TREM2 regulates BV2 microglia activation and influences corticosterone-induced neuroinflammation in depressive disorders.

Depressive disorders is a serious mental illness, and its underlying pathological mechanisms remain unclear. The overactivation of microglia and neuroinflammation are thought to play an essential role in the occurrence and development of depressive disorders. TREM2, an immune protein mainly expressed in microglia, is an important part of nerve cells involved in inflammatory response. Corticosterone (CORT) is often referred to as a stress hormone and plays a role in the immune system and stress response. Therefore, this study investigated the role of TREM2 in CORT-induced BV2 cell damage and preliminarily analyzed the effects of TREM2 on JAK2/STAT3 signaling pathway and microglia polarization. The cell model of CORT-induced depression in vitro was established, and the effect of CORT on the activity of BV2 microglia was detected by CCK8. Plasmid transfection was used to overexpress and interfere with TREM2 in BV2 cells cultured by CORT. Western blotting, PCR, and ELISA analyzed the expression of related proteins and inflammatory factors. The results showed that CORT could affect BV2 cell proliferation and TREM2 levels. In the presence of CORT, overexpression of TREM2 decreased the levels of TNF-α, IL-1ß, and IL-6 and increased the levels of IL-10. Interference with TREM2 increased the levels of TNF-α, IL-1ß, and IL-6 and decreased the levels of IL-10. TREM2 can affect the release of inflammatory factors through the JAK2/STAT3 signaling pathway and regulate the M1/M2 phenotypic transformation of microglia. TREM2 plays a role in regulating CORT-induced inflammatory responses, revealing the influence of TREM2 on the neuroinflammatory pathogenesis of depressive disorders and suggesting that TREM2 may be a new target for the prevention and treatment of depressive disorders.

Establishment of a risk prediction model for suicide attempts in first-episode and drug naïve patients with major depressive disorder.

BACKGROUND: Suicide is common in patients with major depressive disorder (MDD) and has serious consequences for individuals and families. This study aims to establish a risk prediction model for suicide attempts in MDD patients to make the detection of suicide risk more accurate and effective. METHODS: A cross-sectional survey, clinical examination, and biochemical indicator tests were performed on 1718 first-episode and drug naïve patients with major depressive disorder. We used Machine Learning to establish a risk prediction model for suicide attempts in FEDN patients with MDD. RESULTS: Five predictors were identified by LASSO regression analysis from a total of 20 variables studied, namely psychotic symptoms, anxiety symptoms, thyroid peroxidase antibodies (ATPO), total cholesterol (TC), and high-density lipoprotein-cholesterol (HDL-C). The model constructed using the five predictors displayed moderate predictive ability, with an area under the ROC of 0.771 in the training set and 0.720 in the validation set. The DCA curve showed that the nomogram could be applied clinically if the risk threshold was between 22 % and 60 %. The risk threshold was found to be between 20 % and 60 % in external validation. CONCLUSION: Introducing psychotic symptoms, anxiety symptoms, ATPO, TC, and HDL-C to the risk nomogram increased its usefulness for predicting suicide risk in patients with MDD. It may be useful in clinical decision-making or in discussions with patients, especially in crisis interventions.

Thyroid dysfunction in young, first-episode and drug-naïve patients with major depressive disorder: prevalence and associated clinical factors.

Objective: The incidence of thyroid dysfunction (TD) and major depressive disorder (MDD) is increasing year by year in the general population. However, the prevalence and correlates of TD in first-episode drug-naive (FEDN) MDD patients have not been explored. This study sought to fill this gap and examine the association between TD and MDD. Methods: We recruited 1,289 FEDN MDD patients aged 18 ~ 45 years. A total of 1,289 FEDN MDD outpatients were recruited. Demographical and suicide data were collected for each patient, and lipid profiles, thyroid function, and fasting blood glucose (FBG) levels were measured. The Hamilton Depression Scale 17 (HAMD-17) was assessed for depression. Results: The prevalence of TD in young FEDN MDD patients was 64.86%. Compared with those without TD, patients with TD had longer duration of illness, greater HAMD score, higher BMI, TG, TC, and LDL-C levels, and higher suicide attempt rates, but lower HDL-C and FBG levels. Further logistic regression indicated that duration of illness, HAMD score, TC, HDL-C, BMI, and FBG levels were significantly associated with TD. Limitations: No causal relationship can be drawn due to the cross-sectional design. Conclusion: TD is common in young FEDN MDD patients. So clinicians should monitor thyroid function in patients with MDD.

Sex differences in residual somatic symptoms in patients with first-episode depression after acute-phase treatment.

