Association between metabolic syndrome components and cardiac autonomic modulation in southern Indian adults with pre-metabolic syndrome: hyperglycemia is the major contributing factor.

Metabolic syndrome (MetS) involves multi-factorial conditions linked to an elevated risk of type 2 diabetes mellitus and cardiovascular disease. Pre-metabolic syndrome (pre-MetS) possesses two MetS components but does not meet the MetS diagnostic criteria. Although cardiac autonomic derangements are evident in MetS, there is little information on their status in pre-MetS subjects. In this study, we sought to examine cardiac autonomic functions in pre-MetS and to determine which MetS component is more responsible for impaired cardiac autonomic functions. A total of 182 subjects were recruited and divided into healthy controls (n=89) and pre-MetS subjects (n=93) based on inclusion and exclusion criteria. We performed biochemical profiles on fasting blood samples to detect pre-MetS. Using standardized protocols, we evaluated anthropometric data, body composition, baroreflex sensitivity (BRS), heart rate variability (HRV), and autonomic function tests (AFTs). We further examined these parameters in pre-MetS subjects for each MetS component. Compared to healthy controls, we observed a significant cardiac autonomic dysfunction (CAD) through reduced BRS, lower overall HRV, and altered AFT parameters in pre-MetS subjects, accompanied by markedly varied anthropometric, clinical and biochemical parameters. Furthermore, all examined BRS, HRV, and AFT parameters exhibited an abnormal trend and significant correlation toward hyperglycemia. This study demonstrates CAD in pre-MetS subjects with reduced BRS, lower overall HRV, and altered AFT parameters. Hyperglycemia was considered an independent determinant of alterations in all the examined BRS, HRV, and AFT parameters. Thus, hyperglycemia may contribute to CAD in pre-MetS subjects before progressing to MetS.

Risperidone Reduces Matrix Metalloproteinase-9 and Increases Neurotrophin-3 in Schizophrenia Spectrum of Disorder.

Even though earlier studies have reported alteration in the markers of synaptic plasticity (Matrix metalloproteinase-9 [MMP-9] and Neurotrophin-3 [NT-3]), there are no reports about the effect of risperidone on the same. The present study was designed to assess the effect of risperidone on NT-3 and MMP-9 levels in patients with schizophrenia spectrum of disorder and to investigate whether these markers can be used to predict the treatment response in these patients. 62 schizophrenia spectrum of disorder patients were enrolled in the study and were treated with 4 mg of risperidone OD. Serum NT-3 and MMP-9 levels were compared at baseline and after 6 weeks following risperidone treatment. Severity of the disease was assessed using Positive and Negative Syndrome Scale (PANSS). MMP-9 was significantly reduced and NT-3 was significantly increased in schizophrenia spectrum of disorder after treatment with risperidone. We also found a significant reduction in MMP-9 levels in the non-responders group. At a cut off of 1225 ng/mL, MMP-9 can predict response to treatment with 64% sensitivity and 62% specificity and at a cut off of 957 pg/mL, NT-3 predicted the response to treatment with 60% sensitivity and 62% specificity. We conclude that risperidone decreases the serum levels of MMP-9 and increases the NT-3 levels in schizophrenia spectrum of disorder. MMP-9 and NT-3 can predict the response to treatment with risperidone.

DNA Methylation as a Biomarker of Treatment Response Variability in Serious Mental Illnesses: A Systematic Review Focused on Bipolar Disorder, Schizophrenia, and Major Depressive Disorder.

So far, genetic studies of treatment response in schizophrenia, bipolar disorder, and major depression have returned results with limited clinical utility. A gene × environment interplay has been proposed as a factor influencing not only pathophysiology but also the treatment response. Therefore, epigenetics has emerged as a major field of research to study the treatment of these three disorders. Among the epigenetic marks that can modify gene expression, DNA methylation is the best studied. We performed a systematic search (PubMed) following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines for preclinical and clinical studies focused on genome-wide and gene-specific DNA methylation in the context of schizophrenia, bipolar disorders, and major depressive disorder. Out of the 112 studies initially identified, we selected 31 studies among them, with an emphasis on responses to the gold standard treatments in each disorder. Modulations of DNA methylation levels at specific CpG sites have been documented for all classes of treatments (antipsychotics, mood stabilizers, and antidepressants). The heterogeneity of the models and methodologies used complicate the interpretation of results. Although few studies in each disorder have assessed the potential of DNA methylation as biomarkers of treatment response, data support this hypothesis for antipsychotics, mood stabilizers and antidepressants.

Correlation among Poincare plot and traditional heart rate variability indices in adults with different risk levels of metabolic syndrome: a cross-sectional approach from Southern India.

OBJECTIVES: Heart rate variability (HRV) is an important marker of cardiac autonomic modulation. Metabolic syndrome (MetS) can alter cardiac autonomic modulation, raising the risk of cardiovascular disease (CVD). Poincaré plot analysis (PPA) is a robust scatter plot-based depiction of HRV and carries similar information to the traditional HRV measures. However, no prior studies have examined the relationship between PPA and traditional HRV measures among different risk levels of MetS. We evaluated the association between the Poincare plot and traditional heart rate variability indices among adults with different risk levels of MetS. METHODS: We measured anthropometric data and collected fasting blood samples to diagnose MetS. The MetS risk was assessed in 223 participants based on the number of MetS components and was classified as control (n=64), pre-MetS (n=49), MetS (n=56), and severe MetS (n=54). We calculated the Poincaré plot (PP) and traditional HRV measures from a 5 min HRV recording. RESULTS: Besides the traditional HRV measures, we found that various HRV indices of PPA showed significant differences among the groups. The severe MetS group had significantly lower S (total HRV), SD1 (short-term HRV), SD2 (long-term HRV), and higher SD2/SD1. The values of S, SD1, SD2, and SD2/SD1 were significantly correlated with most traditional HRV measures. CONCLUSIONS: We found gradual changes in HRV patterns as lower parasympathetic and higher sympathetic activity alongside the rising number of MetS components. The HRV indices of PPA integrating the benefits of traditional HRV indices distinguish successfully between different risk levels of MetS and control subjects.

Matrixmetalloproteinase-9 gene polymorphism (rs 17576) increases the risk of depressive symptoms in bipolar disorder.

Objectives: Plasticity of neural synapses is known to be involved in the complications in bipolar disorder (BD) patients. Matrix metalloproteinases (MMPs) play a role in synaptic plasticity and memory. Even though elevated MMP-9 levels are reported in neuropsychiatric disorders, there is limited data about MMP-9 gene polymorphism in BD. The objectives of the study was to investigate genotype frequency and allele frequency of MMP-9 genetic variant (rs 17576) in BD and its association with disease severity. Materials and Methods: Eighty BD cases and 80 controls were recruited in the study. MMP-9 genotyping and allele frequency and plasma MMP-9 levels were analyzed in both the groups. Hamilton depression rating scale and Young's Mania Rating Scale (YMRS) were used to evaluate severity of BD. Results: The genotype and minor allele (G allele) frequency were not significant between BD and controls. MMP-9 levels were significantly increased in BD patients with AG (P < 0.001) and GG (P = 0.022) genotypes compared to controls. BD patients with GG genotype (P = 0.038, OR: 3.26 (1.16-9.09), and G (mutant) allele (P = 0.013, OR 2.03(1.18-3.48) confer increased risk of depressive symptoms. MMP-9 was positively correlated with YMRS scale (r = 0.227, P = 0.043) in BD. Conclusion: MMP-9 gene polymorphism (rs 17576) is linked with depressive symptoms in BD.