Association Plasma Aß42 Levels with Alzheimer's Disease and Its Influencing Factors in Chinese Elderly Population.

Background and Purpose: Intracerebral Aß protein deposition is an important pathological mechanism of Alzheimer's disease (AD) and is one of the indicators of early diagnosis of AD. However, invasive lumbar puncture and Aß PET are difficult to perform in primary units, resulting delays in early diagnosis of AD. In recent years, it has been found that plasma Aß can reflect the pathological state of AD in early stage, but the results are not consistent. The objective of this study was to explore the association between plasma Aß42 levels and AD cognitive impairment and its influencing factors in Chinese elderly population, so as to provide guidance for the clinical application of plasma Aß42 as a blood biomarker of AD. Methods: This is a cross-sectional study based on the community population. Plasma samples were collected from 604 healthy controls (HC), 508 mild cognitive impairment (MCI) and 202 dementia with Alzheimer's type (DAT) patients from three cities. We analyzed the correlation between plasma Aß42 levels and cognitive function and the influence of confounding factors on the relationship between plasma Aß42 levels and AD. The independent influencing factors of plasma Aß42 levels were determined by covariance and linear regression analysis. Results: Our results suggest that there is a special linear relationship between plasma Aß42 and cognitive impairment of AD in Chinese elderly population, with Aß42 levels slightly decreased in early AD and significantly increased in moderate-to-severe AD (P<0.01). There are many factors influencing the association between plasma Aß42 levels and AD cognitive impairment, and sample source, gender and BMI are independent influencing factors of plasma Aß42. Conclusion: This indentifies that plasma Aß42 may be a peripheral biomarker for AD screening in Chinese elderly population, but it is necessary to establish standardized detection methods and establish different demarcation criteria for various influencing factors.

Reliability and validity of clinically useful depression outcome scale identifying mixed features in patients with manic episode.

OBJECTIVES: This study aims to explore the reliability, validity, and feasibility of Clinically Useful Depression Outcome Scale (CUDOS) in screening mixed features in patients diagnosed with mania. METHODS: A total of 109 patients with (hypo-) manic episode were recruited. The reliability of Chinese version of CUDOS (CUDOS-C) were analyzed with Cronbach's alpha and intraclass correlation coefficient (ICC). Spearman correlation coefficient was used to analyze the validity by comparing the correlation between CUDOS-C and Patient Health Questionnaire-9 (PHQ-9), 32-item Hypomania Checklist (HCL-32). The score of MINI (hypo-) manic episode with mixed features-DSM-5 Module-Chinese version(MINI-M-C) ≥ 2 was considered as the gold standard of mixed features, and the receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cut-off values of CUDOS-C score. RESULTS: The Cronbach's alpha value of CUDOS-C was 0.898, and the ICC of CUDOS-C test-retest was 0.880 (95% CI: 0.812-0.923, p < .05).The CUDOS-C score was significantly correlated with PHQ-9 score (r = 0.893, p = .000), but not with HCL-32 score(r = 0.088, p = .364).The area under ROC curve was 0.909 (95% CI: 0.855 to 0.963, p < .001) for CUDOS-C identifying mixed features in mania. The optimal cut-off value was 11 with a sensitivity of 0.854 and a specificity of 0.868. The CUDOS-C (score ≥ 12) identified 40.4% of the patients with mixed features, which was higher than those diagnosed by clinicians (18.3%) and screened using MINI-M-C (37.6%). CONCLUSIONS: The results indicate the CUDOS-C is a reliable and valid self-administered questionnaire for assessing depressive symptoms and screening patients with mixed mania.

Reliability and validity of the Chinese version of the CUDOS-M in patients with mood disorders: A multicenter study across China.

