Cortical activation for adolescent-onset minor depression and major depressive disorder: an fNIRS study.

BACKGROUND: While depression is increasing worldwide, some patients are diagnosed as having Major Depressive Disorder (MDD), but others are diagnosed with minor depression, however, the potential neuro mechanism is unknown. METHODS: Sixty-two patients with minor depression, 44 adolescents with MDD and 54 healthy adolescents participated in this study. Functional near-infrared spectroscopy (fNIRS), both HAMD and HAMA data were collected from all of the participants. RESULTS: The result indicates the pervasively decreased activation of BA, 11, 21, 45 and 46 were observed in the MDD group and reduced activation of BA 45 was observed in the minor depression group. However, cortical activation was not observed between the minor depression or MDD groups. Cortical activation was also not correlated with the depressive/anxious score in the minor and MDD groups separately. CONCLUSIONS: Cortical activation was pervasively decreased in the MDD group and slightly reduced in the minor depression group, which may be a potential neural mechanism. As reduced cortical activation in minor depression, interventions in the early stages of minor depression may help slow or even modify the development of the illness.

Psychological characteristics and emotional difficulties underlying school refusal in adolescents using functional near-infrared spectroscopy.

BACKGROUND: This study aims to explore the psychological characteristics, related emotional problems and potential NIR brain function mechanism of adolescents who refuse to attend school. METHODS: The study included 38 adolescents (12-18 years old) who were not attending school and 35 healthy controls (12-18 years old) who are attending school regularly. Participants completed (1) general demographics, (2) Eysenck Personality Questionnaire (EPQ), (3) Zung Self-Rating Depression Scale (SDS), (4) Zung Self-Rating Anxiety Scale (SAS), and (5) Symptom Checklist-90 (SCL-90). In addition to the clinical tests, participants completed functional near-infrared spectroscopy (fNIRS). Mental health, personality, and emotional state were evaluated in both groups to explore the differences and to understand the underlying mechanisms of school refusal during adolescence. RESULTS: Adolescents who did not attend school had higher neuroticism scores on the Eysenck Personality Questionnaire than healthy controls (p(FDR) < 0.001), introversion and concealment scores were lower than those of healthy controls (p(FDR) < 0.001), there was no significant difference in psychoticism scores between groups. SDS, SAS, SCL-90 scores and factor scores were higher than those of healthy control group (p(FDR) < 0.001), NIR functional brain imaging was different from healthy control group in the 12 and 27 channels (p(FDR) = 0.030, p(FDR) = 0.018), and no difference was found in the remaining channels (p(FDR) > 0.05). There were statistically significant differences in age and gender between the adolescents who refused school and the control group (p(FDR) < 0.001). CONCLUSION: School refusal adolescents are relatively introverted and sensitive and need more attention in daily life. Although the adolescents' emotional problems did not reach the diagnostic criteria of depressive disorder and anxiety disorder, their scores were still higher than those of the control group, suggesting that we should pay more attention to their emotional problems in order to better help them return to school. Using fNIRS, it was found that abnormalities in frontal lobe regions in adolescents with school refusal behaviors, which would contribute to early diagnosis and timely intervention of school refusal behaviors.

Efficacy, Safety, and Tolerability of Ansofaxine (LY03005) Extended-Release Tablet for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Phase 2 Clinical Trial.

BACKGROUND: Ansofaxine (LY03005) extended-release tablet is a potential triple reuptake inhibitor of serotonin, norepinephrine, and dopamine. This study assessed the efficacy, safety, and appropriate dosage of ansofaxine for the treatment of major depressive disorder (MDD). METHODS: A multicenter, randomized, double-blind, placebo-controlled, dose-finding, Phase 2 clinical trial was conducted in China. Eligible patients with MDD (18-65 years) were randomly assigned to receive fixed-dose ansofaxine extended-release tablets (40, 80, 120, or 160 mg/d) or placebo for 6 weeks. The primary outcome measure was a change in the total score on the 17-item Hamilton Depression Rating Scale from baseline to week 6. RESULTS: A total of 260 patients were recruited from October 2015 to September 2017, and 255 patients received the study drug as follows: 40 mg (n = 52), 80 mg (n = 52), 120 mg (n = 51), and 160 mg (n = 51) ansofaxine and placebo (n = 49). Significant differences were found in mean changes in 17-item Hamilton Depression Rating Scale total scores at week 6 in the 4 ansofaxine groups vs placebo (-12.46; χ2 = -9.71, P = .0447). All doses of ansofaxine were generally well-tolerated. Treatment-related adverse events occurred in 141 patients (303 cases), yielding incidence rates of 51.92%, 65.38%, 56.86%, and 62.75% in the 40-, 80-, 120-, and 160-mg ansofaxine groups and 38.78% in the placebo group. CONCLUSION: Active doses (40, 80, 120, and 160 mg/d) of ansofaxine in a controlled setting were safe, tolerated, and effective in improving depression symptoms in MDD patients.

