Psychiatric disorders are closely linked to immune dysregulation, yet the genetic relationships between peripheral immune organs, particularly the spleen, and different psychiatric disorders remain poorly understood. This study aimed to explore these associations. Linkage disequilibrium score regression (LDSC) was used to evaluate the genetic correlations between spleen volume and schizophrenia, bipolar disorder, and depression. For the two traits showing significant genetic correlation, MAGMA gene-level analysis was further performed to identify significant overlapping genes as shared genes. KEGG and GO enrichment analyses were then conducted for these shared genes. In addition, a protein–protein interaction (PPI) network was constructed based on the STRING database, and hub genes were identified using the CytoHubba plugin in Cytoscape. Meanwhile, cell-type enrichment analysis was performed using single-cell transcriptomic reference datasets from the human cortex, hippocampus, and midbrain to localize the potential cellular context underlying the relevant genetic signals. To further investigate the potential functional genomic effects of spleen volume-associated genetic signals in depression-relevant brain regions, transcriptome-wide association study (TWAS) analyses were performed for spleen volume in the human prefrontal cortex and hippocampus. Functional enrichment analyses were subsequently conducted for the overlapping TWAS-associated genes identified in these two regions. Among the three major psychiatric disorders, only depression showed a significant genetic correlation with spleen volume. Spleen volume and depression shared 25 genes, which were mainly enriched in immune- and inflammation-related pathways, including antigen processing and presentation, natural killer cell-mediated cytotoxicity, NF-κB signaling, MAPK signaling, phagosome, and lysosome biogenesis. PPI network analysis further identified several hub genes closely related to immune regulation. Single-cell analysis revealed that the relevant genetic signals were significantly enriched in microglia across the cortex, hippocampus, and midbrain. Additional TWAS analyses in the prefrontal cortex and hippocampus identified 19 overlapping spleen volume-associated transcriptomic genes, with enrichment in immune-inflammatory regulation, monoamine neurotransmitter metabolism, apoptosis, and tryptophan metabolism-related pathways. Spleen volume and depression may share an immunoinflammatory genetic basis and may be linked through microglia-mediated central immune mechanisms, providing new genetic evidence for understanding spleen–brain axis interactions in depression.

Evidence on betahistine for cognitive impairment in schizophrenia is limited. This study evaluated its feasibility, safety, and preliminary efficacy to lay the groundwork for future randomized controlled trials. Thirty-one inpatients with schizophrenia, aged 18-60 years, undergoing treatment with olanzapine received betahistine (16 mg, three times daily) for 12 weeks. Cognitive function, clinical symptoms, and side effects were assessed at baseline and again at 12 weeks postintervention. After 12 weeks of betahistine treatment, patients with schizophrenia showed a significant increase in the total Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery score (p < .01). Increases were observed across multiple cognitive domains, including speed of processing, attention, working memory, verbal and visual learning, and reasoning and problem solving. Reductions in Positive and Negative Syndrome Scale scores were also observed, particularly for negative symptoms and total score (p < .05). Linear regression analysis revealed a significant negative correlation between age and cognitive scores (β = -0.37, p < .05). No adverse effects were reported. In this 12-week, single-arm study, adjunctive betahistine treatment was associated with observed improvements in cognitive performance and reductions in clinical symptom scores during the treatment period in patients with schizophrenia receiving olanzapine. Furthermore, advancing age is a key factor contributing to cognitive decline in the studied population. Betahistine was well-tolerated. This study explores betahistine as an adjunctive treatment for cognitive impairment in schizophrenia, with potential implications for improving cognitive outcomes and informing future treatment strategies. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Objective: Cognitive impairment occurs throughout the entire course of and affects the work and life of patients with major depressive disorder (MDD). The gut microbiota, kynurenine pathway (KP) and inflammatory response may have important roles in the mechanism of cognitive impairment in MDD patients. Consequently, our goal was to investigate the association among the gut microbiota, inflammation, KP, and cognition in MDD. Method: We enrolled patients with MDD (N = 86) and healthy controls (HCs, N =120) in this research. The study involved participant data regarding the levels of serum inflammatory factors (interleukin [IL]-1 beta, IL-4, IL-6, brain-derived neurotropic factor [BNDF], migration inhibitory factor [MIF], tumor necrosis factor [TNF]-alpha, vascular endothelial growth factor [VEGF]), gut microbiota and cognitive function (MCCB) were collected. Results: Patients demonstrated poorer cognitive function. Gut microbiota, such as Bacteroide, Prevotella, Faecalibacterium and Parabacteroides between MDDs and HCs were significantly different. Moreover, in patients with MDD, we found that different microbiomes were related to cognition and that Acidaminococcus was positively correlated with multiple domains of cognition. Allisonella and Acidaminococcus were significantly positively correlated with BDNF and negatively correlated with MIF. Alloprevotella, Blautia, and Megamonas were positively correlated with kynurenine/tryptophan (KYN/TRP). Acidaminococcus was negatively correlated with 3-hydroxykynurenine (3-HK). BDNF levels was significantly positive correlated with kynurenic acid (KA) and quinolinic acid (QA). Conclusion: The results of the present study suggest that the gut microbiota is associated with cognitive function, cytokine levels and KP metabolism in patients with MDD; however, the mechanism of the interaction between cognition and gut microbiota in MDD patients require further investigation.

