NMR-Based Analysis of Plasma Lipoprotein Subclass and Lipid Composition Demonstrate the Different Dietary Effects in ApoE-Deficient Mice.

Plasma lipid levels are commonly measured using traditional methods such as triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and cholesterol (CH). However, the use of newer technologies, such as nuclear magnetic resonance (NMR) with post-analysis platforms, has made it easier to assess lipoprotein profiles in research. In this study involving ApoE-deficient mice that were fed high-fat diets, significant changes were observed in TG, CH, free cholesterol (FC), and phospholipid (PL) levels within the LDL fraction. The varied proportions of TG in wild-type mice and CH, FC, and PL in ApoE-/- mice were strikingly different in very low-density lipoproteins (VLDL), LDL, intermediate-density lipoprotein (IDL), and HDL. This comprehensive analysis expands our understanding of lipoprotein subfractions and the impacts of the APOE protein and high-fat diet in mouse models. The new testing method allows for a complete assessment of plasma lipids and their correlation with genetic background and diet in mice.

Malonyl-CoA Accumulation as a Compensatory Cytoprotective Mechanism in Cardiac Cells in Response to 7-Ketocholesterol-Induced Growth Retardation.

The major oxidized product of cholesterol, 7-Ketocholesterol (7KCh), causes cellular oxidative damage. In the present study, we investigated the physiological responses of cardiomyocytes to 7KCh. A 7KCh treatment inhibited the growth of cardiac cells and their mitochondrial oxygen consumption. It was accompanied by a compensatory increase in mitochondrial mass and adaptive metabolic remodeling. The application of [U-13C] glucose labeling revealed an increased production of malonyl-CoA but a decreased formation of hydroxymethylglutaryl-coenzyme A (HMG-CoA) in the 7KCh-treated cells. The flux of the tricarboxylic acid (TCA) cycle decreased, while that of anaplerotic reaction increased, suggesting a net conversion of pyruvate to malonyl-CoA. The accumulation of malonyl-CoA inhibited the carnitine palmitoyltransferase-1 (CPT-1) activity, probably accounting for the 7-KCh-induced suppression of ß-oxidation. We further examined the physiological roles of malonyl-CoA accumulation. Treatment with the inhibitor of malonyl-CoA decarboxylase, which increased the intracellular malonyl-CoA level, mitigated the growth inhibitory effect of 7KCh, whereas the treatment with the inhibitor of acetyl-CoA carboxylase, which reduced malonyl-CoA content, aggravated such a growth inhibitory effect. Knockout of malonyl-CoA decarboxylase gene (Mlycd-/-) alleviated the growth inhibitory effect of 7KCh. It was accompanied by improvement of the mitochondrial functions. These findings suggest that the formation of malonyl-CoA may represent a compensatory cytoprotective mechanism to sustain the growth of 7KCh-treated cells.

7-Ketocholesterol Induces Lipid Metabolic Reprogramming and Enhances Cholesterol Ester Accumulation in Cardiac Cells.

7-Ketocholesterol (7KCh) is a major oxidized cholesterol product abundant in lipoprotein deposits and atherosclerotic plaques. Our previous study has shown that 7KCh accumulates in erythrocytes of heart failure patients, and further investigation centered on how 7KCh may affect metabolism in cardiomyocytes. We applied metabolomics to study the metabolic changes in cardiac cell line HL-1 after treatment with 7KCh. Mevalonic acid (MVA) pathway-derived metabolites, such as farnesyl-pyrophosphate and geranylgeranyl-pyrophosphate, phospholipids, and triacylglycerols levels significantly declined, while the levels of lysophospholipids, such as lysophosphatidylcholines (lysoPCs) and lysophosphatidylethanolamines (lysoPEs), considerably increased in 7KCh-treated cells. Furthermore, the cholesterol content showed no significant change, but the production of cholesteryl esters was enhanced in the treated cells. To explore the possible mechanisms, we applied mRNA-sequencing (mRNA-seq) to study genes differentially expressed in 7KCh-treated cells. The transcriptomic analysis revealed that genes involved in lipid metabolic processes, including MVA biosynthesis and cholesterol transport and esterification, were differentially expressed in treated cells. Integrated analysis of both metabolomic and transcriptomic data suggests that 7KCh induces cholesteryl ester accumulation and reprogramming of lipid metabolism through altered transcription of such genes as sterol O-acyltransferase- and phospholipase A2-encoding genes. The 7KCh-induced reprogramming of lipid metabolism in cardiac cells may be implicated in the pathogenesis of cardiovascular diseases.

