Diagnosis Of Major Depressive Disorder Research Articles

Higher immune-related gene expression in major depression is independent of CRP levels: results from the BIODEP study

Compelling evidence demonstrates that some individuals suffering from major depressive disorder (MDD) exhibit increased levels of inflammation. Most studies focus on inflammation-related proteins, such as serum or plasma C-reactive protein (CRP). However, the immune-related modifications associated with MDD may be not entirely captured by CRP alone. Analysing mRNA gene expression levels, we aimed to identify broader molecular immune-related phenotypes of MDD. We examined 168 individuals from the non-interventional, case–control, BIODEP study, 128 with a diagnosis of MDD and 40 healthy controls. Individuals with MDD were further divided according to serum high-sensitivity (hs)CRP levels (n = 59 with CRP <1, n = 33 with CRP 1–3 and n = 36 with CRP >3 mg/L). We isolated RNA from whole blood and performed gene expression analyses using RT-qPCR. We measured the expression of 16 immune-related candidate genes: A2M, AQP4, CCL2, CXCL12, CRP, FKBP5, IL-1-beta, IL-6, ISG15, MIF, GR, P2RX7, SGK1, STAT1, TNF-alpha and USP18. Nine of the 16 candidate genes were differentially expressed in MDD cases vs. controls, with no differences between CRP-based groups. Only CRP mRNA was clearly associated with serum CRP. In contrast, plasma (proteins) IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-16, IL-17A, IFN-gamma and TNF-alpha, and neutrophils counts, were all differentially regulated between CRP-based groups (higher in CRP >3 vs. CRP <1 and/or controls), reflecting the gradient of CRP values. Secondary analyses on MDD individuals and controls with CRP values <1 mg/L (usually interpreted as 'no inflammation') confirmed MDD cases still had significantly different mRNA expression of immune-related genes compared with controls. These findings corroborate an immune-related molecular activation in MDD, which appears to be independent of serum CRP levels. Additional biological mechanisms may then be required to translate this mRNA signature into inflammation at protein and cellular levels. Understanding these mechanisms will help to uncover the true immune abnormalities in depression, opening new paths for diagnosis and treatment.

Real-world treatment modalities, health care resource utilization, and costs among commercially insured patients with newly diagnosed major depressive disorder in the United States.

BACKGROUND: In the United States, major depressive disorder (MDD) is one of the most prevalent mental health disorders. Treatment guidelines for MDD recommend pharmacologic and nonpharmacologic therapies tailored to the patient's disease severity, level of function, and comorbid health conditions. While previous studies examined real-world pharmacologic treatment patterns and costs among patients with MDD, few have examined the use of nonpharmacologic treatments and their association with health care resource utilization (HCRU) and cost. OBJECTIVE: To describe prevalence and associations between patient/provider characteristics and treatment modality and characterize HCRU and cost by treatment modality for patients with newly diagnosed MDD. METHODS: Commercially insured US patients, aged 18-62 years with newly diagnosed MDD between January 1, 2017, and September 30, 2019, were retrospectively identified from the Healthcare Integrated Research Database. Eligible patients were continuously enrolled in the health plan for 1 year before and 2 years after the first MDD diagnosis (index date). Those with co-occurring schizophrenia, bipolar disorder, postpartum depression, substance use disorder, and any prior MDD treatments were excluded. Treatment modalities assessed in the 2-year post-index period included antidepressant only (Rx-only), nonpharmacologic only (non-Rx-only), both antidepressant and nonpharmacologic (combination), and no treatment. HCRU and costs were assessed in the 2-year post-index period by treatment modality. Regression models identified associations between patient/provider characteristics and treatment modality, and the relationship between treatment modality and MDD severity changes. RESULTS: In total, 12,657 patients were included (mean age: 36 years; 60% female). During follow-up, 34% of patients received Rx-only, 25% received non-Rx-only, 28% received combination, and 13% received no treatment. MDD severity at diagnosis (26% mild, 54% moderate, 20% severe) was available for 51% of patients. Post-index inpatient hospitalizations were 11% for those with Rx-only, 10% for non-Rx-only, 16% for combination, and 29% for no treatment, whereas all-cause mean monthly total costs were $792, $633, $786, and $1,292, respectively. In multinomial logistic regression, age, sex, geographic region and urbanicity of patient residence, socioeconomic status, diagnosing provider specialty, and initial diagnosis location were significantly associated (P < 0.05) with treatment modality. In multivariable logistic regression, recipients of Rx-only (odds ratio = 2.03, P < 0.01) or combination (odds ratio = 3.26, P < 0.01) had higher odds of improving MDD severity than patients who received no treatment. CONCLUSIONS: In this real-world sample of commercially insured patients, we observed variations in outcomes by treatment modality and an association between treatment modality and disease severity. Further research is needed to explore the underlying causal relationships between treatment modality and patient outcomes. Study Registration: https://doi.org/10.17605/OSF.IO/YQ6B3 DISCLOSURES: Dr Grabner is an employee of Carelon Research, which received funding from the Innovation and Value Initiative for the conduct of the study on which this manuscript is based. Ms Pizzicato and Mr Yang were employees of Carelon Research at the time the study was conducted. Dr Grabner is a shareholder of Elevance Health. Drs Xie and Chapman are employees of the Innovation and Value Initiative.