Background:Cognitive impairment frequently occurs in patients with late-life depression (LLD) and could be associated with variations in homocysteine (Hcy) levels. This study aimed to evaluate the relationship between Hcy levels and cognitive function, with particular attention on how baseline cognitive status may impact this relationship. Methods:This cross-sectional study included 60 patients with LLD meeting Diagnostic and Statistical Manual of Mental Disorders, V Edition (DSM-5) diagnostic criteria and 46 age-matched healthy controls (HCs). Participants were excluded if they had severe physical illnesses. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale and Mini-Mental State Examination (MMSE). Hcy levels were determined. Results:Compared to HCs, LLD patients demonstrated significant impairment across all RBANS subdomains except language (p < 0.001), with elevated Hcy levels (t = 2.688, p = 0.008). Hcy was negatively correlated with cognition, and there was possible evidence of an interaction between Hcy and depression severity, such that this association intensified as depression severity increased (interaction β = 1.385, 95% confidence interval: 0.006-0.589, p = 0.046).Subgroup analysis showed that the negative correlation between Hcy and cognition was exclusively observed in the N-MMSE group (Normal MMSE scores, ≥26; p < 0.05). Limitations:The small sample size and lack of ethnic diversity may limit the generalizability of our results. Conclusion:Patients with LLD often exhibit cognitive impairment and elevated Hcy levels. Notably, the association between Hcy and cognitive function is influenced by the patients' baseline cognitive status. This study offers novel insights into the mechanisms underlying cognitive impairment in patients with depression.

Introduction The suicide risk among discharged psychiatric patients is substantially higher than that among patients with physical diseases and the general population. In China, few cohort studies have investigated suicidal acts in patients discharged from psychiatric facilities, and the factors that convey the risk of post-discharge suicidal acts in this specific population remain unclear. Therefore, we are conducting a prospective multicentre cohort study to investigate the association between suicide attempt history and disease severity in patients with common psychiatric disorders with post-discharge suicidal acts.Methods and analysis This study will recruit 3000 inpatients with one of three common psychiatric disorders, namely schizophrenia, bipolar disorder and major depressive disorder, from three hospitals in North China: Beijing Huilongguan Hospital, Tianjin Anding Hospital and the First Hospital of Shanxi Medical University. Participants will include 1500 inpatients with schizophrenia, 900 inpatients with major depressive disorder and 600 inpatients with bipolar disorder. The baseline assessment includes determining whether each recruited patient meets the diagnostic criteria for schizophrenia, major depressive disorder or bipolar disorder using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth edition (DSM-IV) and obtaining details on prior histories of suicide attempts and the severity of the diagnosed disorders using several questionnaires. A 2-year follow-up will be conducted after the recruited patients have been completely assessed. Follow-ups are scheduled at 3, 6, 12 and 24 months after discharge. The primary outcomes are suicidal acts, including suicide attempts and death, that occurred during the follow-up period. A survival analysis will be performed to test for the supposed associations.Ethics and dissemination This study was approved by the institutional review boards of Beijing Huilongguan Hospital (2022-67-Science), Tianjin Anding Hospital (2022-47) and First Hospital of Shanxi Medical University (2022-K155). All participants will be required to provide written informed consent before the baseline assessment. The recruitment methods will be explained to potential participants, and their confidentiality will be protected throughout the study. The findings of this study will be disseminated to peer-reviewed scientific journals and conference presentations.Trial registration number ChiCTR2200064610.

