Precision diagnosis model for treatment-resistant depression integrating serum metabolomics and clinical risk factors

ObjectiveThis study aimed to construct a high-efficiency dual-modal diagnostic model for treatment-resistant depression (TRD) by integrating serum metabolomics and clinical risk factors, and explore its metabolic pathological mechanisms.MethodsA total of 93 major depressive disorder (MDD) patients (53 TRD, 40 non-TRD) were enrolled for a single-center retrospective study. Serum untargeted metabolomics and clinical baseline data were collected, with differential metabolites and clinical risk factors screened by statistical analysis and multi-step machine learning to identify core features. Five machine learning algorithms were compared to build unimodal and random forest-based dual-modal diagnostic models, and KEGG pathway enrichment analysis was performed.Results3 core clinical risk factors (medical history, HDL, FBG) and 8 core metabolic biomarkers were identified. The dual-modal model achieved AUC 0.996 (training) and 0.911 (validation), outperforming unimodal models. Differential metabolites were mainly enriched in lipid (44.8%) and amino acid (23.9%) metabolism. Fibrinopeptide A516, 12-HETE and the three clinical factors were core driving features.ConclusionThe dual-modal model has high diagnostic efficiency for TRD. TRD is associated with endocannabinoid system hypofunction and metabolic imbalance, which provides an objective diagnostic tool and new insights for TRD mechanism research and therapy development.

Aspects of Quality of Life in Interstitial Lung Disease: Pilot Observational Cross-Sectional Study in a Single Center

Background: Quality of life (QOL) is an important aspect of every chronic disease, including interstitial lung disease (ILD). QOL is perceived as a significant patient-centered outcome. Objective: This study aims to identify factors correlating with different aspects of QOL in patients with various ILDs. Methods: We recruited 57 participants hospitalized in a tertiary care clinical center to this pilot observational cross-sectional study. These included 22 patients with idiopathic interstitial pneumonia (IIP), 19 patients with connective tissue disease–associated ILD (CTD-ILD), and 16 patients with interstitial pneumonia with autoimmune features (IPAF). The Saint George’s Respiratory Questionnaire (SGRQ) and World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) were used to assess QOL, and the Hospital Anxiety and Depression Scale – Modified Version (HADS-M) and Patient Health Questionnaire – 9 (PHQ-9) were used to evaluate depression severity. Functional parameters including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV), transfer lung capacity for carbon monoxide (TLCO), and 6-minute walk distance (6MWD) were assessed. Assessment of QOL was a secondary outcome measure in a multicenter prospective study aimed at determining the characteristics of Polish patients with interstitial pneumonia with autoimmune features. Results: In each study group, positive correlations existed between the WHOQOL-BREF physical domain score and FEV % predicted value (=.001) and TLCO % predicted value (=.03). Regardless of diagnosis, higher depression, anxiety, and aggression scores (ie, worse mental health) correlated negatively with multiple domains of QOL measured using the WHOQOL-BREF. Predictors of QOL aspects varied in each study group. In the IPAF group, the TLCO % predicted value was a predictor of QOL expressed as the SGRQ total score (=.005). In the CTD-ILD group, short 6MWD (<.001) and high HADS-M aggression score (=.01) correlated with low QOL (expressed as a high SGRQ total score). In the IIP group, 6MWD (=.002) and PHQ-9 scores (<.001) were predictors for SGRQ symptoms score. Gender-based differences were revealed: In all study groups, men had higher scores in the psychological, social, and environmental domains of the WHOQOL-BREF, indicating better QOL, without a statistically significant difference in the physical domain scores between genders. Diagnosis-based differences in the psychological aspects of QOL were also revealed: The QOL psychological domain scores were significantly lower in the CTD-ILD and IPAF groups than in the IIP group, indicating worse QOL (=.01). Conclusions: QOL is a multifaceted issue with various factors impacting its assessment. 6MWD, TLCO predicted value, and worse functional ability might specifically impact QoL in ILD. Mental health is an important aspect of QOL in the ILD population, as patients with a chronic, potentially life-limiting disease may be more prone to developing depression or anxiety. Assessment of QOL should be taken into account in clinical decision-making and research on chronic diseases, as this patient-related outcome may impact therapeutic decisions and patient compliance. Trial Registration: ClinicalTrials.gov NCT03870828; https://clinicaltrials.gov/study/NCT03870828

Feasibility of Videoconference-Based Cognitive Behavioral Therapy for Somatic Symptom Disorder: Single-Arm Pilot Trial

