Prevalence, risk factors and clinical correlates of glucose disturbances in a large sample of Han Chinese patients with first-episode drug-naïve major depressive disorder.

Glucose disturbances are a common comorbidity of major depressive disorder (MDD) patients and have been extensively studied in the past. However, few studies have explored glucose disturbances in first-episode drug-naïve (FEDN) MDD patients. The purpose of this study was to examine the prevalence and risk factors of glucose disturbances in FEDN MDD patients to understand the relationship between MDD and glucose disturbances in the acute early phase and provide important implications for therapeutic interventions. Using a cross-sectional design, we recruited a total of 1718 MDD patients. We collected their socio-demographic information, clinical data, and blood glucose indicators.17-item Hamilton Depression Rating Scale (HAMD), 14-item Hamilton Anxiety Rating Scale (HAMA), and the positive symptom subscale of the Positive and Negative Syndrome Scale (PANSS) were used to assess their depression, anxiety, psychotic symptoms, respectively. The prevalence of glucose disturbances in FEDN MDD patients was 13.6%. Depression, anxiety and psychotic symptoms, body mass index (BMI) levels and suicide attempts rates were higher in the group with glucose disorders than in the group without glucose disorders among patients with first-episode drug-naive MDD. Correlation analysis showed that glucose disturbances were associated with HAMD score, HAMA score, BMI, psychotic symptoms and suicide attempts. Furthermore, binary logistic regression showed that HAMD score and suicide attempts were independently associated with glucose disturbances in MDD patients. Our findings suggest that the prevalence of comorbid glucose disturbances is very high in FEDN MDD patients. Moreover, more severe depressive symptoms and higher suicide attempts are correlated with glucose disturbances in MDD FEDN patients in the early stage.

Prevalence and clinical profile of comorbid anxiety in young adult patients with first-episode and drug-naive major depressive disorder.

AIM: Patients with major depressive disorder (MDD) frequently have coexisting anxiety disorders. However, few studies have focused on the prevalence and risk factors of comorbid anxiety symptoms in young adult first-episode and drug-naive (FEDN) MDD patients. METHODS: We recruited 520 FEDN MDD patients and collected their demographic and clinical data. The Hamilton Depression Rating Scale (HAMD), the Hamilton Anxiety Rating Scale (HAMA) and the positive scale of the Positive and Negative Syndrome Scale (PANSS) were used to measure depressive symptoms, anxiety symptoms and psychotic symptoms, respectively. RESULTS: Anxiety symptoms were found in 79.6% of young adult patients. Besides, anxiety group patients had a higher prevalence of psychotic symptoms than the non-anxiety group. Anxiety symptoms were substantially related to suicide attempts in young adult patients. Logistic analysis shows that suicide attempts and total HAMD scores were significantly associated with anxiety symptoms. CONCLUSIONS: The findings show that anxiety symptoms are common in Chinese young adult MDD patients. The anxiety group was more likely to have psychotic symptoms, suicide attempts, and more severe depressive symptoms than the non-anxiety group. Suicide attempts were associated with anxiety symptoms in young adult MDD patients, suggesting the importance of reducing anxiety symptoms in this population to prevent suicides.

Prevalence and clinical correlates of abnormal glucose metabolism in young, first- episode and medication-naïve outpatients with major depressive disorder.

BACKGROUNDS: The high co-morbidity of abnormal glucose metabolism in depressed patients has been extensively studied, but few studies have explored abnormal glucose metabolism in young patients with major depressive disorder (MDD). This study aimed to examine the prevalence and clinical correlates of abnormal glucose metabolism in young patients with first-episode medication-naïve (FEMN) MDD. METHODS: A cross-sectional study was conducted on 1289 young Chinese outpatients with FEMN MDD. All subjects were assessed on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale (HAMA), Positive and Negative Syndrome Scale, and their sociodemographic information was collected, and blood pressure, blood glucose, lipid and thyroid hormone levels were measured. RESULTS: The prevalence of abnormal glucose metabolism was 12.57% in young FEMN MDD outpatients. Thyroid stimulating hormone (TSH) levels and HAMA scale scores were associated with fasting blood glucose levels in patients with FEMN MDD (P<0.05), and TSH could differentiate patients with abnormal normal glucose metabolism from those without abnormal glucose metabolism (Area Under Curve of 0.774). CONCLUSIONS: Our study showed a high prevalence of comorbid glucose metabolism abnormalities in young FEMN MDD outpatients. TSH may be a promising biomarker of abnormal glucose metabolism in young patients with FEMN MDD.

