BACKGROUND: While prior studies have explored the efficacy of Morinda officinalis oligosaccharides (MOs) as a treatment for patients with major depressive disorder (MDD), the mechanistic basis for the effects of MOs on brain function or the default-mode network (DMN) has yet to be characterized. The objective of this was to examine the effects of MOs treatment on functional connectivity in different regions of the DMN.
METHODS: In total, 27 MDD patients and 29 healthy control subjects (HCs) underwent resting-state functional magnetic resonance imaging. The patients were then treated with MOs for 8 weeks, and scanning was performed at baseline and the end of the 8-week treatment period. Changes in DMN homogeneity associated with MOs treatment were assessed using network homogeneity (NH) analyses of the imaging data, and pattern classification approaches were employed to determine whether abnormal baseline NH deficits could differentiate between MDD patients and controls. The ability of NH abnormalities to predict patient responses to MOs treatment was also evaluated.
RESULTS: Relative to HCs, patients exhibited a baseline reduction in NH values in the right precuneus (PCu). At the end of the 8-week treatment period, the MDD patients showed reduced and increased NH values in the right PCu and left superior medial frontal gyrus (SMFG), respectively. Compared to these patients at baseline, the 8-week MOs treatment was associated with reduced NH values in the right angular gyrus and increased NH values in the left middle temporal gyrus and the right PCu. Support vector machine (SVM) analyses revealed that NH abnormalities in the right PCu and left SMFG were the most accurate (87.50%) for differentiating between MDD patients and HCs.
CONCLUSIONS: These results indicated that MOs treatment could alter default-mode NH in patients with MDD. The results provide a foundation for elucidation of the effects of MOs on brain function and suggest that the distinctive NH patterns observed in this study may be useful as imaging biomarkers for distinguishing between patients with MDD and healthy subjects.

UNASSIGNED: Major depressive disorders (MDDs) impose substantial burdens on individuals and society; however, further detailed analysis is still needed for its long-term trends.
UNASSIGNED: This study aimed to analyse the gender-specific temporal trends and cohort variations of MDD incidence among Chinese residents over the past three decades.
UNASSIGNED: Employing the age-period-cohort-interaction model and leveraging data from the Global Burden of Disease Study 2019, this research identified and analysed incidence trends of MDD among Chinese males and females aged 5-94 years from 1990 to 2019 across three dimensions, encompassing age, period and birth cohort.
UNASSIGNED: The analysis reveals age-related effects, indicating heightened MDD risk among adolescents and older adults. Specifically, individuals entering the older adulthood at the age of 65-69 significantly increased the risk of MDD by 64.9%. People aged 90-94 years witnessed a 105.4% increase in MDD risk for the overall population, with females and males in this age group experiencing a 75.1% and 103.4% increase, respectively. In terms of period effects, the risk of MDD displayed a decline from 1990 to 1994, followed by a rebound in 2008. Cohort effects demonstrated diverse generational patterns, with generation I and generation III manifesting opposing \'age-as-level\' trends. Generation II and generation IV exhibited \'cumulative disadvantage\' and \'cumulative advantage\' patterns, respectively. Age effects indicated an overall higher risk of MDD incidence in females, while cohort effects showed greater variations of MDD incidence among females.
UNASSIGNED: The study underscores the substantial effects of age, period and cohort on MDD across genders in China. Priority interventions targeting vulnerable populations, including children, adolescents, older adults, females and the post-millennium birth cohort, are crucial to mitigate the impact of MDD.

