HAM-D Total Score Research Articles

Antidepressant and anxiolytic efficacy and tolerability of agomelatine in the treatment of depression after COVID-19 in daily clinical practice (non-interventional study TELESPHOR)

Depression and anxiety are among the most common disorders observed in patients after COVID-19 coronavirus infection.Objective: to evaluate the antidepressant efficacy and tolerability of agomelatine in patients with a depressive episode (DE) after COVID-19 infection in everyday clinical practice.Material and methods. The multicenter observational study TELESPHOR included outpatients aged 18 to 65 years who developed DE (Hamilton Depression Rating Scale (HAMD-17) score of 8–24) within 3 months of the resolution of a laboratory-confirmed COVID-19 infection and started monotherapy with agomelatine. Patients were assessed at enrolment and subsequently at weeks 2, 4 and 8 of the observation period. The primary endpoint was the change in HAMD-17 scores by week 8 of the observation in patients taking agomelatine as an antidepressant. The main secondary outcome variables were the dynamics of scores for items 10 (psychic anxiety) and 11 (somatic anxiety) of the HAMD-17 scale, the proportion of responders and remitters (according to the HAMD-17 scale) and the impact on quality of life (QOL) according to the SF-36 questionnaire. The tolerability of agomelatine was assessed at each visit. Data from all patients who participated in the study and took agomelatine at least once were included in the efficacy and safety analysis. The final analysis included data from 103 patients, including 73 women (70.9%).Results. Treatment with agomelatine was associated with a significant improvement in depression severity: the mean HAMD-17 total score decreased statistically significantly at weeks 2, 4 and 8 from 16.3±4.7 at study inclusion to 13.7±4.5, 9.5±4.9 and 5.4±3.6 points – by 2.6±3.3, 6.7±5.3 and 10.9±4.9 points, respectively, compared to baseline (p<0.0001 for all time points). The average score for item 10 (psychic anxiety) and item 11 (somatic anxiety) of the HAMD-17 scale also decreased significantly from 1.4±0.9 and 1.3±0.8 at baseline to 0.5±0.6 and 0.6±0.6 points by the eighth week of observation (p<0.0001). The indicators of the scales for physical functioning and mental health of the SF-36 questionnaire improved significantly compared to the initial values – from 39.7±8.4 to 50.5±5.7 points (p<0.0001) and from 37.3±8.6 to 58.7±6.9 points (p<0.0001) respectively, by the eighth week. The proportion of responders was 81.4 %, the proportion of remitters was 71.6%. Agomelatine was well tolerated during the entire observation period. No adverse events were recorded that led to discontinuation of the drug. One patient showed inefficacy of the treatment, so he discontinued participation in the study.Conclusion. The treatment of patients with DE after COVID-19 with agomelatine is characterized by significant antidepressant and anxiolytic efficacy, improved QOL and good tolerability.

Functional connectivity density of different suicidal behaviors in adolescents with major depressive disorders.

Suicidal behavior including suicidal ideation (SI) and suicide attempts (SA) is a common clinical feature of adolescent patients with major depressive disorders (MDD). We hypothesized that differences in functional connectivity density (FCD) exist between adolescent patients with SA and SI, and aimed to investigate the different suicidal behaviors in adolescents patients with MDD17. 37 MDD adolescents with SA, 34 MDD adolescents with SI, 20 MDD adolescents without SA and SI (non-suicidal group), and 20 adolescents healthy controls (HC) were enrolled in this study. All participants were scanned using functional magnetic resonance imaging (fMRI) to evaluated the FCD. Between-group differences of all variables were analyzed. The relationships between FCD values and clinical scale scores were also analyzed. The FCD of the left inferior occipital gyrus in the SI group was higher than those in the other groups. The FCD in the SA group was higher than that in the control group. The FCD of the right dorsolateral superior frontal gyrus in the SI group was lower than that in the other three groups. The FCD values of the left precentral gyrus in the SI group were higher than those in the other three groups. The left inferior occipital gyrus FCD positively correlated with the suicide factor score of Hamilton Depression Scale (HAMD), and the right dorsolateral superior frontal gyrus negatively correlated with the HAMD suicide factor score but not with the HAMD total score. Changes in FCD in adolescent patients with depression and SI can reflect changes in functional connections in the brain.

Effect of combined treatment with transcranial direct current stimulation and repetitive transcranial magnetic stimulation compared to monotherapy for the treatment of chronic insomnia: a randomised, double-blind, parallel-group, controlled trial

