Resting-state fMRI is a novel approach to measure spontaneous brain activity in patients with major depressive disorder (MDD). Although most resting-state fMRI studies have focused on the examination ...of temporal correlations between low-frequency oscillations (LFOs), few studies have explored the amplitude of these LFOs in MDD. In this study, we applied the approaches of amplitude of low-frequency fluctuation (ALFF) and fractional ALFF to examine the amplitude of LFOs in MDD.
A total of 36 subjects, 18 first-episode, treatment-naive patients with MDD matched with 18 healthy controls (HCs) completed the fMRI scans. Compared with HCs, MDD patients showed increased ALFF in the right fusiform gyrus and the right anterior and posterior lobes of the cerebellum but decreased ALFF in the left inferior temporal gyrus, bilateral inferior parietal lobule, and right lingual gyrus. The fALFF in patients was significantly increased in the right precentral gyrus, right inferior temporal gyrus, bilateral fusiform gyrus, and bilateral anterior and posterior lobes of the cerebellum but was decreased in the left dorsolateral prefrontal cortex, bilateral medial orbitofrontal cortex, bilateral middle temporal gyrus, left inferior temporal gyrus, and right inferior parietal lobule. After taking gray matter (GM) volume as a covariate, the results still remained.
These findings indicate that MDD patients have altered LFO amplitude in a number of regions distributed over the frontal, temporal, parietal, and occipital cortices and the cerebellum. These aberrant regions may be related to the disturbances of multiple emotion- and cognition-related networks observed in MDD and the apparent heterogeneity in depressive symptom domains. Such brain functional alteration of MDD may contribute to further understanding of MDD-related network imbalances demonstrated in previous fMRI studies.
Identifying and managing major depressive disorder (MDD) patients with suicidal ideation or behavior (MDSI) is critical for reducing the disease burden. This scoping review aims to map the existing ...evidence related to MDSI in the Chinese population.
A scoping review was conducted to summarize the published evidence regarding epidemiology or disease burden, evaluation, diagnosis, management, and prognosis of MDSI. The search strategy imposed restriction on English or Chinese publications between 1 January 2011 and 28 February 2022.
Of the 14,005 identified records, 133 met the eligibility criteria and were included for analysis. The included studies were characterized as high heterogeneity in evaluation of suicidal ideation or behavior. Compared with MDD patients without suicidal ideation or behavior, MDSI patients were more likely to suffer from psychological and somatic symptoms, social function impairment, and lower quality of life. Younger age, female gender, longer disease course, and comorbid psychological or physical symptoms were consistently found to be risk factors of suicidal ideation or behavior. Relevant research gaps remain regarding comprehensive evaluation of standard clinical diagnosis, disease burden, social-cultural risk factors, and effectiveness of interventions targeting MDSI. Studies with large sample size, representative population are warranted to provide high-quality evidence.
MDD patients with suicidal ideation or behavior should be prioritized in treatment and resource allocation. Heterogeneity exists in the definition and evaluation of MDSI in different studies. To better inform clinical practice, it is imperative to establish a unified standard for evaluation and diagnosis of suicidal ideation or behavior among MDD population.
•Suicidal ideation or behavior adversely affects Chinese patients with MDD in physical, mental, and social functions•Heterogeneity exists in the definition and evaluation of MDSI•Younger age, female gender, longer disease course, and comorbid psychological or physical symptoms were risk factors of MDSI.
•Subjective social support, but not objective social support, was associated with suicide risk.•Negative (but not positive) coping style was associated with suicide risk.•MDD patients with suicide ...risk had high level of perceived stressfulness.•Perceived stressfulness can mediate the effects of subjective social support and negative coping style on suicide risk.
Risk factors for suicide have been widely investigated in patients with major depressive disorder (MDD); However, far less research has been conducted on protective factors for suicide.
The diagnosis of MDD and suicide risk were evaluated by the Mini‐International Neuropsychiatric Interview (MINI). Social support and coping behaviors were assessed by the Social Support Rate Scale (SSRS) and Simplified Coping Style Questionnaire (SCSQ), respectively. Life stressors were captured by the Life Events Scale (LES). Severity of depression was assessed by 17-item Hamilton Depression Rating Scale (HAMD-17). Logistic regression analysis and path analyses were used to test the association of protective factors, risk factors, life stress and suicide risk.
Patients with suicide risk showed a significantly lower level of subjective social support (adjusted P < 0.012), a higher level of perceived stressfulness (P < 0.001) and negative coping style (P = 0.008) compared with patients without suicide risk. Path analysis showed that perceived stressfulness can mediate the protective effect of subjective social support and deleterious effect of negative coping style on suicide risk.
