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Background: How cognition is influenced by electroconvulsive treatment (ECT) and major depressive disorder (MDD) is still debated. The development and etiology of neurocognitive impairment in MDD were examined by investigating the cognitive profile following ECT related to the state, scar, and trait perspectives, with the former predicting improvements parallel with depressive symptoms, while the two latter expected persisting impairments. Executive functions (EF) and attention are central to cognition and alterations in these functions could influence other domains like memory. The main aims of the present study were to examine the short and long-term effects of ECT on EF and attention in patients with major depressive disorder by exploiting the rapid antidepressant effect of this treatment. Methods: A case-control longitudinal follow-up design was used to investigate the effects of unilateral brief-pulse ECT on EF and attention in patients with depression (n = 36) compared to untreated healthy controls (n = 16). EF and attention were measured pre-treatment, approximately two weeks, and six months post-treatment. Results: The patient group showed significantly worse performance on most tests compared to healthy controls pre-treatment, and no short- or long-term worsening of EF and attention following ECT was found. Significant improvement was identified in patients' attention, processing speed and inhibition after ECT. Conclusions: The present study showed that there was no cognitive worsening after ECT treatment. An improvement in several of the tests measuring inhibition, attention, and processing speed was parallel to symptom reduction, with the former showing associations to symptom change, suggesting state-related effects from improved mood. Still, the patient group performed significantly worse on most measures both pre-treatment and at the short and long-term follow-ups, indicating prevailing trait or scar effects on cognitive functions and potential lack of practice effects. Clinical trial number: NCT04348825 (14.04.20). [ABSTRACT FROM AUTHOR]

Objective: An alternative metric for evaluating insulin resistance (IR) is the triglyceride glucose-body mass index (TyG-BMI). However, it is yet unclear how TyG-BMI and suicide attempts (SA) are related. The objective of this research was to explore the correlation between the TyG-BMI index and SA in individuals with untreated first-episode (UFE) major depressive disorder (MDD) in Shanxi Province. Methods: This cross-sectional study was conducted from September 2016 to December 2018 in the psychiatric outpatient clinic of Taiyuan General Hospital and included 1718 patients with UFE MDD, with a mean age of 34.9 ± 12.4 years. The relationship between TyG-BMI and SA was assessed using logistic regression modeling. We investigated threshold effects using a two-piecewise linear regression model. Results: Taking into consideration the potential influence of confounding variables, a comprehensive multivariate logistic regression analysis was conducted, which demonstrated the absence of a statistically significant association between the TyG-BMI index and the occurrence of SA, as evidenced by P-values that were all greater than 0.05. On the other hand, the visual analysis of the smoothed plots revealed a U-shaped relationship between the TyG-BMI index and the incidence of SA, with a notable inflection occurring at a TyG-BMI value of around 210. It was observed that the effect sizes flanking the inflection point, accompanied by their 95% confidence intervals, were 0.985 (95% CI: 0.972 to 0.999, P = 0.031) and 1.012 (95% CI: 1.003 to 1.047, P = 0.005), respectively. Conclusions: In UFE MDD patients, a U-shaped link was observed between TyG-BMI and SA, with the minimal SA incidence noted at a TyG-BMI level of 210, signifying that an augmented risk for SA might be connected to both diminished and augmented TyG-BMI levels. [ABSTRACT FROM AUTHOR]

Background: Previous studies demonstrated thyroid stimulating hormone (TSH) plays an important role in regulating lipid metabolism, but the relationship between the two is controversial. Meanwhile, it has not been reported in a population with major depressive disorder (MDD). Methods: We divided 1718 first-episode and drug naïve patients with MDD into a TSH abnormal group (TSH-AB) and a TSH normal group (TSH-NOR). The participants in the two groups were assessed by the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and the positive subscale of Positive and Negative Syndrome Scale. The patients' blood was tested for TSH, free T3, free T4, fasting blood glucose, lipid indexes and body mass index was recorded. Results: The participants in the TSH-AB group had significantly higher HAMD scores, HAMA scores and total scores of positive symptoms, as well as higher incidence of suicide attempts than those in the TSH-NOR group, accompanied by significantly higher thyroglobulin antibodies, thyroid peroxidase antibodies, fasting blood glucose values, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels compared with those of TSH-NOR patients. However, the high-density lipoprotein cholesterol (HDL-C) of TSH-AB patients was lower than those of TSH-NOR patients. TSH values were positively correlated with TC, TG, and LDL-C values, and negatively correlated with HDL-C value. Conclusion: TSH was highly correlated with abnormal lipid metabolism in patients with MDD. The specific molecular mechanism of the relationship between TSH, lipid metabolism and the development of depression needs to be further in-depth investigation. [ABSTRACT FROM AUTHOR]

Background: Neurocognitive impairment is one of the prominent manifestations of major depressive disorder (MDD). Childhood trauma enhances vulnerability to developing MDD and contributes to neurocognitive dysfunctions. However, the distinct impacts of different types of childhood trauma on neurocognitive processes in MDD remain unclear. Methods: This study comprised 186 individuals diagnosed with MDD and 268 healthy controls. Childhood trauma was evaluated using the 28-item Childhood Trauma Questionnaire-Short Form. Neurocognitive abilities, encompassing sustained attention, vigilance, visual memory, and executive functioning, were measured by the Cambridge Neuropsychological Testing Automated Battery. Results: Multivariable linear regressions revealed that childhood trauma and MDD diagnosis were independently associated with neurocognitive impairment. Physical neglect was associated with impaired visual memory and working memory. MDD diagnosis is associated with working memory and planning. Interactive analysis revealed that physical/sexual abuse was associated with a high level of vigilance and that emotional neglect was linked with better performance on cognitive flexibility in MDD patients. Furthermore, childhood emotional abuse, physical abuse, and emotional neglect were revealed to be risk factors for developing early-onset, chronic depressive episodes. Conclusion: Thus, specific associations between various childhood traumas and cognitive development in depression are complex phenomena that need further study. [ABSTRACT FROM AUTHOR]

Background: Childhood maltreatment (CM) is closely linked to internet addiction (IA), especially in adolescents with Major Depressive Disorder (MDD). Previous studies have shown that adolescents who experience CM are more likely to develop IA and other psychological problems. This study aims to explore the complex relationship between CM and IA through network analysis, particularly identifying the core symptoms and bridge symptoms to better understand the development of IA in these adolescents. Methods: A cross-sectional study was conducted in seven hospitals in Anhui Province, China, involving 332 adolescents diagnosed with MDD using DSM-5 criteria. The Childhood Trauma Questionnaire - Short Form (CTQ-SF) and the Internet Addiction Test (IAT) were used to assess CM and IA symptoms, respectively. Gender-based network analysis was also performed. Results: Network analysis constructed a CM-IA network and identified core and bridge symptoms. "Depress/moody/nervous being offline", "Request an extension for longer time", "Sleep loss due to late-night logins", and "emotional abuse" emerged as central symptoms within the CM-IA network. Additionally, "emotional abuse", "sexual abuse", and "complaints about online time" were identified as key bridge symptoms linking CM and IA. These symptoms demonstrated significant connectivity, underscoring their critical role in linking CM and IA. Conclusion: The findings highlight the complex relationship between CM and IA in adolescents with MDD. Specific symptoms, such as emotional abuse and online-related symptoms, play important roles in understanding and intervening in adolescent IA. Future interventions should target these core and bridge symptoms for more effective prevention and treatment. [ABSTRACT FROM AUTHOR]

Background: The study aimed to explore the influence of gender on the prevalence of various somatic symptoms and their associations with suicidal ideation (SI) among patients with major depressive disorder (MDD). Methods: We recruited 3,275 patients with MDD from the National Survey on Symptomatology of Depression (NSSD), among whom 1,745 patients had SI. The clinical characteristics and the prevalence of somatic symptoms across 20 dimensions in MDD patients with SI were compared between male and female patients. Spearman correlation analysis and logistic regression analysis were used to explore the relationship between somatic symptoms and SI. Results: In patients with SI, 32.2% of female participants attributed the onset of MDD to physical concerns, whereas 27% of male patients held a similar perspective (P = 0.032). Female patients exhibited a higher prevalence of early insomnia (64.6% vs. 70.2%) and a lower prevalence of hypersomnia (17.2% vs. 12.9%) and urinary system symptoms (25.0% vs. 17.8%). Logistic regression analysis indicated that female patients displayed a broader range of somatic symptoms identified as risk factors for SI, including increased appetite, respiratory symptoms, circulatory system symptoms, limb pain, and various others. Conclusion: This study unveils gender-specific patterns in somatic symptoms among MDD patients with SI, highlighting the clinical significance of these symptoms in diagnosis and intervention. Understanding how physical concerns contribute to MDD, especially among females, underscores the need for tailored clinical approaches. Recognizing and addressing these symptoms could guide more effective suicide prevention strategies and enhance MDD management in clinical practice. [ABSTRACT FROM AUTHOR]