BackgroundChronic insomnia increases the risk of various health problems and mental illness. Existing research suggests promise for both transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in treating chronic insomnia individually. However, the combined effects of tDCS and rTMS on this condition remain unclear. This study aimed to verify the efficacy and safety of tDCS combined with rTMS for the treatment of adult patients with chronic insomnia.MethodsThis was a randomised double-blind parallel-group controlled study. Overall, 157 participants with chronic insomnia were randomly assigned to one of three neurotherapy regimens: tDCS + rTMS, sham tDCS + rTMS, or tDCS + sham rTMS. All groups received 20 treatment sessions over 4 consecutive weeks. The primary outcome was the change in patients’ sleep as assessed by the Pittsburgh Sleep Quality Index (PSQI) at 2 weeks, 4 weeks, and 3 months of follow-up. The secondary outcome was the assessment of different dimensions of depression and anxiety in patients through the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA), as well as the occurrence of adverse events.ResultsThroughout the intervention and after the 3-month follow-up, the tDCS + rTMS group had significantly reduced total PSQI scores compared with the other two groups [tDCS + rTMS, 9.21 vs. sham tDCS + rTMS, 10.03; difference − 1.10; 95% confidence interval (CI), − 1.82 to − 0.38; p = 0.003; tDCS + rTMS, 9.21 vs. tDCS + sham rTMS, 10.76; difference − 2.14; 95% CI, − 2.90 to − 1.38; p < 0.001; sham tDCS + rTMS, 10.03 vs. tDCS + sham rTMS, 10.76; difference − 1.04; 95% CI, − 1.82 to − 0.26; p = 0.010), indicating improved overall sleep quality. Total HAMD and insomnia factor scores were significantly lower in the tDCS + rTMS group than in the other two groups after treatment (p < 0.05). Notably, no adverse events or serious adverse reactions were observed during the study period.ConclusionsCombining tDCS with rTMS effectively relieved insomnia symptoms, achieving a significant therapeutic effect after 2-week of intervention, and demonstrating the persistence of treatment effects in later follow-up, emphasising the advantages of combination therapy in improving treatment stability and long-term benefits, reflecting the rapid and effective augmentation of combination therapy. This combined therapy may serve as a safe and effective treatment for adults with chronic insomnia.Trial registrationThis study was registered as a clinical trial with the China Clinical Trial Registration Center (ChiCTR2100052681).

Relationship between thyroid-stimulating hormone and blood lipids in patients with first-episode depression

BackgroundPrevious studies demonstrated thyroid stimulating hormone (TSH) plays an important role in regulating lipid metabolism, but the relationship between the two is controversial. Meanwhile, it has not been reported in a population with major depressive disorder (MDD).MethodsWe divided 1718 first-episode and drug naïve patients with MDD into a TSH abnormal group (TSH-AB) and a TSH normal group (TSH-NOR). The participants in the two groups were assessed by the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and the positive subscale of Positive and Negative Syndrome Scale. The patients’ blood was tested for TSH, free T3, free T4, fasting blood glucose, lipid indexes and body mass index was recorded.ResultsThe participants in the TSH-AB group had significantly higher HAMD scores, HAMA scores and total scores of positive symptoms, as well as higher incidence of suicide attempts than those in the TSH-NOR group, accompanied by significantly higher thyroglobulin antibodies, thyroid peroxidase antibodies, fasting blood glucose values, total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels compared with those of TSH-NOR patients. However, the high-density lipoprotein cholesterol (HDL-C) of TSH-AB patients was lower than those of TSH-NOR patients. TSH values were positively correlated with TC, TG, and LDL-C values, and negatively correlated with HDL-C value.ConclusionTSH was highly correlated with abnormal lipid metabolism in patients with MDD. The specific molecular mechanism of the relationship between TSH, lipid metabolism and the development of depression needs to be further in-depth investigation.

A preliminary comparison of the clinical efficacy of repetitive transcranial magnetic stimulation with facial feature point localization and navigated localization in the treatment of depression

ObjectiveTo compare the clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) under facial feature point (FFP) localization versus neuro-navigated localization for depression. Methods42 depressed patients were randomly assigned to two groups, received 10 Hz rTMS twice daily for 10 consecutive days. Relevant symptom scale assessments were conducted by professionals at baseline, after 10 sessions, and at the end of treatment. The confidence interval was calculated at a 95 % confidence level. The significant level was set at p < 0.05. ResultsThe absolute change in Hamilton Rating Scale for Depression (HAMD) total score from baseline to the end of therapy did not differ significantly between the groups. The generalized estimating equation showed the main effect of time was significant, which showed improvement of depressive symptoms in patients throughout treatment. Upon completion of the treatment, FFP group showed a response rate of 64.7 % and a remission rate of 29.4 %, whereas the navigated group exhibited a response rate of 61.1 % and a remission rate of 44.4 %. There was no serious adverse events occurred during the treatment process. Throughout the study, no intervention was made on the normal medication treatment, and some patients had concomitant antidepressants and benzodiazepines. ConclusionThere was no significant difference in clinical efficacy between FFP localization and navigated localization in the small-sample study. However, due to the limited sample size and lack of rigorous non-inferiority testing, the superiority of one over the other remains uncertain, necessitating rigorous experimental design to validate the efficacy difference between the two localization methods.

Enhanced classification and severity prediction of major depressive disorder using acoustic features and machine learning.