Association between thyroid dysfunction, metabolic disturbances, and clinical symptoms in first-episode, untreated Chinese patients with major depressive disorder: Undirected and Bayesian network analyses.

Aims: Thyroid dysfunction and metabolic disturbances are common in major depressive disorder (MDD) patients. We aimed to assess the relationship between thyroid dysfunction, metabolic disturbances, and clinical symptoms in Chinese first-episode, drug-naïve (FEDN) MDD patients using undirected and Bayesian network methods. Methods: 1718 FEDN MDD patients were recruited. Serum levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroglobulin (TgAb), thyroid peroxidases antibody (TPOAb), total cholesterol (TC), total triglycerides (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), and glucose were assessed. Blood pressure and body mass index were measured. Hamilton Rating Scale for Depression (HAMD), Hamilton Rating Scale for Anxiety, and positive subscale of Positive And Negative Syndrome Scales were used to detect clinical symptoms. An undirected network with EBICglasso default and a directed acyclic graph (DAG) using the Bayesian network approach was conducted. Results: The prevalence rates of clinical symptoms, thyroid dysfunction, and metabolic dysfunction were as follows: anxiety (n=894, 52%), psychotic symptoms (171, 10%), subclinical hypothyroidism (SCH, n=1041, 61%), abnormal TgAb (n=297, 17%), abnormal TPOAb (n=438, 25%), hyperthyroidism (n=5, 0.3%), hypothyroidism (n=3, 0.2%), hyperglycemia (n=241, 14%), hypertriglyceridemia (n=668, 39%), low HDL-C (n=429, 25%), hypercholesterolemia (421, 25%), abnormal TC (357, 21%), abnormal LDL-C (185, 11%). overweight or obesity (n=1026, 60%), and hypertension (n=92, 5.4%). Both networks demonstrated serum TSH and TC levels and the severity of depression played an important role in the pathophysiology of MDD. Conclusions: MDD patients may have thyroid and metabolic dysfunction in the early stage. Targeting hypercholesterolemia, depressive symptoms, and SCH in MDD patients may hold promise in reducing clinical symptoms, metabolic disturbances, and thyroid dysfunction.

Gender differences in prevalence and clinical correlates of anxiety symptoms in first-episode and drug-naïve patients with major depressive disorder.

AIM: Gender differences in major depressive disorder (MDD) are commonly reported; however, gender differences in first-episode and drug-naïve (FEDN) patients with major depressive disorder remain unclear. This study aimed to examine potential gender differences in the prevalence and clinical correlates of comorbid anxiety in FEDN patients with MDD. METHODS: A cross-sectional study was conducted with1718 FEDN patients with MDD. Patients' demographic and clinical data were collected and analyzed using standardized clinical evaluation forms. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Positive and Negative Syndrome Scale (PANSS) were used to evaluate depression, anxiety and psychotic symptoms, respectively. RESULTS: There were no gender-based differences in the comorbidity rates of MDD and anxiety disorders (male: 10.2% vs. female:12.7%, P = 0.123). The prevalence of MDD with severe anxiety symptoms in male patients was similar to that of female patients (80.8%vs. 80.1%, P = 0.749). Male MDD patients were younger, had earlier age of onset, and were less likely to be married. In both the male and female groups, HAMD scores, HAMA scores, suicide attempts, and psychotic symptoms in patients with severe anxiety symptoms were higher than those patients without severe anxiety symptoms (all p ≤ 0.001). Furthermore, binary logistic regression analysis showed that psychotic symptoms and suicide attempts significantly predicted severe anxiety symptoms in both male and female patients with MDD, while body mass index(BMI)significantly predicted severe anxiety symptoms in MDD females only. CONCLUSION: Our study showed that there were no gender differences in the prevalence of comorbid anxiety in FEDN patients with MDD. Suicide attempts and psychiatric symptoms were associated with severe anxiety symptoms in both men and women with MDD, whereas BMI was only correlated with severe anxiety symptoms in women.

The relationship between overweight and thyroid function in first-episode, untreated Chinese patients with major depressive disorder with different ages of onset.

