Metabolic features of adolescent major depressive disorder: A comparative study between treatment-resistant depression and first-episode drug-naive depression.

Major depressive disorder (MDD) is a psychiatric illness that can jeopardize the normal growth and development of adolescents. Approximately 40% of adolescent patients with MDD exhibit resistance to conventional antidepressants, leading to the development of Treatment-Resistant Depression (TRD). TRD is associated with severe impairments in social functioning and learning ability and an elevated risk of suicide, thereby imposing an additional societal burden. In this study, we conducted plasma metabolomic analysis on 53 adolescents diagnosed with first-episode drug-naïve MDD (FEDN-MDD), 53 adolescents with TRD, and 56 healthy controls (HCs) using hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) and reversed-phase liquid chromatography-mass spectrometry (RPLC-MS). We established a diagnostic model by identifying differentially expressed metabolites and applying cluster analysis, metabolic pathway analysis, and multivariate linear support vector machine (SVM) algorithms. Our findings suggest that adolescent TRD shares similarities with FEDN-MDD in five amino acid metabolic pathways and exhibits distinct metabolic characteristics, particularly tyrosine and glycerophospholipid metabolism. Furthermore, through multivariate receiver operating characteristic (ROC) analysis, we optimized the area under the curve (AUC) and achieved the highest predictive accuracy, obtaining an AUC of 0.903 when comparing FEDN-MDD patients with HCs and an AUC of 0.968 when comparing TRD patients with HCs. This study provides new evidence for the identification of adolescent TRD and sheds light on different pathophysiologies by delineating the distinct plasma metabolic profiles of adolescent TRD and FEDN-MDD.

The familial transmission of suicide and non-suicidal self-injury in different income levels in town.

BACKGROUND: Prior researches have established that suicide and non-suicidal self-injury (NSSI) exhibit familial transmission patterns. However, the extent to which these patterns vary across different income levels remains unclear, as well as the specific factors that influence them. This study aimed to explore these questions. METHODS: We analyzed data from 13,988 parent-child pairs in Chongqing, China, where the children were aged from 7 to 12 years old. Six income levels were considered, and the children's depression and anxiety symptoms were assessed using standardized scales (the Center for Epidemiological Studies Depression Scale for Children, [CES-DC], and the Screen for Child Anxiety Related Emotional Disorders [SCARED], respectively). Binary logistic regression analysis was employed to examine the transmission of suicide and NSSI across different income levels. RESULTS: Familial transmission of suicide was significant difference in all income levels except the highest, while familial transmission of NSSI was significant difference in all income levels except the lowest. Notably, in both low- and high-income levels, suicide and NSSI transmissions primarily occurred among male children, mothers with higher education, and children who spent long time with their mothers. Additionally, the transmissions were mediated partially or entirely by children's depression and anxiety symptoms. LIMITATIONS: Future studies should investigate the separate effects of fathers' and mothers' suicide and NSSI histories on familial transmission patterns. CONCLUSION: The familial transmissions of suicide and NSSI exhibited distinct patterns across different income levels.

Correlation between cognitive impairment and serum markers in patients with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Previous studies have revealed that sleep structure and hypoxemia are two important environmental factors for cognitive impairment in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). We hypothesized that the pathophysiological mechanisms between these two factors may also be involved in cognitive impairment in patients with OSAHS. Previous studies have suggested that alterations in serum glucose and lipid metabolism, inflammatory responses, and astrocyte markers not only contribute to sleep structural disorders in OSAHS but also affect the occurrence and development of this disease. Therefore, we hypothesized that alterations in the abovementioned indicators may be involved in cognitive impairment in OSAHS. Additionally, obesity is an important risk factor for OSAHS. This study therefore aimed to explore the correlation between serum indicators and cognitive impairment in patients with OSAHS. METHODS: Patients with OSAHS who underwent polysomnography in our hospital were recruited in this study. The overall cognitive function of patients were evaluated using the Mini mental State Examination (MMSE). Blood biochemical indicators such as glucose (GLU), triglycerides (TG), and triglyceride glucose (TyG) index were measured. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of serum glucagon-like peptide-1 receptor (GLP-1R), fibroblast growth factor 21 (FGF21), S100 calcium binding protein B (S100B), brain derived neurotrophic factor (BDNF), inflammatory factors such as C-reactive protein (CRP), tumor necrosis factor-α (TNFα), interleukin-4 (IL-4), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). Spearman correlation analysis was used to determine if the indicator was related to cognitive function, and backward linear regression analysis was used to identify the main risk factors for cognitive impairment in non-obese and obese patients with OSAHS. RESULTS: Among 34 patients, 19 were non-obese and 15 were obese. Obese patients exhibited higher AHI compared to non-obese individuals, and the difference was statistically significant (p < 0.05). In non-obese patients, Spearman correlation analysis revealed a negative correlation between serum GLU, IL-4, and MMSE scores (p < 0.05); IL-6 was positively correlated with MMSE (p < 0.05). In addition, GLU and IL-6 were independently correlated with MMSE in non-obese patients (p < 0.05). In obese patients, serum TG and TyG were positively correlated with MMSE scores (p < 0.05); age, BMI, and IL-4 were negatively correlated with MMSE scores (p < 0.05). In addition, age and IL-4 were independently correlated with MMSE in obese patients (p < 0.05). CONCLUSIONS: Our data suggested that GLU and IL-6 were independently correlated with cognitive impairment in non-obese patients with OSAHS; age and IL-4 were independently correlated with cognitive impairment in obese patients. Early detection of this difference in heterogeneity may provide theoretical support for future investigations in prevention and treatment of cognitive impairment in patients with OSAHS.