OBJECTIVE: Anxious depression is a prevalent characteristic observed in Asian psychiatric patients diagnosed with major depressive disorder (MDD). This study aims to investigate the prevalence and clinical presentation of anxious depression in Taiwanese individuals diagnosed with MDD.
METHODS: We recruited psychiatric outpatients aged over 18 who had been diagnosed with MDD through clinical interviews. This recruitment took place at five hospitals located in northern Taiwan. We gathered baseline clinical and demographic information from the participants. Anxious depression was identified using a threshold of an anxiety/somatization factor score ≥7 on the 21-item Hamilton Rating Scale for Depression (HAM-D).
RESULTS: In our study of 399 patients (84.21% female), 64.16% met the criteria for anxious depression. They tended to be older, married, less educated, with more children, and an older age of onset. Anxious depression patients had higher HAM-D and Clinical Global Impression-Severity scale score, more panic disorder (without agoraphobia), and exhibited symptoms like agitation, irritability, concentration difficulties, psychological and somatic anxiety, somatic complaints, hypochondriasis, weight loss, and increased insight. Surprisingly, their suicide rates did not significantly differ from non-anxious depression patients. This highlights the importance of recognizing and addressing these unique characteristics.
CONCLUSIONS: Our study findings unveiled that the prevalence of anxious depression among Taiwanese outpatients diagnosed with MDD was lower compared to inpatients but substantially higher than the reported rates in European countries and the United States. Furthermore, patients with anxious depression exhibited a greater occurrence of somatic symptoms.

BACKGROUND: Suicide attempts are one of the most serious comorbidities in patients with major depressive disorder (MDD), and the prevalence of suicide attempts is higher in younger people compared to older people, with significant gender differences. This study aimed to investigate the relationship between suicide attempts, clinical symptoms, thyroid hormones, and metabolic parameters in young first-episode and drug-naïve (FEND) MDD patients of different genders.
METHODS: A total of 1289 FEND MDD patients were recruited. Depression, anxiety, and psychotic symptoms were assessed using the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the Positive and Negative Syndrome Scale (PANSS) positive subscale, respectively. Thyroid hormones and glucolipid metabolism indicators were also tested. Network analysis was employed to delineate the interplay between thyroid dysfunction, clinical symptoms, and metabolic disorders.
RESULTS: Among young FEND MDD patients, the rate of suicide attempts was 17.4% in males and 19.8% in females, showing no significant gender difference in the incidence of suicide attempts (χ2 = 1.06, p = 0.303). In the network model, PANSS positive subscale (Expected Influence = 0.578) and HAMD scores (Expected Influence = 0.576) were identified as the individual symptoms that most affected male patients, whereas TSH (Thyroid-Stimulating Hormone) (Expected Influence = 0.972) and PANSS positive subscale (Expected Influence = 0.937) were identified as the individual symptoms that most affected female patients. In addition, we found that TSH (Expected Influence = 0.438) was a pivotal node connecting metabolic disturbances and clinical symptoms.
CONCLUSIONS: Our findings emphasize the important role of psychotic symptoms in young MDD patients with suicide attempts. Moreover, our results highlight the pivotal role of serum TSH levels in the pathophysiology of young female MDD patients with suicide attempts.

Background: The administration of omega-3 polyunsaturated fatty acid supplements is recommended as an adjuvant therapy for adults diagnosed with major depressive disorder. The evaluation of replicated data in combination treatment with omega-3 has been extensively conducted in adults over the past decade. However, the generalizability of these findings to pediatric groups is still uncertain. The objectives of this evaluation were twofold: (1) to evaluate the effectiveness of omega-3 and associated combination therapies in reducing the severity of depressive symptoms, and (2) to include remission rates (i.e., reduction of more than 50% in depression symptoms) as a measure of therapeutic efficacy. Methods: We conducted a literature search on PubMed/EMBASE from inception to October 2023. Data analyses were conducted using Stata (version 17.0). Results: We identified a total of 3168 articles. After eligibility screening of identified studies, nine studies (n = 561 participants) were included in our analysis herein. Pairwise comparisons revealed no significant improvement in depression symptoms for any intervention versus placebo. However, a clustered ranking plot identified omega-3 plus inositol as the most effective treatment for pediatric depression (77.3% efficacy). Omega-3 paired with psychoeducational psychotherapy significantly lowered the remission rate compared to placebo (standardized mean difference = 0.44, 95% confidence interval: 0.00-0.87, p = 0.048), resulting in a 91.5% remission rate, making it the most effective treatment in the study. Conclusions: Taken together, this network meta-analysis presents compelling evidence supporting the antidepressant effects of omega-3 in pediatric groups with depression. Future research should aim to investigate omega-3 as monotherapy for young individuals with depression, as well as investigate the efficacy of omega-3 in comparison to psychosocial interventions for affected individuals.