Previous studies have classified major depression and healthy control groups based on vocal acoustic features, but the classification accuracy needs to be improved. Therefore, this study utilized deep learning methods to construct classification and prediction models for major depression and healthy control groups. 120 participants aged 16-25 participated in this study, included 64 MDD group and 56 HC group. We used the Covarep open-source algorithm to extract a total of 1200 high-level statistical functions for each sample. In addition, we used Python for correlation analysis, and neural network to establish the model to distinguish whether participants experienced depression, predict the total depression score, and evaluate the effectiveness of the classification and prediction model. The classification modelling of the major depression and the healthy control groups by relevant and significant vocal acoustic features was 0.90, and the Receiver Operating Characteristic (ROC) curves analysis results showed that the classification accuracy was 84.16%, the sensitivity was 95.38%, and the specificity was 70.9%. The depression prediction model of speech characteristics showed that the predicted score was closely related to the total score of 17 items of the Hamilton Depression Scale(HAMD-17) (r=0.687, P<0.01); and the Mean Absolute Error(MAE) between the model's predicted score and total HAMD-17 score was 4.51. This study's results may have been influenced by anxiety comorbidities. The vocal acoustic features can not only effectively classify the major depression and the healthy control groups, but also accurately predict the severity of depressive symptoms.

Exploring the mediating role of the ventral attention network and somatosensory motor network in the association between childhood trauma and depressive symptoms in major depressive disorders

BackgroundChildhood trauma is closely tied to adult depression, but the neurobiological mechanisms remain unclear. Previous studies suggested associations between depression and large-scale brain networks such as the Ventral Attention Network (VAN) and Somatosensory Motor Network (SMN). This study hypothesized that functional connectivity (FC) within and between these networks mediates the link between childhood trauma and adult depression. MethodsThe Childhood Trauma Questionnaire (CTQ) assessed developmental experiences, and the Hamilton Rating Scale for Depression (HAMD-17) gauged depressive symptoms. Resting-state functional magnetic resonance imaging (fMRI) analyzed FC within and between the VAN and SMN. ResultsDepression group exhibited significantly higher HAMD and CTQ scores, as well as elevated FC within the VAN and between the VAN and SMN (P < 0.05). Positive correlations were found between HAMD total score and FC within the VAN (P < 0.05, r = 0.35) and between the VAN and SMN (P < 0.05, r = 0.34), as well as with CTQ total score (P < 0.05, r = 0.27). Positive correlations were also observed between CTQ total score and FC within the VAN (P < 0.05, r = 0.31) and between the VAN and SMN (P < 0.05, r = 0.29). In the mediation model, FC within and between the VAN and SMN significantly mediated childhood trauma and depression. LimitationsThe cross-sectional design limits causal inference. The sample size for different trauma types is relatively small, urging caution in generalizing findings. ConclusionsThe study underscores the association between depression severity, VAN dysfunction, abnormal VAN-SMN FC, and childhood trauma. These findings contribute to understanding the neurobiological mechanisms underlying childhood trauma and depression.

Efficacy of Low-dose Olanzapine in Combination with Sertraline on Negative Symptoms and Psychosocial Functioning in Schizophrenia: A Randomized Controlled Trial.

Evidence for the efficacy of a low dose of olanzapine (OLA) in combination with antidepressants has been limited and without positive trials in first-episode (FE) patients with schizophrenia (SCH). This study aimed to compare the efficacy in treating negative and depressive symptoms between those FE patients with SCH treated with a combination of OLA plus sertraline and those treated with OLA monotherapy. One hundred and ninety-six first-episode and drug naïve patients with SCH were randomized to receive low-dose OLA (7.5-10 mg/day) combined with sertraline (50-100 mg/day) (OS group) or normal-dose OLA monotherapy (12.5-20 mg/day) (NO group). Clinical symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS), and the depressive symptoms were evaluated by the Hamilton Depression Scale (HAMD). Psychosocial functioning was assessed by the Personal and Social Performance Scale (PSP). In the intent-to-treat efficacy analysis, the OS group had greater decreases in negative and depressive symptoms (pall < 0.01) and a greater increase in PSP total score compared with the NO group (p < 0.01). Moreover, reductions in HAMD total score and PANSS negative subscore and sex were associated with the improvements in psychosocial functioning from baseline to week 24, after controlling for baseline psychosocial function, age, and onset age. This study demonstrates that low-dose OLA in combination with sertraline had clinically meaningful improvements not only in the negative and depressive symptoms but also in psychosocial functioning in patients with FE-SCH, while not affecting positive symptoms.

Effect of add-on transcranial alternating current stimulation (tACS) in major depressive disorder: A randomized controlled trial