Background and objective: Genetic polymorphism studies in families and twins indicated the heritability of depression. However, the association between genes with genetic polymorphism and depression provides various findings and remains unclear. Therefore, we conducted a systematic review and meta-analysis to determine the genes with their polymorphism associated with the symptomatic depression known as major depressive disorder (MDD). Materials and methods: PubMed and Scopus were searched for relevant studies published before May 22, 2023 (1968–2023), and 62 were selected for this review. The study's bias risk was investigated using the Newcastle–Ottawa scale. Gene functional enrichment analysis was investigated for molecular function (MF) and biological process (BP) and pathways. A meta-analysis of the studied genes that were replicative in the same single nucleotide polymorphism was conducted using a random-effect model. Results: The 49 genes involved in MDD were studied and engaged in several pathways, such as tryptophan metabolism or dopaminergic and serotonergic synapses. Based on gene overlapping in MF and BP, 13 genes with polymorphisms were identified as related to MDD. Most of them were only studied once. Solute carrier family 6 member 4 (SLC6A4) overlapping between MF and BP and brain-derived neurotrophic factor (BDNF) as unique to BP were replicative studied and used in the meta-analysis. The polymorphism of SLC6A4 SS and LS genotypes increased the occurrence of MDD development but not significantly [odd ratio (OR) = 1.39; 95% confidence interval (CI) = 0.87–2.22; P = 0.16 and OR = 1.13; 95% CI = 0.84–1.53; P = 0.42, respectively]. A similar result was observed for BDNF rs6265 GG (OR = 1.26; 95% CI = 0.78–2.06; P = 0.35) and BDNF rs6265 AA genotypes (OR = 1.12; 95% CI = 0.77–1.64; P = 0.56). These studies indicated low bias and significant heterogeneity. Conclusion: At least 13 studied genes with polymorphisms were involved in MDD development according to MF and BP, but not significantly. These results suggest that MDD development risk factors might require genetic and other factors for interaction and induction. [ABSTRACT FROM AUTHOR]

Objective: Major depressive disorder (MDD) is often accompanied by psychotic symptoms. However, few studies have examined the relationship between psychotic symptoms and endocrine factors in adolescent patients with MDD. Therefore, this study aimed to investigate the prevalence and related endocrine clinical factors of psychotic symptoms in Chinese adolescent patients with MDD. Methods: In total, 601 patients (aged 12–18) with MDD were recruited. The Patient Health Questionnaire – 9 items (PHQ – 9) was utilized for assessing depressive symptoms. Psychotic symptoms were assessed through clinical interviews. Prolactin (PRL), thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), and free thyroxine (FT4) were also measured. Results: The incidence of psychotic symptoms in adolescent patients with MDD was 22.6%. The findings demonstrated that age, self-harming behavior, PHQ-9 score, FT4, and normalized PRL were independently associated with psychotic symptoms in patients with MDD (All p < 0.05). Conclusions: PRL and FT4 levels are more likely to be abnormally elevated in major depressive adolescents with psychotic symptoms. Prolactin and thyroid hormones in patients with MDD should be paid more attention. [ABSTRACT FROM AUTHOR]

Abstract Backgrounds Patients with major depressive disorder (MDD) have a high rate of metabolic syndrome (MetS), which could worsen disease progression. One of the most serious progressions in MDD is suicide attempts (SAs). Previous studies have found gender differences in MetS and SAs among MDD patients respectively. Therefore, we aimed to explore gender differences of SAs in first-episode and drug-naïve (FEDN) MDD patients with comorbid MetS. Methods 1718 outpatients with FEDN MDD were recruited. Depression, anxiety and psychotic symptoms were evaluated using the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA) and Positive and Negative Syndrome Scale (PANSS) positive subscale, respectively. Blood sugar, blood fat, blood pressure and body mass index (BMI) were measured to evaluate MetS. Results 34.4% patients with FEDN MDD were diagnosed as MetS and those subjects with or without MetS differed in the distribution of SAs and gender. In MetS subgroup, 29.5% and 29.7% of male and female subjects had SAs respectively, without significant differences. However, compared with non-suicide attempters, suicide attempters had higher level of blood pressure in female subjects, while there are no differences in any clinical variables in male subjects. Additionally, the influencing factors for SAs differed by gender. The HAMA scores and BMI were variables associated with SAs in male patients while HAMA scores, marital status and systolic blood pressure (SBP) were associated with SAs in female patients. Furthermore, the receiver operating characteristics (ROC) curves, demonstrating the combination all influencing factors by gender, showed good performance and model accuracy. Conclusions In FEDN MDD patients with comorbid MetS, there were no gender differences in SAs. However, clinical characteristics and influencing factors of SAs differed in different gender groups.

Abstract Objective An alternative metric for evaluating insulin resistance (IR) is the triglyceride glucose-body mass index (TyG-BMI). However, it is yet unclear how TyG-BMI and suicide attempts (SA) are related. The objective of this research was to explore the correlation between the TyG-BMI index and SA in individuals with untreated first-episode (UFE) major depressive disorder (MDD) in Shanxi Province. Methods This cross-sectional study was conducted from September 2016 to December 2018 in the psychiatric outpatient clinic of Taiyuan General Hospital and included 1718 patients with UFE MDD, with a mean age of 34.9 ± 12.4 years. The relationship between TyG-BMI and SA was assessed using logistic regression modeling. We investigated threshold effects using a two-piecewise linear regression model. Results Taking into consideration the potential influence of confounding variables, a comprehensive multivariate logistic regression analysis was conducted, which demonstrated the absence of a statistically significant association between the TyG-BMI index and the occurrence of SA, as evidenced by P-values that were all greater than 0.05. On the other hand, the visual analysis of the smoothed plots revealed a U-shaped relationship between the TyG-BMI index and the incidence of SA, with a notable inflection occurring at a TyG-BMI value of around 210. It was observed that the effect sizes flanking the inflection point, accompanied by their 95% confidence intervals, were 0.985 (95% CI: 0.972 to 0.999, P = 0.031) and 1.012 (95% CI: 1.003 to 1.047, P = 0.005), respectively. Conclusions In UFE MDD patients, a U-shaped link was observed between TyG-BMI and SA, with the minimal SA incidence noted at a TyG-BMI level of 210, signifying that an augmented risk for SA might be connected to both diminished and augmented TyG-BMI levels.

Abstract Background Previous studies demonstrated thyroid stimulating hormone (TSH) plays an important role in regulating lipid metabolism, but the relationship between the two is controversial. Meanwhile, it has not been reported in a population with major depressive disorder (MDD). Methods We divided 1718 first-episode and drug naïve patients with MDD into a TSH abnormal group (TSH-AB) and a TSH normal group (TSH-NOR). The participants in the two groups were assessed by the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and the positive subscale of Positive and Negative Syndrome Scale. The patients’ blood was tested for TSH, free T3, free T4, fasting blood glucose, lipid indexes and body mass index was recorded. Results The participants in the TSH-AB group had significantly higher HAMD scores, HAMA scores and total scores of positive symptoms, as well as higher incidence of suicide attempts than those in the TSH-NOR group, accompanied by significantly higher thyroglobulin antibodies, thyroid peroxidase antibodies, fasting blood glucose values, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels compared with those of TSH-NOR patients. However, the high-density lipoprotein cholesterol (HDL-C) of TSH-AB patients was lower than those of TSH-NOR patients. TSH values were positively correlated with TC, TG, and LDL-C values, and negatively correlated with HDL-C value. Conclusion TSH was highly correlated with abnormal lipid metabolism in patients with MDD. The specific molecular mechanism of the relationship between TSH, lipid metabolism and the development of depression needs to be further in-depth investigation.

Abstract Background Neurocognitive impairment is one of the prominent manifestations of major depressive disorder (MDD). Childhood trauma enhances vulnerability to developing MDD and contributes to neurocognitive dysfunctions. However, the distinct impacts of different types of childhood trauma on neurocognitive processes in MDD remain unclear. Methods This study comprised 186 individuals diagnosed with MDD and 268 healthy controls. Childhood trauma was evaluated using the 28-item Childhood Trauma Questionnaire-Short Form. Neurocognitive abilities, encompassing sustained attention, vigilance, visual memory, and executive functioning, were measured by the Cambridge Neuropsychological Testing Automated Battery. Results Multivariable linear regressions revealed that childhood trauma and MDD diagnosis were independently associated with neurocognitive impairment. Physical neglect was associated with impaired visual memory and working memory. MDD diagnosis is associated with working memory and planning. Interactive analysis revealed that physical/sexual abuse was associated with a high level of vigilance and that emotional neglect was linked with better performance on cognitive flexibility in MDD patients. Furthermore, childhood emotional abuse, physical abuse, and emotional neglect were revealed to be risk factors for developing early-onset, chronic depressive episodes. Conclusion Thus, specific associations between various childhood traumas and cognitive development in depression are complex phenomena that need further study.