Childhood adversity, adulthood adversity and suicidal ideation in Chinese patients with major depressive disorder: in line with stress sensitization.

The stress sensitization model indicates that early adversity (e.g., childhood stress) sensitizes individuals to subsequent proximal stress (e.g., stressful life events in adult life), thereby increasing their vulnerability to psychiatric disorders. However, the effect of stress sensitization on suicidality in patients with major depressive disorder (MDD) has not been previously investigated. Data for the present study were derived from the Objective Diagnostic Markers and Personalized Intervention in MDD Patients (ODMPIM) study. The psychiatric diagnosis and suicidal ideation were evaluated by the Mini-International Neuropsychiatric Interview (M.I.N.I.). We used a multiple logistic analysis to examine the association among childhood adversity (CA), adulthood adversity (AA) and suicidal ideation. Among 1084 MDD patients, 48.6% had suicidal ideation and 65.6% experienced life adversity during their childhood or adulthood. Patients who reported suicidal ideation were more likely to report CA (46.7% vs. 38.7%, P = 0.008) or AA (49.5% vs. 40.9%, P = 0.004) than patients without suicidal ideation. Patients who experienced two waves of adversity (both CA and AA) were associated with higher rates of suicidal ideation (odds ratio = 1.68, 95% CI = 1.19-2.37, P = 0.003); however, neither CA nor AA alone was associated with suicidal ideation. This study first verifies the hypothesis of stress sensitization on suicidal ideation in patients with MDD. Focusing on stress sensitization may enhance the early identification of MDD patients at suicidal risk and the ability to provide timely and appropriate intervention. Clinicaltrials.gov identifier: NCT02023567.

Abnormal gut microbiota and bile acids in patients with first-episode major depressive disorder and correlation analysis.

AIM: Gut microbiota and its metabolite bile acids may play a significant role in the occurrence and development of major depressive disorder (MDD). Therefore, this study analyzes gut microbiota and bile acids, as well as their correlation in patients. METHODS: Thirty-one patients with MDD and 29 healthy controls (HCs) were enrolled in this study. We collected their both blood and feces. Plasma bile acid content was determined by liquid chromatography-mass spectrometry and gut microbiota was detected by 16SrRNA gene sequencing and subsequently analyzed. We also analyzed the correlation between different gut microbiota, bile acids, and Hamilton Depression (HAMD) score. RESULTS: The α-diversity analysis found that Simpson and Pielou evenness index was much higher in HCs than in the patients with MDD. The ß-diversity of the two groups were differences by nonmetric multidimensional scaling analysis. Linear discriminant analysis effect size analysis identified 16 different strains. Bile acids detection showed that 23-nordeoxycholic acid in patients with MDD was significantly higher than in HCs, whereas taurolithocholic acid (TLCA), glycolithocholic acid (GLCA), and lithocholic acid 3-sulfate were significantly lower. Spearman correlation analysis showed that Turicibacteraceae, Turicibacterales, and Turicibacter were positively related with TLCA, GLCA, glycodeoxycholic acid (GDCA), and taurodeoxycholic acid, and were negatively correlated with HAMD score. At the same time, TLCA, GLCA, and GDCA were negatively correlated with HAMD score. CONCLUSIONS: Gut microbiota and bile acids metabolism are disturbances in MDD, and there exists a correlation between gut microbiota and bile acids metabolism. Moreover, their interaction may be related to the pathophysiological mechanism of MDD.

Severe sleep disturbance is associated with executive function impairment in patients with first-episode, treatment-naïve major depressive disorders.