BACKGROUND: Major depressive disorder (MDD) and obesity are common. There are many differences in many aspects of MDD patients at different ages of onset (AOO); however, there are currently no studies on differences in obesity or overweight. This study aims to evaluate whether thyroid function changes with body weight, and to explore the related factors of overweight in MDD patients with different AOOs. METHODS: A total of 1716 first-episode, untreated Chinese Han outpatients with MDD were recruited from a general hospital. Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and Positive Symptom subscale of the Positive and Negative Syndrome Scale (PANSS) were used to evaluate anxiety, depression and psychotic symptoms, respectively. The participants were divided into two groups: early adulthood onset (EAO, <45 years old) and mid-adulthood onset (MAO, >=45 years old). RESULTS: Compared with EAO patients, MAO patients scored higher on the HAMD, HAMA, CGI-S and PANSS positive symptoms subscale, and they also had higher systolic and diastolic blood pressure (BP), higher serum levels of thyroid stimulating hormone (TSH), FBG, cholesterol (TC) and low-density lipoprotein, but they had lower serum levels of free triiodothyronine 3 and high-density lipoprotein. TSH, anti-thyroglobulin (TgAb), TC and systolic BP were correlated with overweight in MAO patients, while TSH and FBG were correlated with overweight of EAO patients. CONCLUSIONS: The results indicate that TSH is related to overweight in both AOO subgroups, and the influencing factors of overweight related to thyroid function may be different in different AOOs.

Sex difference in association of symptoms and white matter deficits in first-episode and drug-naive schizophrenia.

Accumulating evidence shows that disruption of white matter (WM) may be involved in the pathophysiology of schizophrenia, even at the onset of psychosis. However, very few studies have explored sex difference in its association with psychopathology in schizophrenia. This study aims to compare sex differences in clinical features and WM abnormalities in first-episode and drug-naive (FEDN) schizophrenia among Han Chinese inpatients. The WM fractional anisotropy (FA) values of the whole-brain were determined using voxel-based diffusion tensor imaging (DTI) in 39 (16 males and 23 females) FEDN patients with schizophrenia and 30 healthy controls (13 males and 17 females) matched for gender, age, and education. Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS).Our results showed that compared with the controls, the patients showed widespread areas of lower FA, including corpus callosum, brainstem, internal capsule, cingulate, and cerebellum (all adjusted p < 0.01). Further, male patients showed lower FA values in left cingulate (F = 4.92, p = 0.033), but higher scores on the PANSS total, positive, and general psychopathology subscale scores (all p < 0.01) than female patients. Multivariate regression analysis showed that for male patients, FA values in right corpus callosum were positively associated with the PANSS total (beta = 0.785, t = 3.76, p = 0.002) and the negative symptom scores (beta = 0.494, t = 2.20, p = 0.044), while for female patients, FA values in left cingulate were negatively associated with the PANSS positive symptom score (beta = -0.717, t = -2.25, p = 0.041). Our findings indicate sex difference in white matter disconnectivity and its association with psychopathological symptoms in an early course of schizophrenia onset.

Protein kinase C signaling pathway involvement in cardioprotection during isoflurane pretreatment.

The well­known cardioprotective effect of isoflurane, a type of volatile anesthetic, against myocardial ischemia/reperfusion (I/R) injury has become an important focus in cardiovascular research. During reperfusion numerous oxidants, such as H2O2, are produced. Aldehyde dehydrogenase 2 (ALDH2) is a protective factor in myocardial I/R, and once phosphorylated and activated ALDH2 may confer cardioprotection. The present study investigated whether cardioprotection by isoflurane depends on the activation of ALDH2 and aimed to determine how protein kinase C (PKC)δ is involved in isoflurane­induced cardioprotection. Anaesthetized rats were used to produce I/R injury models by imposing 40 min of coronary artery occlusion followed by 120 min of reperfusion. The animals were assigned randomly to the following groups: Untreated controls, and isoflurane preconditioning with and without the PKCδ inhibitor. I/R injury was estimated by the activity of lactate dehydrogenase (LDH) and creatine kinase­MB (CK­MB). Isoflurane pretreatment was observed to attenuate the release of LDH and CK­MB, and enhance the phosphorylation of ALDH2. Activation of ALDH2 and cardioprotection induced by isoflurane preconditioning were enhanced by a PKCδ inhibitor. The results suggest that the activation of ALDH2 by the inhibition of the mitochondrial translocation of PKCδ is important in the protection of the myocardium from I/R injury, and that the effect of PKCδ on isoflurane preconditioning is directly opposed to that of PKCε. PKCε activation was involved in isoflurane pretreatment, which consequently activated downstream signaling pathways and aided cardioprotection. Isoflurane pretreatment also led to attenuated mitochondrial translocation of PKCδ.

Isoflurane preconditioning confers cardioprotection by activation of ALDH2.