Abstract Background Childhood maltreatment (CM) is closely linked to internet addiction (IA), especially in adolescents with Major Depressive Disorder (MDD). Previous studies have shown that adolescents who experience CM are more likely to develop IA and other psychological problems. This study aims to explore the complex relationship between CM and IA through network analysis, particularly identifying the core symptoms and bridge symptoms to better understand the development of IA in these adolescents. Methods A cross-sectional study was conducted in seven hospitals in Anhui Province, China, involving 332 adolescents diagnosed with MDD using DSM-5 criteria. The Childhood Trauma Questionnaire - Short Form (CTQ-SF) and the Internet Addiction Test (IAT) were used to assess CM and IA symptoms, respectively. Gender-based network analysis was also performed. Results Network analysis constructed a CM-IA network and identified core and bridge symptoms. “Depress/moody/nervous being offline”, “Request an extension for longer time”, “Sleep loss due to late-night logins”, and “emotional abuse” emerged as central symptoms within the CM-IA network. Additionally, “emotional abuse”, “sexual abuse”, and “complaints about online time” were identified as key bridge symptoms linking CM and IA. These symptoms demonstrated significant connectivity, underscoring their critical role in linking CM and IA. Conclusion The findings highlight the complex relationship between CM and IA in adolescents with MDD. Specific symptoms, such as emotional abuse and online-related symptoms, play important roles in understanding and intervening in adolescent IA. Future interventions should target these core and bridge symptoms for more effective prevention and treatment.

Abstract Background and objective Genetic polymorphism studies in families and twins indicated the heritability of depression. However, the association between genes with genetic polymorphism and depression provides various findings and remains unclear. Therefore, we conducted a systematic review and meta-analysis to determine the genes with their polymorphism associated with the symptomatic depression known as major depressive disorder (MDD). Materials and methods PubMed and Scopus were searched for relevant studies published before May 22, 2023 (1968–2023), and 62 were selected for this review. The study’s bias risk was investigated using the Newcastle–Ottawa scale. Gene functional enrichment analysis was investigated for molecular function (MF) and biological process (BP) and pathways. A meta-analysis of the studied genes that were replicative in the same single nucleotide polymorphism was conducted using a random-effect model. Results The 49 genes involved in MDD were studied and engaged in several pathways, such as tryptophan metabolism or dopaminergic and serotonergic synapses. Based on gene overlapping in MF and BP, 13 genes with polymorphisms were identified as related to MDD. Most of them were only studied once. Solute carrier family 6 member 4 (SLC6A4) overlapping between MF and BP and brain-derived neurotrophic factor (BDNF) as unique to BP were replicative studied and used in the meta-analysis. The polymorphism of SLC6A4 SS and LS genotypes increased the occurrence of MDD development but not significantly [odd ratio (OR) = 1.39; 95% confidence interval (CI) = 0.87–2.22; P = 0.16 and OR = 1.13; 95% CI = 0.84–1.53; P = 0.42, respectively]. A similar result was observed for BDNF rs6265 GG (OR = 1.26; 95% CI = 0.78–2.06; P = 0.35) and BDNF rs6265 AA genotypes (OR = 1.12; 95% CI = 0.77–1.64; P = 0.56). These studies indicated low bias and significant heterogeneity. Conclusion At least 13 studied genes with polymorphisms were involved in MDD development according to MF and BP, but not significantly. These results suggest that MDD development risk factors might require genetic and other factors for interaction and induction.

Abstract Background The study aimed to explore the influence of gender on the prevalence of various somatic symptoms and their associations with suicidal ideation (SI) among patients with major depressive disorder (MDD). Methods We recruited 3,275 patients with MDD from the National Survey on Symptomatology of Depression (NSSD), among whom 1,745 patients had SI. The clinical characteristics and the prevalence of somatic symptoms across 20 dimensions in MDD patients with SI were compared between male and female patients. Spearman correlation analysis and logistic regression analysis were used to explore the relationship between somatic symptoms and SI. Results In patients with SI, 32.2% of female participants attributed the onset of MDD to physical concerns, whereas 27% of male patients held a similar perspective (P = 0.032). Female patients exhibited a higher prevalence of early insomnia (64.6% vs. 70.2%) and a lower prevalence of hypersomnia (17.2% vs. 12.9%) and urinary system symptoms (25.0% vs. 17.8%). Logistic regression analysis indicated that female patients displayed a broader range of somatic symptoms identified as risk factors for SI, including increased appetite, respiratory symptoms, circulatory system symptoms, limb pain, and various others. Conclusion This study unveils gender-specific patterns in somatic symptoms among MDD patients with SI, highlighting the clinical significance of these symptoms in diagnosis and intervention. Understanding how physical concerns contribute to MDD, especially among females, underscores the need for tailored clinical approaches. Recognizing and addressing these symptoms could guide more effective suicide prevention strategies and enhance MDD management in clinical practice.

Abstract Objective Major depressive disorder (MDD) is often accompanied by psychotic symptoms. However, few studies have examined the relationship between psychotic symptoms and endocrine factors in adolescent patients with MDD. Therefore, this study aimed to investigate the prevalence and related endocrine clinical factors of psychotic symptoms in Chinese adolescent patients with MDD. Methods In total, 601 patients (aged 12–18) with MDD were recruited. The Patient Health Questionnaire – 9 items (PHQ – 9) was utilized for assessing depressive symptoms. Psychotic symptoms were assessed through clinical interviews. Prolactin (PRL), thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), and free thyroxine (FT4) were also measured. Results The incidence of psychotic symptoms in adolescent patients with MDD was 22.6%. The findings demonstrated that age, self-harming behavior, PHQ-9 score, FT4, and normalized PRL were independently associated with psychotic symptoms in patients with MDD (All p

Abstract Background Major depressive disorder (MDD) is a disabling mental illness that can affect all aspects of daily life and is a leading cause of healthcare resource utilisation (HCRU). Aims We aimed to characterise patients with MDD with moderate-to-high-suicide-intent, compare their HCRU to patients with MDD without moderate-to-high-suicide-intent, and better understand their patient pathways. Methods This retrospective cohort study used data collected from primary care electronic health records from Clinical Practice Research Datalink (CPRD), linked to Hospital Episode Statistics, Mental Health Services Data Set, and Office for National Statistics in England. Adults diagnosed with ≥ 1 MDD diagnosis between 04/2007 and 11/2015 were categorised by suicide intent. Results 307,476 patients with MDD were included (294,259 patients without moderate-to-high-suicide-intent and 13,217 with moderate-to-high-suicide-intent). Patients with MDD with moderate-to-high-suicide-intent were younger on average (39.0 vs. 44.8 years) and included a lower percentage of females (58% vs. 65%) compared to patients without moderate-to-high-suicide-intent. HCRU was greater among patients with moderate-to-high-suicide-intent than patients without moderate-to-high-suicide-intent during the first follow-up year for general practitioner consultations (38.5 vs. 29.4), psychiatric outpatient visits (1.5 vs. 0.1), psychiatrist visits (3.6 vs. 0.3), emergency visits (1.5 vs. 0.3), and hospitalisations (86% vs. 26%). Overall, 56% of patients with moderate-to-high-suicide-intent had an antidepressant prescription within 30 days from the initial moderate-to-high-suicide-intent. Conclusions Patients with MDD and moderate-to-high-suicide-intent were younger, included more males and incurred greater HCRU than those without moderate-to-high-suicide-intent. These results suggest a greater need for effective medical care and appropriate treatments for patients with moderate-to-high-suicide-intent, which could help reduce associated symptoms, mortality, and HCRU.

Abstract Background Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) are two high-prevalent conditions where the Endocannabinoid system (ECS) is believed to play an important role. The ECS regulates how different neurotransmitters interact in both disorders, which is crucial for controlling emotions and responses to stress and reward stimuli. Measuring peripheral endocannabinoids (eCBs) in human serum and plasma can help overcome the limitations of detecting endocannabinoid levels in the brain. This systematic review aims to identify levels of peripheral eCBs in patients with MDD and/or AUD and find eCBs to use as diagnostic, prognostic biomarkers, and potential therapeutic targets. Methods We conducted a systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines from the earliest manuscript until October 22, 2023, in three electronic databases. We included studies of human adults who had a current diagnosis of AUD and/or MDD and evaluated plasma or serum endocannabinoids. We carefully considered known variables that may affect endocannabinoid levels. Results We included 17 articles in this systematic review, which measured peripheral eCBs in 170 AUD and 359 MDD patients. Stressors increase peripheral 2-arachidonyl-glycerol (2-AG) concentrations, and 2-AG may be a particular feature of depression severity and chronicity. Anxiety symptoms are negatively correlated with anandamide (AEA) concentrations, and AEA significantly increases during early abstinence in AUD. Studies suggest a negative correlation between Oleoylethanolamide (OEA) and length of abstinence in AUD patients. They also show a significant negative correlation between peripheral levels of AEA and OEA and fatty acid amide hydrolase (FAAH) activity. Eicosapentaenoylethanolamide (EPEA) is correlated to clinical remission rates in depression. Included studies show known variables such as gender, chronicity, symptom severity, comorbid psychiatric symptoms, length of abstinence in the case of AUD, and stress-inducibility that can affect peripheral eCBs. Conclusions This systematic review highlights the important role that the ECS plays in MDD and AUD. Peripheral eCBs appear to be useful biomarkers for these disorders, and further research may identify potential therapeutic targets. Using accessible biological samples such as blood in well-designed clinical studies is crucial to develop novel therapies for these disorders.