Design, implementation and preliminary results of a type-2 hybrid cluster-randomized trial of integrating screening and treatment for major depressive disorder into specialty clinics providing opioid agonist therapies in Ukraine

IntroductionUkraine has a high prevalence of co-occurring disorders (COD), defined as having both substance use (SUD) and psychiatric disorders. Major depressive disorder (MDD) is the most prevalent psychiatric disorder among people with SUD. People with COD experience poor health outcomes, and international agencies propose integrated COD care. In Ukraine, treatment for SUD is delivered in specialized substance use clinics, without providing any other medical services for comorbidities, including MDD. Here we present the protocol, along the with the preliminary results of the MEDIUM project, including observations over the first 6 months. MethodsA cluster-randomized type-2 hybrid trial was conducted to integrate MDD treatment into specialty clinics providing opioid agonist therapies (OAT) in Ukraine. Twelve clinics in four regions underwent randomization to control (N = 1) vs experimental arms (N = 2) in each region. Clinicians at experimental sites received tele-education through modified project ECHO using a facilitated screening, evaluation, and treatment algorithm of depression, with or without financial incentives. Service-, patient- and provider-level data were collected for the analysis every 6 months for 24 months. Preliminary resultsFor service delivery outcomes, 4421 patients enrolled on OAT across all sites were assessed for MDD for screening (76.7%), evaluation with diagnosis (43.5%) and treatment (30.7%) for MDD; 13.8% continued treatment at least for 6 months. For patient-level outcomes, 1345 patients and 54 providers participated in serial surveys every six months. ConclusionThis study will be the first to explore integrated COD care in Ukraine and generate evidence on effective service integration and delivery strategies for people with COD receiving treatment at substance use clinics with broader implications for Eastern Europe and Central Asia region.

