Lowered serum cesium levels in schizophrenia: association with immune-inflammatory biomarkers and cognitive impairments

Objectives: A previous study has shown that schizophrenia (SCZ) is accompanied by lowered levels of trace/metal elements, including cesium. However, it is not clear whether changes in cesium, rubidium, and rhenium are associated with activated immune-inflammatory pathways, cognitive impairments, and the symptomatology of SCZ. Methods: This study measured cesium, rubidium, and rhenium, cognitive impairments (using the Brief Assessment of Cognition in Schizophrenia [BACS]), and the levels of cytokines/chemokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and eotaxin (CCL11) in 120 patients with SCZ and 54 healthy controls. Severity of illness was assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale, and the Hamilton Depression Rating Scale (HAM-D). Results: Serum cesium was significantly lower in patients with SCZ as compared with controls. Further, serum cesium was significantly and inversely associated with CCL11 and TNF-α, but not IL-1β, in patients with SCZ; significant inverse associations were also noted between serum cesium levels and BPRS, FF, HAM-D, and SANS scores. Finally, cesium was positively correlated with neurocognitive probe results including the Tower of London, Symbol Coding, Controlled Word Association, Category Instances, Digit Sequencing Task, and List Learning tests. Conclusion: The results suggest that lowered serum cesium levels may play a role in the pathophysiology of SCZ, contributing to specific symptom domains including negative, depressive and fatigue symptoms, neurocognitive impairments (spatial working, episodic, and semantic memory and executive functions), and neuroimmune pathways.

Novel identification and characterisation of Transient receptor potential melastatin 3 ion channels on Natural Killer cells and B lymphocytes: effects on cell signalling in Chronic fatigue syndrome/Myalgic encephalomyelitis patients

BACKGROUND: Transient receptor potential melastatin 3 (TRPM3) cation channels are ubiquitously expressed by multiple cells and have an important regulatory role in calcium-dependent cell signalling to help maintain cellular homeostasis. TRPM3 protein expression has yet to be determined on Natural Killer (NK) cells and B lymphocytes. Multiple single nucleotide polymorphisms have been reported in TRPM3 genes from isolated peripheral blood mononuclear cells, NK and B cells in Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) patients and have been proposed to correlate with illness presentation. The object of the study was to assess TRPM3 surface expression on NK and B lymphocytes from healthy controls, followed by a comparative investigation examining TRPM3 surface expression, and cytoplasmic and mitochondrial calcium influx in CD19+ B cells, CD56bnght and CD56dim cell populations from CFS/ME patients. RESULTS: TRPM3 cell surface expression was identified for NK and B lymphocytes in healthy controls (CD56bright TRPM3 35.72 % ± 7.37; CD56dim 5.74 % ± 2.00; B lymphocytes 2.05 % ± 0.19, respectively). There was a significant reduction of TRPM3 surface expression on CD19+ B cells (1.56 ± 0.191) and CD56bright NK cells (17.37 % ± 5.34) in CFS/ME compared with healthy controls. Anti-CD21 and anti-IgM conjugated biotin was cross-linked with streptavidin,and subsequently treatment with thapsigargin. This showed a significant reduction in cytoplasmic calcium ion concentration in CD19+ B lymphocytes. CD56bright NK cells also had a significant decrease in cytoplasmic calcium in the presence of 2-APB and thapsigargin in CFS/ME patients. CONCLUSIONS: The results from this preliminary investigation identify, for the first time, TRPM3 surface expression on both NK and B lymphocytes in healthy controls. We also report for the first time, significant reduction in TRPM3 cell surface expression in NK and B lymphocytes, as well as decreased intracellular calcium within specific conditions in CFS/ME patients. This warrants further examination of these pathways to elucidate whether TRPM3 and impaired calcium mobilisation has a role in CFS/ME.