Association between gastrointestinal symptoms and depression among older adults in Taiwan: A cross-sectional study.

BACKGROUND: Older adults with depression more frequently experience somatic and gastrointestinal (GI) problems compared with people without depression and younger adults with depression. However, whether GI symptoms are predictive of elevated rates of depression among older adults is unclear. METHODS: We enrolled 106 older adults (>60 years old); 69 had late-life depression (LLD), and 37 were controls. All participants gave ratings on the Gastrointestinal Symptom Rating Scale (GSRS) and Hamilton Depression Rating Scale. Food consumption was assessed using a food frequency questionnaire, and a Mediterranean diet score was used as a covariate. RESULTS: Compared with the controls, patients with LLD reported higher levels of depressive and GI symptoms and reported more reflux, abdominal pain, and dyspepsia symptoms, and these symptoms were correlated with Hamilton Depression Rating Scale scores (GSRS total: ß = 0.47; reflux: ß = 1.47; abdominal pain: ß = 1.98; dyspepsia: ß = 1.02; all p < 0.01). After demographic variables and Mediterranean diet score were controlled for, a logistic regression analysis indicated that total GSRS score was an independent determinant of LLD (odds ratio: 1.20, 95% CI: 1.04-1.38). Moreover, a stratified analysis by depression severity indicated that higher total GSRS score may contribute to greater depression severity (odds ratio: 1.25, 95% CI: 1.04-1.52). CONCLUSION: We provide evidence that GI symptoms are associated with depressive symptoms among patients with LLD. Older people with more specific GI symptoms, such as reflux, abdominal pain, and dyspepsia, are potentially at greater risk of having LLD.

Risk Score for Predicting Mortality in People With Dementia: A Nationwide, Population-Based Cohort Study in Taiwan With 11 Years of Follow-Up.

OBJECTIVE: Many researchers and physicians attempt to determine the prognosis and short- and long-term mortality risks of dementia for formulating suitable care plans for patients and their families. However, the published prediction models have been insufficient for this purpose and have worked only in certain specific populations. For medical autonomy and end-of-life decisions, an informative tool to predict 6-month, 1-year, 2-year, 3-year, and 5-year mortality rates for dementia patients merits further investigation. METHODS: Patients aged ≥ 65 years who received ICD-9-CM diagnoses of dementia between 2002 and 2009 were identified from Taiwan's National Health Insurance Research Database and followed until the end of 2013. Patient characteristics and comorbidities that were considered potential risk factors for mortality were assessed. Mortality-predicting risk scores were developed using a regression coefficient-based scoring approach. In total, 6,556 patients were identified and then randomly divided into a derivation cohort (n = 4,371) and validation cohort (n = 2,185). RESULTS: By the end of the study, 1,693 of the 4,371 dementia patients (38.7%) in the derivation cohort were deceased. Mean duration of follow-up was 6.26 years. Eleven acute and chronic factors were identified for building the predictive score model, which produced scores from 0 to 24 points (higher scores indicated higher mortality). The score model exhibited good predictive power for various life expectancies (area under receiver operating characteristic curve: 6-month = 0.852, 1-year = 0.779, 2-year = 0.725, 3-year = 0.721, 5-year = 0.703) and good calibration in the validation cohort (Hosmer-Lemeshow test, χ² = 4.709, P = .788). CONCLUSIONS: The developed predictive score model may be the first tool that uses the same clinical factors to determine both short- and long-term mortality risks in patients with dementia.

A Novel Murine Model Expressing a Chimeric mSCARB2/hSCARB2 Receptor Is Highly Susceptible to Oral Infection with Clinical Isolates of Enterovirus 71.