BackgroundThe effect of transcranial alternating current stimulation (tACS) on major depressive disorder (MDD) was not confirmed. ObjectiveTo evaluate the feasibility, safety, and efficacy of tACS as an add-on treatment for the symptoms of depression and to understand how tACS affects brain activity. MethodsThe 4-week, double-blind, randomized, sham-controlled trial was performed from January 29, 2023 to December 22, 2023. Sixty-six participants were recruited and randomly assigned to receive 20 40-min sessions of either active (77.5Hz, 15 mA) or sham stimulation, with one electrode on the forehead and two on the mastoid, each day (n = 33 for each group) for four weeks (till Week 4). The participants were followed for 4 more weeks (till Week 8) without stimulation for efficacy/safety assessment. During the 4-week trial, all participants were required to take 10–20 mg of escitalopram daily. The primary efficacy endpoint was the change in HAMD-17 scores from baseline to Week 4 (with 20 treatment sessions completed). Resting-state electroencephalography (EEG) was collected with a 64-channel EEG system (Brain Products, Germany) at baseline and the Week 4 follow-up. The chi-square test, Fisher's exact test, independent-sample t-test, or Wilcoxon rank-sum test were used, as appropriate, to compare the differences in variables between groups. The effect of the intervention on the HAMD-17 score was also evaluated with linear mixed modeling (LMM) as sensitivity analysis. The correlation between the mean reduction in EEG and the mean reduction in the HAMD-17 total score was evaluated using Spearman correlation analysis. ResultsA total of 66 patients (mean [SD] age, 28.4 [8.18] years; 52 [78.8 %] female) were randomized, and 57 patients completed the study. Significant differences were found in the reductions in the HAMD-17 scores at Week 4 (t = 3.44, P = 0.001). Response rates at Week 4 were significantly higher in the active tACS group than in the sham tACS group (22 out of 33 patients [66.7 %] versus 11 out of 33 [33.3 %], P = 0.007). In the active tACS group, a correlation between the mean change in alpha power and HAMD-17 scores at Week 4 was found (r = 2.38, P = 0.024), and the mean change in alpha power was significantly bigger for responders (Z = 2.46, P = 0.014). No serious adverse events were observed in this trial. ConclusionThe additional antidepressant effect of tACS is significant, and the combination of tACS with antidepressants is a feasible and effective approach for the treatment of MDD. The antidepressant mechanism of tACS may be the reduction in alpha power in the left frontal lobe. Future research directions may include exploring more appropriate treatment parameters of tACS.

Analysis of potential diagnostic markers and therapeutic targets for rheumatoid arthritis with comorbid depression immunologic indicators

ObjectiveDepression can impact the severity of rheumatoid arthritis (RA). This study aimed to investigate the relationship between Th1, Th2, Th17, Treg cell subsets, and their associated cytokines (e.g., IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α), and the occurrence of RA both with and without comorbid depression. The objective is to identify potential biological markers, therapeutic targets, and the therapeutic effects of RA with comorbid depression. Results53 RA patients,46 RA with comorbid depression patients and 51 healthy subjects were included in the RA,RD and HC group from August 2021 and October 2022. Among RA patients, 46.46 % were comorbid with depression. IL-6 concentrations were significantly higher in RD group than in RA group.Comparison between the HC and RA and RD groups revealed that Th1 %, Th17 %, Th1, Th17, Th1/Th2, Th17/Treg and Th1/Treg were significantly higher in the RA and RD groups, and conversely, Th2 %, Treg%, Th2 and Treg were significantly lower than in the HC group.The RA group compared to the RD group found that Th17 %, Th17 and Th17/Treg were significantly higher in the RD group than in the RA group, however, Th1 %, Treg and Th2/Treg were significantly lower than in the RA group. The total HAMD score had a medium strength positive correlation with IL-6. ConclusionThese findings suggest that elevated the autoimmunity status was overactivated in RA with or without depression activates patients, IL-6 may be a predictor of the severity of RA with comorbid depression, IL-6 concentrations and an imbalance in the Th17/Treg may underlie the comorbidity of RA and depression, offering potential targets for therapeutic intervention, prompting further evaluation of the role of indirect inflammatory markers in RA with comorbid depression, highlighting the need for additional research to clarify the complex relationship between inflammation and psychological health.

Cognitive–behavioral therapy for patients with somatoform disorders: A pilot preliminary randomized controlled trial

Background and objective: Cognitive–behavioral therapy (CBT) for somatoform disorders (SFDs) is understudied in China. Western findings may not be applicable to Chinese culture. This preliminary study evaluated the efficacy of CBT for patients in China, relative to treatment-as-usual (TAU). Methods: Seventy patients with SFDs randomly received either combined CBT and TAU (CBT + TAU), or TAU alone between January 2018 to May 2019. The CBT + TAU group received 12 weekly individual 50-minute CBT sessions. Participants were blindly assessed at 4 timepoints (baseline, week 6, end of treatment: week 12; 12 weeks post-treatment: week 24) using the following outcome measures: SQSS (Self-screening Questionnaire for Somatic Symptoms); PHQ-15 (Patient-Health-Questionnaire-15) and the WI (Whiteley Index); GAD-7 (General Anxiety Disorder-7); HAMD-17 (Hamilton Depression Rating Scale-17); Family Burden Interview Schedule (FBIS); Sheehan Disability Scale (SDS); and the Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). The primary endpoint was the difference between the SQSS total score at week 24 and the baseline. A mixed model for repeated measures was used to analyze inter- and intra-group changes from the baseline. Results: At week 24, The least-squares mean (LSM) change of the total score on the SQSS was −18.87 points and −9.69 points, respectively in the CBT + TAU group and in the TAU group (LSM difference, −9.18 points; 95% confidence interval, −15.72 to −2.64; P = 0.0068). At week 24, the LSM changes from baseline in the WI, HAMD, PHQ15, FBIS and SDS total scores were significantly different between the two groups, however, there was no significant difference in the Q-LES-Q-SF. The SQSS of group effect sizes were 0.63 at 24 weeks. The dropout rates of the CBT + TAU and TAU groups were comparable (22.9% and 19.3%). Conclusions: These preliminary findings suggest that CBT may be helpful for improving the symptoms of patients with SFDs in China.