BACKGROUND: A useful scale for identification of mixed features in major depressive episodes (MDE) patients is urgent in China. This study aimed to evaluate the reliability and validity of the Chinese version of the Clinically Useful Depression Outcome Scale supplemented with questions for the DSM-5 mixed features specifier (Chinese-CUDOS-M) in MDE patients. METHODS: A total of 152 MDE patients were recruited and assessed using Chinese-CUDOS-M, Patient Health Questionnaire-9 (PHQ-9) and 32-item Hypomania Checklist (HCL-32). Principal component analysis (PCA) and exploratory factor analysis (EFA) were conducted. The predictive validity was calculated by the area under the receiver operating characteristic curve (AUROC). RESULTS: The Cronbach's alpha of Chinese-CUDOS-M was 0.85. PCA showed three common factors with eigenvalue greater than 1; the eigenvalue of factor I was 4.96, with 38.1% of variance explanation. Chinese-CUDOS-M depression subscale was associated with PHQ-9 (r = 0.83, p<0.01), and manic subscale was associated with HCL-32 (r = 0.73, p< 0.01). AUROC of the Chinese-CUDOS-M for patients with mixed depression was 0.90 (95%CI: 0.85-0.95), with a cut-off value of 7, sensitivity of 0.95, and specificity of 0.73. Furthermore, AUROC was 0.88 in patients with major depressive disorder (MDD), with a cut-off value of 7, sensitivity of 0.96, and specificity of 0.71. AUROC was 0.92 in bipolar disorder (BD) depression patients, with a cut-off value of 9, sensitivity of 0.89, and specificity of 0.87. CONCLUSION: Our study shows that the Chinese-CUDOS-M can identify mixed features in both MDD and BD depression with satisfactory reliability and validity.

Association Analysis of Polymorphisms in BIN1, MC1R, STARD6 and PVRL2 with Mild Cognitive Impairment in Elderly Carrying APOE ε4 Allele.

BACKGROUND: Apolipoprotein (APOE) ε4 is recognized as an independent risk factor for mild cognitive impairment (MCI). However, not everyone with the ε4 allele develops MCI, suggesting that other susceptibility genes exist. This study aimed to identify MCI susceptibility genes, including BIN1, MC1R, STARD6, and PVRL2, in elderly Han Chinese and to verify their association with APOE ε4 allele in MCI onset. METHODS: To determine whether polymorphisms in BIN1 (rs6733839, rs7561528), MC1R (rs2228479), STARD6 (rs10164112), and PVRL2 (rs6859) occurred in elderly MCI patients carrying APOE ε4 allele, we carried out a case-control study including 285 MCI patients and 326 healthy controls. RESULTS: Statistically significant differences in the proportion of APOE ε4 carriers, and BESCI, ADAS-cog, and CNT scores existed between the NC and MCI groups (all P < 0.01). Frequencies of the rs10164112 T and rs6859 A alleles were significantly higher in the latter than in the former (P = 0.01; 0.029). However, no significant differences in allele and genotype distribution of BIN1 (rs6733839, rs7561528) and MC1R (rs2228479) existed between samples in our two groups (all P > 0.05). When stratified by APOE ε4 status (carriers/non-carriers), genotype frequencies of BIN1 rs7561528, STARD6 rs10164112, and PVRL2 rs6859 among the four groups (NCε4+, NCε4-, MCIε4+, MCIε4-) were significantly different. Additionally, our results suggest a significant association between MCI and BIN1 rs7561528, STARD6 rs10164112, and PVRL2 rs6859 (all P<0.05) in elderly carriers. CONCLUSION: This suggests that among the Han Chinese, MCI in elderly APOE ε4 carriers may be related to the BIN1 (rs7561528), STARD6 (rs10164112) and PVRL2 (rs6859). Genotype AA of rs7561528 and TT of rs10164112 might be protective factors against MCI in elderly APOE ε4 carriers.

ATP-binding cassette transporter 13 mRNA expression level in schizophrenia patients.

The objective of this study was to investigate the expression and clinical role of ATP-binding cassette transporter 13 (ABCA13) gene previously shown to be associated with schizophrenia (SZ) through Genome-wide association studies studies. Thirty-two first-episode drug-naive SZ patients and forty-eight age and gender-matched healthy controls were enrolled in this study. We measured ABCA13 mRNA expression levels using quantitative real-time PCR at baseline and 12 weeks after antipsychotic therapy. Moreover, clinical symptoms were measured by the Positive and Negative Syndrome Scale (PANSS) at baseline and 12-week follow-up. We found that ABCA13 mRNA levels were significantly lower in SZ patients compared with healthy controls at baseline. SZ patients' symptoms were decreased, but ABCA13 mRNA levels were increased after 12 weeks antipsychotic therapy. In addition, there was a significant difference in ABCA13 mRNA levels among SZ patients at baseline and 12-week follow-up. The ABCA13 mRNA levels were not associated with age, BMI, years of education. Of the clinical symptoms measured, the ABCA13 mRNA levels were negatively associated with the PANSS scores at baseline and 12-week follow-up. The results indicated that the ABCA13 mRNA expression level is of interest, and upon further studies, it could be used as a biomarker for SZ treatment outcome.