BACKGROUND: Residual somatic symptoms (RSS) are common in depressed patients, predicting treatment effectiveness. However, sex differences in RSS have received little systematic study. This study was conducted to compare sex differences of RSS in patients with first-episode depression (FED). METHODS: Nine hundred eighty-two patients with FED were selected and treated for 8 to 12 weeks. We evaluated the subjects' socio-demographic characteristics and residual depressive symptoms. Using the Patient Health Questionnaire-15 (PHQ-15) scale to assess residual somatic symptoms, the Sheehan Disability Scale (SDS) for the assessment of patients' function, the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) for quality of life. RESULTS: The incidence of RSS with FED was 46.4%. For patients with residual symptoms, the age and age of onset in females were higher than males, but males had more years of education than females. The degree of "stomach pain" in females was more severe than in males, while "trouble sleeping" in males was more severe than that in females. Multiple regression analysis showed that the total Q-LES-Q-SF score was an independent influencing factor of RSS in both males and females, while the total SDS score only affected female RSS. CONCLUSIONS: The prevalence of RSS in FED after acute-phase treatment is high. The symptom of "stomachache" is more pronounced in females, while "trouble sleeping" is more severe in males. Quality of life plays an essential role in RSS in both genders. Thus, sex needs to be considered when assessing the relationship between RSS and therapeutic effect in depression.

Association of high BMI with subclinical hypothyroidism in young, first-episode and drug-naïve patients with major depressive disorder: a large-scale cross-sectional study.

Thyroid dysfunction is known to be associated with obesity, but the reliability of this relationship is easily affected by drug treatment, age, and subclinical hypothyroidism (SCH) with no apparent symptoms. Our research aims to compare obese and overweight BMI ranges with SCH and without SCH in a large sample of young, first-episode and drug-naïve (FEDN) patients with major depressive disorder (MDD), which has received little systemic investigation. A total of 1289 FEDN MDD young outpatients were recruited for this study. Serum thyroid function and lipid level parameters were measured; HAMD and PANSS scales were used to assess patients' depression and positive symptoms. A self-administered questionnaire collected other clinical and demographic data. The prevalence of SCH in FEDN MDD young patients was 58.26%. Compared to patients without SCH, the patients with SCH had a more prolonged illness duration, higher BMI levels, increased prevalence of overweight and obesity, higher HAMD score and PANSS-positive symptom scores, higher levels of TG, TC, LDL-C, and lower levels of HDL-C. Further logistic regression indicated that overweight BMI, obese BMI, illness duration, HAMD score, HDL-C, and TC were significantly associated with SCH. Our results indicate that obesity and overweight may be associated with SCH in young, FEDN MDD patients. The importance of regular thyroid function assessment in young FEDN MDD patients with high BMI should be taken into account.

Rural-urban differences in prevalence and correlates of suicidal ideation in adolescent patients with depression in a large sample of Chinese.

BACKGROUND: Suicidal ideation (SI) is severe comorbidity of depression that has been extensively studied in the past. Residence differences between SI have rarely been systematically studied, especially in parental rearing behavior. This large-scale explored the residence differences in the prevalence and correlation of SI adolescent patients with depression. METHODS: A total of 1417 patients with depression were recruited, and their demographic data and clinical data were collected. The Children's Depression Inventory (CDI) and the Egna Minnen Beträffande Uppfostran (EMBU) scale were used to assess depression, and parental rearing behavior, respectively. RESULTS: The prevalence of suicidal ideation was higher in urban patients than in rural patients (43.7 % vs.37.7 %, P < 0.05). Patients with SI scored higher on total CDI scores, parental punishment, parental rejection, and paternal overprotection compared to their respective patients without SI. In the urban group, patients with SI had lower parental emotional warmth scores and higher parental intervention scores compared to patients without SI. Logistic regression analysis showed that total CDI score, gender, alcohol consumption, father's emotional warmth, father's rejection, and mother's intervention were significantly associated with SI in urban patients (P < 0.05); total CDI score and mother's rejection were significantly associated with SI in rural patients (P < 0.05). LIMITATIONS: No causal relationship could be drawn due to the cross-sectional design. CONCLUSIONS: The results of this study showed significant residential differences in risk and associated factors for SI among adolescents with depression. Focusing on the parenting styles of adolescent patients can help with the early identification and intervention of SI.

Repetitive transcranial magnetic stimulation combined with cognitive behavioral therapy treatment in alcohol-dependent patients: A randomized, double-blind sham-controlled multicenter clinical trial.