The preponderance of major depressive disorder among women of reproductive age and the clinical utility of sertraline

IntroductionMajor depressive disorder (MDD) is twice as common in women than men and is more frequently reported during their reproductive years (Shi et al. Front. Psychiatr 2021; 12 589687). MDD affects up to 12.7% of pregnant women and can significantly impact foetal and maternal health. Hence, clinical practice guidelines recommend focused screening and expedited management of MDD in women (Guo et al. Obstet. Gynecol 2018; 131(4) 671-679). Despite this, drug labelling or dosing recommendations rarely account for gender or physiological differences between sexes, even though sex steroid level variations can impact drug absorption, distribution, metabolism, and activity both pharmacokinetically and pharmacodynamically (Soldin et al. Clin Pharmacokinet. 2009; 48(3): 143–157). Sertraline, an SSRI approved for the treatment of MDD, is one of the safer agents which can be given to childbearing or breastfeeding women (Cuomo et al. Expert Opin Drug Saf 2018; 17(7) 719-725). However, studies on the efficacy of sertraline for the treatment of MDD among women of childbearing age are limited.ObjectivesThis post-hoc pooled analysis evaluated the efficacy of sertraline in women with MDD, with a particular focus on women of reproductive age.MethodsA pooled data analysis of 8 short-term clinical studies of sertraline in persons with MDD (comprising 1600 participants from North America and Europe, of whom 947 were females; with moderate to severe MDD [mean±SD baseline HAM-D17 score was 23.73±3.58 for sertraline and 23.37± 3.47 for placebo]; sertraline dose, 50-200 mg) was performed. HAM-D17 total score was used to assess the efficacy of sertraline compared with placebo. The study period was 8 weeks. An MMRM method was used to analyse changes over time and ANCOVA to evaluate the change from baseline at week 8 with LOCF employed to manage missing data.ResultsThe analysis set consisted of 947 women (sertraline, 612; placebo, 335). The change from baseline in HAM-D17 total score was significantly higher for sertraline than for placebo at the end of 8 weeks (LS mean difference, 95% CI: -1.81 [-3.01, -0.62], p=0.0029, Figure 1A). This change from baseline was statistically significant starting from week 2 and increased over time (Week 2-8; Figure 2A).The analysis set for women of child-bearing age consisted of 572 participants aged 18-44 (sertraline, 359; placebo, 213) from 7 clinical studies. The change from baseline in HAM-D17 total score was significantly higher for sertraline than for placebo at the end of 8 weeks (LS mean difference, 95% CI: -2.08 [-3.52, -0.64], p=0.0047, Figure 1B). This change from baseline was statistically significant starting from week 2 (Figure 2B).Image:Image 2:Conclusions Significant improvement in HAM-D17 scores was observed in the analysis, suggesting that sertraline is efficacious in treating women with MDD, including those in the childbearing age.Disclosure of InterestA. Fagiolini Grant / Research support from: Angelini, Boheringer Ingelheim, Janssen, Consultant of: Angelini, Biogen, Boheringer Ingelheim, Lundbeck, Janssen, Mylan, Neuraxpharm, Otsuka, Pfizer, Recordati, Rovi, Sanofi Aventis, Viatris, Speakers bureau of: Angelini, Apsen, Biogen, Boheringer Ingelheim, Glaxo Smith Kline, Lundbeck, Janssen, Mylan, Neuraxpharm, Otsuka, Pfizer, Recordati, Rovi, Sanofi Aventis, Viatris, Vifor, M. Mariano Consultant of: Johnson &amp; Johnson, Otsuka Pharmaceutical Inc., Speakers bureau of: Viatris Pharmaceuticals, Inc. Otsuka (Philippines) Pharmaceutical, Inc. H. Lundbeck A/S, Johnson &amp; Johnson Philippines, Inc., E. Biesheuvel Employee of: Viatris Inc. Netherlands, P. Purushottamahanti Employee of: Viatris Inc. India

Long-term safety and frequency of repeat zuranolone treatment in patients with major depressive disorder rolling over from the randomised CORAL Study into the open-label SHORELINE Study