Cross-sectional design, and retrospective recall of stressful life events.
This study suggests that subjective social support and negative coping style may be regarded as a protective factor and a risk factor for suicide risk in MDD patients, respectively, and perceived stressfulness mediates their roles in suicide. Further suicide prevention and intervention strategies should focus on increasing individual subjective social support and improving coping strategies to enhance their resilience.
Although we have some basic understanding of the neurochemical mechanisms of the antidepressants, the network-level effect of antidepressant treatment is still not fully understood. This study was ...conducted to investigate the effects of antidepressant on functional brain networks of patients with major depressive disorder (MDD). We performed resting-state fMRI scans on 20 first-episode drug-naive MDD patients at baseline and after escitalopram medication for 8 weeks. Twenty healthy controls also received MRI scans with an 8-week interval. The graph theory indices, long- and short-range functional connectivity strength (FCS), were computed to characterize the brain connectivity. The analysis of covariance was conducted on FCS maps of patients and controls to obtain the interaction effect of group and time, which indicate treatment-related effect. Following treatment, increased long-range FCS in the bilateral posterior cingulate cortex/precuneus and right thalamus in MDD patients at baseline were reduced. Meanwhile, increased short-range FCS in the bilateral ventromedial prefrontal cortex and left amygdala in patients were reduced, while reduced short-range FCS in the right parahippocampal gyrus was increased. Results suggest that the brain regions associated with negative emotional processing and regulation, and self-referential function could be modulated by escitalopram treatment; long- and short-range FCS are differentially affected by antidepressant.
The response rate (defined as the rate of reduction from baseline in the PANSS total score>30%) was also evaluated. The variables with P <0.2 in single factor analysis were included in multivariate ...logistic regression analysis. The response rate was 50.5% (311/616) for aripiprazole at the second week, and it rose to 84.4% (493/584) and 96.3% (523/543) at the fourth and eighth weeks, respectively. The proportions of patients with abnormal metabolic indicators including fasting blood glucose, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were decreased from baseline, but proportion of patients with abnormal triglyceride increased slightly Figure 1A.
•Distant spatial profiles were observed in the low amplitudes of the slow-4 versus slow-5 frequency bands derived from resting-state fMRI signals.•MDD patients showed altered ALFF and fALFF in widely ...distributed brain regions.•The alteration in ALFF and fALFF in MDD patients were dependent on the choice of different frequency bands.
We conducted this fMRI study to examine whether the alterations in amplitudes of low-frequency oscillation (LFO) of major depressive disorder (MDD) patients were frequency dependent.
The LFO amplitudes (as indexed by amplitude of low-frequency fluctuation ALFF and fractional ALFF fALFF) within 4 narrowly-defined frequency bands (slow-5: 0.01–0.027Hz, slow-4: 0.027–0.073Hz, slow-3: 0.073–0.198Hz, and slow-2: 0.198–0.25Hz) were computed using resting-state fMRI data of 35 MDD patients and 32 healthy subjects. Repeated-measures analysis of variance (ANOVA) was performed on ALFF and fALFF both within the low frequency bands of slow-4 and slow-5 and within all of the four bands.
We observed significant main effects of group and frequency on ALFF and fALFF in widely distributed brain regions. Importantly, significant group and frequency interaction effects were observed in the ventromedial prefrontal cortex, inferior frontal gyrus, precentral gyrus, in a left-sided fashion, the bilateral posterior cingulate and precuneus, during ANOVA both within slow-4 and slow-5 bands and within all the frequency bands.
The results suggest that the alterations of LFO amplitudes in specific brain regions in MDD patients could be more sensitively detected in the slow-5 rather than the slow-4 bands. The findings may provide guidance for the frequency choice of future resting-state fMRI studies of MDD.