The volatile anesthetic, isoflurane, protects the heart from ischemia/reperfusion (I/R) injury. Aldehyde dehydrogenase 2 (ALDH2) is thought to be an endogenous mechanism against ischemia-reperfusion injury possibly through detoxification of toxic aldehydes. We investigated whether cardioprotection by isoflurane depends on activation of ALDH2.Anesthetized rats underwent 40 min of coronary artery occlusion followed by 120 min of reperfusion and were randomly assigned to the following groups: untreated controls, isoflurane preconditioning with and without an ALDH2 inhibitor, the direct activator of ALDH2 or a protein kinase C (PKCε) inhibitor. Pretreatment with isoflurane prior to ischemia reduced LDH and CK-MB levels and infarct size, while it increased phosphorylation of ALDH2, which could be blocked by the ALDH2 inhibitor, cyanamide. Isolated neonatal cardiomyocytes were treated with hypoxia followed by reoxygenation. Hypoxia/reoxygenation (H/R) increased cardiomyocyte apoptosis and injury which were attenuated by isoflurane and forced the activation of ALDH2. In contrast, the effect of isoflurane-induced protection was almost abolished by knockdown of ALDH2. Activation of ALDH2 and cardioprotection by isoflurane were substantially blocked by the PKCε inhibitor. Activation of ALDH2 by mitochondrial PKCε plays an important role in the cardioprotection of isoflurane in myocardium I/R injury.

Mechanisms of cardioprotection by isoflurane against I/R injury.

Myocardial infarction is responsible for most cardiovascular mortality as well as the pathogenesis of myocardial damage during and after infarction. Efforts are underway to modulate the development of ischemia-reperfusion (I-R) injury. Recently, the protective effect of isoflurane against myocardial I-R injury emerged as a possibility. Nitric oxide, nitric oxide synthases, factors related to energy metabolism, adenosine triphosphate-sensitive potassium channels, phosphatidylinositol-3-kinase and hypoxia-inducible factor1-alpha have been shown to participate in the mechanisms of cardioprotection elicited by isoflurane against I-R injury. In this review, we focus on the mechanisms of cardioprotection offered by isoflurane against I-R injury.

[Association study between Protein Kinase C gamma gene polymorphism and major depressive disorder].

OBJECTIVE: To explore the genetic association of PKCgamma gene rs3745406 polymorphism with major depressive disorder (MDD) and their clinical phenotypes. METHODS: A total of 453 Chinese Han MDD patients with an initial episode were recruited from our hospital. The symptomatic phenotypes of these cases were evaluated by HAMD. Polymerase chain reaction (PCR) and direct sequencing analysis were used to detect the genotype of rs3745406. Associations of allele, genotype and quantitative character were analyzed using the UNPHASED software. RESULTS: (1) The distributions of genotypes in both study and control samples were in a Hardy-Weinberg equilibrium (chi(2) = 1.46, P = 0.25); (2) No significant allelic and genotypic association was found in these samples (P > 0.05); (3) Further analyses revealed a significant association between rs3745406 locus and HAMD suicidal phenotypes (chi(2) = 4.746, P = 0.0360). CONCLUSION: The PKCgamma rs3745406 polymorphism is not significantly associated with MDD whereas it has a marked association with suicidal symptoms in MDD.

Association between the serotonin 1A receptor C(-1019)G polymorphism and major depressive disorder in the northern Han ethnic group in China.

BACKGROUND: Recent studies have suggested that susceptibility to major depressive disorder (MDD) might be related to the serotonin 1A receptor (5-HTR1A) C (-1019) G polymorphism. In this study, we aimed to assess the association between 5-HTR1A C (-1019) G polymorphism and MDD in the Northern Han ethnic group of China. METHODS: The C (-1019) G of 5-HTR1A was detected with polymerase chain reaction (PCR) in 400 patients with MDD and 400 unrelated age- and sex-matched healthy control subjects. Association between the C (-1019) G and MDD was statistically analyzed. RESULTS: There was a statistically significant difference between MDD patients and controls in both the genotype distribution (Chi(2) = 10.913, df = 2, P = 0.004) and the allele frequency (Chi(2) = 10.379, df = 1, P = 0.001), and a significant difference in the genotype distribution and the allele frequency was found both in the female subjects (Genotype distribution: Chi(2) = 15.406, df = 2, P = 0.000; allele frequency: Chi(2) = 15.552, df = 1, P = 0.000) and the late-onset subjects (Genotype distribution: Chi(2) = 7.771, df = 2, P = 0.021; allele frequency: Chi(2) = 8.007, df = 1, P = 0.005) in the two groups. CONCLUSION: These results suggest that 5-HTR1A C (-1019) G polymorphism is probably associated with MDD and it is likely to be the susceptible gene locus for the female and late-onset MDD.