Enterovirus 71 (EV71) infection is generally associated with hand-foot-and-mouth disease (HFMD) and may cause severe neurological disorders and even death. An effective murine oral infection model for studying the pathogenesis of various clinical EV71 isolates is lacking. We developed a transgenic (Tg) mouse that expresses an EV71 receptor, that is, human scavenger receptor class B member 2 (hSCARB2), in a pattern highly similar to that of endogenous murine SCARB2 (mSCARB2) protein. A FLAG-tagged SCARB2 cDNA fragment composed of exons 3 to 12 was inserted into a murine Scarb2 gene-containing bacterial artificial chromosome (BAC) clone, and the resulting transgene was used for establishment of chimeric receptor-expressing Tg mice. Tg mice intragastrically (i.g.) infected with clinical isolates of EV71 showed neurological symptoms, such as ataxia and paralysis, and fatality. There was an age-dependent decrease in susceptibility to viral infection. Pathological characteristics of the infected Tg mice resembled those of encephalomyelitis in human patients. Viral infection was accompanied by microglial activation. Clodronate treatment of the brain slices from Tg mice enhanced viral replication, while lipopolysaccharide treatment significantly inhibited it, suggesting an antiviral role for microglia during EV71 infection. Taken together, this Tg mouse provides a model that closely mimics natural infection for studying EV71 pathogenesis and for evaluating the efficacy of vaccines or other antiviral drugs.IMPORTANCE The availability of a murine model of EV71 infection is beneficial for the understanding of pathogenic mechanisms and the development and assessment of vaccines and antiviral drugs. However, the lack of a murine oral infection model thwarted the study of pathogenesis induced by clinically relevant EV71 strains that are transmitted via the oral-oral or oral-fecal route. Our Tg mice could be intragastrically infected with clinically relevant EV71 strains in an efficient way and developed neurological symptoms and pathological changes strikingly resembling those of human infection. Moreover, these mice showed an age-dependent change in susceptibility that is similar to the human case. This Tg mouse, when combined with the use of other genetically modified mice, potentially contributes to studying the relationship between developmental changes in immunity and susceptibility to virus.

Association of Polypharmacy With Mild Cognitive Impairment and Cognitive Ability: A Nationwide Survey in Taiwan.

BACKGROUND: Polypharmacy, defined as the concomitant use of 5 or more medications, has a documented negative association with cognitive impairment such as delirium and is associated, potentially, with a higher risk of dementia. However, whether polypharmacy contributes to increased risk of mild cognitive impairment (MCI) or decreased cognitive capacity requires further investigation. This nationwide population survey investigated the association among polypharmacy, MCI, and dementia. METHODS: Through random sampling based on the proportion of all Taiwan counties, subjects were recruited and received in-person interviews between December 2011 and March 2013. Demographic data and clinical information included medical histories, medication use, and mental status measured by the Taiwanese Mini-Mental State Examination (TMSE) and Clinical Dementia Rating (CDR). Data on lifestyle and habits were collected, and subjects were distributed to cognitively normal, MCI, or all-cause dementia groups based on criteria by the National Institute on Aging and the Alzheimer's Association. RESULTS: A total of 7,422 people aged 65 years or older were recruited. After adjustment for age, sex, body mass index, education, medical comorbidities, and lifestyle and habits, polypharmacy was associated with a 1.75-fold increased odds of MCI and 2.33-fold increased odds of dementia. Polypharmacy was associated with a 0.51-point decrease in TMSE scores (P = .001) and a 0.10-point increase in CDR score (P < .001). Additionally, for those without specific vascular comorbidities, polypharmacy had a greatly more negative impact on cognitive capacity. CONCLUSIONS: Polypharmacy is common in the elderly and is associated with significantly lower cognitive capacity and higher risks of MCI and dementia, especially for persons without diabetes, hypertension, hyperlipidemia, or cerebrovascular diseases.

Anti-enterovirus 71 activities of Melissa officinalis extract and its biologically active constituent rosmarinic acid.

Enterovirus 71 (EV71) infection is endemic in the Asia-Pacific region. No specific antiviral drug has been available to treat EV71 infection. Melissa officinalis (MO) is a medicinal plant with long history of usage in the European and Middle East. We investigated whether an aqueous solution of concentrated methanolic extract (MOM) possesses antiviral activity. MOM inhibited plaque formation, cytopathic effect, and viral protein synthesis in EV71-infected cells. Using spectral techniques, we identified rosmarinic acid (RA) as a biologically active constituent of MOM. RA reduced viral attachment and entry; cleavage of eukaryotic translation initiation factor 4 G (eIF4G); reactive oxygen species (ROS) generation; and translocation of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) from nucleus to cytoplasm. It alleviated EV71-induced hyperphosphorylation of p38 kinase and EPS15. RA is likely to suppress ROS-mediated p38 kinase activation, and such downstream molecular events as hnRNP A1 translocation and EPS15-regulated membrane trafficking in EV71-infected cells. These findings suggest that MO and its constituent RA possess anti-EV71 activities, and may serve as a candidate drug for therapeutic and prophylactic uses against EV71 infection.