BACKGROUND: Sleep disturbance and executive function impairment are common in patients with major depressive disorder (MDD), though the relationship between the two remains unclear. We investigated this association in first-episode, treatment-naïve patients with MDD. METHODS: We analyzed data from 242 patients with MDD. We divided the patients into 2 groups based on sleep disturbance severity and compared the executive function odds ratios between the groups. RESULTS: A total of 121 pairs of patients were matched (age 39.4 ± 10.1, 70.2% female). After propensity score matching, the odds ratios for cognitive impairment in patients with MDD and severe sleep disturbance were 1.922 (1.068-3.459, P = 0.029, q = 0.044) in executive functioning; 2.023 (1.211-3.379, P = 0.007, q = 0.021) in executive shifting. CONCLUSIONS: Sleep disturbance is associated with executive functioning impairment in first-episode, treatment-naïve patients with MDD. Severe sleep disturbance can be a marker and aid in recognizing executive function impairment in patients with first-episode treatment-naïve MDD. Severe sleep disturbance can be a potential modifiable factor to improve executive function in MDD, as well as an effective measurement to improve cognition for sleep symptom management that should be enforced at initial treatment of first-episode MDD. Further study is required to confirm our results. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02023567 ; registration date: December 2013.

Injuries in Left Corticospinal Tracts, Forceps Major, and Left Superior Longitudinal Fasciculus (Temporal) as the Quality Indicators for Major Depressive Disorder.

At present, the etiology and pathogenesis of major depressive disorder (MDD) are still not clear. Studies have found that the risk of first-degree relatives of MDD is 2-3 times that of the general population. Diffusion tensor imaging (DTI) has been previously used to explore the pathogenesis of MDD. The purpose of this study is to explore the etiology of MDD by DTI and further to explore the correlation between its clinical characteristics and the structural changes of white matter in the brain. The study included 27 first-episode, drug-naive patients with MDD, 16 first-degree relatives without MDD, and 28 healthy control subjects with no family history of MDD (HC). Results showed that the fractional anisotropy (FA) differences among the three groups were mainly in the left anterior thalamic radiation (LATR), right anterior thalamic radiation (RATR), left corticospinal tracts (LCST), forceps major (FMa), right inferior longitudinal fasciculus (RILF), and left superior longitudinal fasciculus (temporal) (LSLF(T)). Among the 6 sites, LCST, FMa, and LSLF(T) showed significant differences between MDD and First-degree relatives compared to HC. MDD patients had significant emotional symptoms, somatic symptoms, and cognitive impairment. FMa FA was significantly positively correlated with delayed memory score (r = 0.43, P = 0.031), and RILF FA was significantly negatively correlated with the FSS score (r = -0.42, P = 0.028). These results revealed that the white matter characteristics of MDD-susceptible patients were LCST, FMa, and LSLF(T) lesions, all of which may be quality indicators of MDD.

Impact on mental health and perceptions of psychological care among medical and nursing staff in Wuhan during the 2019 novel coronavirus disease outbreak: A cross-sectional study.

The severe 2019 outbreak of novel coronavirus disease (COVID-19), which was first reported in Wuhan, would be expected to impact the mental health of local medical and nursing staff and thus lead them to seek help. However, those outcomes have yet to be established using epidemiological data. To explore the mental health status of medical and nursing staff and the efficacy, or lack thereof, of critically connecting psychological needs to receiving psychological care, we conducted a quantitative study. This is the first paper on the mental health of medical and nursing staff in Wuhan. Notably, among 994 medical and nursing staff working in Wuhan, 36.9% had subthreshold mental health disturbances (mean PHQ-9: 2.4), 34.4% had mild disturbances (mean PHQ-9: 5.4), 22.4% had moderate disturbances (mean PHQ-9: 9.0), and 6.2% had severe disturbance (mean PHQ-9: 15.1) in the immediate wake of the viral epidemic. The noted burden fell particularly heavily on young women. Of all participants, 36.3% had accessed psychological materials (such as books on mental health), 50.4% had accessed psychological resources available through media (such as online push messages on mental health self-help coping methods), and 17.5% had participated in counseling or psychotherapy. Trends in levels of psychological distress and factors such as exposure to infected people and psychological assistance were identified. Although staff accessed limited mental healthcare services, distressed staff nonetheless saw these services as important resources to alleviate acute mental health disturbances and improve their physical health perceptions. These findings emphasize the importance of being prepared to support frontline workers through mental health interventions at times of widespread crisis.

Functional connectivity between the thalamus and the primary somatosensory cortex in major depressive disorder: a resting-state fMRI study.