Background: Alcohol dependence (AD) is a complex addictive disorder with a high relapse rate. Previous studies have shown that both repetitive transcranial magnetic stimulation (rTMS) and cognitive behavioral therapy (CBT) may be effective for AD, and we aim to explore more effective treatment options to reduce relapse rates for AD. Materials and methods: A total of 263 AD patients were recruited. They were divided into six groups according to the location and the type of rTMS: left dorsolateral prefrontal cortex (DLPFC), right DLPFC, sham stimulation, and whether they received CBT treatment: with a fixed schedule (C1) and without a fixed plan (C0). There were included in sham rTMS + C0 group (n = 50), sham rTMS + C1 group (n = 37), right rTMS + C0 group (n = 45), right rTMS + C1 group (n = 42), left rTMS + C0 group (n = 49), left rTMS + C1 group (n = 40). We used obsessive compulsive drinking scale (OCDS), visual analogue scale (VAS), alcohol dependence scale (ADS), montreal cognitive assessment (MoCA), generalized anxiety disorder-7 (GAD-7), patient health questionnaire-9 items (PHQ-9), and Pittsburgh sleep quality index (PSQI) to assess alcohol cravings, alcohol dependence, cognition, anxiety, depression, and sleep quality. They were followed up and evaluated for relapse. Results: The sham rTMS + C0 group relapse rate was significantly higher than the right rTMS + C1 group (P = 0.006), the left rTMS + C0 group (P = 0.031), the left rTMS + C1 group (P = 0.043). The right rTMS + C0 group showed significantly higher relapse rate compared to the right rTMS + C1 group (P = 0.046). There was no significant difference in relapse rates between other groups. The repeated-measures ANOVA showed an interaction effect between group and time was significant in the rate of patient health questionnaire-9 items (PHQ-9) scale reduction (P = 0.020). Logistic analysis indicated that smoking and alcohol consumption were independent determinants of relapse (P < 0.05). At 24 weeks of follow-up, Kaplan-Meier survival analysis reveal that there is statistically significant relapse rate between six groups (P = 0.025), left rTMS + C1 group has the best treatment effect for alcohol dependent patients. Cox regression analysis confirmed that current smoking, total cholesterol, and total bilirubin (TBIL) level were risk factors of relapse (P < 0.05). Conclusion: This study is the first to suggest that the combination of rTMS and CBT may be a potentially effective treatment for reducing relapse.

Association of serum lipid levels with psychotic symptoms in young, first-episode and drug naïve outpatients with major depressive disorder: A large-scale cross-sectional study.

BACKGROUND: Major depressive disorder (MDD) patients with psychotic symptoms have more complex clinical symptoms and higher relapse rates. The purpose of this study was to compare serum lipid differences between psychotic major depressive disorder (PMD) and non-psychotic major depressive disorder (NPMD) in a large sample of young first-episode drug naïve (FEDN) patients. METHODS: We recruited 1289 young MDD patients. Socio-demographic information, clinical data, and lipid parameters were collected. The Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the positive symptom subscale of the Positive and Negative Syndrome Scale were used to assess patients' depressive, anxiety and psychotic symptoms, respectively. RESULTS: Compared with the NPMD group, the PMD group had higher HAMD, HAMA scores, and higher TC, TG, and LDL-C levels. Correlation analysis showed that psychotic symptoms were significantly associated with the total score of HAMD and HAMA, and the levels of serum lipid. In addition, logistic regression analysis found that TC was associated with psychotic symptoms in young FEDN MDD patients. CONCLUSION: Our results suggest TC levels may be associated with psychotic symptoms in young MDD patients. The importance of regular psychotic symptom assessment in young MDD patients with high TC levels should be taken into account.

MiR-124 Regulates IQGAP1 and Participates in the Relationship Between Morphine Dependence Susceptibility and Cognition.