Abstract Background The different symptoms of major depressive disorder (MDD) in adolescents compared to adults suggested there may be differences in the pathophysiology between adolescents and adults with MDD. However, despite the amygdala being considered critical in the pathophysiology, there was limited knowledge about the commonalities and differences in the resting-state functional connectivity (rsFC) of amygdala subregions in MDD patients of different age groups. Methods In the current study, 65 adolescents (46 with MDD and 19 controls) and 91 adults (35 with MDD and 56 controls) were included. A seed-based functional connectivity analysis was performed for each of the amygdala subregions. A 2 × 2 ANOVA was used to analyze the main effect of age, diagnosis, and their interaction on the rsFC of each subregion. Results A significant main effect of age was revealed in the rsFC of bilateral centromedial (CM) subregions and right laterobasal (LB) subregion with several brain regions in the limbic system and frontoparietal network. The significant main effect of diagnosis showed MDD patients of different ages showed higher connectivity than controls between the right LB and left middle frontal gyrus (MFG). Conclusions The rsFC of specific amygdala subregions with brain regions in the limbic system and frontoparietal network is affected by age, indicating a distinct amygdala connectivity profile in adolescents. The decreased rsFC between the right LB and the left MFG in adolescents and adults with MDD could serve as a diagnostic biomarker and a target of nonpharmacological treatment for MDD.

Abstract Background Bipolar depression (BPD) is often misdiagnosed as a major depressive disorder (MDD) in clinical practice, which may be attributed to a lack of robust biomarkers indicative of differentiated diagnosis. This study analysed the differences in various hormones and inflammatory markers to explore peripheral biomarkers that differentiate BPD from MDD patients. Methods A total of 2,048 BPD and MDD patients were included. A panel of blood tests was performed to determine the levels of sex hormones, stress hormones, and immune-related indicators. Propensity score matching (PSM) was used to control for the effect of potential confounders between two groups and further a receiver operating characteristic (ROC) curve was used to analyse the potential biomarkers for differentiating BPD from MDD. Results Compared to patients with MDD, patients with BPD expressed a longer duration of illness, more hospitalisations within five years, and an earlier age of onset, along with fewer comorbid psychotic symptoms. In terms of biochemical parameters, MDD patients presented higher IgA and IgM levels, while BPD patients featured more elevated neutrophil and monocyte counts. ROC analysis suggested that combined biological indicators and clinical features could moderately distinguish between BPD and MDD. In addition, different biological features exist in BPD and MDD patients of different ages and sexes. Conclusions Differential peripheral biological parameters were observed between BPD and MDD, which may be age-sex specific, and a combined diagnostic model that integrates clinical characteristics and biochemical indicators has a moderate accuracy in distinguishing BPD from MDD.

Abstract Background Existing evidence suggests that alterations in the gut microbiome are closely associated with major depressive disorder (MDD). We aimed to reveal the causal relationships between MDD and various microbial taxa in the gut. Methods We used the two-sample Mendelian randomization (TSMR) to explore the bidirectional causal effects between gut microbiota and MDD. The genome-wide association studies summary results of gut microbiota were obtained from two large consortia, the MibioGen consortium and the Dutch Microbiome Project, which we analyzed separately. Results Our TSMR analysis identified 10 gut bacterial taxa that were protective against MDD, including phylum Actinobacteria, order Clostridiales, and family Bifidobacteriaceae (OR: 0.96 ∼ 0.98). Ten taxa were associated with an increased risk of MDD, including phyla Firmicutes and Proteobacteria, class Actinobacteria, and genus Alistipes (OR: 1.01 ∼ 1.09). On the other hand, MDD may decrease the abundance of 12 taxa, including phyla Actinobacteria and Firmicutes, families Bifidobacteriaceae and Defluviitaleaceae (OR: 0.63 ∼ 0.88). MDD may increase the abundance of 8 taxa, including phylum Bacteroidetes, genera Parabacteroides, and Bacteroides (OR: 1.12 ∼ 1.43). Conclusions Our study supports that there are mutual causal relationships between certain gut microbiota and the development of MDD suggesting that gut microbiota may be targeted in the treatment of MDD.

Abstract Objectives Electroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines. Methods In this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. Results We identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT. Conclusion Even if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long.

Abstract Background Cognitive impairment is a recognized fundamental deficit in individuals diagnosed with schizophrenia (SZ), bipolar II disorder (BD II), and major depressive disorder (MDD), among other psychiatric disorders. However, limited research has compared cognitive function among first-episode drug-naïve individuals with SZ, BD II, or MDD. Methods This study aimed to address this gap by assessing the cognitive performance of 235 participants (40 healthy controls, 58 SZ patients, 72 BD II patients, and 65 MDD patients) using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after 12 weeks of treatment in SZ, BD II, and MDD patients. To clarify, the healthy controls only underwent RBANS testing at baseline, whereas the patient groups were assessed before and after treatment. The severity of symptoms in SZ patients was measured using the Positive and Negative Syndrome Scale (PANSS), and depression in BD II and MDD patients was assessed using the Hamilton Depression Scale-24 items (HAMD-24 items). Results Two hundred participants completed the 12-week treatment period, with 35 participants dropping out due to various reasons. This group included 49 SZ patients, 58 BD II patients, and 53 MDD patients. Among SZ patients, significant improvements in immediate and delayed memory were observed after 12 weeks of treatment compared to their initial scores. Similarly, BD II patients showed significant improvement in immediate and delayed memory following treatment. However, there were no significant differences in RBANS scores for MDD patients after 12 weeks of treatment. Conclusions In conclusion, the findings of this study suggest that individuals with BD II and SZ may share similar deficits in cognitive domains. It is important to note that standardized clinical treatment may have varying degrees of effectiveness in improving cognitive function in patients with BD II and SZ, which could potentially alleviate cognitive dysfunction.

Abstract Objective Accumulating evidence supports the idea that inflammation may contribute to the pathophysiology of major depressive disorder (MDD). Duloxetine, a serotonin-norepinephrine reuptake inhibitor, exhibits anti-inflammatory effects both in vitro and in vivo. In this study, we investigated the impact of duloxetine on changes in serum proinflammatory cytokine levels among individuals diagnosed with MDD. Methods A cohort of 23 drug-naïve individuals diagnosed with MDD and 23 healthy controls were included in this study. The severity of depressive symptoms was evaluated using the 24-item Hamilton Depression Scale (HAMD-24). A panel of 7 proinflammatory cytokines, including interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), were quantified using multiplex Luminex assays. The levels of serum cytokines in healthy controls and patients with MDD were compared at baseline. All patients received duloxetine at a dosage range of 40–60 mg/day for a duration of 4 weeks. The HAMD-24 scores and serum cytokine levels were compared before and after duloxetine treatment. Results Compared with healthy controls, patients with MDD had significantly greater levels of IL-2, IL-6, IL-8, IL-12, TNF-α, and IFN-γ (P 0.05). Conclusions These findings present compelling evidence, potentially for the first time, indicating that duloxetine treatment may effectively reduce the serum concentrations of IL-8, IL-12, and IFN-γ in individuals diagnosed with MDD. However, the precise mechanisms underlying this effect remain unclear and warrant further investigation.

Abstract Introduction Psychotic depression (PD) is characterized by the co-occurrence of emotional dysfunction and psychotic symptoms such as delusions and hallucinations with poor clinical outcomes. TSH may involve in the development of PD. This study aims to explore relationship between TSH and PD. Methods A total of 1718 outpatients diagnosed as FEDN MDD were recruited in this study. The relationship between PD and TSH was evaluated using multivariable binary logistic regression analysis. To assess the presence of non-linear associations, a two-piecewise linear regression model was employed. Furthermore, interaction and stratified analyses were conducted with respect to sex, education, marital status, comorbid anxiety, and suicide attempt. Results Multivariable logistic regression analysis revealed that TSH was positively associated with the risk of PD after adjusting for confounders (OR = 1.26, 95% CI: 1.11 to 1.43; p

Background: Major depressive disorder (MDD) is a disabling mental illness that can affect all aspects of daily life and is a leading cause of healthcare resource utilisation (HCRU). Aims: We aimed to characterise patients with MDD with moderate-to-high-suicide-intent, compare their HCRU to patients with MDD without moderate-to-high-suicide-intent, and better understand their patient pathways. Methods: This retrospective cohort study used data collected from primary care electronic health records from Clinical Practice Research Datalink (CPRD), linked to Hospital Episode Statistics, Mental Health Services Data Set, and Office for National Statistics in England. Adults diagnosed with ≥ 1 MDD diagnosis between 04/2007 and 11/2015 were categorised by suicide intent. Results: 307,476 patients with MDD were included (294,259 patients without moderate-to-high-suicide-intent and 13,217 with moderate-to-high-suicide-intent). Patients with MDD with moderate-to-high-suicide-intent were younger on average (39.0 vs. 44.8 years) and included a lower percentage of females (58% vs. 65%) compared to patients without moderate-to-high-suicide-intent. HCRU was greater among patients with moderate-to-high-suicide-intent than patients without moderate-to-high-suicide-intent during the first follow-up year for general practitioner consultations (38.5 vs. 29.4), psychiatric outpatient visits (1.5 vs. 0.1), psychiatrist visits (3.6 vs. 0.3), emergency visits (1.5 vs. 0.3), and hospitalisations (86% vs. 26%). Overall, 56% of patients with moderate-to-high-suicide-intent had an antidepressant prescription within 30 days from the initial moderate-to-high-suicide-intent. Conclusions: Patients with MDD and moderate-to-high-suicide-intent were younger, included more males and incurred greater HCRU than those without moderate-to-high-suicide-intent. These results suggest a greater need for effective medical care and appropriate treatments for patients with moderate-to-high-suicide-intent, which could help reduce associated symptoms, mortality, and HCRU. [ABSTRACT FROM AUTHOR]