IntroductionZuranolone (ZRN) is a positive allosteric modulator of both synaptic and extrasynaptic gamma-aminobutyric acid type A receptors and a neuroactive steroid approved as an oral, once-daily, 14-day treatment course for adults with postpartum depression in the US and under investigation for adults with major depressive disorder (MDD). The randomised, double-blind, placebo-controlled, Phase 3 CORAL Study assessed the efficacy and safety of ZRN 50 mg vs placebo, each co-initiated with an open-label standard-of-care antidepressant (ADT). Patients who completed CORAL could roll over into open-label SHORELINE, which assessed the safety and tolerability of ZRN 50 mg and need for repeat treatment courses in adults with MDD.ObjectivesTo assess the safety and tolerability (primary endpoint) and need for repeat ZRN 50 mg treatment courses (secondary endpoint) in adults with MDD who previously enrolled in CORAL.MethodsCORAL enrolled adults (18–64 years) with MDD and 17-item Hamilton Rating Scale for Depression (HAMD-17) total score ≥24. After completing the 6-week CORAL Study, patients who enrolled in SHORELINE could enter a 46-week observation period to assess the safety and need for 14-day repeat ZRN treatment course(s), with a total of ≤4 repeat treatment courses permitted. Patients were screened every 2 weeks with the 9-item Patient Health Questionnaire, and scores ≥10 prompted a HAMD-17 assessment within 1 week. Patients with HAMD-17 total score ≥20 were eligible for repeat ZRN course(s) ≥8 weeks after completing the prior ZRN treatment course.ResultsAmong the 190 patients from CORAL who rolled over into SHORELINE and received ≥1 ZRN treatment course in either study, 133 (70.0%) had received ZRN+ADT and 57 (30.0%) received placebo+ADT in CORAL. Overall, 118 rollover patients received ≥1 open-label ZRN treatment course in SHORELINE. For patients who received ≥1 ZRN treatment course in either study, 76.8% received 1 (54.2%; 103/190) or 2 (22.6%; 43/190) total ZRN treatment courses across both studies in up to 1 year in study. The most common (&gt;5%) treatment-emergent adverse events (TEAEs) during treatment and 14 days following the last ZRN dose were somnolence (16.1% of patients), dizziness (8.5%), headache (8.5%), fatigue (7.6%), sedation (5.9%), and nausea (5.1%); study-period TEAEs (73.7%; 87/118) for the majority of patients were mild/moderate (69.5%; 82/118) in severity and occurred primarily during the treatment period (58.5%; 69/118). No signals for increased suicidal ideation/behaviour were observed.ConclusionsSafety and tolerability among rollover patients were consistent with previous studies; most of the TEAEs reported by adults with MDD who received ZRN were mild/moderate in severity. Most patients who rolled over from CORAL to SHORELINE received ≤2 total treatment courses in up to 1 year in study.Disclosure of InterestG. Mattingly Grant / Research support from: Akili, Alkermes, Allergan (now AbbVie), Axsome, Boehringer, Janssen, Lundbeck, Medgenics, NLS-1 Pharma AG, Otsuka, Reckitt Benckiser, Roche, Sage, Sunovion, Supernus, Takeda, and Teva, Consultant of: Akili, Alkermes, Allergan (now AbbVie), Axsome, Ironshore, Intra-Cellular Therapies, Janssen, Lundbeck, Neos Therapeutics, Otsuka, Purdue, Rhodes, Sage, Sunovion, Takeda, and Teva, Speakers bureau of: Alkermes, Allergan (now AbbVie), Ironshore, Janssen, Lundbeck, Otsuka, Sunovion, and Takeda, S. Mathew Grant / Research support from: Biohaven Pharmaceuticals, Boehringer-Ingelheim, Janssen, Merck, Sage Therapeutics, Inc., and VistaGen Therapeutics, Consultant of: Allergan (now AbbVie), Alkermes, Almatica Pharma, Axsome Therapeutics, BioXcel Therapeutics, Boehringer-Ingelheim, Clexio Biosciences, COMPASS Pathways, Eleusis, EMA Wellness, Engrail Therapeutics, Greenwich Biosciences, Intra-Cellular Therapies, Janssen, Levo Therapeutics, Perception Neurosciences, Praxis Precision Medicines, Neumora, Neurocrine, Relmada Therapeutics, Sage Therapeutics, Inc., Seelos Therapeutics, Signant Health, and Sunovion, S. Parikh Grant / Research support from: Aifred, Assurex, Janssen, Mensante, Sage Therapeutics, Inc., and Takeda, S. Aaronson Grant / Research support from: COMPASS Pathways and Neuronetics; has served as a consultant to Genomind, Inc., Janssen, LivaNova PLC, Neuronetics; and Sage Therapeutics, Inc., Speakers bureau of: Janssen and Sunovion Pharmaceuticals, Inc., B. Baune Speakers bureau of: Angelini, AstraZeneca, Biogen, Bristol Myers Squibb, Janssen, LivaNova, Lundbeck, Novartis, Otsuka, Pfizer, Servier, Sumitomo Pharma, Wyeth, and Boehringer-Ingelheim, A. Czysz Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., I. Nandy Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., V. Ona Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., C. Brown Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., S. Kyaga Employee of: Biogen Inc., F. Forrestal Employee of: Biogen Inc., S. Levin Employee of: Biogen Inc., J. Doherty Shareolder of: Sage Therapeutics, Inc., Employee of: Sage Therapeutics, Inc., G. Mattingly: None Declared

