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.

Short-term cognitive effects of repeated-dose esketamine in adolescents with major depressive disorder and suicidal ideation: a randomized controlled trial.

BACKGROUND: Ketamine and its enantiomer have rapid and robust effects on depressive symptom and suicidal ideation. Little is known about their cognitive effects in adolescents. We aimed to evaluate the short-term effect of esketamine on cognition in adolescents with major depressive disorder (MDD) and suicidal ideation. METHOD: In this randomized-controlled trial, 51 participants aged 13-18 with MDD and suicidal ideation received three intravenous infusions of either esketamine (0.25 mg/kg) or midazolam (0.02 mg/kg). Four dimensions of the MATRICS Consensus Cognitive Battery (MCCB), including processing speed, working memory, verbal learning and visual learning, were assessed at Days 0, 6 and 12. RESULTS: In the linear mixed model, a significant time main effect (F = 12.803, P < 0.001), drug main effect (F = 6.607, P = 0.013), and interaction effect (F = 3.315, P = 0.041) was found in processing speed. Other dimensions including working memory and verbal learning showed significant time main effect (all P < 0.05), but no significant drug or interaction effect (all P > 0.05). Esketamine group showed improvement in processing speed from baseline to Days 6 and 12, and working memory from baseline to Day 12 (all P < 0.05). The generalized estimation equation showed no significant association between baseline cognition and antidepressant or antisuicidal effect (both P > 0.05). CONCLUSIONS: The present study suggested that three-dose subanesthetic esketamine infusions did not harm cognition among adolescents with MDD and suicidal ideation. Instead, esketamine may be associated with improvement in processing speed. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trials Registry ( http://www.chictr.org.cn , ChiCTR2000041232).

Efficacy of repeated intravenous esketamine in adolescents with anxious versus non-anxious depression.

Background: Patients with anxious major depressive disorder (MDD) are more likely to have poorer outcomes than those with non-anxious MDD. However, the effect of esketamine on adolescents with anxious versus non-anxious MDD has remained unknown. Aims: We compared the efficacy of esketamine in adolescents with MDD and suicidal ideation, both anxious and non-anxious. Methods: Fifty-four adolescents with anxious (n=33) and non-anxious (n=21) MDD received three infusions of esketamine 0.25 mg/kg or active-placebo (midazolam 0.045 mg/kg) over 5 days, with routine inpatient care and treatment. Suicidal ideation and depressive symptoms were assessed using the Columbia Suicide Severity Rating Scale and the Montgomery-Åsberg Depression Rating Scale. Multiple-sample proportional tests were used to compare the differences between groups on treatment outcomes 24 hours after the final infusion (day 6, primacy efficacy endpoint) and throughout the 4-week post-treatment (days 12, 19 and 33). Results: In subjects who received esketamine, a greater number of patients in the non-anxious group than the anxious group achieved antisuicidal remission on day 6 (72.7% vs 18.8%, p=0.015) and day 12 (90.9% vs 43.8%, p=0.013), and the non-anxious group had a higher antidepressant remission rate compared with the anxious group on day 33 (72.7% vs 26.7%, p=0.045). No significant differences in treatment outcomes were observed between the anxious and non-anxious groups at other time points. Conclusions: Three infusions of esketamine as an adjunct to routine inpatient care and treatment had a greater immediate post-treatment antisuicidal effect in adolescents with non-anxious MDD than in those with anxious MDD; however, this benefit was temporary and was not maintained over time. Trial registration number: ChiCTR2000041232.

CACNB2 rs11013860 polymorphism correlates of prefrontal cortex thickness in bipolar patients with first-episode mania.

BACKGROUND: The ß2 subunit of the voltage-gated l-type calcium channel gene(CACNB2) rs11013860 polymorphism is a putative genetic susceptibility marker for bipolar disorder (BD). However, the neural effects of CACNB2 rs11013860 in BD are largely unknown. METHODS: Forty-six bipolar patients with first-episode mania and eighty-three healthy controls (HC) were genotyped for CACNB2 rs11013860 and were scanned with a 3.0 Tesla structural magnetic resonance imaging system to measure cortical thickness of prefrontal cortex (PFC) components (superior frontal cortex, orbitofrontal cortex, middle and inferior frontal gyri). RESULTS: Cortical thickness was thinner in patients on all PFC measurements compared to HC (p < 0.050). Moreover, we found a significant interaction between CACNB2 genotype and diagnosis for the right superior frontal cortical thickness (F = 8.190, p = 0.040). Bonferroni corrected post-hoc tests revealed that, in CACNB2 A-allele carriers, patients displayed thinner superior frontal thickness compared to HC (p < 0.001). In patients, CACNB2 A-allele carriers also exhibited reduced superior frontal thickness compared to CACNB2 CC-allele carriers (p = 0.016). LIMITATIONS: Lithium treatment may influence our results, and the sample size in our study is relatively small. CONCLUSIONS: Our results suggest that the CACNB2 rs11013860 might impact PFC thickness in patients with first-episode mania. These findings provide evidence to support CACNB2 rs11013860 involvement in the emotion-processing neural circuitry abnormality in the early stage of BD, which will ultimately contribute to revealing the link between the variation in calcium channel genes and the neuropathological mechanism of BD.