Background: Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) are two high-prevalent conditions where the Endocannabinoid system (ECS) is believed to play an important role. The ECS regulates how different neurotransmitters interact in both disorders, which is crucial for controlling emotions and responses to stress and reward stimuli. Measuring peripheral endocannabinoids (eCBs) in human serum and plasma can help overcome the limitations of detecting endocannabinoid levels in the brain. This systematic review aims to identify levels of peripheral eCBs in patients with MDD and/or AUD and find eCBs to use as diagnostic, prognostic biomarkers, and potential therapeutic targets. Methods: We conducted a systematic literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines from the earliest manuscript until October 22, 2023, in three electronic databases. We included studies of human adults who had a current diagnosis of AUD and/or MDD and evaluated plasma or serum endocannabinoids. We carefully considered known variables that may affect endocannabinoid levels. Results: We included 17 articles in this systematic review, which measured peripheral eCBs in 170 AUD and 359 MDD patients. Stressors increase peripheral 2-arachidonyl-glycerol (2-AG) concentrations, and 2-AG may be a particular feature of depression severity and chronicity. Anxiety symptoms are negatively correlated with anandamide (AEA) concentrations, and AEA significantly increases during early abstinence in AUD. Studies suggest a negative correlation between Oleoylethanolamide (OEA) and length of abstinence in AUD patients. They also show a significant negative correlation between peripheral levels of AEA and OEA and fatty acid amide hydrolase (FAAH) activity. Eicosapentaenoylethanolamide (EPEA) is correlated to clinical remission rates in depression. Included studies show known variables such as gender, chronicity, symptom severity, comorbid psychiatric symptoms, length of abstinence in the case of AUD, and stress-inducibility that can affect peripheral eCBs. Conclusions: This systematic review highlights the important role that the ECS plays in MDD and AUD. Peripheral eCBs appear to be useful biomarkers for these disorders, and further research may identify potential therapeutic targets. Using accessible biological samples such as blood in well-designed clinical studies is crucial to develop novel therapies for these disorders. [ABSTRACT FROM AUTHOR]

Background: Bipolar depression (BPD) is often misdiagnosed as a major depressive disorder (MDD) in clinical practice, which may be attributed to a lack of robust biomarkers indicative of differentiated diagnosis. This study analysed the differences in various hormones and inflammatory markers to explore peripheral biomarkers that differentiate BPD from MDD patients. Methods: A total of 2,048 BPD and MDD patients were included. A panel of blood tests was performed to determine the levels of sex hormones, stress hormones, and immune-related indicators. Propensity score matching (PSM) was used to control for the effect of potential confounders between two groups and further a receiver operating characteristic (ROC) curve was used to analyse the potential biomarkers for differentiating BPD from MDD. Results: Compared to patients with MDD, patients with BPD expressed a longer duration of illness, more hospitalisations within five years, and an earlier age of onset, along with fewer comorbid psychotic symptoms. In terms of biochemical parameters, MDD patients presented higher IgA and IgM levels, while BPD patients featured more elevated neutrophil and monocyte counts. ROC analysis suggested that combined biological indicators and clinical features could moderately distinguish between BPD and MDD. In addition, different biological features exist in BPD and MDD patients of different ages and sexes. Conclusions: Differential peripheral biological parameters were observed between BPD and MDD, which may be age-sex specific, and a combined diagnostic model that integrates clinical characteristics and biochemical indicators has a moderate accuracy in distinguishing BPD from MDD. [ABSTRACT FROM AUTHOR]

Background: The different symptoms of major depressive disorder (MDD) in adolescents compared to adults suggested there may be differences in the pathophysiology between adolescents and adults with MDD. However, despite the amygdala being considered critical in the pathophysiology, there was limited knowledge about the commonalities and differences in the resting-state functional connectivity (rsFC) of amygdala subregions in MDD patients of different age groups. Methods: In the current study, 65 adolescents (46 with MDD and 19 controls) and 91 adults (35 with MDD and 56 controls) were included. A seed-based functional connectivity analysis was performed for each of the amygdala subregions. A 2 × 2 ANOVA was used to analyze the main effect of age, diagnosis, and their interaction on the rsFC of each subregion. Results: A significant main effect of age was revealed in the rsFC of bilateral centromedial (CM) subregions and right laterobasal (LB) subregion with several brain regions in the limbic system and frontoparietal network. The significant main effect of diagnosis showed MDD patients of different ages showed higher connectivity than controls between the right LB and left middle frontal gyrus (MFG). Conclusions: The rsFC of specific amygdala subregions with brain regions in the limbic system and frontoparietal network is affected by age, indicating a distinct amygdala connectivity profile in adolescents. The decreased rsFC between the right LB and the left MFG in adolescents and adults with MDD could serve as a diagnostic biomarker and a target of nonpharmacological treatment for MDD. [ABSTRACT FROM AUTHOR]

Background: Existing evidence suggests that alterations in the gut microbiome are closely associated with major depressive disorder (MDD). We aimed to reveal the causal relationships between MDD and various microbial taxa in the gut. Methods: We used the two-sample Mendelian randomization (TSMR) to explore the bidirectional causal effects between gut microbiota and MDD. The genome-wide association studies summary results of gut microbiota were obtained from two large consortia, the MibioGen consortium and the Dutch Microbiome Project, which we analyzed separately. Results: Our TSMR analysis identified 10 gut bacterial taxa that were protective against MDD, including phylum Actinobacteria, order Clostridiales, and family Bifidobacteriaceae (OR: 0.96 ∼ 0.98). Ten taxa were associated with an increased risk of MDD, including phyla Firmicutes and Proteobacteria, class Actinobacteria, and genus Alistipes (OR: 1.01 ∼ 1.09). On the other hand, MDD may decrease the abundance of 12 taxa, including phyla Actinobacteria and Firmicutes, families Bifidobacteriaceae and Defluviitaleaceae (OR: 0.63 ∼ 0.88). MDD may increase the abundance of 8 taxa, including phylum Bacteroidetes, genera Parabacteroides, and Bacteroides (OR: 1.12 ∼ 1.43). Conclusions: Our study supports that there are mutual causal relationships between certain gut microbiota and the development of MDD suggesting that gut microbiota may be targeted in the treatment of MDD. [ABSTRACT FROM AUTHOR]

Objectives: Electroconvulsive therapy (ECT) is one of the most effective treatments in mood disorders, mainly in major depressive episode (MDE) in the context of either unipolar (MDD) or bipolar disorder (BD). However, ECT remains a neglected and underused treatment. Older people are at high risk patients for the development of adverse drug reactions. In this context, we sought to determine the duration of MDEs and the number of lines of treatment before the initiation of ECT in patients aged 65 years or over according to the presence or absence of first-line indications for using ECT from international guidelines. Methods: In this multicenter, retrospective study including patients aged 65 years or over with MDEs in MDD or BD who have been treated with ECT for MDEs, data on the duration of MDEs and the number of lines of treatment received before ECT were collected. The reasons for using ECT, specifically first-line indications (suicidality, urgency, presence of catatonic and psychotic features, previous ECT response, patient preference) were recorded. Statistical comparisons between groups used standard statistical tests. Results: We identified 335 patients. The mean duration of MDEs before ECT was about 9 months. It was significantly shorter in BD than in MDD- about 7 and 10 months, respectively. The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. The presence of first-line indications for using ECT from guidelines did not reduce the duration of MDEs before ECT, except where there was a previous response to ECT. The first-line indications reduced the number of lines of treatment before starting ECT. Conclusion: Even if ECT seems to be a key treatment in the elderly population due to its efficacity and safety for MDEs, the delay before this treatment is still too long. Key points: • The mean duration of depression before ECT was 8.8 months. • The duration before ECT for Bipolar Disorder (vs Major Depressive Disorder) is shorter. • The co-occurrence of chronic medical disease increased the duration before ECT in the MDD group. • Focusing on the first-line indications for using ECT, only a previous response reduces the duration of depression before ECT. [ABSTRACT FROM AUTHOR]

