among Japanese females: medical history and reproductive factors.

AIM: The aim of the present study was to examine the influence of medical history and reproductive factors on the development of systemic lupus erythematosus (SLE) among Japanese females. METHODS: One hundred and sixty female SLE patients and 660 female volunteers were studied in a case-control study. Unconditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CIs). RESULTS: The present study demonstrated that medical histories of operations without blood transfusion (OR = 1.64, 95% CI = 1.10-2.44) and operations with blood transfusion (OR = 4.44, 95% CI = 1.93-10.23) increased the risk of SLE with adjustment for age, region, smoking and alcohol drinking. Among 91 SLE patients and 284 control subjects who had the experience of married life, nulliparity (OR = 2.29, 95% CI = 1.05-5.17), increased the risk of SLE, while the risk decreased according to the number of children (one to two vs. none, OR = 0.27, 95% CI = 0.10-0.73; three or more vs. none, OR = 0.14, 95% CI = 0.04-0.51; P for trend < 0.01). CONCLUSIONS: Several factors are suggested to be associated with the development of SLE among Japanese females.

Modifying effect of N-acetyltransferase 2 genotype on the association between systemic lupus erythematosus and consumption of alcohol and caffeine-rich beverages.

OBJECTIVE: N-acetyltransferase 2 (NAT2) is involved in the metabolism of various environmental substances, both with and without carcinogenic potential. Alcoholic and nonalcoholic caffeine-rich beverages may be associated with markers of inflammation. Systemic lupus erythematosus (SLE) is a chronic, multifaceted inflammatory disease. We investigated the effects of alcoholic and nonalcoholic caffeine-rich beverages on risk of SLE and determined whether the effects were modified by NAT2 status. METHODS: The NAT2 polymorphism was genotyped in 152 SLE cases and 427 healthy controls, all women and Japanese. We assessed effect modification by testing an interaction term for the NAT2 polymorphism and consumption of beverages. RESULTS: Consumption of black tea (odds ratio [OR] 1.88, 95% confidence interval [95% CI] 1.03-3.41) and coffee (OR 1.57, 95% CI 0.95-2.61), but not green tea, was associated with an increased risk of SLE, while alcohol use (OR 0.33, 95% CI 0.20-0.55) was associated with a decreased risk of SLE. There were significant interactions between the NAT2 polymorphism and either alcohol use (Pinteraction = 0.026) or consumption of black tea (Pinteraction = 0.048). CONCLUSION: The NAT2 polymorphism significantly modified the effects of alcohol use and black tea consumption on SLE, emphasizing the importance of incorporating genetic and metabolic information in studies on management of SLE. Additional studies are warranted to confirm the findings suggested in this study.

Psychological stress in a Japanese population with systemic lupus erythematosus: finding from KYSS study.

OBJECTIVES: Daily psychological stress has been proposed as a risk factor for systemic lupus erythematosus (SLE) in Western countries. However, there is little information about the relationship between daily psychological stress and the risk of SLE in a Japanese population. We examined the association between SLE and daily psychological stress. METHODS: A case-control study was conducted to examine the relationship between daily psychological stress and SLE in Japanese females. The participants were 160 female SLE patients and 660 female volunteers. Unconditional logistic regression was used to compute OR and 95% confidence interval (CI), with adjustment for several covariates. RESULTS: Smoking (OR = 2.59; 95% CI, 1.74-3.86), walking (OR = 1.75; 95% CI, 1.81-2.56) and daily psychological stress (OR = 1.88; 95% CI, 1.14-3.10) were increased in patients with SLE after adjusting for age, region and all factors. Smokers with daily psychological stress (OR = 4.70; 95% CI = 2.53-8.77) were more prevalent than nonsmokers without daily psychological stress in SLE. The multiplicative interaction measures between smoking status and daily psychological stress did not reach statistical significance. CONCLUSIONS: The present study suggests the possibility that daily psychological stress as well as smoking might be associated with an increased risk of SLE.

Cigarette smoking, alcohol consumption, and risk of systemic lupus erythematosus: a case-control study in a Japanese population.

OBJECTIVE: Cigarette smoking may be associated with increased risk of systemic lupus erythematosus (SLE), whereas the role of alcohol consumption is unknown. We examined the association between SLE risk and smoking or drinking. METHODS: We investigated the relationship of smoking and drinking compared to SLE risk among 171 SLE cases and 492 healthy controls in female Japanese subjects. Unconditional logistic regression was used to compute OR and 95% CI, with adjustments for several covariates. RESULTS: Compared with nonsmoking, current smoking was significantly associated with increased risk of SLE (OR 3.06, 95% CI 1.86-5.03). The higher the level of exposure to cigarette smoke, the higher the risk of SLE. Inhalation was also associated with increased SLE risk (OR 3.73, 95% CI 1.46-9.94 for moderate inhalation; OR 3.06, 95% CI 1.81-5.15 for deep inhalation). In contrast, light/moderate alcohol consumption had a protective effect on SLE risk (OR 0.38, 95% CI 0.19-0.76). As for beer, the risks for non-beer drinkers and beer drinkers were similar. This also applies to alcoholic beverages other than beer. CONCLUSION: Our results suggest that smoking was positively associated with increased SLE risk whereas light/moderate alcohol consumption was inversely associated with SLE risk, irrespective of the type of alcoholic beverage. Additional studies are warranted to confirm these findings.