The ADAMTS9 gene is associated with cognitive aging in the elderly in a Taiwanese population.

Evidence indicates that the pathophysiologic mechanisms associated with insulin resistance may contribute to cognitive aging and Alzheimer's diseases. In this study, we hypothesize that single nucleotide polymorphisms (SNPs) within insulin resistance-associated genes, such as the ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9), glucokinase regulator (GCKR), and peroxisome proliferator activated receptor gamma (PPARG) genes, may be linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. A total of 547 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examinations (MMSE) were administered to all subjects, and MMSE scores were used to measure cognitive functions. Our data showed that four SNPs (rs73832338, rs9985304, rs4317088, and rs9831846) in the ADAMTS9 gene were significantly associated with cognitive aging among the subjects (P = 1.5 x 10-6 ~ 0.0002). This association remained significant after performing Bonferroni correction. Additionally, we found that interactions between the ADAMTS9 rs9985304 and ADAMTS9 rs76346246 SNPs influenced cognitive aging (P < 0.001). However, variants in the GCKR and PPARG genes had no association with cognitive aging in our study. Our study indicates that the ADAMTS9 gene may contribute to susceptibility to cognitive aging independently as well as through SNP-SNP interactions.

The rs1277306 Variant of the REST Gene Confers Susceptibility to Cognitive Aging in an Elderly Taiwanese Population.

BACKGROUND/AIMS: There is growing evidence that the RE1-silencing transcription factor (REST) gene may contribute to cognitive aging and Alzheimer diseases. In this replication study, we reassessed whether single nucleotide polymorphisms (SNPs) within the REST gene are linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. METHODS: A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examination (MMSE) scores were performed for all subjects to weigh cognitive functions. RESULTS: Our data showed that the REST rs1277306 SNP was significantly associated with cognitive aging among all subjects (p = 0.0052). Furthermore, the association remained significant for individuals without APOE ε4 allele (p = 0.0092), but not for individuals with at least 1 APOE ε4 allele. This association remained significant after Bonferroni correction. Additionally, we found the interactions between the rs1713985 and rs1277306 SNPs on cognitive aging (p = 0.016). However, the 3-marker haplotype derived from the rs1713985, rs3796529, and rs7680734 SNPs in the REST gene demonstrated no association with cognitive aging. CONCLUSION: Our study indicates that the REST gene may contribute to susceptibility to cognitive aging independently as well as through SNP-SNP and APOE-REST interactions.

In-vivo evaluation of the permeability of the blood-brain barrier to arsenicals, molybdate, and methylmercury by use of online microdialysis-packed minicolumn-inductively coupled plasma mass spectrometry.

To study the permeability of the blood-brain barrier (BBB) to arsenates, arsenite, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), molybdate, and methylmercury, and the transfer behavior of these species, we constructed an automatic online analytical system comprising a microdialysis sampling device, a minicolumn packed with nonfunctionalized poly(vinyl chloride) beads, and an inductively coupled plasma mass spectrometer for continuous in-vivo measurement of their dynamic variation in the extracellular space of the brains of living rats. By using ion-polymer interactions as a novel working mechanism for sample pretreatment of volume-limited microdialysate, we simplified the operating procedure of conventional solid-phase extraction and reduced the contribution to the blank of the chemicals used. After optimizing this hyphenated system, we measured its performance by analysis of NIST standard reference materials 1640a (trace elements in natural water) and 2672a (trace elements in human urine) and by in-vivo monitoring of the dynamic variation of the compounds tested in the extracellular fluid (ECF) of rat brain. We found that intraperitoneal administration led to observable BBB permeability of arsenates, arsenite, DMA, MMA, and molybdate. Nevertheless, the limited sensitivity of the system and the size of microdialysis samples meant that detection of MeHg in ECF remained problematic, even when we administered a dose of 20 mg MeHg kg(-1) body weight. On the basis of these practical demonstrations, we suggest that our analytical system could be used not only for dynamic monitoring of the transfer kinetics of the four arsenicals and molybdate in the rat brain but also to describe associated neurotoxicity in terms of exposure to toxic metals and their species.

Daytime sleepiness: a risk factor for poor social engagement among the elderly.