OBJECTIVE: Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile. However, the dose-response relationships of vortioxetine for MDD is not well established. We aimed to conduct dose-response meta-analyses to fill this gap.
METHODS: We systematically searched multiple electronic databases for randomized controlled trials of vortioxetine for MDD, with the last search conducted on 08 February, 2024. The dose-response relationship was evaluated using a one-stage random-effects dose-response meta-analysis with restricted cubic spline model. The primary outcome was efficacy (mean change in depression scale score), with secondary outcomes including response, dropout for any reasons (acceptability), dropout for adverse events (tolerability), and any adverse events (safety).
RESULTS: The dose-response meta-analysis comprised 16 studies, with 4,294 participants allocated to the vortioxetine group and 2,299 participants allocated to the placebo group. The estimated 50% effective dose was 4.37 mg/day, and the near-maximal effective dose (95% effective dose) was 17.93 mg/day. Visual inspection of the dose-efficacy curve suggests that a plateau possibly had not been reached yet at 20 mg/day. Acceptability, tolerability and safety decreased as the dose increased. Subgroup analysis indicated that no significant differences were observed in acceptability, tolerability and safety among the dosage groups.
CONCLUSIONS: Vortioxetine may potentially provide additional therapeutic benefits when exceeding the current licensed dosage without significantly impacting safety. Conducting clinical trials exceeding the current approved dosage appears necessary to fully comprehend its efficacy and risk.

UNASSIGNED: Sleep is associated with psychiatric disorders. However, their causality remains unknown.
UNASSIGNED: The study explored the causal relationship between seven sleep parameters (sleep duration, insomnia, sleep apnea, chronotype, daytime dozing, napping during the day, and snoring) and three psychiatric disorders including major depressive disorder (MDD), schizophrenia, and attention-deficit/hyperactivity disorder (ADHD) using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS) summary data for sleep parameters were obtained from the United Kingdom biobank, FinnGen biobank, and EBI databases. MR-Egger, weighted median, inverse-variance weighted (IVW), simple mode, weighted mode, maximum likelihood, penalized weighted median, and IVW(fixed effects) were used to perform the MR analysis. The heterogeneity was detected by Cochran\'s Q statistic. The horizontal pleiotropy was detected by MR Egger. The sensitivity was investigated by the leave-one-out analysis.
UNASSIGNED: Insomnia (OR = 2.02, 95%CI = 1.34-3.03, p = 0.001, False-discovery rate (FDR) corrected p-value = 0.011) and napping during the day (OR = 1.81, 95%CI = 1.34-2.44, FDR corrected p-value<0.001) were associated with an increased risk of MDD. Longer sleep duration (OR = 2.20, 95%CI = 1.24-3.90, FDR corrected p-value = 0.049) had an association with the increased risk of schizophrenia, while daytime dozing (OR = 4.44, 95%CI = 1.20-16.41, corrected p-value = 0.088)and napping during the day (OR = 2.11, 95%CI = 1.11-4.02, FDR corrected p-value = 0.088) had a suggestive association with an increased risk of schizophrenia. Longer sleep duration had a suggestive association with a decreased risk of ADHD (OR = 0.66, 95%CI = 0.42-0.93, FDR corrected p-value = 0.088).
UNASSIGNED: This study provides further evidence for a complex relationship between sleep and psychiatric disorders. Our findings highlight the potential benefits of addressing sleep problems in the prevention of psychiatric disorders.