BACKGROUND: Studies have confirmed that the thalamus and the primary somatosensory cortex (SI) are associated with cognitive function. These two brain regions are closely related in structure and function. The interactions between SI and the thalamus are of crucial significance for the cognitive process. Patients with major depressive disorder (MDD) have significant cognitive impairment. Based on these observations, we used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate whether there is an abnormality in the SI-thalamic functional connection in MDD. Furthermore, we explored the clinical symptoms related to this abnormality. METHODS: We included 31 patients with first-episode major depressive disorder and 28 age-, gender-, and education-matched healthy controls (HC). The SI-thalamic functional connectivity was compared between the MDD and HC groups. The correlation analyses were performed between areas with abnormal connectivity and clinical characteristics. RESULTS: Compared with healthy subjects, the MDD patients had enhanced functional connectivity between the thalamus and SI (p < 0.05, corrected). Brain areas with significantly different levels of connectivity had a negative correlation with the Assessment of Neuropsychological Status total score (r = - 0.383, p = 0.033), delayed memory score (r = - 0.376, p = 0.037) and two-digit continuous operation test score (r = - 0.369, p = 0.041) in MDD patients. CONCLUSIONS: These results demonstrate that SI-thalamic functional connectivity is abnormal and associated with the core clinical symptoms in MDD. The SI-thalamic functional connectivity functions as a neurobiological feature and potential biomarker for MDD.

Adjunctive antidepressant use in schizophrenia in China: A national survey (2002-2012).

OBJECTIVE: This study examined the pattern of adjunctive antidepressant use in schizophrenia patients and its demographic and clinical correlates in a nationwide survey in China. METHODS: Fourteen thousand and thirteen patients in 45 Chinese psychiatric hospitals or centers were interviewed (4,486 in 2002, 5,288 in 2006, and 4,239 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Chi-square test, independent-samples t test, Mann-Whitney U test, and multiple logistic regression analysis were used in data analyses. RESULTS: Antidepressant use was found in 5.2% of the study population with 4.6% in 2002, 4.3% in 2006, and 6.9% in 2012, respectively. A significant increase in use from 2006 to 2012 was found (p < .001). Multiple logistic regression analyses in the whole population revealed that patients receiving adjunctive antidepressants were more likely to be outpatients in tertiary referral centers (level-III hospitals) and who had an earlier age of onset, less severe global illness, but more depressive symptoms. They were less likely to receive first-generation antipsychotics but more likely to receive benzodiazepines (R2  = 0.255, p < .001). CONCLUSIONS: Despite an increasing trend, the frequency of antidepressant use in schizophrenia in China was considerably lower than in Western countries. The benefits and risks associated with concomitant use of antidepressants in schizophrenia need to be studied further.

Electroconvulsive Therapy in Schizophrenia in China: A National Survey.

OBJECTIVE: Little is known about electroconvulsive therapy (ECT) use in the treatment of schizophrenia in China. This study examined the frequency of ECT use, its trend between 2006 and 2012, and its independent demographic and clinical correlates in a nationwide survey in China. METHODS: A total of 5162 inpatients in 45 Chinese psychiatric hospitals/centers were interviewed (2696 in 2006 and 2466 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. RESULTS: Electroconvulsive therapy was used in 6.1% of the whole sample; 4.7% in 2006 and 7.7% in 2012 (P < 0.001) with wide interprovince variations. Multiple logistic regression analyses of the whole sample revealed that patients receiving ECT were more likely to be women, receive second-generation antipsychotics, treated in tertiary referral centers (level III hospitals), had a shorter illness duration, and more positive and depressive symptoms (R = 0.181; P < 0.001). CONCLUSIONS: Electroconvulsive therapy for schizophrenia has increased between 2006 and 2012 in China. Its percentage was higher than the figures reported in most other countries. Reasons for the substantial variations in the frequency of ECT across different provinces in China require further investigations.

Homotopic connectivity in drug-naïve, first-episode, early-onset schizophrenia.