Background: Somatic symptom disorder (SSD) is a mental disorder marked by persistent somatic symptoms and maladaptive health-related thoughts, feelings, or behaviors. Cognitive behavioral therapy has been shown to be effective in treating SSD, reducing patients’ somatic symptoms, depressive symptoms, and anxiety symptoms. However, challenges remain—including limited access to treatment. Videoconference-based cognitive behavioral therapy (vCBT) has emerged as a promising approach, offering flexible and tailored treatment while addressing the shortage of medical resources and potentially reducing patient dropout. Objective: This study examined the feasibility of vCBT for patients with SSD and explored secondary outcomes related to the physical component of health-related quality of life (HRQOL) as assessed using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) score and other exploratory clinical outcomes. Methods: This single-arm pilot trial evaluated feasibility as the primary outcome assessed via recruitment rate, retention rate, session completion rate, and safety. Ten participants with SSD were enrolled, and all received 6 weekly 50-minute vCBT sessions. Secondary outcomes included physical HRQOL (SF-36 PCS) as the key secondary outcome, as well as mental HRQOL, depressive symptoms, somatic symptom severity, anxiety symptoms, health anxiety, pain, insomnia, and generic HRQOL. These outcomes were measured at the preintervention (week 0) and postintervention (week 6) time points and 1-month follow-up (week 10) and were analyzed using 2-sided paired tests. Results: All feasibility criteria were met, with a recruitment rate of 83.3% (10/12), a retention rate of 100% (10/10), a session completion rate of 100% (10/10), and no adverse events reported. The SF-36 PCS score improved by 4.99 points at the postintervention time point, representing a large within-group effect (Cohen =0.99, 95% CI 0.21‐1.74). Medium to large improvements were also observed in mental HRQOL, depressive symptoms, anxiety symptoms, health anxiety, pain, insomnia, and generic HRQOL, and most of these improvements were observed at the 1-month follow-up. Conclusions: Our findings indicate that vCBT is a feasible and safe approach for SSD, with findings suggesting acceptability and preliminary evidence of effectiveness. Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000046138; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000052664
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/983b4d444e460efb73d39ec554707350" />

Impact of Restriction-Resumption Protocols on Mood and Anxiety in Healthy Adults: Randomized Controlled Trial

<strong>Background:</strong> Simple behavioral and cognitive actions can reduce symptoms of anxiety and depression. However, there is limited research investigating whether restricting those same actions increases symptoms and whether resuming those actions reduces symptoms. <strong>Objective:</strong> The primary aim was to examine the impact of restricting, then resuming (the “restriction-resumption protocol”), 5 groups of actions called the Things You Do (TYD), on symptoms of depression and anxiety. Participant satisfaction with life and perceptions of changes in behavior and mental health were also evaluated. <strong>Methods:</strong> In total, 70 adults were randomly allocated to an intervention group (IG) or a control group (CG). IG participants completed a 3-phase protocol over 8 weeks: a 2-week baseline period (phase A), 2 weeks of restricted TYD actions (phase B), and a 4-week resumption phase (phase C). CG participants were instructed to maintain their usual activities and routines. Primary outcomes included symptoms of depression (Patient Health Questionnaire–9), anxiety (Generalized Anxiety Disorder–7), and frequency of TYD actions. Secondary outcomes included satisfaction with life and perceived changes in mental well-being. Outcomes were measured weekly throughout the 8-week trial and again after the trial at week 9. <strong>Results:</strong> Scores on outcome measures did not differ between groups during phase A and after the trial. However, by the end of phase B, IG participants showed significantly increased symptoms of depression and anxiety compared to CG participants (<i>P</i>s&lt;.001). Large within-group effect sizes were observed on the Patient Health Questionnaire–9 and Generalized Anxiety Disorder–7 from baseline to the end of phase B (Cohen <i>d</i>&gt;1.8) and from phase B to after the trial (Cohen <i>d</i>&gt;1.9). Changes in satisfaction with life and evaluations of mental health corresponded with symptom changes. <strong>Conclusions:</strong> These findings demonstrate a relationship between the frequency of performing specific actions and symptoms of depression and anxiety. The restriction-resumption protocol has the potential to increase our understanding of causal mechanisms underlying common mental disorders and may lead to the development of new models of prevention and treatment. <strong>Trial Registration:</strong> Australian and New Zealand Clinical Trials Registry ACTRN12624001491550; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=388828&amp;isReview=true

Anti-Inflammatory Drug Could Help Some People with Depression

Research led by the University of Bristol suggests treatment with an anti-inflammatory drug, already approved to treat arthritis, could help some people with depression.

The study, published in JAMA Psychiatry,  was small but showed gradual improvement in the severity of depression and physical symptoms like fatigue, as well as a lowering of anxiety in those treated with tocilizumab versus placebo.

“Low-grade systemic inflammation is a putative causal factor in depression, present in approximately 30% of patients,” write co-lead author Golam Khandakar, MD, PhD, a professor and researcher at the University of Bristol, and colleagues.

“Individuals with difficult-to-treat depression have higher cytokine, e.g., interleukin 6 (IL-6) and C-reactive protein (CRP) levels, than treatment-responsive patients and controls.”

Tocilizumab is a humanized monoclonal antibody that blocks the IL‑6 receptor and is used as an immunosuppressive drug in several inflammatory and cytokine‑driven conditions. For example, it is approved by the FDA to treat rheumatoid arthritis and cytokine release syndrome in patients with severe COVID-19.

To test whether IL-6 inhibition could help people with depression, the authors carried out a small randomized controlled trial as a proof-of-concept study. Overall, 14 participants were given a tocilizumab infusion, and 16 participants were randomly assigned to receive a saline placebo infusion.