Depression is a growing public health concern, and exercise is an adjunctive treatment modality to improve depression, but the optimal form of exercise and the optimal dose are still unclear. This systematic review examined the efficacy of four major types of exercise (aerobic, resistance, mixed, and mind-body) on depression, as well as the dose-response relationship between total and specific exercise and depressive symptoms. We included randomized controlled trials that included participants aged 18 years or older with a diagnosis of major depressive disorder or a depressive symptom score above a threshold as determined by a validated screening measure, implemented one or more exercise therapy groups, and assessed depressive symptoms at baseline and follow-up. Forty-six studies (3164 patients) were included in the meta-analysis. Aerobic (standardised mean difference (SMD) = -0.93; 95% CI: -1.25 to -0.62) and mind-body exercise (SMD) = -0.81; 95% CI: -1.19 to -0.42) improved depressive symptoms better compared to controls, followed by mixed (SMD = -0.77; 95% CI: -1.20 to -0.34) and resistance exercise (SMD = -0.76; 95% CI: -1.24 to -0.28). This dose-response meta-analysis showed a U-shaped curve between exercise dose and depressive symptoms. The minimum effective dose was estimated to be 320 metabolic equivalent (METs) -min per week and the optimal response was 860 METs-min per week. These findings lead us to advocate that clinicians carefully select the appropriate dose of exercise based on the patient\'s individual characteristics and needs, in conjunction with psychological care interventions.

BACKGROUND: Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are psychiatric disorders that can present with overlapping symptoms and shared risk factors. However, the extent to which these disorders share common underlying neuropathological mechanisms remains unclear. To investigate the similarities and differences in task-evoked brain activation patterns between patients with PTSD and MDD.
METHODS: A coordinate-based meta-analysis was conducted across 35 PTSD studies (564 patients and 543 healthy controls) and 125 MDD studies (4049 patients and 4170 healthy controls) using anisotropic effect-size signed differential mapping software.
RESULTS: Both PTSD and MDD patients exhibited increased neural activation in the bilateral inferior frontal gyrus. However, PTSD patients showed increased neural activation in the right insula, left supplementary motor area extending to median cingulate gyrus and superior frontal gyrus (SFG), and left fusiform gyrus, and decreased neural activation in the right posterior cingulate gyrus, right middle temporal gyrus, right paracentral lobule, and right inferior parietal gyrus relative to MDD patients.
CONCLUSIONS: Our meta-analysis suggests that PTSD and MDD share some similar patterns of brain activation, but also have distinct neural signatures. These findings contribute to our understanding of the potential neuropathology underlying these disorders and may inform the development of more targeted and effective treatment and intervention strategies. Moreover, these results may provide useful neuroimaging targets for the differential diagnosis of MDD and PTSD.

UNASSIGNED: Major depressive disorder (MDD) is associated with cognitive impairment through unclear mechanisms. We examined the relationship between sleep electroencephalogram (EEG) power and attention level in MDD.
UNASSIGNED: Forty-seven untreated patients with MDD and forty-seven age- and sex-matched controls were included. We examined relative EEG power during non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep by fast Fourier transform. The Attention Network Test (ANT) was performed to evaluate attention levels.
UNASSIGNED: Compared to controls, patients with MDD had lower theta power during NREM (P = 0.018) and REM (P = 0.002) sleep, while higher beta power (P = 0.050) during NREM sleep and delta power (P = 0.018) during REM sleep. Regarding attention level, patients with MDD had lower levels of accuracy (P = 0.021), longer mean reaction time (P < 0.001), poorer manifestations of the alerting effect (P = 0.038) and worse executive control (P = 0.048). Moreover, decreased theta power during NREM sleep was correlated with worsened accuracy (β = 0.329, P = 0.040), decreased theta power during REM sleep was correlated with worsened alerting effect (β = 0.355, P = 0.020), and increased delta power during REM sleep was correlated with longer mean reaction time (β = 0.325, P = 0.022) in patients with MDD. No association between ANT performance and other frequency bands was observed in patients with MDD.
UNASSIGNED: Our findings suggest that patients with MDD manifest impaired selective attention function that is associated with decreased theta power during NREM/REM sleep and increased delta power during REM sleep.