0323 Natural Evolution of Insomnia in Major Depressive Disorders

Abstract Introduction Insomnia is a fairly common sleep disturbance affecting nearly one third of the general population. Although its predictive value for major depressive disorder (MDD) has been well documented, little is known about its role in the appearance of a first episode or in the recurrence. In this study, we examine the predictive value of insomnia symptoms in the incidence and recurrence of MDD. Methods In this longitudinal study, 2 interview waves were conducted between 2002 and 2015. The initial interviews (wave 1 [W1]) were carried out with 12,218 individuals aged ≥18 years from the general population in 8 US states. At follow-up 3 years later (wave 2 [W2]), 10,931 of the initial participants agreed to be interviewed again. Data were analyzed for the individuals who participated in both interviews (N=10,931). A diagnosis of MDD was made according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria. Insomnia symptoms were defined according to DSM-5 criteria A, C, and D for insomnia disorder. Results The 12-month prevalence of MDD was 9.5% (95% CI, 9.0%-10.0%) and 12.1% (95% CI, 11.5%-12.7%) in W1 and W2, respectively. Over the course of the study, 2.6% of participants experienced recurrence of depression (95% CI, 2.3%-2.9%). After adjusting for age, gender, race, and body mass index, participant characteristics in W1 that predicted recurrent MDD in W2 included early morning awakenings (EMA) (relative risk [RR], 3.2; 95% CI, 2.3-4.4), being dissatisfied with one’s sleep (RR, 2.8; 95% CI, 2.1-3.7), nocturnal awakenings (RR, 2.4; 95% CI, 1.8-3.2), and difficulty initiating sleep (DIS) (RR, 2.0; 95% CI, 1.5-2.9). MDD incidence was predicted by DIS (RR, 3.8; 95% CI, 2.5-5.9), being dissatisfied with one’s sleep (RR, 2.1; 95% CI, 1,4-3.2), and EMA (RR, 2.0; 95% CI, 1.2-3,2) at W1. Conclusion Insomnia symptoms appear to play an important part in predicting both the development of a first depressive episode as well as the recurrence of depression. Support (if any) Data analysis study were funded by Takeda Pharmaceutical Company.

1006 How Insomnia Masked a Young Man's First Episode Psychosis

Abstract Introduction Sleep disturbance is a common sign across many mental health disorders. Particularly, insomnia is a frequent issue among patients with mood disorders. However, there is increasing evidence that suggests that sleep disturbance may be a risk factor for developing psychosis, or conversely, an early warning sign of psychosis. In this case report, we describe a young patient’s first episode of psychosis, which was masked by an initial presentation of insomnia, diagnosed as major depressive disorder, and the patient decompensated further until his psychosis was appropriately diagnosed and treated. Report of case(s) A 20-year-old African-American male was evaluated at a major tertiary hospital after he was found calling his mother while crying and speaking incoherently. He was eventually admitted there for two weeks with the diagnosis of Major Depressive Disorder, and discharged on Bupropion 300 milligrams(mg) daily for depression, with Quetiapine 50mg and Trazodone 100mg at night for sleep. Following discharge from this hospital, the patient’s psychiatric history was significant only for one additional outpatient psychiatry clinic visit at a major community hospital, where he was again diagnosed with Major Depressive Disorder, and prescribed Zoloft 25mg daily. The patient eventually presented to our hospital with reports of worsening depression, poor sleep, poor appetite, and more recently, increasingly bizarre behavior. The patient initially presented to the unit disorganized (nursing staff frequently described patient as looking "lost"), staring blankly at the walls, internally preoccupied and laughing inappropriately as if responding to internal stimuli. Patient had episodes of emotional outbursts with aggression and bizarre behavior that required emergent medication. The patient’s Bupropion was discontinued in favor of oral Risperidone, titrated up to 4mg twice daily. Patient’s symptoms, including his sleep, gradually improved with the single antipsychotic regimen, and was eventually discharged after returning to his baseline. Patient was also evaluated by a clinical psychology team who also supported the assessment of first episode of psychosis. Conclusion This case highlights the importance of evaluating sleep disturbances in accurately diagnosing mental disorders. Studies show sleep is an important risk factor in the precipitation of many mental illnesses, while sleep disturbances are also frequently resolved by treating the underlying mental illness. Support (if any)

Addressing multi-site functional MRI heterogeneity through dual-expert collaborative learning for brain disease identification.

Several studies employ multi-site rs-fMRI data for major depressive disorder (MDD) identification, with a specific site as the to-be-analyzed target domain and other site(s) as the source domain. But they usually suffer from significant inter-site heterogeneity caused by the use of different scanners and/or scanning protocols and fail to build generalizable models that can well adapt to multiple target domains. In this article, we propose a dual-expert fMRI harmonization (DFH) framework for automated MDD diagnosis. Our DFH is designed to simultaneously exploit data from a single labeled source domain/site and two unlabeled target domains for mitigating data distribution differences across domains. Specifically, the DFH consists of a domain-generic student model and two domain-specific teacher/expert models that are jointly trained to perform knowledge distillation through a deep collaborative learning module. A student model with strong generalizability is finally derived, which can be well adapted to unseen target domains and analysis of other brain diseases. To the best of our knowledge, this is among the first attempts to investigate multi-target fMRI harmonization for MDD diagnosis. Comprehensive experiments on 836 subjects with rs-fMRI data from 3 different sites show the superiority of our method. The discriminative brain functional connectivities identified by our method could be regarded as potential biomarkers for fMRI-related MDD diagnosis.