Cigarette smoking, STAT4 and TNFRSF1B polymorphisms, and systemic lupus erythematosus in a Japanese population.

OBJECTIVE: Recent studies have identified signal transducer and activator of transcription 4 (STAT4) as a susceptibility gene for systemic lupus erythematosus (SLE) in different populations. Similarly, tumor necrosis factor receptor superfamily, member 1B (TNFRSF1B) has been reported to be associated with SLE risk in Japanese populations. Along with environmental factors such as smoking, both polymorphisms may modulate an individual's susceptibility to SLE. We investigated these relationships in a case-control study to evaluate risk factors for SLE among Japanese women. METHODS: We investigated the relationship of the STAT4 rs7574865 and TNFRSF1B rs1061622 polymorphisms to SLE risk with special reference to their combination and interaction with cigarette smoking among 152 SLE cases and 427 controls. RESULTS: The TT genotype of STAT4 rs7574865 was significantly associated with increased risk of SLE (OR 2.21, 95% CI 1.10-4.68). Subjects with at least one G allele of TNFRSF1B rs1061622 had an increased risk of SLE (OR 1.56, 95% CI 0.99-2.47). The attributable proportion due to the interaction between the TNFRSF1B rs1061622 genotypes and smoking was estimated to be 0.49 (95% CI 0.07-0.92), indicating that 49% of the excess risk for SLE in smokers with at least one G allele was due to an additive interaction. A lack of significant associations of STAT4 with smoking was observed. No significant gene-gene interactions were found among polymorphisms of STAT4 and TNFRSF1B. CONCLUSION: Our findings suggest that the association between cigarette smoking and SLE could be differentiated by the TNFRSF1B rs1061622 T allele among female Japanese subjects. This preliminary exploratory result should be confirmed in a larger study.

Combination of TNF-RII, CYP1A1 and GSTM1 polymorphisms and the risk of Japanese SLE: findings from the KYSS study.

OBJECTIVES: Association of the polymorphisms of the genes, TNF receptor type II gene (TNF-RII), cytochrome P4501A1 gene (CYP1A1) and glutathione S-transferase M1 gene (GSTM1), with SLE was investigated. TNF-RII mediates inflammatory and immune response, whereas CYP1A1 and GSTM1 are involved in the metabolism of xenobiotics. These three genes are involved in the generation of reactive oxygen species (ROS), which play a critical role for autoimmune diseases. METHODS: A total of 152 SLE patients and 427 healthy individuals in a female Japanese population were enrolled in the study. Case-control studies were performed for the polymorphisms of these three genes. RESULTS: The carriers of TNF-RII 196R were at a significantly increased risk for SLE with odds ratio (OR) of 1.59 (95% CI = 1.01, 2.52). CYP1A1 3801C homozygotes had a significantly increased risk of SLE (OR = 2.47, 95% CI = 1.28, 4.78). On the other hand, GSTM1 null genotype was not associated with SLE risk. As for combination action of two loci, CYP1A1 3801C/GSTM1 null combination was more strongly associated with an increased risk of SLE (OR = 4.35; 95% CI = 1.76, 10.73). Moreover, TNF-RII 196M/CYP1A1 3801C/GSTM1 null genotype combination was most significantly associated with SLE (OR = 5.83; 95% CI = 2, 17.04). CONCLUSIONS: The individuals carrying two or more 'at-risk' genotypes of TNF-RII, CYP1A1 and GSTM1 had a significantly more increased risk for SLE compared with those having each 'at-risk' genotype. Combination of the risk genotypes will be important to more clearly identify the population at risk for SLE.

Smoking, drinking, sleeping habits, and other lifestyle factors and the risk of systemic lupus erythematosus in Japanese females: findings from the KYSS study.

Many risk factors have been proposed for systemic lupus erythematosus (SLE). However, there is little information about the relationship between lifestyles and SLE in Japan. Two case control studies were conducted in Kyushu, southern Japan, and in Hokkaido, northern Japan, to examine the relationship between lifestyles and development of SLE in females. The participants were 78 patients and 329 controls in Kyushu and 35 patients and 188 controls in Hokkaido. Smoking was associated with an increased risk of SLE after adjusting for age in both regions. However, in Hokkaido, this association between smoking and SLE did not reach statistical significance after adjusting for alcohol drinking. The present study suggests that smoking may increase the risk of SLE among Japanese females.