BACKGROUND:The tryptophan-kynurenine (TRP-KYN) pathway may be implicated in the pathophysiology of cognitive impairment and pain severity in major depressive disorder (MDD); however, few studies have explored the intricacies of their interaction. AIM:To investigate the relationship between the TRP-KYN pathway and cognitive function in MDD patients with and without painful physical symptoms (PPS). METHODS:Seventy patients with MDD were recruited, including 33 and 37 with and without PSS, respectively. The Hamilton Depression Scale, the Hamilton Anxiety Scale, and the Short-form of McGill pain questionnaire (SFMPQ) were used to assess clinical symptoms. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB) score. TRP-KYN pathway metabolites' serum levels were measured using high-performance liquid chromatography-tandem mass spectrometry. RESULTS:The with PPS group exhibited significantly higher TRP-KYN ratios than did the without PPS group; in the former, the SFMPQ scores positively and negatively correlated with the TRP-KYN ratio and total MCCB score, respectively. Regression analysis indicated that body mass index and SFMPQ scores were significantly associated with the TRP-KYN ratio, predicting 30% of the variance. CONCLUSION:The TRP-KYN ratio is a potential biomarker for identifying patients with depression accompanied by pain symptoms, and targeting it may represent a novel therapeutic strategy for managing pain in these individuals. Further elucidation of the biological mechanisms underlying cognitive impairment in MDD patients with PPS is warranted.

BACKGROUND:Cognitive impairment is one of the common clinical manifestations of depression, causing negative distress to patients. Elevated homocysteine (Hcy) concentrations and gut microbiome dysfunction may be observed in patients with depression. AIM:To investigate the relationship between Hcy, microbiome, and cognition in depressive patients. METHODS:We recruited 67 patients with major depressive disorder (MDD) (MDD group) and 94 healthy controls (HCs) individuals (HCs group). Serum Hcy levels were determined using the enzyme circulation method. 16s rRNA sequencing was used to classify and identify the fecal bacteria. 17 Hamilton depression rating scale and MATRICS consensus cognitive battery were used to evaluate mood states and cognition in patients with MDD. Correlation analysis was performed to explore the correlation between fecal flora, Hcy, and depressive cognitive function. RESULTS:Elevated serum levels of Hcy were seen in patients with MDD compared to healthy individuals. Patients with MDD indicated significant decreases in cognitive scores (P < 0.001) in six modules: Speed of processing, working memory, visual learning, reasoning and problem-solving, social cognition, and total scores. Hcy levels showed a negative correlation with processing speed, social cognition, and total MDD scores (P < 0.05). Hcy was also significantly negatively correlated with Alistipes, Ruminococcae, Tenericides, and Porphyromonas (P < 0.05). CONCLUSION:Our results highlight that Hcy was correlated with cognition and gut microbiome in MDD. This interaction may be related to the physiological and pathological mechanisms underlying cognitive deficits in depression.

IntroductionFacial and vocal emotion recognition deficits are common in individuals with schizophrenia.MethodsIn this observational, single-center study, 106 patients with schizophrenia (SCZ) and 118 age- and sex-matched healthy controls underwent cognitive and emotional function assessments. The Temporal Experience of Pleasure Scale (TEPS), Personal and Social Performance Scale, Positive and Negative Symptom Scale, and Brief Negative Symptom Scale were used to evaluate psychotic symptoms in the SCZ group. Participants were assessed using the MATRICS Consensus Cognitive Battery (MCCB), the Positive and Negative Syndrome Scale, and emotion recognition tests involving 42 facial and 42 vocal emotional tasks.ResultsThe SCZ group had significant impairments in facial and vocal emotion recognition, with lower accuracy across all emotional categories. Mean scores in the SCZ group were significantly lower than those in the control group (facial, 23.55 ± 7.10 vs. 31.86 ± 5.16; vocal, 18.64 ± 9.48 vs. 29.42 ± 5.01, respectively; p<0.001). Emotion recognition deficits and demographic or clinical characteristics were not significantly correlated. Network analysis revealed strong intercorrelations among different cognitive domains, linking MCCB performance to emotion recognition abilities (r>0.9; p<0.001). Integration of tests of cognitive function (MCCB, area under the curve [AUC]=91.90%, p<0.01), emotion recognition abilities (facial, AUC=82.56%; vocal, AUC=82.82%; p<0.01), and TEPS (AUC=91.13%, p<0.01) proved useful for distinguishing patients with schizophrenia from healthy individuals.DiscussionThese findings underscore the importance of emotion recognition impairments in schizophrenia and their strong association with cognitive deficits. Future interventions should focus on targeted cognitive and affective training strategies. Incorporating multimodal assessments into clinical evaluations may enhance diagnostic accuracy.