Objective: Accumulating evidence supports the idea that inflammation may contribute to the pathophysiology of major depressive disorder (MDD). Duloxetine, a serotonin-norepinephrine reuptake inhibitor, exhibits anti-inflammatory effects both in vitro and in vivo. In this study, we investigated the impact of duloxetine on changes in serum proinflammatory cytokine levels among individuals diagnosed with MDD. Methods: A cohort of 23 drug-naïve individuals diagnosed with MDD and 23 healthy controls were included in this study. The severity of depressive symptoms was evaluated using the 24-item Hamilton Depression Scale (HAMD-24). A panel of 7 proinflammatory cytokines, including interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), were quantified using multiplex Luminex assays. The levels of serum cytokines in healthy controls and patients with MDD were compared at baseline. All patients received duloxetine at a dosage range of 40–60 mg/day for a duration of 4 weeks. The HAMD-24 scores and serum cytokine levels were compared before and after duloxetine treatment. Results: Compared with healthy controls, patients with MDD had significantly greater levels of IL-2, IL-6, IL-8, IL-12, TNF-α, and IFN-γ (P < 0.05). Moreover, there was a significant decrease in HAMD-24 scores observed pre- and post-treatment (t = 13.161, P < 0.001). Furthermore, after 4 weeks of treatment, the serum levels of IL-8 (t = 3.605, P = 0.002), IL-12 (t = 2.559, P = 0.018), and IFN-γ (t = 3.567, P = 0.002) decreased significantly. However, there were no significant differences in other cytokines, including IL-1β, IL-2, IL-6, and TNF-α, before and after treatment (P > 0.05). Conclusions: These findings present compelling evidence, potentially for the first time, indicating that duloxetine treatment may effectively reduce the serum concentrations of IL-8, IL-12, and IFN-γ in individuals diagnosed with MDD. However, the precise mechanisms underlying this effect remain unclear and warrant further investigation. [ABSTRACT FROM AUTHOR]

Abstract Background Major depressive disorder (MDD) is a severe mental illness with high relapse rates and high mortality. Depression not only severely limits psychosocial functioning but also reduces quality of life. It can also negatively affect patients’ clinical parameters, including lipid metabolism markers. This study aimed to investigate the prevalence and risk factors of hyperlipidemia (HL) in patients with MDD who were hospitalized for the first time. Methods In this study, we enrolled 981 patients with MDD who were hospitalized for the first time, collected their demographic data and biochemical indicators, and evaluated their clinical symptoms. We divided the patients into HL and non-HL subgroups based on whether they had co-morbid HL. We compared whether there were significant differences between the two groups regarding demographics and general clinical information. Results A total of 708 of 981 MDD patients were described as being in the hyperlipidemic group, with an incidence of 72.17%. Clinical Global Impression Scale-Severity of Illness (CGI-SI) score and Hamilton Depression Scale (HAMD) score are risk factors for co-morbid HL in patients with MDD. The area under the ROC curve for the CGI-SI and HAMD score and their combined discriminatory ability was approximately 63%, 67%, and 68%, respectively. Conclusion The prevalence of HL was high in patients with MDD who were first hospitalized; Higher HAMD score and CGI-SI score were risk factors for the development of HL in MDD; The HAMD score and the CGI-SI score are predictive of the severity of HL.

Abstract Background Low concentrations of S100B have neurotrophic effects and can promote nerve growth and repair, which plays an essential role in the pathophysiological and histopathological alterations of major depressive disorder (MDD) during disease development. Studies have shown that plasma S100B levels are altered in patients with MDD. In this study, we investigated whether the plasma S100B levels in MDD differ between genders. Methods We studied 235 healthy controls (HCs) (90 males and 145 females) and 185 MDD patients (65 males and 120 females). Plasma S100B levels were detected via multifactor assay. The Mahalanobis distance method was used to detect the outliers of plasma S100B levels in the HC and MDD groups. The Kolmogorov–Smirnov test was used to test the normality of six groups of S100B samples. The Mann–Whitney test and Scheirer-Ray-Hare test were used for the comparison of S100B between diagnoses and genders, and the presence of a relationship between plasma S100B levels and demographic details or clinical traits was assessed using Spearman correlation analysis. Results All individuals in the HC group had plasma S100B levels that were significantly greater than those in the MDD group. In the MDD group, males presented significantly higher plasma S100B levels than females. In the male group, the plasma S100B levels in the HC group were significantly higher than those in the MDD group, while in the female group, no significant difference was found between the HC and MDD groups. In the male MDD subgroup, there was a positive correlation between plasma S100B levels and years of education. In the female MDD subgroup, there were negative correlations between plasma S100B levels and age and suicidal ideation. Conclusions In summary, plasma S100B levels vary with gender and are decreased in MDD patients, which may be related to pathological alterations in glial cells.

Abstract Background Evidence regarding the relationship between fasting blood glucose (FBG) and suicide attempts (SA) in patients with major depressive disorder (MDD) was limited. Therefore, the objective of this research was to investigate whether FBG was independently related to SA in Chinese patients with first-episode drug-naïve (FEDN) MDD after adjusting for other covariates. Methods The present study was a cross-sectional study. A total of 1718 participants (average age: 34.9 ± 12.4 years, 65.8% females) with FEDN MDD were involved in a hospital in China from September 2016 to December 2018. Multiple logistic regression analysis and smooth curve fitting were used to estimate the association between FBG and the risk of SA. The threshold effect was examined by the two-piecewise linear regression model. Interaction and stratified analyses were conducted according to sex, education, marital status, comorbid anxiety, and psychotic symptoms. Results The prevalence of SA in patients with FEDN MDD was 20.1%. The result of fully adjusted binary logistic regression showed FBG was positively associated with the risk of SA (odds ratio (OR) = 1.62, 95% CI: 1.13–2.32). Smoothing plots also revealed a nonlinear relationship between FBG and SA, with the inflection point of FBG being 5.34 mmol/l. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 0.53 (0.32–0.88, P = 0.014) and 1.48 (1.04–2.10, P = 0.030), respectively. Conclusions A U-shaped relationship between FBG and SA in FEDN MDD patients was found, with the lowest risk of SA at a FBG of 5.34 mmol/l, indicating that both the lower and higher FBG levels may lead to an increased risk of SA.

Abstract Objective This study aims to conduct an exhaustive evaluation of Vilazodone's safety in clinical application and to unearth the potential adverse event (AE) risks associated with its utilization based on FDA Adverse Event Reporting System (FAERS) database. Methods This research employed data spanning from the first quarter of 2011 to the third quarter of 2023 from the FAERS database. Various signal detection methodologies, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were utilized to ascertain the correlation between Vilazodone and specific AEs. Results The study compiled a total of 17,439,268 reports of drug AEs, out of which 5,375 were related to Vilazodone. Through signal mining, 125 Preferred Terms (PTs) encompassing 27 System Organ Classes (SOCs) were identified. The findings indicated a higher prevalence among females and patients within the 45 to 65 age bracket. The principal categories of AEs included Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders, with prevalent incidents of Diarrhoea, Nausea, and Insomnia. Moreover, the study identified robust signals of novel potential AEs, notably in areas such as sleep disturbances (Sleep paralysis, Hypnagogic hallucination, Rapid eye movements sleep abnormal, Sleep terror, Terminal insomnia, Tachyphrenia), sexual dysfunctions (Female orgasmic disorder, Orgasm abnormal, Disturbance in sexual arousal, Spontaneous penile erection, Anorgasmia, Sexual dysfunction, Ejaculation delayed), and other symptoms and injuries (Electric shock sensation, Violence-related symptom, Gun shot wound). Conclusion Although Vilazodone presents a positive prospect in the management of MDD, the discovery of AEs linked to its use, particularly the newly identified potential risks such as sleep and sexual dysfunctions, necessitates heightened vigilance among clinicians.

Abstract Background Patients with major depressive disorder (MDD) have an increased risk of breast cancer (BC), implying that these two diseases share similar pathological mechanisms. This study aimed to identify the key pathogenic genes that lead to the occurrence of both triple-negative breast cancer (TNBC) and MDD. Methods Public datasets GSE65194 and GSE98793 were analyzed to identify differentially expressed genes (DEGs) shared by both datasets. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape to identify key PPI genes using cytoHubba. Hub DEGs were obtained from the intersection of hub genes from a PPI network with genes in the disease associated modules of the Weighed Gene Co-expression Network Analysis (WGCNA). Independent datasets (TCGA and GSE76826) and RT-qPCR validated hub gene expression. Results A total of 113 overlapping DEGs were identified between TNBC and MDD. The PPI network was constructed, and 35 hub DEGs were identified. Through WGCNA, the blue, brown, and turquoise modules were recognized as highly correlated with TNBC, while the brown, turquoise, and yellow modules were similarly correlated with MDD. Notably, G3BP1, MAF, NCEH1, and TMEM45A emerged as hub DEGs as they appeared both in modules and PPI hub DEGs. Within the GSE65194 and GSE98793 datasets, G3BP1 and MAF exhibited a significant downregulation in TNBC and MDD groups compared to the control, whereas NCEH1 and TMEM45A demonstrated a significant upregulation. These findings were further substantiated by TCGA and GSE76826, as well as through RT-qPCR validation. Conclusions This study identified G3BP1, MAF, NCEH1 and TMEM45A as key pathological genes in both TNBC and MDD.

