Efficacy of single and repeated ketamine administration for suicidal ideation in adults with psychiatric disorders: A meta-analysis.

BACKGROUND: Previous studies have demonstrated rapid-onset anti-suicidal ideation effects of ketamine. This study aimed to compare the efficacy and duration of anti-suicidal thoughts following single- and repeated-dose ketamine administration. METHODS: We retrieved published studies on ketamine for suicidal ideation (SI) from PubMed, OVID (MEDLINE), Web of Science, and Embase, spanning from inception to May 1, 2024. Standardized mean differences (SMD) in the SI scores were calculated for continuous outcomes. RESULTS: This study included 49 independent clinical trials involving 3982 participants. After a single ketamine administration, a significant reduction in SI was observed at 4 h (SMD = -0.607, 95 % confidence interval (CI) = [-0.797, -0.418], I2 = 40.69 %), with peak effects observed at 24 h (SMD = -0.955, 95 % CI = [-1.229, -0.682], I2 = 63.66 %) and effects persisted for one month (SMD = -0.948, 95 % CI = [-1.611, -0.285], I2 = 74.32 %). Similar anti-suicidal effects were observed at the treatment endpoint (SMD = -1.228, 95 % CI = [-1.506, -0.950], I2 = 94.56 %) and during a follow-up period of greater than or equal to 1 month (SMD = -1.012, 95 % CI = [-1.695, -0.330], I2 = 80.44 %) with multiple doses of ketamine administration. CONCLUSIONS: Single ketamine treatment may have a significant and lasting (up to 1 month) beneficial effect on SI. There was no statistical difference in the efficacy and duration of anti-suicidal thoughts between single and serial ketamine administration.

Structural covariance network activity in the medial prefrontal cortex is modulated by childhood abuse in adolescents with depression.

Aberrant structural covariance (SC) in the medial prefrontal cortex (mPFC) is believed to play a crucial role in adolescent-onset major depressive disorder (AO-MDD). However, the effect of childhood abuse (CA) on SC in AO-MDD patients is still unknown. Here, we measured anomalous SC in the mPFC of AO-MDD patients and assessed the potential modulation of this feature by CA. We acquired T1-weighted structural images of AO-MDD patients (n = 93) and healthy controls (HCs, n = 81). Using voxel-based morphometry analysis, we calculated gray matter volumes for each subject. Subsequently, we classified abnormal SC in the mPFC into three subtypes according to overall CA. Compared with HCs, AO-MDD patients showed alterations in the structural covariance network of the mPFC, which is a central region in the default mode network (DMN). We also found an anterior-posterior dissociation in the structural covariance connectivity of the DMN. A history of CA modulated bilateral mPFC SC. These changes were primarily focused on the SC between the mPFC and the limbic system, indicating a gap in the rate of neural maturation between these regions. In summary, the DMN and frontal-limbic system, which are involved in emotional processing, appear to play a significant role in the development of AO-MDD. These findings highlight the crucial effects of CA on neurophysiological alterations in individuals with AO-MDD.

Mediating effect of inflammation on the relationship between sleep disruption and suicidal ideation in major depressive disorder.

BACKGROUND: Sleep disruption, particularly insomnia, is a notable characteristic of depression and is associated with an increased risk of suicide in patients diagnosed with major depressive disorder (MDD). Moreover, the pathophysiology of depression and suicide has been linked to inflammation, specifically proinflammatory cytokines. However, the complex interplay among these factors in individuals with MDD remains poorly understood. This study investigated the mediating role of inflammatory cytokines in the relationship between sleep disruption and suicidal ideation (SI), with a particular emphasis on gender differences. METHODS: This study used a cross-sectional design in which 281 individuals diagnosed with MDD were recruited from psychiatric clinics. The main assessments included the evaluation of sleep disruption, inflammatory markers, and SI. The Beck Scale for Suicide Ideation (SSI) scores was employed to quantify SI, whereas HAMD-SLD, a component of the Hamilton Rating Scale (HAMD-17), was used to evaluate sleep disruption. Blood analysis was performed to measure inflammatory markers. RESULT: For females diagnosed with MDD, significant associations between sleep disruption and the levels of IL-6 (B = 0.994, p = 0.013) and TNF-α (B = 1.986, p = 0.016) were found when IL-6 or TNF-α were considered as mediators in the regression model. In addition, IL-6 (B = 5.689, p < 0.001) and TNF-α (B = 9.916, p = 0.006) exhibited strong correlation with SSI scores. CONCLUSIONS: The primary results of this study indicate that IL-6 and TNF-α could function as potential mediators in the relationship between sleep disruption and SI among female patients diagnosed with MDD. CLINICAL TRIAL: Name of the registry: Zhejiang University Trial registration number: ChiCTR1800017626 Date of registration: 2018-08-07, 'Retrospectively registered' URL of trial registry record: https://www.chictr.org.cn/showproj.html?proj=27321.