Med Check: Zuranolone for Depression, Uzedy for Schizophrenia, and More

Back to table of contents Previous article Next article Med CheckFull AccessMed Check: Zuranolone for Depression, Uzedy for Schizophrenia, and MoreTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:25 May 2023https://doi.org/10.1176/appi.pn.2023.06.6.1Zuranolone Found to Quickly Reduce Major Depression SymptomsAdults with major depressive disorder may experience mood improvements within days of taking zuranolone (50 mg/day), a study published in May in The American Journal of Psychiatry (AJP) suggests. Zuranolone is an oral, once-daily neuroactive steroid that acts on GABA-A receptors.The phase 3 trial included patients who were between the ages of 18 and 64 years, had received a diagnosis of major depressive disorder, had been experiencing symptoms of depression for a least four weeks, and had a Hamilton Depression Rating Scale (HAM-D) score of at least 24 at screening and before they started taking the assigned study medication.The researchers randomized 534 participants to take either 14 days of treatment with zuranolone 50 mg/day or placebo in the evening. The researchers evaluated the participants 10 times over the course of the 42-day trial using such assessments as the HAM-D, the Columbia–Suicide Severity Rating Scale, the Clinical Global Impressions severity score, and more.Compared with patients who took placebo, those who took zuranolone demonstrated a statistically significant improvement in depressive symptoms at day 15. “Numerically greater improvements in depressive symptoms for zuranolone versus placebo were observed by day 3 (least squares mean change from baseline HAM-D score, −9.8 vs. −6.8), which were sustained at all visits throughout the treatment and follow-up periods of the study,” the researchers wrote.FDA Approves Uzedy for Treating SchizophreniaIn April the U.S. Food and Drug Administration (FDA) approved Uzedy (risperidone extended-release injectable suspension) for the treatment of schizophrenia in adults, Teva and MedinCell announced. Uzedy is a long-acting subcutaneous antipsychotic that may be given in one- or two-month dosing intervals.In the phase 3 RISE trial, 544 patients aged 13 to 65 years with schizophrenia were randomized to receive a subcutaneous injection of Uzedy (either once per month or once every two months) or placebo. Those who received Uzedy once per month or once every two months had a reduction of 80.0% and 62.5% in the risk to relapse compared with those who received placebo, respectively. Results were similar in the phase 3 SHINE trial, which examined the long-term safety of the drug for up to 56 weeks in 336 patients aged 13 to 65 years with schizophrenia.A companion survey of participants in the SHINE trial found that 89% of patients and 92% of health professionals rated administration of Uzedy as easy when asked how easy or difficult it was to receive or administer the medication in its current form. Further, 70% of patients reported that Uzedy provided a better injection experience than their previous long-acting injectables (LAIs).Abilify Asimtufii Approved for Schizophrenia, Bipolar I TreatmentAbilify Asimtufii (aripiprazole extended release injectable suspension) has been approved by the FDA for the treatment of schizophrenia in adults and as a monotherapy treatment of bipolar I disorder in adults, Otsuka and Lundbeck announced in April. Abilify Asimtufii is a long-acting subcutaneous atypical antipsychotic that may be given every two months.The approval was based on safety and efficacy data from trials of Abilify Maintena, which is for once monthly dosing, and on the results of a phase 1-2 study. In the phase 1-2 study, 266 adults with schizophrenia or bipolar I disorder were randomly assigned to receive either Abilify Asimtufii 960 mg every 56 days, for a total of four injections or Abilify Maintena 400 mg administered every 28 days for a total of eight injections. Treatment with Abilify Asimtufii resulted in similar aripiprazole plasma concentrations and efficacy to Abilify Maintena. ■ ISSUES NewArchived

