Dose adjustment of paroxetine based on CYP2D6 activity score inferred metabolizer status in Chinese Han patients with depressive or anxiety disorders: a prospective study and cross-ethnic meta-analysis.

BACKGROUND: Understanding the impact of CYP2D6 metabolism on paroxetine, a widely used antidepressant, is essential for precision dosing. METHODS: We conducted an 8-week, multi-center, single-drug, 2-week wash period prospective cohort study in 921 Chinese Han patients with depressive or anxiety disorders (ChiCTR2000038462). We performed CYP2D6 genotyping (single nucleotide variant and copy number variant) to derive the CYP2D6 activity score and evaluated paroxetine treatment outcomes including steady-state concentration, treatment efficacy, and adverse reaction. CYP2D6 metabolizer status was categorized into poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). The influence of CYP2D6 metabolic phenotype on paroxetine treatment outcomes was examined using multiple regression analysis and cross-ethnic meta-analysis. The therapeutic reference range of paroxetine was estimated by receiver operating characteristic (ROC) analyses. FINDINGS: After adjusting for demographic factors, the steady-state concentrations of paroxetine in PMs, IMs, and UMs were 2.50, 1.12, and 0.39 times that of EMs, with PM and UM effects being statistically significant (multiple linear regression, P = 0.03 and P = 0.04). Sex and ethnicity influenced the comparison between IMs and EMs. Moreover, poor efficacy of paroxetine was associated with UM, and a higher risk of developing adverse reactions was associated with lower CYP2D6 activity score. Lastly, cross-ethnic meta-analysis suggested dose adjustments for PMs, IMs, EMs, and UMs in the East Asian population to be 35%, 40%, 143%, and 241% of the manufacturer's recommended dose, and 62%, 68%, 131%, and 159% in the non-East Asian population. INTERPRETATION: Our findings advocate for precision dosing based on the CYP2D6 metabolic phenotype, with sex and ethnicity being crucial considerations in this approach. FUNDING: National Natural Science Foundation of China; Academy of Medical Sciences Research Unit.

Dulaglutide treatment reverses depression-like behavior and hippocampal metabolomic homeostasis in mice exposed to chronic mild stress.

INTRODUCTION: Treatment strategies for depression based on interventions for glucose and lipid metabolism disorders are receiving increasing attention. Investigating the mechanism of their antidepressant effect and exploring new diagnostic and therapeutic biomarkers have attracted increasing attention. Dulaglutide, a long-acting GLP-1 receptor agonist, has been reported to alleviate cognitive deficits and neuronal damage. However, the antidepressant effect of dulaglutide and, especially, the underlying mechanism are still poorly understood. In this study, we aimed to explore the underlying biomarkers of depression and potential modulatory targets of dulaglutide in chronic mild stress (CMS) mice. METHODS: Sixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3 mg/kg dulaglutide group (Low Dula group), and a CMS+0.6 mg/kg dulaglutide group (High Dula group). Numerous behavioral tests, mainly the open field test, forced swimming test, and tail suspension test, were applied to evaluate the potential effect of dulaglutide treatment on anxiety- and depression-like behaviors in mice exposed to chronic stress. Furthermore, a liquid chromatography-tandem mass spectrometry-based metabolomics approach was utilized to investigate the associated mechanisms of dulaglutide treatment. RESULTS: Three weeks of dulaglutide treatment significantly reversed depressive-like but not anxiety-like behaviors in mice exposed to chronic stress for 4 weeks. The results from the metabolomics analysis showed that a total of 20 differentially expressed metabolites were identified between the CON and CMS+Veh groups, and 46 metabolites were selected between the CMS+Veh and High Dula groups in the hippocampus of the mice. Comprehensive analysis indicated that lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism were disrupted in model mice that experienced depression and underwent dulaglutide therapy. CONCLUSION: The antidepressant effects of dulaglutide in a CMS depression model were confirmed. We identified 64 different metabolites and four major pathways associated with metabolic pathophysiological processes. These primary data provide a new perspective for understanding the antidepressant-like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression.

Associations between triglyceride glucose index and depression in middle-aged and elderly adults: A cross-sectional study.

The pathogenesis of depression is unclear, and it responds poorly to treatment. It is thus urgent to identify the pathogenesis of depression and possible therapeutic targets. There may be interactions between insulin resistance (IR) and depression. The purpose of this study was to explore the relationship between depression, triglyceride glucose (TyG) index. The study participants were 198 middle-aged and elderly patients who were admitted to the Hebei General Hospital between January 1, 2021, and August 31, 2022, together with 189 healthy adults as controls. Depression was diagnosed according to ICD-10 diagnostic criteria for depression. IR was assessed by the TyG index. Compared with the control group, patients suffering from depression had higher TyG index (P = .00); There were significant differences in the sex ratio (P = .00), family history (P = .00), body mass index (P = .008), total cholesterol (P = .00), fasting blood glucose (P = .004), high-density lipoprotein (P = .00), and low-density lipoprotein (P = .001) levels between the 2 groups. After excluding other confounding factors, the TyG index was found to be independently associated with depression, with an OR of 2.75. These data support an association of depression with the TyG index. IR thus appears to be a risk factor for depression.