Waon Therapy is Effective as the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome / 日本温泉気候物理医学会雑誌

Background: Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) is an illness characterized by disabling fatigue. We examined the applicability of Waon therapy as a new method of fatigue treatment in patients with ME/CFS. Methods: Nine female ME/CFS patients (mean age, 38.4±11.2 years old; range, 21-60) who fulfilled the criteria of the Canadian clinical case definition of ME/CFS participated in this study. Patients received 30 sessions of modified Waon therapy, infrared-ray dry sauna maintained at an even temperature of 40°C or 45°C for 15 minutes twice a day for 3 weeks in a hospital, or once a day for five weeks at an outpatient clinic. Their functional health and well-being scores were determined using SF-36 and compared with those of six ME/CFS patients who did not undergo Waon therapy. Results: Seven of nine Waon therapy patients experienced a significant improvement in physical and mental condition, and the effect continued throughout the observation period. Waon therapy brought improvements in the scores of: Role physical (p<0.05); Bodily pain (p<0.05); General health perceptions (p<0.05); and Role emotional (p<0.05) of SF-36 in those who responded well (good responders) to the therapy. In two patients who responded poorly (poor responders) to Waon therapy, and in the non-Waon therapy patients, no significant improvement in the scores was observed. Conclusions: Waon therapy is effective for the treatment of ME/CFS.

Waon Therapy is Effective as the Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome / 日本温泉気候物理医学会雑誌

<b>Background</b>: Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) is an illness characterized by disabling fatigue. We examined the applicability of Waon therapy as a new method of fatigue treatment in patients with ME/CFS.<BR><b>Methods</b>: Nine female ME/CFS patients (mean age, 38.4±11.2 years old; range, 21-60) who fulfilled the criteria of the Canadian clinical case definition of ME/CFS participated in this study. Patients received 30 sessions of modified Waon therapy, infrared-ray dry sauna maintained at an even temperature of 40°C or 45°C for 15 minutes twice a day for 3 weeks in a hospital, or once a day for five weeks at an outpatient clinic. Their functional health and well-being scores were determined using SF-36 and compared with those of six ME/CFS patients who did not undergo Waon therapy.<BR><b>Results</b>: Seven of nine Waon therapy patients experienced a significant improvement in physical and mental condition, and the effect continued throughout the observation period. Waon therapy brought improvements in the scores of: Role physical (p<0.05); Bodily pain (p<0.05); General health perceptions (p<0.05); and Role emotional (p<0.05) of SF-36 in those who responded well (good responders) to the therapy. In two patients who responded poorly (poor responders) to Waon therapy, and in the non-Waon therapy patients, no significant improvement in the scores was observed.<BR><b>Conclusions</b>: Waon therapy is effective for the treatment of ME/CFS.

S1-4 Waon therapy for myalgic encephalomyelitis/chronic fatigue syndrome / 日本温泉気候物理医学会雑誌

Objective: Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) is an illness characterized by disabling fatigue lasting for at least 6 months. There are many controlled trials and case-control treatment studies that utilized immunological substances, pharmacological products, nutritional supplements, physical therapies, and cognitive behavioral therapy. Because of the unclear etiology, diagnostic uncertainty, and the resultant heterologeneity of the ME/CFS population, there are no firmly established treatment recommendation for ME/CFS. Recently Tei et al reported 2 CFS cases in whom thermal therapy improved the subjective symptoms. Thermal therapy has been reported to increase stroke volume and cardiac output in patients and improve the quality of life, sleep quality, and general well-being of these subjects. Thermal therapy using far-infrared ray dry sauna may be a promising method for the treatment of ME/CFS. We examined the applicability of Waon therapy (soothing warmth therapy) as a new treatment for patients with ME/CFS. Methods: Nine female ME/CFS patients (mean age, 38.4±11.2 years old; range, 21-60) who fulfilled the criteria of the Ministry of Health, Labor and Welfare of Japan and Canadian clinical case definition of ME/CFS participated in this study. The mean illness duration was 3.1±1.8 years (range, 1-6). The mean performance state was 6.9±0.9. The patients were placed in the sitting position in a infrared-ray dry sauna maintained at an even temperature of 45°C for 15 minutes, and then transferred to a room maintained at 26-27°C where they were covered with a warm blanket from the neck down to keep them warm for 30 minutes. They received thermal therapy twice a day for 3 weeks in hospital or once a day at the outpatient clinic for 5weeks. Their functional health and well-being scores were determined using SF-36 before treatment, after 30 treatments and during follow-up (mean follow-up period, 27.9±10.5 months; range 7-40). Results: Seven patients experienced a significant improvement in physical and mental condition by Waon therapy, and the effect continued throughout the observation period. In two patients, no improvement of symptoms was observed. Waon therapy brought the improvement in the score of Physical functioning(p<0.05), Role physical(RP)(p<0.05), Bodily pain(p<0.001), General health perceptions(p<0.03) and Role emotional(RE)(p<0.005) of FS-36 in good responders. However, the therapy did not bring any improvement in the score of Vitality, Social functioning and Mental health.   In poor responders, no improvement was observed in the score of FS-36. Mean duration of illness in poor responders was longer than in good responders (4.5±0.7ys:2.7±1.9ys, p<0.09). The performance state at the admission was almost same between poor responders and good responders (7±0:6.9±1.1). Conclusion: Waon therapy is effective for the treatment of ME/CFS. Although the present study included only 10 patients, the effects observed in our patients were dramatic. Further clinical studies in larger ME/CFS patient populations are required to confirm the effects of this method of treatment.