A high homocysteine (Hcy) level is a risk factor for schizophrenia, depression, and bipolar disorder. However, the role of hyperhomocysteinemia as either an independent factor or an auxiliary contributor to specific psychiatric symptoms or disorders remains unclear. This study aimed to examine Hcy levels in first-episode inpatients with psychotic symptoms and various psychiatric diseases to elucidate the association between Hcy levels and psychiatric disorders. This study enrolled 191 patients (aged 18–40 years) with psychiatric disorders. Seventy-five patients were diagnosed with schizophrenia, 48 with acute and transient psychotic disorders, 36 with manic episodes with psychosis, 32 with major depressive episodes with psychosis, and 56 healthy controls. Serum Hcy levels were measured using the enzyme cycle method. A Hcy concentration level of > 15 μmol/L was defined as hyperhomocysteinemia. Hcy levels were significantly higher in first-episode patients with psychiatric disorders compared to healthy controls (5.99 ± 3.60 vs. 19.78 ± 16.61 vs. 15.50 ± 9.08 vs. 20.00 ± 11.33 vs. 16.22 ± 12.06, F = 12.778, P < 0.001). Hcy levels were significantly higher in males with schizophrenia, acute and transient psychotic disorder, and major depressive disorder but not in mania [schizophrenia, (t = -4.727, P < 0.001); acute and transient psychotic disorders, (t = -3.389, P = 0.001); major depressive episode with psychosis, (t = -3.796, P < 0.001); manic episodes with psychosis, (t = -1.684, P = 0.101)]. However, serum Hcy levels were not significantly different among the psychiatric disorder groups (F = 0.139, P = 0.968). Multivariate linear regression showed that males had an increased risk for homocysteinemia. (95% CI = 8.192–15.370, P < 0.001). These results suggest that first-episode patients with psychiatric disorders have higher Hcy levels than in the general population, and men are at greater risk for psychiatric disorders. In conclusion, elevated Hcy levels may contribute to the pathogenesis of first-episode patients with psychotic symptoms.

Objective: To investigate the relationship between plasma aripiprazole (ARI) and its metabolite dehydroaripiprazole (DARI) concentrations and prolactin (PRL) levels in Chinese children and adolescents. Methods: This was a retrospective cross-sectional study and the data were collected at Beijing HuiLongGuan Hospital, a Beijing City owned psychiatric hospital, between January 1 and December 31, 2021. Fifty-two child and adolescent inpatients (17 males, 35 females) aged 13-18 years and received ARI regardless of diagnosis were included. The steady-state ARI and DARI plasma concentrations were measured using high-performance liquid chromatography-tandem mass spectrometry. The serum PRL levels were measured by chemiluminescence immunoassay. Results: The plasma concentrations of ARI, DARI, and the total of ARI and DARI were negatively correlated with serum PRL levels in female children and adolescents. Approximately 15% of child and adolescent inpatients treated with ARI exhibited subnormal PRL serum levels. Conclusions: The results suggest that in addition to regularly monitoring PRL levels, therapeutic drug monitoring for ARI and its main metabolite DARI can help to mitigate the adverse medical consequences associated with PRL reduction. Thus, clinicians should consider the ARI-induced reduction of PRL levels when prescribing ARI to child and adolescent patients, particularly among females.