Altered regional brain activity moderating the relationship between childhood trauma and depression severity.

OBJECTIVE: Childhood trauma (CT) is a major environmental risk factor for an adverse course and treatment outcome of major depressive disorder (MDD). Evidence suggests that an altered regional brain activity may play a crucial role in the relationship between CT and MDD. This study aimed to clarify the relationship between CT, regional brain activity, and depression severity. METHODS: In this study, 96 patients with MDD and 82 healthy controls (HCs) participated. Regional brain activity was measured using the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). These measures were compared between the MDD and HC groups, and the values of different brain regions were extracted as moderators. RESULTS: Increased fALFF and ReHo values were observed in the left middle temporal gyrus in the MDD group compared with the HC group (p < 0.001). Furthermore, the fALFF and ReHo values moderated the positive correlation between the Childhood Trauma Questionnaire (CTQ) score, 17-item Hamilton Depression Rating Scale (HAMD-17) total score, and retardation factor score in the MDD group (all, p < 0.05). Finally, as the fALFF and ReHo values increased, the positive correlations between CTQ, HAMD-17 total, and retardation dimension scores became stronger. CONCLUSION: Our study highlighted the crucial role of altered brain function in connecting childhood maltreatment with depressive symptoms. Our findings indicate that an altered regional brain activity could explain the potential neurobiological mechanisms of MDD symptoms, offering the opportunity to function as a powerful diagnostic biomarker.

Long-term quality of life after repeated ketamine infusions in anxious and nonanxious patients with depression.

BACKGROUND: There have been many studies on the benefits of repeated ketamine infusions on patients' depression but few on the impact of ketamine on patients' long-term quality of life (QoL). This study investigated long-term QoL in individuals with depression, both anxious and nonanxious. METHODS: A total of 107 individuals with a diagnosis of depression were included in the study. The patients were evaluated on Days 0, 13 and 26 and Months 6 and 9, and they received six ketamine infusions over the course of two weeks. The World Health Organization Quality of Life-BREF (WHOQOL-BREF) Scale and the Patient Health Questionnaire-9 (PHQ-9) Scale were used to measure depressive symptoms and QoL. Linear mixed models were used to evaluate depressive symptoms and QoL during ketamine treatment. RESULTS: A total of 67.2 % of patients were diagnosed with anxious depression. In the long term, there were no significant differences in the time-by-group interactions for general QoL (F = 0.510; P = 0.676), physical QoL (F = 2.092; P = 0.102), psychological QoL (F = 0.102; P = 0.959), social QoL (F = 2.180; P = 0.091), or environmental QoL (F = 1.849; P = 0.139) between the two groups. LIMITATIONS: The main limitation of this study is its open-label design. CONCLUSION: The improvement in depression symptoms and QoL following ketamine treatment was not impacted by the presence or absence of anxiety in patients who were depressed prior to treatment. Only occasionally did depressed individuals with anxiety experience a worsening of their quality of life compared to those without anxiety.

The core inflammatory factors in patients with major depressive disorder: a network analysis.

Introduction: The symptoms of major depressive disorder (MDD) vary widely. Psycho-neuro-inflammation has shown that MDD's inflammatory factors can accelerate or slow disease progression. This network analysis study examined the complex interactions between depressed symptoms and inflammatory factors in MDD prevention and treatment. Measures: We gathered participants' inflammatory factor levels, used the Hamilton Depression Scale (HAMD-17), and network analysis was used to analyzed the data. Network analysis revealed the core inflammatory (nodes) and their interactions (edges). Stability and accuracy tests assessed these centrality measures' network robustness. Cluster analysis was used to group persons with similar dimension depressive symptoms and examine their networks. Results: Interleukin-1ß (IL-1ß) is the core inflammatory factor in the overall sample, and IL-1ß-interleukin-4 (IL-4) is the strongest correlation. Network precision and stability passed. Network analysis showed significant differences between Cluster 1 (with more severe anxiety/somatization and sleep disruption) and Cluster 3 (with more severe retardation and cognitive disorders), as well as between Cluster 2 (with more severe anxiety/somatization, sleep disruption and body weight) and Cluster 3. IL-1ß is the core inflammatory factor in Cluster 1 and Cluster 2, while tumor necrosis factor alpha (TNF-α) in Cluster 3. Conclusion: IL-1ß is the central inflammatory factor in the network, and there is heterogeneity in the core inflammatory factor of MDD with specific depressive dimension symptoms as the main manifestation. In conclusion, inflammatory factors and their links should be prioritized in future theoretical models of MDD and may provide new research targets for MDD intervention and treatment.

