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        Distinct Inflammation Biomarkers in Healthy Individuals and Patients with Schizophrenia: A Reliability Testing of Multiplex Cytokine Immunoassay by Bland-Altman Analysis

        Ta-Chuan Yeh,Hsuan-Te Chu,Chia-Kuang Tsai,Hsin-An Chang,Fu-Chi Yang,San-Yuan Huang,Chih-Sung Liang 대한신경정신의학회 2019 PSYCHIATRY INVESTIGATION Vol.16 No.8

        Objective Since the inflammatory process has been implicated in the pathophysiology of psychiatric disorder, an important issue emerging is to assess the test-retest reliability of cytokine measurement in healthy individuals and patients with schizophrenia. The objective of the present study was to investigate the test-retest reliability of bead-based multiplex immunoassay technology (BMIT) for cytokine measurement by using a Bland-Altman plot (BAP). Methods Twenty healthy individuals and twenty patients with schizophrenia were enrolled, and a 17-plex cytokine assay was used to measure inflammatory biomarkers at baseline and two weeks later. The test-retest reliability was examined by BAP, 95% limits of agreement (LOA), intraclass correlation coefficient (ICC), and coefficient of repeatability (CoR). Results In the healthy controls, only interleukin (IL)-2, IL-13, IL-10, IL-17, and macrophage inflammatory protein-1β showed excellent ICC. The BAP with 95% LOA determined that 13 cytokines showed acceptable 95% LOA for a 2-week test-retest reliability, and only IL-1β, IL-12 and tumor necrosis factor (TNF)-α had significant test-retest bias. The CoR of cytokines varied significantly, ranging from 1.72 to 218.1. Compared with healthy controls, patients with schizophrenia showed significantly higher levels of IL-5, IL-13, and TNF-α and significantly lower levels of IL-4, IL-12, and interferon-gamma (IFN-γ). Of these six cytokines, IL-12 and TNF-α were considered suboptimal reliability. Conclusion The findings from ICC and CoR implied that the test-retest reliability of BMIT for cytokine measurement were suboptimal. However, the BAP with 95% LOA confirmed that BMIT can reliably distinguish schizophrenia from healthy individuals in cytokine measurement, while significant within-subject variation and between-group overlapping were evident in cytokine expression.

      • KCI등재

        Incongruent Expression of Brain-Derived Neurotrophic Factor and Cortisol in Schizophrenia: Results from a Randomized Controlled Trial of Laughter Intervention

        Shu-Li Cheng,Fu-Chi Yang,Hsuan-Te Chu,Chia-Kuang Tsai,Shih-Chieh Ku,Yu-Ting Tseng,Ta-Chuan Yeh,Chih-Sung Liang 대한신경정신의학회 2020 PSYCHIATRY INVESTIGATION Vol.17 No.12

        Objective Schizophrenia has been associated with dysfunction of the hypothalamic-pituitary-adrenal axis. Furthermore, alterations in neurotrophic factors might contribute to the pathogenesis of schizophrenia. We aimed to evaluate the effects of a simulated laughter intervention on the levels of cortisol and BDNF and to determine whether the effects associated with simulated laughter could be sustained after discontinuation of the intervention. Methods In this randomized controlled study, patients with schizophrenia according to DSM-IV clinical criteria were randomly assigned to receive either 8-week-long simulated laughter intervention (n=32) or treatment-as-usual group (control group, n=27). The serum levels of BDNF and cortisol were measured at baseline, week 8, and four weeks after discontinuation (week 12) of the intervention program. Results After an 8-week simulated laughter intervention, the laughter group had significantly higher levels of BDNF; however, four weeks after discontinuation of the intervention, the levels of BDNF significantly dropped. Interestingly, the levels of cortisol did not change significantly at week 8, but they were significantly elevated at week 12. The levels of BDNF and cortisol in the control group did not change significantly between week 0 and week 8. Conclusion These findings suggest that the simulated laughter intervention has an early effect on neurogenesis with a significant delayed effect on stress regulation in subjects with schizophrenia.

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        Oxygen-loaded microbubble-mediated sonoperfusion and oxygenation for neuroprotection after ischemic stroke reperfusion

        Yi‑Ju Ho,Hsiang‑Lung Cheng,Lun‑De Liao,Yu‑Chun Lin,Hong‑Chieh Tsai,Chih‑Kuang Yeh 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

        Background Ischemic stroke-reperfusion (S/R) injury is a crucial issue in the protection of brain function after thrombolysis. The vasodilation induced by ultrasound (US)-stimulated microbubble cavitation has been applied to reduce S/R injury through sonoperfusion. The present study uses oxygen-loaded microbubbles (OMBs) with US stimulation to provide sonoperfusion and local oxygen therapy for the reduction of brain infarct size and neuroprotection after S/R. Methods The murine S/R model was established by photodynamic thrombosis and thrombolysis at the remote branch of the anterior cerebral artery. In vivo blood flow, partial oxygen pressure ( pO2), and brain infarct staining were examined to analyze the validity of the animal model and OMB treatment results. The animal behaviors and measurement of the brain infarct area were used to evaluate long-term recovery of brain function. Results The percentage of blood flow was 45 ± 3%, 70 ± 3%, and 86 ± 2% after 60 min stroke, 20 min reperfusion, and 10 min OMB treatment, respectively, demonstrating sonoperfusion, and the corresponding pO2 level was 60 ± 1%, 76 ± 2%, and 79 ± 4%, showing reoxygenation. After 14 days of treatment, a 87 ± 3% reduction in brain infarction and recovery of limb coordination were observed in S/R mice. The expression of NF-κB, HIF-1α, IL-1β, and MMP-9 was inhibited and that of eNOS, BDNF, Bcl2, and IL-10 was enhanced, indicating activation of anti-inflammatory and anti-apoptosis responses and neuroprotection. Our study demonstrated that OMB treatment combines the beneficial effects of sonoperfusion and local oxygen therapy to reduce brain infarction and activate neuroprotection to prevent S/R injury.

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