Sequenced treatment alternatives to relieve adolescent depression (STAR-AD): a multicentre open-label randomized controlled trial protocol.

BACKGROUND: Adolescent major depressive disorder (MDD) is a prevalent mental health problem with low treatment success rates. Whether fluoxetine or fluoxetine combined with cognitive-behavioural therapy (CBT) is the more effective initial treatment for adolescent MDD remains controversial, and few studies have investigated whether treatment switching or augmentation is preferred when the initial treatment is not working well. METHODS: We developed a multicentre open-label Sequential Multiple Assignment Randomized Trial (SMART) design, consisting of two phases lasting 8 weeks each. In phase 1 (at baseline), patients will be recruited and grouped in fluoxetine group or fluoxetine combined with CBT group by patient self-selection. In phase 2 (after 8 weeks of treatment), the nonresponders will be randomly assigned to six groups, in which participants will switch to sertraline, vortioxetine, or duloxetine or added aripiprazole, olanzapine, or lithium carbonate to fluoxetine. After the full 16 weeks of treatment, we will assess the long-term sustainability of the treatment effects by evaluating participants during their subsequent naturalistic treatment. The primary outcome will be the response rate, determined by the Children's Depression Rating Scale-Revised (CDRS-R). Secondary outcomes include the change in scores on the Beck Depression Inventory (BDI), the Screen for Child Anxiety-Related Emotional Disorders (SCARED) and the Safe Assessment. DISCUSSION: The results from this study will aid clinicians in making informed treatment selection decisions for adolescents with MDD. TRIAL REGISTRATION: This protocol was registered at ClinicalTrials.gov with Identifier: NCT05814640.

Relationship between slow-wave sleep and serum γ-glutamine transaminase in non-obese men with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a disease characterized with intermittent hypoxia and sleep fragmentation. Obesity and gender are major risk factors for the onset of OSAHS. Previous studies on obese men with OSAHS have been performed, while few studies on non-obese men with OSAHS have been carried out. The purpose of this study was to explore the clinical characteristics of polysomnography and blood biochemical indexes in non-obese men with OSAHS and to identify the possible influencing factors. METHODS: This retrospective study included patients with OSAHS who underwent polysomnography in our hospital. General clinical data such as overnight polysomnography and biochemical indicators were recorded. The patients were divided into two groups according to the apnea-hypopnea index (AHI): mild to moderate OSAHS and severe OSAHS. The differences in biochemical parameters such as the levels of γ-glutamine transaminase (GGT), triglyceride (TG), glucose (GLU), and sleep structure parameters such as N1, N2, slow-wave sleep (SWS), and rapid eye movement (REM) sleep were compared and analyzed. Spearman correlation analysis and logistic regression were used to identify the risk factors of non-obese men with OSAHS. ROC curves were used to evaluate the predictive ability of SWS and GGT on disease severity. RESULTS: Of 94 non-obese men with OSAHS, 49 had mild to moderate OSAHS and 45 had severe OSAHS. Our data suggested that the levels of low oxygen saturation (L-SaO2), mean oxygen saturation (M-SaO2), SWS, and GGT were significantly changed in the mild to moderate OSAHS group compared with the severe group (p < 0.05). For patients with OSAHS, the proportion of SWS in the group with severe OSAHS was higher than that in the mild to moderate group (p < 0.05), and the serum GGT enzyme levels were significantly elevated in the severe group compared to the mild to moderate group (p < 0.05). Using logistic regression analyses, our data revealed that both SWS and GGT enzyme levels were independent risk factors for AHI (p < 0.05). In addition, the results of correlation analysis indicated that SWS was related to triglyceride (TG), total cholesterol (TC), apolipoprotein E (APOE), and triglyceride glucose (TyG) index (p < 0.05); GGT was related to TG, TC, APOE, and TyG index (p < 0.05). Furthermore, SWS was independently associated with GGT (p < 0.05). The area under the ROC curve plotted with the combined coefficient of SWS and serum GGT was 0.728, which was predictive of the disease severity. CONCLUSIONS: These results suggest that SWS and GGT are independent associated factors of the severity of the disease. However, TyG index was not an independent associated factor of the severity of disease in non-obese men with OSAHS. In addition, SWS and GGT were negatively correlated. SWS combined with serum GGT may be predictive of the severity of the disease. This study may have added to our understanding of the pathogenesis of OSAHS in non-obese men.