Abstract Background While some evidence suggests that l-arginine may improve sexual function and alleviate depression, it has not been investigated in women with depression to assess both its effects on the depression and sexual function concurrently. Methods Patients who had received a diagnosis of major depressive disorder, as determined by predetermined inclusion and exclusion criteria, were enrolled in this triple-blind clinical trial. Patients were divided into two groups: group A, received L-arginine 1 gram twice daily, and group B, received a placebo for four weeks. They were evaluated at baseline, after four and eight weeks with the Hamilton Depression Rating Scale (HDRS), and Rosen’s questionnaire or Female Sexual Function Index (FSFI). Results A decrease in the severity of depression was observed in all patients, which was determined due to Hamilton’s questionnaire (P-value

Abstract Background To explore the demographic and clinical features of current depressive episode that discriminate patients diagnosed with major depressive disorder (MDD) from those with bipolar I (BP-I) and bipolar II (BP-II) disorder who were misdiagnosed as having MDD . Methods The Mini-International Neuropsychiatric Interview (MINI) assessment was performed to establish DSM-IV diagnoses of MDD, and BP-I and BP-II, previously being misdiagnosed as MDD. Demographics, depressive symptoms and psychiatric comorbidities were compared between 1463 patients with BP-I, BP-II and MDD from 8 psychiatric settings in mainland China. A multinomial logistic regression model was performed to assess clinical correlates of diagnoses. Results A total of 14.5% of the enrolled patients initially diagnosed with MDD were eventually diagnosed with BP. Broad illness characteristics including younger age, higher prevalence of recurrence, concurrent dysthymia, suicidal attempts, agitation, psychotic features and psychiatric comorbidities, as well as lower prevalence of insomnia, weight loss and somatic symptoms were featured by patients with BP-I and/or BP-I, compared to those with MDD. Comparisons between BP-I and BP-II versus MDD indicated distinct symptom profiles and comorbidity patterns with more differences being observed between BP-II and MDD, than between BP-I and MDD . Conclusion The results provide evidence of clinically distinguishing characteristics between misdiagnosed BP-I and BP- II versus MDD. The findings have implications for guiding more accurate diagnoses of bipolar disorders.

Abstract Background Major depressive disorder (MDD) is the most disabling and burdensome mental disorder, negatively affecting an individual’s quality of life and daily functioning. the current study was conducted with the aim of investigating the clinical effects of intravenous ketamine on symptoms of MDD and suicidal ideation. Methods The current randomized clinical trial was carried out on 64 patients diagnosed with treatment-resistant major depressive disorder between April and August 2022. The participants were randomly assigned to two groups: the intervention group received a dose of 0.5 mg/kg of ketamine, while the control group received normal saline. The Montgomery-Asberg Depression Scale and Beck’s Suicidal Ideation Scale were utilized to assess depression and suicidal ideation, respectively. Results One hour after the administration of ketamine treatment, there was a notable and significant improvement in both depression symptoms (35.16 ± 8.13 vs. 14.90 ± 10.09) and suicidal ideation (6.74 ± 6.67 vs. 0.42 ± 1.52). Moreover, there were statistically significant differences in depression scores between the two groups at one hour, four hours, one day, three days, one week, one month, and two months after the administration of ketamine (p-value

Abstract Background This study aimed to explore the gut microbiota and inflammatory factor characteristics in major depressive disorder (MDD) patients with anorexia and to analyze the correlation between gut microbiota and inflammatory factors, anorexia, and HAMD scores. Methods 46 MDD patients and 46 healthy controls (HC) were included in the study. The 46 MDD patients were divided into two groups according to whether they had anorexia:20 MDD without anorexia (MDA0 group) and 26 MDD with anorexia (MDA1 group). We used the Hamilton Depression Scale-24 (HAMD-24) to evaluate the depression status of all participants and 16 S ribosomal RNA (16 S rRNA)sequencing to evaluate the composition of the gut microbiota. Inflammatory factors in peripheral blood such as C-reactive protein (CRP) were detected using enzyme-linked immunosorbent assay (ELISA). Spearman’s correlation analysis was used to evaluate the correlation between gut microbiota and inflammatory factors, HAMD scores, and anorexia. Results 1). CRP was significantly higher in the MDA0, MDA1, than HC. 2). An analysis of α-diversity shows: the Simpson and Pielou indices of the HC group are higher than the MDA1 group (P

Abstract Background In addition to having higher negative affect and lower positive affect overall, depressed individuals exhibit heightened affective reactivity to external stimuli than non-depressed individuals. Sleep may contribute to day-to-day fluctuations in depressed individuals, given that sleep disturbance is a common symptom of depression. Yet, little is known about changes in daily affect as a function of nightly sleep duration in depressed adults and non-depressed adults. The current study examined whether and how naturally-occurring sleep duration is associated with negative and positive affect, and how these associations differ between depressed vs. non-depressed adults. Methods Data were drawn from the second wave of the National Study of Daily Experiences (NSDE), a daily diary project of the Midlife in the United States (MIDUS) study. The sample of 2,012 adults (Mage=56.5; 57% female; 84% white) completed eight-day diary interviews via telephone on their daily experiences including nightly sleep duration and negative and positive affect. They also completed assessments of the Composite International Diagnostic Interview-Short form, and depressed status was determined based on DSM-III. Multilevel regression models with linear, quadratic, and cubic terms of sleep duration examined the nonlinear relationship between nightly sleep duration and daily affect. Interaction terms with depression status were added to examine differences between depressed and non-depressed adults. Results Depressed adults exhibited significant and greater fluctuations in daily affect as a function of nightly sleep duration than non-depressed adults. Specifically, the degree of decrease in positive affect and increase in negative affect was greater when depressed adults slept 2 or more hours less or longer than their usual sleep hours. Non-depressed adults exhibited relatively stable daily affect regardless of their nightly sleep hours. Conclusions Sleep duration is nonlinearly associated with affect in daily lives of depressed adults, highlighting that both having too little sleep and excessive sleep are associated with adverse daily affective well-being. Implementing sleep interventions to promote an appropriate sleep duration may help improve daily affect among depressed adults.

Abstract Background Few studies have focused on functional impairment in depressed patients during symptomatic remission. The exact relationship between cognitive performance and functional outcomes of patients with Major depressive disorder (MDD) remains unclear. Methods Participants diagnosed with MDD were included and interviewed at both baseline and follow-up. Cognitive function was assessed during acute episodes using the Cambridge Neuropsychological Test Automated Battery (CANTAB), which targeted attention (Rapid Visual Processing - RVP), visual memory (Pattern Recognition Memory - PRM), and executive function (Intra-Extra Dimensional Set Shift - IED). The 17-item Hamilton Depression Scale (HAMD) was used for symptom assessment. Participants were divided into two groups based on their SDSS (Social Disability Screening Schedule) scores, and the differences between their demographic information, HAMD scores, and baseline CANTAB test results were compared. Logistic regression analysis was used to identify cognitive predictors of social function during symptomatic remission. Results According to the SDSS score at follow-up, 103 patients were divided into the normal social function group (n = 81,78.6%) and the poor social function group (n = 22, 21.4%) during clinical remission. Participants with poorer social function performed worse in the visual memory (PRM) and executive function tests (IED) at the baseline. Logistic regression analysis suggested that performance on the PRM (95%CI = 0.31–0.93, p = 0.030) and IED (95%CI = 1.01–1.13, p = 0.014) tests, instead of less severe symptoms, significantly contributed to functional outcomes. Conclusion Better performance in visual memory and executive function during acute episodes may predict better social functional outcomes in individuals with MDD. A potential early intervention to improve social function in individuals with MDD could include the treatments for executive function and visual memory.

Abstract Background Distinguishing untreated major depressive disorder without medication (MDD) from schizophrenia with depressed mood (SZDM) poses a clinical challenge. This study aims to investigate differences in fractional amplitude of low-frequency fluctuations (fALFF) and cognition in untreated MDD and SZDM patients. Methods The study included 42 untreated MDD cases, 30 SZDM patients, and 46 healthy controls (HC). Cognitive assessment utilized the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted, and data were processed using fALFF in slow-4 and slow-5 bands. Results Significant fALFF changes were observed in four brain regions across MDD, SZDM, and HC groups for both slow-4 and slow-5 fALFF. Compared to SZDM, the MDD group showed increased slow-5 fALFF in the right gyrus rectus (RGR). Relative to HC, SZDM exhibited decreased slow-5 fALFF in the left gyrus rectus (LGR) and increased slow-5 fALFF in the right putamen. Changes in slow-5 fALFF in both RGR and LGR were negatively correlated with RBANS scores. No significant correlations were found between remaining fALFF (slow-4 and slow-5 bands) and RBANS scores in MDD or SZDM groups. Conclusions Alterations in slow-5 fALFF in RGR may serve as potential biomarkers for distinguishing MDD from SZDM, providing preliminary insights into the neural mechanisms of cognitive function in schizophrenia.