(015) Vulvar Lichen Sclerosus is Associated with New Diagnoses of Mood Disorders

Abstract Introduction Vulvar lichen sclerosus (VLS) often presents with chronic pruritus. While VLS is associated with feelings of isolation, risk of mood disorders among females with VLS has yet to be quantified on a large scale. Objective Our objective was to assess the association of VLS with development of depressive episode, anxiety disorder, major depressive disorder (MDD), and prescription of antidepressants and benzodiazepines, and to evaluate the impact of VLS treatment. Methods A US claims database network (TriNetX Diamond Network) was queried from 2009 to 2022. Cohorts included women aged ≥18 with lichen sclerosus (LS) (ICD-10: L90.0) without prior diagnosis of MDD (F33), depressive episode (F32), or anxiety disorder (F40-F48) or previously prescribed antidepressants (VA: CN600) or benzodiazepines (CN302). We compared a control cohort of women with LS sparing the vulva with women with LS affecting the vulva (N90.4). We conducted a sub-analysis by age (18-40, 41-55, and &amp;gt;55 years). We compared women aged ≥18 with VLS who received treatment (topical steroids (DE200), vaginal estrogen (GU500), prednisone (8640), hydroxyzine (5553), amitriptyline (704), gabapentin (25480), or tacrolimus (42316)) with women aged ≥18 with VLS who did not receive treatment within 6 months of VLS diagnosis. Finally, we compared women receiving only topical VLS treatment (topical steroids, vaginal estrogen, and tacrolimus) with those receiving no treatment. Outcomes of interest were depressive episodes, anxiety disorder, MDD or prescription of antidepressants or benzodiazepines within 6 months of VLS diagnosis. Propensity score matching was performed for age, ethnicity, race, type 1 diabetes (E10), vitiligo (L80), autoimmune thyroiditis (E06.3), alopecia areata (L63), pernicious anemia (D51.0), overweight and obesity (E66), type 2 diabetes (E11), hyperlipidemia (E78), essential hypertension (I10), and alcohol abuse (F10.10). Results 124,237 patients had LS sparing the vulva and 16,676 had VLS. VLS was associated with increased risk of depressive episode (risk ratio (RR) [95% Confidence Interval] 1.62 [1.32-1.99]), anxiety disorder (RR 1.82 [1.50-2.22]), and MDD (RR 2.61 [1.69-4.03]) (Table 1) compared to LS sparing the vulva. Women with VLS were also more likely to receive antidepressants (RR 1.91 [1.60-2.29]) and benzodiazepines (RR 1.70 [1.44-2.01]). Among menopausal women, VLS was associated with increased risk of anxiety disorder (RR 2.00 [1.10-3.63]) (Table 2). Among postmenopausal women, VLS was associated with increased risk of depressive episode (RR 1.73 [1.38-2.17]), MDD (RR 2.60 [1.64-4.12]), anxiety disorder (RR 1.58 [1.29-1.94]), antidepressants (RR 1.55 [1.30-1.86]), and benzodiazepines (RR 1.48 [1.24-1.76]). Among women with VLS, VLS treatment was associated with decreased risk of depressive episode (RR 0.68 [0.47-0.98]) and increased risk of antidepressants (RR 2.00 [1.54-2.59]) and benzodiazepines (RR 1.70 [1.31-2.20]) compared to women without VLS treatment (Table 3). Stratifying by treatment type, women treated solely with topicals had numerically, but not significantly, lower risk of developing depressive episode (RR 0.73 [0.48-1.11]) compared to women without VLS treatment. Conclusions We demonstrate that women with VLS, compared to those with LS sparing the vulva, have an increased risk of antidepressant and benzodiazepine prescriptions and development of depressive episode, anxiety disorder, or MDD. Patients with VLS should be screened for these conditions, and VLS treatment should be considered. Disclosure No

The Ongoing Mental Health Plight of Depressed College Students: Clinical Recommendations and the Importance of Early Screening and Detection

The COVID-19 pandemic disrupted the lives of college students. The psychological distress from the pandemic increased risk for provisional rates of Major Depression Disorder (MDD) during an already crucial developmental period. Using an online survey, participants were assessed for a provisional diagnosis of MDD using a validated screening tool, along with Generalized Anxiety Disorder (GAD) and psychosocial correlates. Findings showed a significant increase in the prevalence of MDD, and significant differences in social support, loneliness, substance use, GAD and suicidality were identified. Early screening and detection for potential MDD symptoms can reduce the severity, duration, and reoccurrence of future MDD episodes for college students.