BACKGROUND: The disconnection hypothesis of schizophrenia has been extensively tested in adults. Recent studies have reported the presence of brain disconnection in younger patients, adding evidence to support the neurodevelopmental hypothesis of schizophrenia. Because of drug confounds in chronic and medicated patients, it has been extremely challenging for researchers to directly investigate abnormalities in the development of connectivity and their role in the pathophysiology of schizophrenia. The present study aimed to examine functional homotopy - a measure of interhemispheric connection - and its relevance to clinical symptoms in first-episode drug-naïve early-onset schizophrenia (EOS) patients. METHODS: Resting-state functional magnetic resonance imaging was performed in 26 first-episode drug-naïve EOS patients (age: 14.5 ± 1.94, 13 males) and 25 matched typically developing controls (TDCs) (age: 14.4 ± 2.97, 13 males). We were mainly concerned with the functional connectivity between any pair of symmetric interhemispheric voxels (i.e., functional homotopy) measured by voxel-mirrored homotopic connectivity (VMHC). RESULTS: Early-onset schizophrenia patients exhibited both global and regional VMHC reductions in comparison with TDCs. Reduced VMHC values were observed within the superior temporal cortex and postcentral gyrus. These interhemispheric synchronization deficits were negatively correlated with negative symptom of the Positive and Negative Syndrome Scale. Moreover, regions of interest analyses based on left and right clusters of temporal cortex and postcentral gyrus revealed abnormal heterotopic connectivity in EOS patients. CONCLUSIONS: Our findings provide novel neurodevelopmental evidence for the disconnection hypothesis of schizophrenia and suggest that these alterations occur early in the course of the disease and are independent of medication status.

Epigenetic mechanisms are involved in the regulation of ethanol consumption in mice.

BACKGROUND: Repeated alcohol exposure is known to increase subsequent ethanol consumption in mice. However, the underlying mechanisms have not been fully elucidated. One postulated mechanism involves epigenetic modifications, including histone modifications and DNA methylation of relevant genes such as NR2B or BDNF. METHODS: To investigate the role of epigenetic mechanisms in the development of alcohol drinking behavior, an established chronic intermittent ethanol exposure reinforced ethanol drinking mouse model with vapor inhalation over two 9-day treatment regimens was used. The DNA methyltransferase inhibitor, 5-azacytidine or the histone deacetylase inhibitor, Trichostatin A was administered (intraperitoneally) to C57BL/6 mice 30 min before daily exposure to chronic intermittent ethanol. Changes in ethanol consumption were measured using the 2-bottle choice test. RESULTS: The results indicated that systemic administration of Trichostatin A (2.5 µg/g) facilitated chronic intermittent ethanol-induced ethanol drinking, but systemic administration of 5-azacytidine (2 µg/g) did not cause the same effect. However, when 5-azacytidine was administered by intracerebroventricular injection, it facilitated chronic intermittent ethanol-induced ethanol drinking. Furthermore, the increased drinking caused by chronic intermittent ethanol was prevented by injection of a methyl donor, S-adenosyl-L-methionine. To provide evidence that chronic intermittent ethanol- or Trichostatin A-induced DNA demethylation and histone modifications of the NR2B promoter may underlie the altered ethanol consumption, we examined epigenetic modifications and NR2B expression in the prefrontal cortex of these mice. Chronic intermittent ethanol or Trichostatin A decreased DNA methylation and increased histone acetylation in the NR2B gene promoter, as well as mRNA levels of NR2B in these mice. CONCLUSIONS: Taken together, these results indicate that epigenetic modifications are involved in regulating ethanol drinking behavior, partially through altering NR2B expression.

Efficacy and safety of prolonged-release trazodone in major depressive disorder: a multicenter, randomized, double-blind, flexible-dose trial.

OBJECTIVE: To investigate the efficacy, safety, and clinical benefit of prolonged-release trazodone (Trittico) in the treatment of major depressive disorder (MDD). METHODS: In this study, 363 Chinese patients with MDD were randomized 1:1 to receive either prolonged-release trazodone (150-450 mg) or placebo treatment for 6 weeks. The primary efficacy measurement was the change of the 17-item Hamilton Depression Rating Scale (HAMD-17) total score from baseline to the end of the study. The secondary efficacy measurements were the response and remission rates, the Clinical Global Impression - Improvement of Illness (CGI-I) score at the end of the study, and the change of the HAMD-14 total score and quality of sleep [evaluated by the Pittsburgh Sleep Quality Index (PSQI) scale] during the study period. RESULTS: The mean maximum daily dose was 273.11 mg for the trazodone group and 290.92 mg for the placebo group. At the end of the study, there was a significant difference between the two groups in the HAMD-17 change score (trazodone vs. placebo: -11.07 vs. -8.29, p < 0.001). Trazodone showed advantages at 1 week of treatment, and the effect lasted until the end of the study (week 6). The response and remission rates of the trazodone group were significantly higher than those in the placebo group (response rate: 59.6 vs. 37.2%, p < 0.001; remission rate: 35.5 vs. 22.2%, p = 0.005). The majority of the adverse reactions of trazodone were mild to moderate, and the most frequent adverse reactions (≥5%) were dizziness, dry mouth, somnolence, and nausea. CONCLUSIONS: Prolonged-release trazodone was more effective than placebo in MDD and was well tolerated.