Omega-3 fatty acids for inflamed depression – A match/mismatch study

Despite decades of research on the pathophysiology of depression, the development of new therapeutic interventions has been slow, and no biomarkers of treatment response have been clinically implemented. Several lines of evidence suggest that the clinical and biological heterogeneity among patients with major depressive disorder (MDD) has hampered progress in this field. MDD with low-grade inflammation – “inflamed depression” – is a subtype of depression that may be associated with a superior antidepressant treatment response to anti-inflammatory compounds. Omega-3 fatty acid eicosapentaenoic acid (EPA) has anti-inflammatory properties, and preliminary data suggest that it may be particularly efficacious in inflamed depression. In this study we tested the hypothesis that add-on EPA has greater antidepressant efficacy in MDD patients with high baseline high-sensitivity C-reactive protein (hs-CRP) compared to MDD patients with low hs-CRP. All subjects received 2.2 g EPA, 400 mg docosahexaenoic acid and 800 mg of other fatty acids daily for 8 weeks, added to stable ongoing antidepressant treatment. The primary outcome was change in the 17-item Hamilton Depression Rating Scale (HAMD-17). Patients and raters were blind to baseline hs-CRP status. In an intention-to-treat analysis including all subjects with at least one post baseline visit (n = 101), ahs-CRPcut-off of ≥1 mg/L, but not ≥3 mg/L, was associated with a greater improvement in HAMD-17 total score. In addition to a general antidepressant effect among patients with hs-CRP ≥ 1 mg/L, adjuvant EPA treatment improved symptoms putatively related to inflamed depression such as fatigue and sleep difficulties. This adds to the mounting evidence that delineation of MDD subgroups based on inflammation may be clinically relevant to predict treatment response to anti-inflammatory interventions.

Ghrelin and depressive symptoms in patients with first-episode drug-naïve major depressive disorder: The mediating role of hypothalamic-pituitary-adrenal axis.

Major depressive disorder (MDD) is one of the global burdens of disease, and its pathogenesis remains unclear. An increasing amount of research indicates that ghrelin regulates mood in patients with MDD. Still, current results are inconsistent, and the mechanisms underlying how ghrelin modulates depressive symptoms are inconclusive, especially in first-episode drug-naïve MDD patients. Therefore, this study aims to investigate the relationship and potential mechanism between ghrelin and first-episode drug-naïve MDD. Ninety first-episode drug-naïve MDD patients and 65 healthy controls (HCs) were included. Hamilton Depression Scale (HAMD-17) as a measure of depressive symptoms. Plasma levels of ghrelin and hypothalamic-pituitary-adrenal axis (HPA-axis) hormones were measured in all participants. Compared to HCs, the ghrelin levels were higher in the MDD (p < .001) and still showed significance after covarying for sex, age, and Body Mass Index (BMI). Ghrelin was positively related to corticotropin-releasing-hormone (CRH) levels (r = .867, p < .001), adrenocorticotropic hormone (ACTH) levels (r = .830, p < .001), and cortisol levels (r = .902, p < .001) in partial correlation analysis. In addition, there was a positive correlation between HAMD total score and ghrelin levels (r = .240, p = .026). Other than that, the HAMD total score also had a positive correlation with the CRH (r = .333, p = .002) and cortisol (r = .307, p = .004) levels. Further mediation analysis demonstrated that the relationship between ghrelin and HAMD total score was mediated by CRH (ab-path; β = .4457, 95% CI = 0.0780-1.0253, c-path; β = .2447, p = .0260, c'-path; β = -.2009, p = .3427). These findings revealed that plasma ghrelin provides a pivotal link to depressive symptoms in first-episode drug-naive MDD patients. CRH mediated the relationship between ghrelin and HAMD total score. It might provide new insights into understanding the pathogenesis of MDD, contributing to intervention and treatment from this approach.

Comparative Analysis of Personality Traits in Major Depressive Disorder and Bipolar Disorder: Impact, Differences, and Associations with Symptoms.

This cross-sectional study aimed to compare the personality traits of patients with major depressive disorder (MDD) and bipolar disorder (BD) with those of healthy individuals. The goal was to gain insight into the potential impact of personality traits on the development and manifestation of mood disorders. One hundred seventy-eight patients with mood disorders were analyzed as either MDD or BD, with each group containing euthymic and depressive members: e-MDD, d-MDD, e-BD, and d-BD. Mood status was assessed using the Young Mania Rating Scale (YMRS), and the 17-item Hamilton Depression Rating Scale (HAMD-17). Ninety-five healthy individuals served as controls. Personality traits were assessed with the Eysenck Personality Questionnaire. The scores for neuroticism in the patient groups were comparable, but each group had higher scores compared to the control group (P < 0.001). Each patient group exhibited significantly lower scores for extraversion compared to the control group, with e-MDD, d-MDD, and d-BD showing particularly notable differences (P < 0.001); these groups scored significantly lower than the e-BD (P = 0.041, 0.009, 0.038). In patients with BD, there was an inverted association between extraversion score and HAMD total score (P = 0.010, r = -0.27), and a positive association with the YMRS total score (P = 0.022, r = 0.24). In the MDD group, there was a positive association between the neuroticism score and HAMD total score (P = 0.021, r = 0.25). Patients with mood disorders are characterized by lower extraversion and higher neuroticism. Level of neuroticism associated with depression severity in MDD. Patients with BD may be more extraverted, but their extraversion can be affected by depressive episodes. Extraversion may be a feature of BD, and may differentiate BD from MDD. Personality traits are related to disease diathesis and state, and shaped by symptom manifestations.