Head-To-Head Comparison of Vortioxetine Versus Desvenlafaxine in Patients With Major Depressive Disorder With Partial Response to SSRI Therapy: Results of the VIVRE Study.

Objective: To compare the efficacy of vortioxetine and the serotonin-norepinephrine reuptake inhibitor (SNRI) desvenlafaxine in patients with major depressive disorder (MDD) experiencing partial response to initial treatment with a selective serotonin reuptake inhibitor (SSRI).Methods: This randomized, double-blind, active-controlled, parallel-group, 8-week study of vortioxetine (10 or 20 mg/d; n = 309) versus desvenlafaxine (50 mg/d: n = 293) was conducted from June 2020 to February 2022 in adults with a DSM-5 diagnosis of MDD who experienced partial response to SSRI monotherapy. The primary endpoint was mean change from baseline to week 8 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Differences between groups were analyzed using mixed models for repeated measures.Results: Non-inferiority of vortioxetine versus desvenlafaxine was established in terms of mean change from baseline to week 8 in MADRS total score; however, a numeric advantage was observed in favor of vortioxetine (difference, -0.47 MADRS points [95% CI, -1.61 to 0.67]; P = .420). At week 8, significantly more vortioxetine-treated than desvenlafaxine-treated patients had achieved symptomatic and functional remission (ie, Clinical Global Impressions-Severity of Illness scale [CGI-S] score ≤ 2) (32.5% vs 24.8%, respectively; odds ratio = 1.48 [95% CI, 1.03 to 2.15]; P = .034). Vortioxetine-treated patients also experienced significantly greater improvements in daily and social functioning assessed by the Functioning Assessment Short Test (P = .009 and .045 vs desvenlafaxine, respectively) and reported significantly greater satisfaction with their medication assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire (P = .044). Treatment-emergent adverse events (TEAEs) were reported in 46.1% and 39.6% of patients in the vortioxetine and desvenlafaxine groups, respectively; these were mostly mild or moderate in intensity (> 98% of all TEAEs in each group).Conclusions: Compared with the SNRI desvenlafaxine, vortioxetine was associated with significantly higher rates of CGI-S remission, better daily and social functioning, and greater treatment satisfaction in patients with MDD and partial response to SSRIs. These findings support the use of vortioxetine before SNRIs in the treatment algorithm in patients with MDD.Trial Registration: ClinicalTrials.gov Identifier: NCT04448431.

EFFECT OF AGOMELATINE AND SERTRALINE ON SLEEP QUALITY AMONG PATIENTS WITH CHRONIC KIDNEY DISEASE AND MAJOR DEPRESSIVE DISORDER: A DOUBLE-BLINDED RANDOMIZED CONTROLLED TRIAL

Background: Depression is a common comorbid disease among patients with chronic kidney disease (CKD). Insomnia, a symptom related to these conditions, negatively impacts disease progression and quality of life. Unfortunately, no consensus has been reached concerning treatment guidelines and choices of antidepressants suitable for treating depression among patients with CKD.&#x0D; Objectives: The study aimed to evaluate the efficacy to sleep quality, depressive symptoms, safety and tolerability of agomelatine and sertraline in treating major depressive disorder among patients with CKD.&#x0D; Methods: A double-blinded randomized controlled trial was conducted in the Nephrology Unit, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand. Patients with CKD and a diagnosis of major depressive disorder were randomly assigned to receive once-daily, fixed-dose sertraline 50 mg/d and agomelatine 25 mg/d. The treatment outcome was evaluated at 4 and 8 weeks. The Pittsburgh Sleep Quality Index score (PSQI) was used to measure sleep quality, and the Hamilton rating scale of depression, the Thai version (Thai HRSD-17), was used to evaluate depressive symptoms. Other outcomes included overall quality of life, side effects and tolerability.&#x0D; Results: Agomelatine significantly improved sleep quality based on PSQI score throughout the observed period (p=0.002). Also, agomelatine more efficiently reduced depressive symptoms than sertraline (p=&lt;0.001). In addition, patients receiving agomelatine as a treatment could continue their medication, whereas 52% of patients receiving sertraline discontinued because of side effects.&#x0D; Conclusion: Agomelatine significantly improved sleep quality and tolerated well compared to sertraline.&#x0D; Trial registration: thaiclinicaltrials.org ID: TCTR20200319005