BACKGROUNDAlthough anhedonia is a key symptom of major depressive disorder (MDD), there is neither a concise nor effective method to distinguish and define anhedonia in MDD. The current study ...attempts to answer two questions based on validating the Dimensional Anhedonia Rating Scale (DARS) in Chinese MDD patients: 1) whether anhedonia subgroup can be identified? 2) whether patients with anhedonia display unique psychosocial and clinical features? METHODSIn the discovery sample, 533 MDD patients and 124 healthy controls were recruited into a multicenter study. For replication, a further 112 first-episode, drug-naïve MDD patients were recruited. Latent profile analysis (LPA) was used to identify the latent subgroups based on their hedonic function measured by the DARS. According to the categorization, ROC curves were applied to find the cut-off value. Lasso regression was performed to characterize psychological and clinical features linked to anhedonia. RESULTSThe data-driven approach identified and validated the anhedonia subgroup, and proposed that the cut-off value for distinguishing anhedonia was 28.5 based on the total score of DARS. Lasso regression demonstrated that melancholia, lower levels of positive affect and education, more severe depressive symptoms, older age were associated with anhedonia in MDD patients. CONCLUSIONThis study used a data-driven approach to propose a new and convenient method for distinguishing the anhedonia of MDD patients with unique psychological and clinical features. Identifying the subtype may contribute to pinpointing more specific biomarkers in shedding light on the mechanisms of anhedonia in MDD. TRIAL REGISTRATIONTNDTAD study, NCT03294525; TOSD study, NCT03148522.
High levels of anxiety symptoms are common in individuals with major depressive disorder (MDD). Adjunctive anxiolytics are widely used in such patients; however, only a few studies have examined the ...strategy using tandospirone. This study aimed to evaluate the efficacy and safety of adjunctive tandospirone in individuals with MDD and high level of anxiety symptoms.
A multicenter, randomized, parallel-controlled, open-label study was conducted to evaluate the efficacy and safety of tandospirone coupled with selective serotonin reuptake inhibitors (SSRIs) in patients with MDD and high level of anxiety symptoms. Two hundred and forty-five patients fulfilling the DSM-IV-TR criteria for MDD were randomly assigned to 6 weeks of either SSRIs and tandospirone or SSRIs alone treatment. The efficacy was measured by HAMA total scores, HAMD-17 total scores, and Clinical Global Impressions severity subscale (CGI-S) score.
After a 6-week follow-up, two hundred and thirty patients completed this study. Tandospirone coupled with SSRIs significantly improved depressive and anxiety symptoms compared to monotherapy with SSRIs as assessed by HAMD-17 total score (P = 0.003), HAMA total score (P = 0.010), and CGI-S score at week 6 (P = 0.003). The incidence rate of treatment-emergent adverse events (TEAEs) was similar in both groups; the therapy was well-tolerated.
Short-term tandospirone augmentation was effective and well-tolerated in this study. Addition of tandospirone may improve outcomes in MDD patients with high anxiety.
•Tandospirone augmentation was superior to monotherapy in reducing depressive and anxiety symptoms, as well as, somatic anxiety symptoms.•Participants were generally safe and well-tolerated the therapy.•A placebo-controlled with long follow-up study on this treatment is essential.
Despite the best treatments, about 20% of patients with major depressive disorder (MDD) receiving drugs and psychological intervention show little or no improvement. There is no trial comparing ...different treatment methods in patients with anxiety/somatic subtype MDD.
To compare the efficacy and safety of various treatments in patients with anxiety/somatic subtype MDD.
This was a preliminary multicenter randomized controlled trial at eight participating hospitals in China (09/2016-06/2019) (ClinicalTrials.gov #NCT03219008). The patients were randomized to mirtazapine/SNRIs, mirtazapine/SNRIs+cognitive behavioral therapy (CBT), mirtazapine+SNRIs, or mirtazapine+SNRIs+physical therapies (modified electroconvulsive treatment or repetitive transcranial magnetic stimulation). The primary endpoint was the 17-item Hamilton Depression Scale (HAMD-17). The Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) and Quality of Life (QOL)-6 were the secondary endpoints. The adverse events (AEs) were monitored. The patients were assessed at baseline (0 weeks), and at the end of the 2nd, 4th, 6th, 8th, and 12th week during treatment.
Finally, 107 patients were included: mirtazapine/SNRIs (n=36), mirtazapine/SNRIs+CBT (n=28), mirtazapine+SNRIs (n=29), and mirtazapine+SNRIs+physical therapies (n=14). The 17-HDRS and QIDS-SR scores decreased in all four groups, and the QOL-6 scores increased. There were no differences in the 17-HDRS (P=0.099), QIDS-SR (P=0.407), and QOL-6 (P=0.485) scores among the four groups. There were no differences in the occurrence of AEs among the four groups (P=0.942).
This preliminary trial suggests that all four interventions (mirtazapine/SNRIs, mirtazapine/SNRIs+CBT, mirtazapine+SNRIs, or mirtazapine+SNRIs+physical therapies) achieved similar response and remission rates in patients with anxiety/somatic subtype MDD. The safety profile was manageable.
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