BACKGROUND:Cognitive and emotional impairment are among the core features of schizophrenia; assessment of vocal emotion recognition may facilitate the detection of schizophrenia. We explored the differences between cognitive and social aspects of emotion using vocal emotion recognition and detailed clinical characterization.METHODS:Clinical symptoms and social and cognitive functioning were assessed by trained clinical psychiatrists. A vocal emotion perception test, including an assessment of emotion recognition and emotional intensity, was conducted. One-hundred-six patients with schizophrenia (SCZ) and 230 healthy controls (HCs) were recruited.RESULTS:Considering emotion recognition, scores for all emotion categories were significantly lower in SCZ compared to HC. Considering emotional intensity, scores for anger, calmness, sadness, and surprise were significantly lower in the SCZs. Vocal recognition patterns showed a trend of unification and simplification in SCZs. A direct correlation was confirmed between vocal recognition impairment and cognition. In diagnostic tests, only the total score of vocal emotion recognition was a reliable index for the presence of schizophrenia.CONCLUSIONS:This study shows that patients with schizophrenia are characterized by impaired vocal emotion perception. Furthermore, explicit and implicit vocal emotion perception processing in individuals with schizophrenia are viewed as distinct entities. This study provides a voice recognition tool to facilitate and improve the diagnosis of schizophrenia.

BACKGROUND:Major depressive disorder (MDD) is underscored by daytime dysfunction-associated features, including mood disturbances, impaired cognition, fatigue, and daytime sleepiness. Importantly, the gut-brain axis may represent a potential mechanistic link between MDD and daytime dysfunction. Therefore, this study aimed to explore the gut microbiome composition and daytime dysfunction in Chinese patients with MDD.METHODS:We enrolled 36 patients with MDD and 45 healthy controls (HCs) matched by age, sex, and body mass index (BMI). Daytime function including emotion, fatigue, and sleepiness were assessed using the Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). 16S rRNA sequencing was employed to characterize the gut microbiota in stool samples.RESULTS:The operational taxonomic units (OTUs) OTU255, OUT363 were positively correlated with HAMD and HAMA. OTU244, OTU542 and OTU221 were positively correlated with ESS, HAMD and HAMA. OTU725 and OTU80 were positively correlated with FSS, ESS, HAMD and HAMA, while OTU423 and OTU502 were negatively correlated with all above. Flavonifractor positively correlated with fatigue in patients with MDD and all individuals simultaneously. The correlation between gut microbiome and daytime function was different in MDD and HCs.CONCLUSIONS:We identified several OTUs associated with the severity of fatigue, depression, daytime sleepiness and anxiety in all individuals. Our results revealed the differences in microbiome found between patients with MDD and HCs. These findings provide insights into the potential microbiota changes that occur in MDD, and will enable the development of specific therapeutic strategies for targeting the various symptoms of depression.

OBJECTIVES:To investigate the relationship between the tryptophan-kynurenine (TRP-KYN) pathway and painful physical symptoms (PPS) in major depressive disorder (MDD).METHODS:Eighty-four patients with MDD (40 patients with PPS and 44 without PPS) and forty-six healthy controls (HC) were recruited. The serum levels of tryptophan (TRP), kynurenine(KYN), kynurenic acid (KA), quinolinic acid (QA), 3-hydroxy-kynurenine (3-HK), serotonin (5-HT) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Depression, anxiety and pain were assessed using Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA) and Short-form McGill pain questionnaire (SFMPQ) respectively.RESULTS:Patients in the MDD group exhibited significantly lower KA and 5-HT levels than HC, whereas MDD patients with PPS showed higher KYN and QA levels, and a higher KYN/TRP ratio than those without. There was a positive correlation between the scores of SFMPQ and QA levels and a negative correlation between the scores of SFMPQ and TRP levels or KA/QA ratios in MDD patients with PPS group. Stepwise multiple regression analysis showed that the KYN/TRP ratios, the KA/QA ratios, and the HAMD scores were significant predictor factors for SFMPQ scores.CONCLUSIONS:These results demonstrated that the TRP-KYN pathway may play a role in the pathophysiology of pain in patients with major depressive disorder, suggesting that further studies of this pathway as a potential biomarker or therapeutic target are required.