Psychotic symptoms and neurocognition among patients with major depressive disorder: A chained mediation model of depressive symptoms and socio-occupational functioning.

BACKGROUND: Depressive symptom and psychotic symptom have been identified as risk factors for impaired socio-occupational functioning in patients with major depressive disorder (MDD), while neurocognitive functioning is considered to be a potential protective factor against socio-occupational functioning. Nevertheless, little is known about the complex relationship among these factors in patients with MDD. The purpose of this research was to explore whether the relationship between depressive symptom severity and social-occupational functioning is mediated by neurocognitive functioning and psychotic symptom severity in MDD patients. METHODS: A total of 659 eligible MDD patients included male and female, and their depressive symptoms and psychotic symptoms at baseline were assessed by the 17-item Hamilton Depression Scale (HAMD-17) and The Brief Psychiatric Rating Scale (BPRS) respectively. Cognitive domains were assessed by the MATRICS Consensus Cognitive Battery (MCCB), and subjective and objective functioning were measured by the Global Assessment of Functioning (GAF). LIMITATION: The analysis is cross-sectional, which limits causal inference. RESULT: (1) The correlation between depressive symptoms and thought disturbance was positive (r = 0.125, p = 0.001), whereas the correlations with visual learning and memory (r = -0.146, p < 0.001) and socio-occupational functioning (r = -0.175, p < 0.001) were negative. (2) Depressive symptoms mainly affect the socio-occupational functioning of MDD patients via three indirect effects: the single mediating effect of psychotic symptoms and neurocognitive functioning, and the chain mediating effect of psychotic symptoms and neurocognitive functioning. CONCLUSIONS: The results suggest that the relationship between depressive symptom severity and socio-occupational functioning in MDD patients is partially mediated by psychotic symptom severity and neurocognitive functioning.

Pooled Analysis of the Accuracy of Xpert Ebola Assay for Diagnosing Ebola Virus Infection.

BACKGROUND: West Africa has witnessed the unprecedented outbreak of Ebola virus disease (EVD). The Ebola virus (EBOV) can cause Ebola hemorrhagic fever, which is documented as the most deadly viral hemorrhagic fever in the world. RT-PCR had been suggested to be employed in the detection of Ebola virus; however, this method has high requirements for laboratory equipment and takes a long time to determine Ebola infection. Although Xpert Ebola is a fast and simple instrument for the detection of Ebola virus, its effect is still unclear. This study is aimed at evaluating the accuracy of Xpert Ebola in diagnosing Ebola virus infection. METHODS: Using the keywords "Xpert" and "Ebola virus", relevant studies were retrieved from the database of PubMed, Embase, Web of Science, and Cochrane. RT-PCR was employed as a reference standard to evaluate whether the study is eligible to be included in the meta-analysis. Data from these included studies were extracted by two independent assessors and were then analyzed by the Meta-DiSc 1.4 software to produce the heterogeneity of sensitivity (SEN), specificity (SP), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic advantage ratio (DOR) of the study. The results of pooled analysis were plotted, together with the summary receiver operating characteristic (SROC) curve plotted by calculating the area under the curve (AUC). Generated pooled summary estimates (95% CIs) were calculated for the evaluation of the overall accuracy of this study. RESULTS: Five fourfold tables were made from the four studies that were included in the meta-analysis. The pooled sensitivity of Xpert Ebola was 0.98 (95% confidence interval (CI) (0.95, 0.99)), and the pooled specificity was 0.98 (95% CI (0.97, 0.99)). The pooled values of positive likelihood ratio was 53.91 (95% CI (12.82, 226.79)), with negative likelihood ratio being 0.04 (95% CI (0.02, 0.08)) and diagnostic odds ratio being 2649.45 (95% CI (629.61, 11149.02)). The AUC was 0.9961. CONCLUSIONS: Compared with RT-PCR, Xpert Ebola has high sensitivity and specificity. Therefore, it is a valued alternative method for the clinical diagnosis of Ebola virus infection. However, the Xpert Ebola test is a qualitative test that does not provide quantitative testing of EBOV concentration. Whether it can completely replace other methods or not calls for further evidences.