BACKGROUND: The aim of this study was to investigate the relationship between social engagement and daytime sleepiness among aged residents of a veterans' housing facility in Taiwan. METHODS: A total of 597 men were enrolled in this cross-sectional study. Each subject was assessed with the Resident Assessment Instrument-Minimum Data Set, Geriatric Depression Scale, Pittsburgh Sleep Quality Index, and Mini-Mental State Examination. Social engagement was measured with the Index of Social Engagement (ISE), and daytime sleepiness was defined according to the relevant Pittsburgh Sleep Quality Index subcomponent. Subjects were divided into two groups according to their ISE levels. A multivariate logistic regression model was used to examine the association between ISE and other variables. RESULTS: The sample's mean age was 80.8 ± 5.0 years (range: 65-99 years). Mean ISE score was 1.5 ± 1.3 (range 0-5), with 52% of participants reporting poor social engagement (ISE = 0-1). Mean Pittsburgh Sleep Quality Index global score was 5.6 ± 3.6 (range: 0-18), and 31% of participants reported daytime sleepiness. The analysis was adjusted for level of depression, cognitive impairment, dependence in activities of daily life, unsettled relationships, and illiteracy. After adjustment, daytime sleepiness was found to be independently associated with subjects' level of social engagement (odds ratio: 2.5; 95% confidence interval: 1.7-3.8; P < 0.001). CONCLUSIONS: Daytime sleepiness and poor social engagement are common among aged residents of a veterans' housing facility. Subjects experiencing daytime sleepiness but not poor general sleep quality were at increased risk of poor social engagement. The clinical care of older residents must focus on improving daytime sleepiness to enhance their social engagement.

Cognitive and neuropsychiatric correlates of EEG dynamic complexity in patients with Alzheimer's disease.

This study assessed the utility of multiscale entropy (MSE), a complexity analysis of biological signals, to identify changes in dynamics of surface electroencephalogram (EEG) in patients with Alzheimer's disease (AD) that was correlated to cognitive and behavioral dysfunction. A total of 108 AD patients were recruited and their digital EEG recordings were analyzed using MSE methods. We investigate the appropriate parameters and time scale factors for MSE calculation from EEG signals. We then assessed the within-subject consistency of MSE measures in different EEG epochs and correlations of MSE measures to cognitive and neuropsychiatric symptoms of AD patients. Increased severity of AD was associated with decreased MSE complexity as measured by short-time scales, and with increased MSE complexity as measured by long-time scales. MSE complexity in EEGs of the temporal and occipitoparietal electrodes correlated significantly with cognitive function. MSE complexity of EEGs in various brain areas was also correlated to subdomains of neuropsychiatric symptoms. MSE analysis revealed abnormal EEG complexity across short- and long-time scales that were correlated to cognitive and neuropsychiatric assessments. The MSE-based EEG complexity analysis may provide a simple and cost-effective method to quantify the severity of cognitive and neuropsychiatric symptoms in AD patients.

Effects of age, sex, index admission, and predominant polarity on the seasonality of acute admissions for bipolar disorder: a population-based study.

Bipolar disorder seasonality has been documented previously, though information on the effect of demographic and clinical variables on seasonal patterns is scant. This study examined effects of age, sex, index admission, and predominant polarity on bipolar disorder seasonality in a nationwide population. An inpatient cohort admitted to hospital exclusively for mental illness was derived from the Taiwan National Health Insurance Research Database for 2002-2007. The authors identified 9619 inpatients with bipolar disorder, who had generated 15 078 acute admission records. An empirical mode decomposition method was used to identify seasonal oscillations in bipolar admission data, and regression and cross-correlation analyses were used to quantify the degree and timing of bipolar admission seasonality. Results for seasonality timing found that manic or mixed episodes peak in spring or summer, and depressive episodes peak in winter. Analysis for degree of seasonality revealed that (1) the polarity of patients' index admission predicted the seasonality of relapse admissions; (2) seasonality was significant in female admissions for depressive episodes and in male admissions for manic episodes; (3) young adults displayed a higher degree of seasonality for acute admissions than middle-aged adults; and (4) patients with predominantly depressive admissions displayed a higher degree of seasonality than patients with predominantly manic admissions. Demographic and clinical variables were found to affect the seasonality of acute admissions for bipolar disorders. These findings highlight the need for research on identification and management of seasonal features in bipolar patients.

Suicide and media reporting: a longitudinal and spatial analysis.