Abstract Background Suicide stands as both a primary symptom and the direst outcome of major depressive disorder (MDD). The scarcity of effective treatment strategies makes managing MDD patients with suicide especially challenging. Hence, it is crucial to investigate disease characteristics and efficacious therapeutic strategies for these patients, drawing insights from disease databases and real-world data. Methods In this retrospective study, MDD patients hospitalized between January 2013 and December 2020 were investigated using Electronic Health Records (EHR) data from Beijing Anding Hospital. The study enrolled 4138 MDD patients with suicidal ideation or behavior (MDS) and 3848 without (MDNS). Demographic data, clinical attributes, treatment approaches, disease burden, and re-hospitalization within one year of discharge were extracted and compared. Results Patients in the MDS group were predominantly younger and female, exhibiting a higher prevalence of alcohol consumption, experiencing frequent life stress events, and having an earlier onset age. Re-hospitalizations within six months post-discharge in the MDS group were significantly higher than in the MDNS group (11.36% vs. 8.91%, p

Abstract Background Inflammation has become a critical pathological mechanism of Major Depressive Disorder (MDD). NLRP3 is a critical inflammatory pathway to maintain the immune balance. Recently, preclinical evidence showed that Resolvin D1 might potentially offer a new option for antidepressant treatment due to its protective effects through the inhibition of neuroinflammation. However, whether they have clinical value in the diagnosis and treatment evaluation of adolescent depression was unclear. Methods Forty-eight untreated first-episode adolescent patients with moderate to severe major depressive disorder, as well as 30 healthy adolescents (HCs, age and gender-matched), were enrolled for this study. Their ages ranged from 13 to 18 (15.75 ± 1.36) years. The patients were treated with fluoxetine for 6–8 weeks. HDRS-17 was used to evaluate the severity of depressive symptoms. Venous blood samples were collected at baseline for the two groups and at the time-point of post-antidepressant treatment for the patients. Serum concentrations of RvD1, NLRP3, IL-1β, IL-18, and IL-4 were measured by enzyme-linked immunosorbent assays (ELISA) pre- and post-fluoxetine treatment. Results Serum levels of RvD1 and anti-inflammatory cytokine IL-4 were significantly elevated in adolescents with MDD compared to healthy adolescents, but no significant difference in NLRP3, IL-1β, and IL-18 between the two groups. Meanwhile, RvD1 (positively) and IL-4 (negatively) were correlated with the severity of symptoms (HDRS-17 scores) after adjusting age, gender, and BMI. Interestingly, fluoxetine treatment significantly reduced the serum levels of RvD1, NLRP3, IL-1β, and IL-18 in MDD adolescents but increased the levels of IL-4 relative to baseline. Furthermore, we observed that serum levels of RvD1 might be an excellent distinguishing indicator for depression and healthy adolescents. Conclusions Our study is the first to compare RvD1 and NLRP3 between adolescent MDD and HCs. Our findings of reactive increase of RvD1 in adolescent MDD comprised a novel and critical contribution. Our results showed the presence of inflammation resolution unbalanced in adolescents with MDD and indicated that RvD1 might be an ideal biomarker for diagnosing and treating adolescent MDD.

Abstract Background Prior studies have identified a correlation between breakfast skipping and a heightened risk of mental health issues. This investigation aimed to employ a Two-Sample Mendelian Randomization (MR) approach to explore the potential causal links between breakfast skipping and various psychiatric, neurological disorders, cognitive performance, and frailty. Methods Utilizing data from genome-wide association studies within European demographics, this research scrutinized the association between breakfast habits and several neuropsychiatric conditions and physical health outcomes, including Alzheimer’s disease (AD), Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder (BD), Major Depressive Disorder (MDD), Narcolepsy, Insomnia, cognitive performance, and frailty. In this MR analysis, the Inverse Variance Weighted (IVW) method was primarily utilized for evaluation. Outcomes were reported as Odds Ratios (OR) and regression coefficients (β), and underwent validation through False Discovery Rate (FDR) corrections, thereby offering a rigorous evaluation of the effects of breakfast habits on both mental and physical health dimensions. Results Findings demonstrate a significant causal link between skipping breakfast and an increased risk of ADHD (OR = 2.74, 95%CI: 1.54–4.88, P FDR = 0.003) and MDD (OR = 1.7, 95%CI: 1.22–2.37, P FDR = 0.005). Conversely, no substantial causal associations were identified between breakfast skipping and AD, BD, narcolepsy, or insomnia (P FDR > 0.05). Moreover, a notable causal relationship was established between skipping breakfast and a reduction in cognitive performance (β = -0.16, 95%CI: -0.29–0.04, P FDR = 0.024) and an increase in frailty (β = 0.29, 95%CI: 0.12–0.45, P FDR = 0.003). Conclusion The MR analysis reveals that skipping breakfast is associated with an increased risk of ADHD, MDD, decreased cognitive performance, and greater frailty, while showing no associations were found with AD, BD, narcolepsy, or insomnia. These findings warrant further investigation into the underlying mechanisms and emphasize the importance of regular breakfast consumption for mental and physical well-being.

Abstract Background Both genetic and environmental factors play crucial roles in the development of major depressive disorder (MDD) and suicide attempts (SA). However, the interaction between both items remains unknown. This study aims to explore the interactions between the genetic variants of the serotonin 2 A receptor (HTR2A) and the nitric oxide synthase 1 (NOS1) and environmental factors in patients who experience MDD and SA. Methods A total of 334 patients with MDD and a history of SA (MDD-SA) were recruited alongside 518 patients with MDD with no history of SA (MDD-NSA), and 716 healthy controls (HC). The demographic data and clinical characteristics were collected. Sequenom mass spectrometry was used to detect eight tag-single nucleotide polymorphisms (tagSNPs) in HTR2A (rs1328683, rs17068986, and rs3125) and NOS1 (rs1123425, rs2682826, rs3741476, rs527590, and rs7959232). Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-environment interactions. Results Four tagSNPs (rs17068986, rs3125, rs527590, and rs7959232) exhibited significant differences between the three groups. However, these differences were not significant between the MDD-SA and MDD-NSA groups after Bonferroni correction. A logistic regression analysis revealed that negative life events (OR = 1.495, 95%CI: 1.071–2.087, P = 0.018), self-guilt (OR = 2.263, 95%CI: 1.515–3.379, P

Background One of the most robust risk factors for developing a mood disorder is having a parent with a mood disorder. Unfortunately, mechanisms explaining the transmission of mood disorders from one generation to the next remain largely elusive. Since timely intervention is associated with a better outcome and prognosis, early detection of intergenerational transmission of mood disorders is of paramount importance. Here, we describe the design of the Mood and Resilience in Offspring (MARIO) cohort study in which we investigate: 1. differences in clinical, biological and environmental (e.g., psychosocial factors, substance use or stressful life events) risk and resilience factors in children of parents with and without mood disorders, and 2. mechanisms of intergenerational transmission of mood disorders via clinical, biological and environmental risk and resilience factors. Methods MARIO is an observational, longitudinal cohort study that aims to include 450 offspring of parents with a mood disorder (uni- or bipolar mood disorders) and 100-150 offspring of parents without a mood disorder aged 10-25 years. Power analyses indicate that this sample size is sufficient to detect small to medium sized effects. Offspring are recruited via existing Dutch studies involving patients with a mood disorder and healthy controls, for which detailed clinical, environmental and biological data of the index-parent (i.e., the initially identified parent with or without a mood disorder) is available. Over a period of three years, four assessments will take place, in which extensive clinical, biological and environmental data and data on risk and resilience are collected through e.g., blood sampling, face-to-face interviews, online questionnaires, actigraphy and Experience Sampling Method assessment. For co-parents, information on demographics, mental disorder status and a DNA-sample are collected. Discussion The MARIO cohort study is a large longitudinal cohort study among offspring of parents with and without mood disorders. A unique aspect is the collection of granular data on clinical, biological and environmental risk and resilience factors in offspring, in addition to available parental data on many similar factors. We aim to investigate the mechanisms underlying intergenerational transmission of mood disorders, which will ultimately lead to better outcomes for offspring at high familial risk.

Abstract Background Depression is one of the most common mental disorders that leads to anxiety, sleep disturbances, and suicidal thoughts. Due to the high cost of treatment and the reluctance of many patients to seek medical help, major depressive disorder (MDD) is becoming more prevalent. Therefore, alternative methods like smartphone applications can help prevent and improve depression symptoms. The present study aimed to determine the effect of the newly developed Yara smartphone application on anxiety, sleep quality, and suicidal thoughts in patients with MDD. Methods This randomized controlled trial with a pretest-posttest design was conducted on Iranian patients with MDD in 2022. Sixty-four patients were recruited using convenience sampling and randomly assigned to two control and intervention groups. The intervention was conducted using the Yara smartphone application for three months. Data were collected using the Spielberger State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), and Beck Scale for Suicidal Ideation (BSSI). Data were first entered into IBM SPSS Statistics for Windows, version 22 (IBM Corp., Armonk, N.Y., USA) and then analyzed using descriptive and analytical statistics. Results There was no statistically significant difference in the mean score of anxiety and sleep quality between the intervention and control groups before the intervention (p ≥ .05). However, this difference in the mean score of anxiety and sleep quality was statistically significant in the two groups after the intervention (p < .05). The results showed no statistically significant difference in the mean score of suicidal thoughts between the two groups before and after the intervention (p ≥ .05). The use of the Yara smartphone application had a significant positive effect on anxiety and sleep quality in depressed patients (p < .001). At the same time, it had no significant effect on suicidal thoughts (p ≥ .05). Conclusion Considering the positive effect of using the Yara smartphone application on reducing anxiety and improving sleep quality in depressed patients, this application can help alleviate the problems of depressed patients alongside existing treatment methods. Thus, this application is recommended for this group of patients in psychiatric clinics and departments. The Yara application's effectiveness was not approved on suicidal thoughts in this study so that further investigation would be necessary. Trial Registration Iranian Registry of Clinical Trial approval code (IRCT# IRCT20131112015390N7).