Evaluation of Inflammatory Markers in Patients with Depressed Episodes in Major Depressive Disorder and Bipolar Disorder before and after Treatment.

Depression is one of the current dilemmas in both developed and developing societies. Studies show that the severity of psychiatric symptoms is directly related to the degree of inflammation caused by cytokines secreted by the immune system. Hence, evaluating serum cytokine levels in patients with depression can help to understand the pathogenesis of the disease and make the best therapeutic decisions. The present study investigated the levels of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) in patients with major depression or bipolar disorder during depressive episodes (BDDE) before and after a 6-month pharmaceutical intervention. Patients referring to 3 clinics were recruited for the study. The diagnosis of major depression or bipolar disorder in a depressive phase was made according to the Diagnostic and Statistical Manual of Mental Disorders -5(DSM-5) criteria. There was a significant difference in depression levels between the pre-intervention and 6-month follow-up in both groups. After 6 months, IL-1 and IL-6 levels in the bipolar disorder group had decreased while TNF-α levels had increased. There was also a significant difference between pre-intervention and follow-up levels of IL-1. Serum levels of IL-1 and IL-6 decreased significantly in both groups after the 6-month follow-up, and symptom improvement was observed. TNF-α levels, on the other hand, decreased in the major depression group but increased in the bipolar disorder group. Considering that inflammation is a major outcome of depression, treatment strategies to reduce inflammation could be a practical approach to improving psychiatric symptoms.

Depressive and Anxiety Disorders Increase Risk for Recurrent Anterior Shoulder Pain Following Arthroscopic Suprapectoral Biceps Tenodesis