Case report: Anxiety and depression as initial symptoms in a patient with acute hypoxia and patent foramen ovale.

The prevalence of patent foramen ovale (PFO) is 15-35% among adults. The role of right-to-left shunting through the PFO, anxiety, depression, and hypoxemia in the systemic circulation remains poorly understood. Herein, we present the case of a 52-year-old woman with no heart or lung disease, who was admitted due to anxiety for 5 months and had symptom exacerbation with dizziness for 4 days and presented with cyanosis. She was noted to have acute hypoxemia, with an oxygen saturation of 94.48% on room air, and arterial blood gas showed an oxygen tension of 65.64 mmHg. Agitated saline contrast echocardiography showed right-to-left shunting due to PFO. Arteriovenous fistula, pneumonia, pulmonary embolism, pulmonary hypertension, congestion peripheral cyanosis, ischemic peripheral cyanosis, and methemoglobin were excluded. Additionally, the patient improved by taking Paroxetine, Oxazepam, and Olanzapine. Her oxygen tension returned to 90.42 mmHg, and her symptoms resolved. In the case of severe anxiety and depression, right-to-left shunting through the PFO may cause acute systemic hypoxemia via a flow-driven mechanism, occasionally manifesting as cyanosis. When anxiety improved, hypoxia also improved. Thus, the treatment of anxiety and depression seems effective in improving hypoxemia. Notably, this is a rare report, and we hope to draw the attention of psychosomatic specialists, psychiatrists, and clinicians to seek the relationship between anxiety appearing as acute stress and PFO. This may be a new therapeutic method for treating severe anxiety disorder.

Association of triglyceride-glucose index with major depressive disorder: A cross-sectional study.

The triglyceride-glucose (TyG) index has been proposed as a new marker for insulin resistance, which is associated with a risk of major depressive disorder (MDD). This study aims to explore whether the TyG index is correlated with MDD. In total, 321 patients with MDD and 325 non-MDD patients were included in the study. The presence of MDD was identified by trained clinical psychiatrists using the International Classification of Diseases 10th Revision. The TyG index was calculated as follows: Ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The results revealed that the MDD group presented higher TyG index values than the non-MDD group (8.77 [8.34-9.17] vs 8.62 [8.18-9.01], P < .001). We also found significantly higher morbidity of MDD in the highest TyG index group than in the lower TyG index group (59.9% vs 41.4%, P < .001). Binary logistic regression revealed that TyG was an independent risk factor for MDD (odds ratio [OR] 1.750, 95% confidence interval: 1.284-2.384, P < .001). We further assessed the effect of TyG on depression in sex subgroups. The OR was 3.872 (OR 2.014, 95% confidence interval: 1.282-3.164, P = .002) for the subgroup of men. It is suggested that the TyG index could be closely associated with morbidity in MDD patients; thus, it may be a valuable marker for identifying MDD.

Reliability and validity of the brief psychosomatic symptom scale (BPSS) in patients from general hospitals.

OBJECTIVES: To verify the Brief Psychosomatic Symptom Scale (BPSS) among patients with psychosomatic-related disorders in general hospitals and determine the threshold of BPSS. METHODS: The BPSS is a shortened 10-item version of the psychosomatic symptoms scale (PSSS). Data from 483 patients and 388 healthy controls were included for psychometric analyses. Internal consistency, construct validity, and factorial validity were verified. The threshold of BPSS in distinguishing psychosomatic patients from healthy controls were determined using receiver operating characteristic (ROC) curve analysis. The ROC curve of the BPSS was compared with that of the PSSS and patient health questionnaire-15 (PHQ-15) by using Venkatraman's method with 2000 times Monte-Carlo simulations. RESULTS: The reliability of the BPSS was good with Cronbach's α of 0.831. BPSS was significantly correlated with PSSS (r = 0.886, P < 0.001), PHQ-15 (r = 0.752, P < 0.001), PHQ-9 (r = 0.757, P < 0.001) and GAD-7 (r = 0.715, P < 0.001), which indicated good construct validity. ROC analyses demonstrated that the AUC of the BPSS was comparable with that of PSSS. The gender-specific threshold of BPSS was determined as ≥8 in males and ≥ 9 in females. CONCLUSIONS: The BPSS is a brief and validated instrument for screening common psychosomatic symptoms.