S1-4Waon therapy for myalgic encephalomyelitis/chronic fatigue syndrome / 日本温泉気候物理医学会雑誌

<b>Objective: </b>Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS) is an illness characterized by disabling fatigue lasting for at least 6 months. There are many controlled trials and case-control treatment studies that utilized immunological substances, pharmacological products, nutritional supplements, physical therapies, and cognitive behavioral therapy. Because of the unclear etiology, diagnostic uncertainty, and the resultant heterologeneity of the ME/CFS population, there are no firmly established treatment recommendation for ME/CFS. Recently Tei et al reported 2 CFS cases in whom thermal therapy improved the subjective symptoms. Thermal therapy has been reported to increase stroke volume and cardiac output in patients and improve the quality of life, sleep quality, and general well-being of these subjects. Thermal therapy using far-infrared ray dry sauna may be a promising method for the treatment of ME/CFS. We examined the applicability of Waon therapy (soothing warmth therapy) as a new treatment for patients with ME/CFS.<BR><b>Methods: </b>Nine female ME/CFS patients (mean age, 38.4±11.2 years old; range, 21-60) who fulfilled the criteria of the Ministry of Health, Labor and Welfare of Japan and Canadian clinical case definition of ME/CFS participated in this study. The mean illness duration was 3.1±1.8 years (range, 1-6). The mean performance state was 6.9±0.9. The patients were placed in the sitting position in a infrared-ray dry sauna maintained at an even temperature of 45°C for 15 minutes, and then transferred to a room maintained at 26-27°C where they were covered with a warm blanket from the neck down to keep them warm for 30 minutes. They received thermal therapy twice a day for 3 weeks in hospital or once a day at the outpatient clinic for 5weeks. Their functional health and well-being scores were determined using SF-36 before treatment, after 30 treatments and during follow-up (mean follow-up period, 27.9±10.5 months; range 7-40).<BR><b>Results:</b> Seven patients experienced a significant improvement in physical and mental condition by Waon therapy, and the effect continued throughout the observation period.<BR>In two patients, no improvement of symptoms was observed. Waon therapy brought the improvement in the score of Physical functioning(p<0.05), Role physical(RP)(p<0.05), Bodily pain(p<0.001), General health perceptions(p<0.03) and Role emotional(RE)(p<0.005) of FS-36 in good responders. However, the therapy did not bring any improvement in the score of Vitality, Social functioning and Mental health. <BR>  In poor responders, no improvement was observed in the score of FS-36. Mean duration of illness in poor responders was longer than in good responders (4.5±0.7ys:2.7±1.9ys, p<0.09). The performance state at the admission was almost same between poor responders and good responders (7±0:6.9±1.1).<BR><b>Conclusion:</b> Waon therapy is effective for the treatment of ME/CFS. Although the present study included only 10 patients, the effects observed in our patients were dramatic. Further clinical studies in larger ME/CFS patient populations are required to confirm the effects of this method of treatment.