Objectives The aim of the present study was to investigate a potential relationship between metabolic parameters and steady-state plasma concentrations of olanzapine (OLA) and its metabolite, 4-N'-desmethyl-olanzapine (DMO) in patients with schizophrenia taking therapeutic doses. Methods A total of 352 inpatients, diagnosed with schizophrenia according to the DSM-V criteria and treated with OLA, were investigated. The plasma concentrations of OLA and DMO were measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). Fasting blood samples were measured for insulin, glucose, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), C-reactive protein (CRP) and homocysteine, and differences in these parameters were investigated in relation to plasma concentrations of OLA and DMO. Results Lower plasma DMO concentrations were associated with higher glucose and TG levels and homeostasis model assessment of insulin resistance (HOMA-IR), while higher plasma OLA concentrations were associated with higher CRP and homocysteine levels in the OLA-treated patients with schizophrenia. Conclusion These results demonstrate that OLA and its metabolite DMO may have different effects on OLA-induced metabolic abnormalities. DMO might have a counteracting effects on glucose-insulin homeostasis and lipid metabolic abnormalities, which suggests that regular measure of various metabolic parameters and drug monitoring on both OLA and DMO are recommended in OLA-treated patients with schizophrenia.

Background: There is currently no effective treatment for cognitive impairment associated with schizophrenia (CIAS). Recent studies have shown that increased histamine levels in the brain may help to improve CIAS symptoms. Betahistine is an H1-receptor agonist and H3-receptor antagonist. This study evaluated the effect of high-dose betahistine on cognitive function as well as its safety in Chinese Han patients with schizophrenia.Methods: This randomized double-blind, placebo-controlled trial enrolled 89 patients with schizophrenia who were randomly administered betahistine (72 mg/d) or placebo for 12 weeks. At baseline and at 4, 8, and 12 weeks after commencing the intervention, we measured changes in cognitive function and clinical symptoms using the MATRICS Consensus Cognitive Battery (MCCB) and Positive and Negative Syndrome Scale (PANSS), respectively. Furthermore, we used the Treatment Emergent Symptom Scale (TESS) to assess the adverse effects of the patients' medications.Results: Compared to the placebo group, the betahistine group showed significant improvements in the MCCB composite score after 12 weeks of treatment (p = 0.003) as well as improvements in MCCB verbal learning (p = 0.02) and visual learning (p = 0.001) domain scores. However, there were no significant improvements in the PANSS total scores or subscores (p > 0.05). Generally, high-dose betahistine treatment was considered safe in patients with schizophrenia.Conclusions: Additional use of high-dose betahistine can effectively improve cognitive function but not psychiatric symptoms in patients with schizophrenia. Betahistine (72 mg/d) is well tolerated by Chinese Han patients with schizophrenia.Trial Registration:chictr.org.cn, identifier: ChiCTR1900021078. http://www.chictr.org.cn/edit.aspx?pid=35484&htm=4

Major depressive disorder is a serious chronic and disabling mental disease, which produces a tremendous family-society economic burden due to its high prevalence, high recurrence rate, and high disability rate. Accumulating evidences demonstrate that abnormalities of the kynurenine pathway may be implicated in the pathophysiology of depression. This review systematically elucidates the role of tryptophan-kynurenine pathway and its bioactive metabolites in depression and explains the potential treatment implications of targeted drugs based on kynurenine pathway, which provides a certain theoretical basis for further exploration of the etiology and pathogenesis in depression.

The microbiota–gut–brain axis plays a critical role in the pathogenesis of major depressive disorder (MDD) and related subclinical symptoms. However, studies on the gut microbiota in MDD are inconsistent, and data on MDD's effects on sleep are lacking. This study aimed to analyze the gut microbiota composition and sleep quality of patients with MDD. We performed 16S rRNA sequencing of stool samples from 36 patients with MDD and 45 healthy controls (HC). Sleep quality was assessed using the Pittsburgh Sleep Quality Index, depressive severity with the Hamilton Depression Scale, and insomnia severity using the Insomnia Severity Index. Forty-eight microbiota targets showed significant differences between MDD and HC. In MDD, six microbiota targets were associated with the severity of depression, 11 with sleep quality, and 3 with sleep severity. At the genus level, Dorea was simultaneously related to depression and sleep quality, while Intestinibacter was more closely related to sleep problems. Coprococcus and Intestinibacter were associated with sleep quality independent of the severity of depression. In conclusion, the present findings enable a better understanding of the relationship between gut microbiota and MDD-related symptoms. Gut microbiota alterations may become potential biomarkers and/or treatment targets for sleep quality in MDD.