Prevalence and risk factors for psychotic symptoms in young, first-episode and drug-naïve patients with major depressive disorder

BackgroundMajor depressive disorder (MDD) is a common psychiatric disorder worldwide. Psychotic depression has been reported to be frequently under-diagnosed due to poor recognition of psychotic features. Therefore, the purpose of this study was to reveal the rate and risk factors of psychotic symptoms in young, drug-naïve patients with major depressive disorder at the time of their first episode.MethodsA total of 917 patients were recruited and divided into psychotic and non-psychotic subgroups based on the Positive and Negative Syndrome Scale (PANSS) positive subscale score. Anxiety symptoms and depressive symptoms were measured by the Hamilton Anxiety Rating Scale (HAMA) and the 17-item Hamilton Depression Rating Scale (HAMD-17), respectively. Several biochemical indicators such as total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were also measured.ResultsThe rate of psychotic symptoms among young adult MDD patients was 9.1%. There were significant differences in TSH (p<0.001), FBG (p<0.001), TC (p<0.0001), TG (p = 0.001), HDL-C (p = 0.049), LDL-C (p = 0.010), diastolic blood pressure (DP) (p<0.001), systolic blood pressure (SP) (p<0.001), and HAMD total score (p<0.001) between young MDD patients with and without psychotic depression. HAMD, TSH, TC, and severe anxiety were independently associated with psychotic symptoms in young adult MDD patients. In addition, among young MDD patients, the rate of suicide attempts in the psychotic subgroup was much higher than in the non-psychotic subgroup (45.8% vs. 16.9%).ConclusionsOur findings suggest that psychotic symptoms are common in young MDD patients. Several clinical variables and biochemical indicators are associated with the occurrence of psychotic symptoms in young MDD patients.

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

ObjectiveChildhood 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. MethodsIn 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. ResultsIncreased 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. ConclusionOur 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.

Relationships between depression level and serum inflammatory factors and thyroxine levels in patients with malignant bone tumors associated with depression.

To elucidate the relationships between depression level and serum inflammatory factors and thyroxine levels in patients with malignant bone tumors associated with depression. The depression (n = 28) and non-depression groups (n = 35) were established. Another 35 healthy subjects were selected as the control group. The severity of depression was assessed, and the depression group received the selective serotonin reuptake inhibitor antidepressant sertraline for 4 weeks. Serum levels of inflammatory factors and thyroxine, and the correlation between inflammatory factors, thyroxine, and HAMD-17 score were analyzed. The IL-1β, IL-6, and IL-21 levels were lower and TGF-β1, IL-10, and IL-27 were higher in the depression group after treatment than before treatment. After treatment, T3 levels were higher and T4 levels were lower in the depression group. T4 levels were higher in patients with major depression than those with mild depression. IL-1β and IL-21 levels were elevated in moderately depressed patients [(11.13 ± 1.49) ng/L、(9.71 ± 1.26) ng/L], and IL-1β levels were elevated in severely depressed patients [(11.26 ± 1.95) ng/L], compared to mildly depressed patients [(9.36 ± 1.25) ng/L, (7.95 ± 1.31) ng/L] (all p < 0.05). Serum IL-1β, IL-6, and IL-21 were positively correlated with the total HAMD-17 score, and TGF-β1 and IL-10 were negatively correlated with the total HAMD-17 score. Depression degree in patients with malignant bone tumors correlates with serum inflammatory factors and thyroxine levels. Measurement of serum inflammatory factors and thyroxine levels can assess the progression and prognosis of depressed patients.

Prevalence and clinical profile of comorbid anxiety in young adult patients with first-episode and drug-naive major depressive disorder.

Patients with major depressive disorder (MDD) frequently have coexisting anxiety disorders. However, few studies have focused on the prevalence and risk factors of comorbid anxiety symptoms in young adult first-episode and drug-naive (FEDN) MDD patients. We recruited 520 FEDN MDD patients and collected their demographic and clinical data. The Hamilton Depression Rating Scale (HAMD), the Hamilton Anxiety Rating Scale (HAMA) and the positive scale of the Positive and Negative Syndrome Scale (PANSS) were used to measure depressive symptoms, anxiety symptoms and psychotic symptoms, respectively. Anxiety symptoms were found in 79.6% of young adult patients. Besides, anxiety group patients had a higher prevalence of psychotic symptoms than the non-anxiety group. Anxiety symptoms were substantially related to suicide attempts in young adult patients. Logistic analysis shows that suicide attempts and total HAMD scores were significantly associated with anxiety symptoms. The findings show that anxiety symptoms are common in Chinese young adult MDD patients. The anxiety group was more likely to have psychotic symptoms, suicide attempts, and more severe depressive symptoms than the non-anxiety group. Suicide attempts were associated with anxiety symptoms in young adult MDD patients, suggesting the importance of reducing anxiety symptoms in this population to prevent suicides.