White matter abnormalities in medication-naïve adult patients with major depressive disorder: tract-based spatial statistical analysis.

OBJECTIVE: While increasing evidence suggests that major depressive disorder (MDD) is coincident with the altered white matter microstructure in many brain regions including the prefrontal cortex, parietal lobe, ventral tegmental area and limbic system, it remains controversial in the nature of white matter structural changes and in its relationship with depression syndrome. We believe that the age of patients and the antidepressant treatment to them would contribute to that controversy. Here in this study we explored the microstructural changes of the entire brain white matter of the adult patients with first-episode, antidepressant drug-naïve MDD. DESIGN: We performed the diffusion tensor imaging (DTI) among a relatively large sample size of patients and age-matched control individuals (forty-one MDD patients and forty-one control subjects) and used recently developed tract-based spatial statistics to analyze the difference of mean fractional anisotropy (FA) between patients and control individuals. RESULTS: We surprisingly found that MDD patients exhibited a significantly greater mean FA, which is used to elucidate the structural organization of the neural fibers, than control subjects in the whiter matter of the left superior longitufinal fasciculus. However, this change in the white matter of MDD patient did not correlate with depressive clinical features (HMAD, illness duration and initial age) in the present study. CONCLUSION: Our data suggest that a potential compensatory regeneration of nerve fibers occurs in the early course of MDD development. Advanced understanding of the potential nerve fiber regeneration in the early course of MDD and its associated mechanisms will possibly shade light on a better strategy for MDD prevention and treatment.

Characteristics of gut microbiota and its correlation with hs-CRP and somatic symptoms in first-episode treatment-naive major depressive disorder.

OBJECTIVE: Most patients with major depressive disorder (MDD) have somatic symptoms, but little studies pay attention in the microbial-inflammatory mechanisms of these somatic symptoms. Our study aimed to investigate alterations in gut microbiota and its correlation with inflammatory marker levels and somatic symptoms in first-episode treatment-naive MDD. METHODS: Subjects contained 160 MDD patients and 101 healthy controls (HCs). MDD patients were divided into MDD with somatic symptoms group (MDDS) and MDD without somatic symptoms group (MDDN) based on Somatic Self-rating Scale (SSS). 16S ribosomal RNA sequencing were performed to analyze the composition of the fecal microbiota. The inflammatory factors were measured using enzyme linked immunosorbent assay (ELISA). Correlation among the altered gut microbiota, inflammatory factor and severity of clinical symptoms were analysized. RESULTS: Relative to HCs, MDD patients had higher levels of high-sensitivity C-reactive protein (hs-CRP) as well as disordered α-diversity and ß-diversity of gut microbiota. Linear discriminant effect size (LEfSe) analysis showed that MDD patients had higher proportions of Bifidobacterium, Blautia, Haemophilus and lower proportions of Bacteroides, Faecalibacterium, Roseburia, Dialister, Sutterella, Parabacteroides, Bordetella, and Phascolarctobacterium from the genus aspect. Furthermore, correlation analysis showed Bacteroides and Roseburia had negative correlations with the hs-CRP, HAMD-24, the total and factor scores of SSS in all participants. Further, compared with MDDN, the Pielous evenness was higher in MDDS. Random Forest (RF) analysis showed 20 most important genera discriminating MDD-S and MDDN, HCs. The ROC analysis showed that the AUC was 0.90 and 0.81 combining these genera respectively. CONCLUSION: Our study manifested MDD patients showed disordered gut microbiota and elevated hs-CRP levels, and altered gut microbiota was closely associated with hs-CRP, depressive symptoms, and somatic symptoms.

Immunoregulatory role of the gut microbiota in inflammatory depression.

Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higher Bacteroides and lower Clostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors. Clostridium butyricum administration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.

Latent classes of symptom trajectories among major depressive disorder patients in China.