Surviving the shift: College student satisfaction with emergency online learning during COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) epidemic disrupted education systems by forcing systems to shift to emergency online leaning. Online learning satisfaction affects academic achievement. Many factors affect online learning satisfaction. However there is little study focused on personal characteristics, mental status, and coping style when college students participated in emergency online courses. AIM: To assess factors related to satisfaction with emergency online learning among college students in Hebei province during the COVID-19 pandemic. METHODS: We conducted a cross-sectional survey of 1600 college students. The collected information included demographics, psychological aspects of emergent public health events, and coping style. Single factor, correlation, and multiple linear regression analyses were performed to identify factors that affected online learning satisfaction. RESULTS: Descriptive findings indicated that 62.9% (994/1580) of students were satisfied with online learning. Factors that had significant positive effects on online learning satisfaction were online learning at scheduled times, strong exercise intensity, good health, regular schedule, focusing on the epidemic less than one hour a day, and maintaining emotional stability. Positive coping styles were protective factors of online learning satisfaction. Risk factors for poor satisfaction were depression, neurasthenia, and negative coping style. CONCLUSION: College students with different personal characteristics, mental status, and coping style exhibited different degrees of online learning satisfaction. Our findings provide reference for educators, psychologists, and school administrators to conduct health education intervention of college students during emergency online learning.

MiR-497 promotes microglia activation and proinflammatory cytokines production in chronic unpredictable stress-induced depression via targeting FGF2.

Depression is one of important prevalent psychiatric disorders worldwide. MiR-497 is considered as a diagnostic biomarker and a promising therapeutic target in cancers. However, the role of miR-497 in depression remains unknown. In this study, we demonstrated that CUS induced depression-like behaviors and overexpression of miR-497 in rats. Interestingly, knockdown miR-497 ameliorated CUS-induced depressive-like behavior in rats. Moreover, knockdown of miR-497 inhibited the activation of microglia and the production of proinflammatory cytokines including IL-6, IL-1ß, MCP-1 and TNF-α in CUS-induced rats. Luciferase activity assay proved that Fibroblast Growth Factor-2 (FGF2) was a direct target of miR-497 and modulated by miR-497 in microglia. In rescue experiments, overexpression of FGF2 inhibited miR-497-induced proinflammatory cytokines and iNOS expression. These results showed that miR-497 aggravated hippocampal microglial activation in CUS-induced depression in rat via targeting FGF2, providing a novel potential target for treatment of depression.

Development of the psychosomatic symptom scale (PSSS) and assessment of its reliability and validity in general hospital patients in China.

OBJECTIVES: To develop and verify the Psychosomatic Symptom Scale (PSSS) among psychosomatic patients and the cut-off value of PSSS in distinguishing psychosomatic patients from health controls. METHODS: The PSSS was drafted by an expert workgroup. 996 patients and 366 controls from 14 general hospitals in China were recruited to complete PSSS, Patient Health Questionnaire-15 (PHQ-15) and Symptom Checklist-90 (SCL-90). Student's t-test, Kruskal-Wallis test, Cronbach's α, Spearman's correlation, and confirmatory factor analysis (CFA) were used to verify the PSSS. Receiver operating characteristic (ROC) analyses were used to determine the cut-off value. RESULTS: Cronbach α of PSSS was 0.907. The PSSS was significantly correlated with SCL-90 somatization subscale (r = 0.682, P < 0.001) and PHQ-15 (r = 0.724, P < 0.001). CFA supported the theoretical two-factor structure of the PSSS, with comparative fit index (CFI) = 0.979, Tucker-Lewis index (TLI) = 0.977, root mean square error of approximation (RMSEA) = 0.039 (90% CI: 0.035-0.042), and standardized root mean residual (SRMR) = 0.054. As the sum score of PSSS was significantly higher in female, cut-off values were determined as 11 in females and 10 in males respectively. CONCLUSIONS: The PSSS is a reliable and valid instrument for measuring psychosomatic symptoms.

Serum NT-proBNP on admission can predict ST-segment resolution in patients with acute myocardial infarction after primary percutaneous coronary intervention.

OBJECTIVE: The aim of this study was to investigate the value of initial serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations in ST-segment elevation myocardial infarction (STEMI) patients for predicting ST-segment resolution (STR) after primary percutaneous coronary intervention (pPCI). PATIENTS AND METHODS: Consecutive STEMI patients (n = 218) who underwent pPCI were assigned to an STR group (≥ 50 % resolution) or a non-STR group (< 50 % resolution). All patients were followed up for 12 months, and major adverse cardiac events were recorded. Data related to the pPCI procedure, biochemical parameters, and cardiac markers were compared between the two groups. Predictive factors of non-STR were also identified. RESULTS: STR at 180 min after pPCI occurred in 202 patients (92.7 %). Compared to the STR group, patients in the non-STR group had a significantly lower left ventricular ejection fraction, a larger left ventricular end-diastolic dimension, and significantly higher serum concentrations of glycosylated hemoglobin and NT-proBNP. Multivariate logistic regression analysis indicated that a high serum NT-proBNP level in STEMI patients on hospital admission was the only independent predictive factor of non-STR after pPCI. An NT-proBNP concentration of ≥ 2,563.6 pg/ml had a sensitivity of 81.2 % and a specificity of 65.8 %. CONCLUSIONS: Serum NT-proBNP concentrations in STEMI patients on hospital admission were useful in predicting non-STR after pPCI.