Adults were eligible to be in the study if they had moderate‑to‑severe, difficult‑to‑treat depression despite antidepressants, showed persistent low‑grade inflammation on repeat CRP tests, and had prominent physical depressive symptoms like fatigue.

After receiving a single infusion, the participants were followed up for four weeks with evaluations at one week, two weeks and four weeks. All were taking anti-depressants when enrolled and continued them during the trial.

The trial was not large enough or long enough to show a statistically significant improvement, but it did show a consistent pattern of greater, clinically sized improvement with tocilizumab by the end of the follow-up period, especially in patients with higher baseline CRP.

No real differences were seen at one or two weeks, but at four weeks people given tocilizumab showed bigger improvements in overall depression scores, fatigue, energy levels, anxiety and quality of life than those in the placebo group. Around 54% of participants in the tocilizumab went into remission at four weeks versus 31% of the placebo group.

“This work represents an important milestone in the development of new treatments for depression especially difficult-to-treat depression, which affects millions of people in the U.K. alone,” said Khandakar in a press statement.

“This is one of the first randomized controlled trials to test immunotherapy for depression, the first to test the IL-6 receptor as the treatment target, and the first to use a targeted approach to select patients most likely to benefit, and to show that it works.”

The researchers now want to carry out a larger randomized trial to assess if the effects they saw are significant in a bigger treatment population.

The post Anti-Inflammatory Drug Could Help Some People with Depression appeared first on Inside Precision Medicine.

Sleep quality and its associated factors among women of reproductive age in Ethiopia: a systematic review and meta-analysis

BackgroundQuality sleep is vital for women’s health during reproductive years, affecting both physical and mental well-being. In Ethiopia, socio-economic and cultural factors worsen sleep issues, but data on this demographic are scarce. This systematic review and meta-analysis assesses the prevalence of poor sleep quality among Ethiopian women and identifies contributing factors, aiming to inform interventions and policies to improve sleep health in low-resource settings.MethodThis systematic review followed PRISMA guidelines and searched PubMed, Scopus, and Web of Science for observational studies. We included studies utilizing the Pittsburgh Sleep Quality Index (PSQI), as it is the most widely validated tool for assessing subjective sleep quality across diverse populations. Reviewers independently screened articles using Rayyan and assessed study quality with the Joanna Briggs Institute tools. Data were analyzed using Stata version 17. To account for potential clinical and methodological variability across studies, a random-effects model was employed to pool results, with heterogeneity assessed using statistics and the Cochrane’s Q test. Publication bias and sensitivity analyses were also performed.ResultNine studies involving 4,376 women of reproductive age (15–49 years) in Ethiopia were included. The pooled prevalence of poor sleep quality was 49.17% (95% CI: 35.29, 63.08). Significant predictors of poor sleep quality included intimate partner violence (OR: 3.24), depression (OR: 3.37), unplanned pregnancy (OR: 2.71), multigravidity (OR: 2.61), and substance use (OR: 2.24).ConclusionA systematic review indicates that nearly half of Ethiopian women of reproductive age experience poor sleep quality. Key factors include unplanned pregnancies, substance use history, intimate partner violence, previous depression, stress, being in the third trimester, and comorbidities; these need urgent attention and the implementation of screening and preventive measures. Future research should focus on effective interventions to improve sleep quality in these populations.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023455867.

Detecting bipolarity using the Lebanese Arabic hypomania checklist (HCL-32): validation of shortened HCL versions

IntroductionDue to the under diagnosis of bipolar disorder, screening instruments such as the hypomania checklist 32 items (HCL-32) is used to differentiate between Bipolar Disorder (BD) and Major Depressive Disorder (MDD). However due to its lengthy format, efforts were done to validate a shorter alternative without compromising its ability to differentiate between BD and MDD. We aimed to shorten the HCL-32 and assess the screening performance of the three Lebanese Arabic abbreviated HCL versions (HCL-20, -16, and -8) relative to the full HCL-32 in a sample of clinically diagnosed patients with BD and MDD in Lebanon.MethodsIn a sample of 760 patients (BD-I=29, BD-II=142, MDD=589) clinically diagnosed with BD and MDD, the screening performance of the three Lebanese Arabic abbreviated HCL versions (HCL-20, -16, and -8) as well as the full HCL-32, was assessed, looking at the reliability, sensitivity, and specificity.ResultsAll the shortened HCL versions showed strong reliability (a=0.78-0.90.) They also demonstrated good screening ability (AUC=0.8520- 0.8835) in differentiating BD from MDD. For the sensitivities across the shortened versions, they were consistently higher in BD-II vs MDD compared to BD-I vs MDD across all scales showing that the shortened versions have the ability to detect BD-II cases much more effectively.DiscussionThis study is the first to validate the shortened HCL versions in an Arabic speaking population. The HCL- 16 appears to be the most optimal shortened scale for distinguishing between BD versus MDD. However, these findings should be interpreted in light of the study’s limitations including the use of retrospective data collection and item interdependence of the HCL-32.