Safety and Tolerability of Both Arm Ischemic Conditioning in Patients With Major Depression: A Proof of Concept Study.

PURPOSE: A substantial proportion of patients with major depressive disorder (MDD) does not respond or cannot tolerate to currently available treatments. This study was to assess the safety and tolerability of Remote Limb Ischemic Preconditioning (RLIPC) as an adjunctive therapy in patients with MDD. PATIENTS AND METHODS: Enrolled patients underwent RLIPC, five cycles of simultaneous bilateral arm ischemia, 5 min and followed by reperfusion of each cycle, and once daily for eight consecutive weeks. Depression and anxiety severity, and quality of life were assessed every 2 weeks. Descriptive analysis was used for safety and tolerability data. RESULTS: Thirty-seven participants completed at least one RLIPC. Twenty-four of them (64.9%) completed the study. Twelve patients prematurely discontinued the study due to poor adherence, and one due to a mild side effect. The changes in HRSD-17, GAD-7 and QOL-6 total scores from baseline to the endpoint were significant from the end of second week treatment onwards. The responder and remission rates were 59.46% (22/37) and 54.05% (20/37) at the endpoint, respectively. CONCLUSION: RLIPC was safe and well tolerated, and may be effective in reducing depressive symptoms in patients with MDD. Large studies are warranted to test its efficacy and safety as monotherapy or adjunctive therapy in the treatment of MDD.

Rumination mediates the relationship between overgeneral autobiographical memory and depression in patients with major depressive disorder.

BACKGROUND: Overgeneral autobiographical memory has been identified as a risk factor for the onset and maintenance of depression. However, little is known about the underlying mechanisms that might explain overgeneral autobiographical memory phenomenon in depression. The purpose of this study was to test the mediation effects of rumination on the relationship between overgeneral autobiographical memory and depressive symptoms. Specifically, the mediation effects of brooding and reflection subtypes of rumination were examined in patients with major depressive disorder. METHODS: Eighty-seven patients with major depressive disorder completed the 17-item Hamilton Depression Rating Scale, Ruminative Response Scale, and Autobiographical Memory Test. Bootstrap mediation analysis for simple and multiple mediation models through the PROCESS macro was applied. RESULTS: Simple mediation analysis showed that rumination significantly mediated the relationship between overgeneral autobiographical memory and depression symptoms. Multiple mediation analyses showed that brooding, but not reflection, significantly mediated the relationship between overgeneral autobiographical memory and depression symptoms. CONCLUSIONS: Our results indicate that global rumination partly mediates the relationship between overgeneral autobiographical memory and depressive symptoms in patients with major depressive disorder. Furthermore, the present results suggest that the mediating role of rumination in the relationship between overgeneral autobiographical memory and depression is mainly due to the maladaptive brooding subtype of rumination.

Further evidence supporting the association of NKAPL with schizophrenia.

Schizophrenia (SZ) is a severe chronic mental disorder with complex genetic mechanisms. Increasing evidence implicate immune system dysfunction in the pathogenesis of SZ. The non-synonymous single nucleotide polymorphism (SNP) rs1635 in NKAPL, was identified by a genome-wide association study (GWAS) for SZ in Han Chinese from north China. A replication study failed to detect the association of rs1635 with SZ in Han Chinese from central south of China, while another one confirmed the positive association in Han Chinese from Taiwan. To further clarify these findings, we conducted a case-control association study of rs1635 in a cohort of Han Chinese from east China, including 1406 SZ cases and 1136 healthy controls. We detected a positive association of rs1635 with SZ, with the major allele (G) of rs1635 conferring a risk for SZ (P=0.033, OR=1.14). Our findings add further evidence for the involvement of NKAPL polymorphisms in the development of SZ.