Background: Long-term excessive use of morphine leads to addictive diseases and affects cognitive function. Cognitive performance is associated with genetic characteristics.MiR-124 plays a critical regulatory role in neurogenesis, synaptic development, brain plasticity, and the use of addictive substances. As a scaffold protein, IQGAP1 affects learning and memory dose-dependent. However, the role of miR-124 and its target protein as potential addiction biomarkers and the impact on cognitive function have not been fully explored. Method: A total of 40 patients with morphine dependence and 40 cases of healthy people were recruited. We collected basic and clinical information about the two groups. The Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9(PHQ-9), Montreal Cognition Assessment Scale (MoCA), Pittsburgh Sleep Quality Index (PSQI) were used to assess the severity of depression, anxiety, depressive symptoms, cognitive dysfunction, and sleep quality. Results: Compared to the control group, the morphine-dependent group had higher GAD-7, PHQ-9, PSQI scores, and more elevated miR-124 levels but lower MOCA scores and IQGAP1 levels. MiR-124, IQGAP1, the average intake last year were related to OASI scores.MiR-124, IQGAP1, PHQ-9 were associated with MOCA scores. In the multiple regression model, the levels of miR-124 and IQGAP1 were independent factors influencing the severity of morphine dependence. The level of miR-124 was an independent factor influencing the severity of cognitive impairment in patients with morphine dependence. In addition, the luciferase report confirmed that IQGAP1 mRNA is the direct target of miR-124. Conclusion: MiR-124 and its target protein IQGAP1 are involved in the regulation of addiction and cognitive function in patients with morphine dependence.

Association of serum lipid levels with psychotic symptoms in first-episode and drug naïve outpatients with major depressive disorder: a large-scale cross-sectional study.

Background Major depressive disorder (MDD) is a prevalent psychiatric disorder, with increasing evidence that patients with MDD display psychotic symptoms. Studies have shown the association between lipid levels and MDD, but few have explored the relationship between lipids and psychotic symptoms in MDD. The objective of this study was to compare the differences of lipid levels between patients with psychotic major depressive disorder (PMD) and those with non-psychotic major depressive disorder (NPMD) in first-episode and drug-naive (FEDN) MDD patients. Methods A total of 1718 outpatients with FEDN MDD were recruited. In addition to collecting basic information, their blood specimens were also collected to detect serum TC, HDL-C, TG, and LDL-C. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) were used to assess their depression, anxiety, and psychotic symptoms respectively. Results Compared to those with NPMD, those with PMD had higher scores on HAMD, HAMA, and more elevated serum TC, TG, and LDL-C levels, but lower HDL-C levels (all p < 0.05). Further logistic regression analysis showed that TG, the severity of depressive and anxiety symptoms were significantly associated with psychotic symptoms (p < 0.05). Limitations No causal relationship could be drawn due to the cross-sectional design. Conclusions Psychotic symptoms in patients with MDD may be predicted by lipid levels in the future. Our findings suggest that TG seems to predict the presence of current psychotic features among patients with FEDN MDD.

Validation and Factor Analysis of the Obsessive Compulsive Drinking Scale (OCDS) in the Chinese Population.

Obsessive Compulsive Drinking Scale (OCDS) was established and introduced to measure the craving for alcohol and the severity of alcohol dependence. However, the Chinese version of OCDS is still unavailable and has not been validated in the Chinese population. We tended to translate and validate the OCDS in Chinese. We translated original OCDS into Chinese through bi-direction translations and tested the reliability and validity. We found that Chinese OCDS had high internal consistency and good test-retest reliability. The Chinese OCDS also presented good internal structure to reflect the severity of alcohol dependence. The Chinese OCDS could be used in clinical studies and research among the Chinese population.

Prevalence, risk factors and clinical correlates of suicidal ideation in adolescent patients with depression in a large sample of Chinese.

BACKGROUND: Suicidal ideation (SI) has a high risk in adolescents and is now a significant concern due to its problematic outcome. However, few systemic studies of suicidal ideation have been conducted in adolescent patients. Therefore, the current study was aimed to assess the prevalence and its clinical correlate of suicidal ideation among adolescent patients with depression. METHODS: A total of 1635 adolescent patients (748 males/ 887 females) with depression were recruited in this study. The clinical and demographic data were collected by a self-administered questionnaire. Suicidal ideation was assessed by interview. Children's Depression Inventory (CDI) was used to evaluate depressive symptoms, Adolescent Self-Rating Life Events Check List (ASLEC) was used to assess the stressful life events. RESULTS: The study showed that the prevalence of suicidal ideation in adolescent depression patients was 38.2% (625/1635). Compared to the non-SI patients, SI patients had greater scores on CDI and ASLEC, had inadequate sleeping time, and were more likely to be females. Further logistic regression analysis indicated that suicidal ideation in adolescent patients with depression was significantly associated with females, inadequate sleeping time, the severity of depression, and higher learning pressure. LIMITATIONS: No causal relationship could be drawn due to the cross-sectional design. CONCLUSIONS: Our results suggest a high prevalence of suicidal ideation in adolescents with depression. Moreover, the severity of depression, sex, sleep time, and learning pressure are all related to suicidal ideation. Early recognition and treatment of suicidal ideation can effectively prevent the occurrence of suicide among adolescent patients.