PURPOSE: The impact of media reporting on copycat suicides has been well established in various cases of celebrity suicide. However, knowledge is limited about the spatial and temporal relationship between suicide death and media reporting over a long period of time. This study investigated the association of suicide deaths with suicide news in longitudinal and spatial dimensions. METHODS: All suicides during 2003-2010 (n = 31,364) were included. Suicide news in the study period was retrieved from Google News, and included all available news media in Taiwan. Empirical mode decomposition was used to identify the main intrinsic oscillation, reflecting both major and minor suicide events, and time-dependent intrinsic correlation was used to quantify the temporal correlation between suicide deaths and suicide news. RESULTS: The media reporting of suicide was synchronized with increased suicide deaths during major suicide events such as celebrity death, and slightly lagged behind the suicide deaths for 1 month in other periods without notable celebrity deaths. The means of suicide reported in the media diversely affected the suicide models. Reports of charcoal burning suicide exhibited an exclusive copycat effect on actual charcoal burning deaths, whereas media reports of jumping had a wide association with various suicide models. Media reports of suicide had a higher association with suicide deaths in urban than in rural areas. CONCLUSIONS: This report suggested that a delayed effect of copycat suicide may exist in media reports of minor suicide events. The competitive reporting of minor suicide events must be avoided and addressed by media professionals.

Reduced physiologic complexity is associated with poor sleep in patients with major depression and primary insomnia.

BACKGROUND: Depression is known to be associated with altered cardiovascular variability and increased cardiovascular comorbidity, yet it is unknown whether altered cardiac autonomic function in depression is associated with insomnia, a common symptom comorbid with depression. This study aimed to investigate the long-term diurnal profile of autonomic function as measured by heart rate variability (HRV) in both major depression and primary insomnia patients. METHOD: A total of 52 non-medicated patients with major depression, 47 non-medicated patients with primary insomnia, and 88 matched controls without insomnia were recruited. Each subject was assessed by means of sleep and mood questionnaires and underwent twenty-four-hour ambulatory electrocardiogram monitoring. Standard HRV analysis and a well-validated complexity measure, multiscale entropy, were applied to comprehensively assess the diurnal profiles of autonomic function and physiologic complexity in our study sample. RESULTS: Compared with the controls, the patients with major depression and those with primary insomnia exhibited significant reductions in parasympathetic-related HRV indices, and this association was mainly driven by the presence of poor sleep. Both groups of patients also exhibited significant reductions in physiologic complexity during the sleep period as compared with the healthy controls. Alterations in HRV indices were correlated with perceived sleep questionnaire scores but not with depression scales. CONCLUSIONS: Our findings suggest a pivotal role of sleep disturbance in regulating cardiovascular variability in major depression and primary insomnia patients. These findings could highlight the importance of treating insomnia as an independent disease rather than a symptom.

Sleep state instabilities in major depressive disorder: Detection and quantification with electrocardiogram-based cardiopulmonary coupling analysis.

Sleep disruption is an important aspect of major depressive disorder but lacks an objective and inexpensive means of assessment. We evaluated the utility of electrocardiogram (ECG)-based cardiopulmonary coupling analysis to quantify physiologic sleep stability in patients with major depression. Relative to controls, unmedicated depressed patients had a reduction in high-frequency coupling, an index of stable sleep, an increase in low-frequency coupling, an index of unstable sleep, and an increase in very-low-frequency coupling, an index of wakefulness/REM sleep. The medicated depressed group showed a restoration of stable sleep to a level comparable with that of the control group. ECG-based cardiopulmonary coupling analysis may provide a simple, cost-efficient point-of-care method to quantify sleep quality/stability and to objectively evaluate the severity of insomnia in patients with major depression.

BDNF Val66Met polymorphism alters sympathovagal balance in healthy subjects.

A common polymorphism of the brain-derived neurotrophic factor (BDNF) gene (Val66Met) has been implicated in anxiety, which is associated with lower vagal activity. We hypothesize that the BDNF Val66Met polymorphism may have a modulatory effect on the cardiac sympathovagal balance. A total of 211 healthy Chinese-Han adults (58 male, 153 female, aged 33.3 +/- 10.3 years) were recruited with three BDNF genotypes: Val/Val (47, 22.3%), Val/Met (108, 51.2%), and Met/Met (56, 26.5%). Autonomic function was assessed via an analysis of heart rate variability. Reductions in high-frequency power, an index for parasympathetic activity, and increases in the low-frequency/high-frequency ratio, an index for sympathovagal balance, were found in subjects bearing the Met/Met genotype as compared to the Val/Val group. These results suggest that an altered sympathovagal balance with relatively decreased parasympathetic activity is associated with the Met/Met genotype, suggesting a potential role for the studied BDNF polymorphism in modulating cardiac autonomic functions.