OBJECTIVE: This study aimed to understand the long-term symptom trajectories of Chinese patients with major depressive disorder (MDD) using piecewise latent growth modeling and growth mixture modeling. The investigation also aimed to identify the baseline characteristics indicative of poorer treatment outcomes. METHODS: A total of 558 outpatients with MDD were assessed using a sequence of surveys. The Hamilton Rating Scale for Depression (HRSD), Hamilton Anxiety Rating Scale (HAMA), and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) were used to evaluate baseline depression, anxiety, and cognitive function. Depression symptom severity was subsequently measured at the 1-month, 2-month, 6-month, 1-year, and 2-year follow-ups. RESULTS: Results indicated three depressive symptomology trajectories, including (a) severe, improving class (12.72 %), (b) partially responding, later deteriorating class (6.09 %), and (c) moderate, improving class (81.18 %). Logistic regression analyses showed that a history of cardiovascular disease (CVD) increased the odds of belonging to the partially responding, later deteriorating class, whereas higher baseline depression increased the odds of belonging to the severe, improving class compared to the moderate, improving class. Patients who experienced less depression relief during the first month of treatment had a lower probability of belonging to the moderate, improving class. LIMITATIONS: Participant attrition in this study may have inflated the estimated rate of treatment-resistant patients. CONCLUSIONS: The burden of CVD and poorer initial treatment response are plausible risk factors for poorer treatment outcomes, highlighting targets for intervention in Chinese MDD patients.

A combined study of genetic association and brain imaging on the DAOA gene in schizophrenia.

While there has been no objective biomarker available for both diagnosis and prognosis of schizophrenia, compelling evidence suggests that the glutamatergic system may influence susceptibility to schizophrenia. To test genetic association of the glutamatergic system with schizophrenia and abnormal brain activities in resting-state patients with schizophrenia, a two-stage association study was performed in 454 patients and 480 controls, followed by regional homogeneity (ReHo) analysis of resting-state functional magnetic resonance imaging in 48 first-episode medication-free patients and 43 well-matched controls. The differences in ReHo between genotypes of interest were initially tested by the Student's t-test and the 2 × 2 (genotypes × disease status) ANOVA was then performed to identify the main effects of genotypes, disease status and their interactions in schizophrenia. The stage-1 study showed association of the DAOA and PSEN2 genes with schizophrenia in a small sample; the stage-2 study with an expanded sample confirmed the disease association for 2-SNP and 3-SNP haplotypes, and the cis-phase interactions between rs2391191 and some other SNPs in the DAOA gene. Four clusters with altered ReHo in the bilateral culmen, left putamen and left cuneus were associated with rs2391191. Main effects of rs2391191 genotypes were found in the left putamen. The left cuneus showed a genotype × disease status interaction. In conclusion, the DAOA gene may confer genetic risk of schizophrenia and associate with the altered ReHo in schizophrenia; genotype effect and its interaction with disease status may contribute to the altered ReHo, leading to specific ReHo in schizophrenic brain due to glutamatergic modulation.

Comparative study of regional homogeneity in schizophrenia and major depressive disorder.

Compelling evidence suggests that there is a considerable overlap in structural and functional alternation in the brain between different neuropsychiatric disorders. However, whether these overlaps are specific for schizophrenia has yet to be investigated. A total of 36 patients with paranoid schizophrenia, 43 patients with major depressive disorder (MDD), and 44 healthy controls were recruited to undergo resting-state functional magnetic resonance imaging (rs-fMRI) for analysis of regional homogeneity (ReHo). Twelve regions of interest (ROIs) in the frontal and temporal lobes were generated and one-way ANOVA was performed to test the ReHo differences within these ROIs between the above three groups. The ReHo values within ROIs were extracted to investigate whether a left-right asymmetry existed in a mental disorder. One-way ANOVA showed significant differences in ReHo in the right superior frontal gyrus and left superior temporal gyrus; post hoc analysis revealed that schizophrenic patients had lower ReHo in the left superior temporal gyrus than either control subjects or patients with MDD. Increased ReHo was observed in the right superior frontal gyrus in schizophrenic patients compared with control subjects, and a left-less-than-right asymmetry was also found in this region in schizophrenic patients. The above alterations in ReHo were not affected by age and genders. Our study suggests that the altered ReHo in the superior frontal and temporal gyrus may be specific for schizophrenia rather than MDD. A left-less-than-right asymmetry activation pattern may exist in the resting-state superior frontal gyrus in schizophrenia. This finding would be helpful for better understanding the pathological mechanisms of schizophrenia.