PurposeTo evaluate factors associated with postoperative anterior shoulder pain following arthroscopic suprapectoral biceps tenodesis (ABT) and to determine the clinical impact of postoperative anterior shoulder pain.MethodsA retrospective study of patients that underwent ABT between 2016 and 2020 was conducted. Groups were categorized by the presence (ASP+) or absence (ASP−) of postoperative anterior shoulder pain. Patient-reported outcomes (American Shoulder and Elbow score [ASES], visual analog scale [VAS] for pain, subjective shoulder value [SSV]), strength, range of motion, and complication rates were analyzed. Differences between continuous and categorical variables were tested with two-sample t-tests and chi-squared or Fisher’s exact tests, respectively. Variables collected at different postoperative timepoints were analyzed using mixed models with post hoc comparisons when significant interactions were detected.ResultsA total of 461 (47 ASP+, 414 ASP−) patients were included. A statistically significant lower mean age was observed in the ASP+ group (P < .001). A statistically significant higher prevalence of major depressive disorder (MDD) (P = .03) or any anxiety disorder (P = .002) was observed in the ASP+ group. Prescription medication with psychotropic medications (P = .01) was significantly more prevalent in the ASP+ group. No significant differences were observed in the proportion of individuals reaching the minimal clinical important difference (MCID) for ASES, VAS, or SSV between groups.ConclusionsA pre-existing diagnosis of major depressive disorder or any anxiety disorder, as well as the use of psychotropic medications was associated with postoperative anterior shoulder pain following ABT. Other factors associated with anterior shoulder pain included younger age, participation in physical therapy before surgery, and lower rate of concomitant rotator cuff repair or subacromial decompression. Although the proportion of individuals reaching MCID did not differ between groups, the presence of anterior shoulder pain after ABT resulted in prolonged recovery, inferior PROs, and a higher incidence of repeat surgical procedures. The decision to perform ABT in patients diagnosed with MDD or anxiety should be carefully considered, given the correlation to postoperative anterior shoulder pain and inferior outcomes.Level of EvidenceLevel III, retrospective case-control study. To evaluate factors associated with postoperative anterior shoulder pain following arthroscopic suprapectoral biceps tenodesis (ABT) and to determine the clinical impact of postoperative anterior shoulder pain. A retrospective study of patients that underwent ABT between 2016 and 2020 was conducted. Groups were categorized by the presence (ASP+) or absence (ASP−) of postoperative anterior shoulder pain. Patient-reported outcomes (American Shoulder and Elbow score [ASES], visual analog scale [VAS] for pain, subjective shoulder value [SSV]), strength, range of motion, and complication rates were analyzed. Differences between continuous and categorical variables were tested with two-sample t-tests and chi-squared or Fisher’s exact tests, respectively. Variables collected at different postoperative timepoints were analyzed using mixed models with post hoc comparisons when significant interactions were detected. A total of 461 (47 ASP+, 414 ASP−) patients were included. A statistically significant lower mean age was observed in the ASP+ group (P < .001). A statistically significant higher prevalence of major depressive disorder (MDD) (P = .03) or any anxiety disorder (P = .002) was observed in the ASP+ group. Prescription medication with psychotropic medications (P = .01) was significantly more prevalent in the ASP+ group. No significant differences were observed in the proportion of individuals reaching the minimal clinical important difference (MCID) for ASES, VAS, or SSV between groups. A pre-existing diagnosis of major depressive disorder or any anxiety disorder, as well as the use of psychotropic medications was associated with postoperative anterior shoulder pain following ABT. Other factors associated with anterior shoulder pain included younger age, participation in physical therapy before surgery, and lower rate of concomitant rotator cuff repair or subacromial decompression. Although the proportion of individuals reaching MCID did not differ between groups, the presence of anterior shoulder pain after ABT resulted in prolonged recovery, inferior PROs, and a higher incidence of repeat surgical procedures. The decision to perform ABT in patients diagnosed with MDD or anxiety should be carefully considered, given the correlation to postoperative anterior shoulder pain and inferior outcomes.

A Machine Learning Framework for Major Depressive Disorder (MDD) Detection Using Non-invasive EEG Signals

According to World Health Organization (WHO) report, every 40 seconds a person attempts suicide globally. Depression, one of the world’s most prevailing diseases has become a reason behind these suicides. It is believed that early diagnosis of major depressive disorder (MDD) can reduce the adversity of this heinous deformity. For few years various machine learning and advanced neurocomputing techniques are being utilized in Electroencephalogram (EEG) based detection of multiple neurological diseases. In the proposed study, an EEG based screening of MDD is presented while using various Machine Learning and one Deep Learning approach. The majority of previous EEG based MDD decoding research has concentrated on a limited features. It was necessary to conduct in-depth comparisons of different approaches, besides more detailed feature-based EEG analysis. This research starts with the creation of a complete feature-based framework, which is then further compared against the state of the art end to end techniques. The K-nearest neighbors (KNN) model outperformed the other models and gained an accuracy of 87.5%. While long short term memory (LSTM) model acquired an accuracy of 83.3%. This study can further support in clinical diagnosis of multiple stages of MDD and can attempt to provide an early intervention.

Assessment of Disruptive Life Events for Individuals Diagnosed With Schizophrenia or Bipolar I Disorder Using Data From a Consumer Credit Reporting Agency

There is a dearth of population-level data on major disruptive life events (defined here as arrests by a legal authority, address changes, bankruptcy, lien, and judgment filings) for patients with bipolar I disorder (BPI) or schizophrenia, which has limited studies on mental health and treatment outcomes. To conduct a population-level study on disruptive life events by using publicly available data on disruptive life events, aggregated by a consumer credit reporting agency in conjunction with electronic health record (EHR) data. This study used EHR data from 2 large, integrated health care systems, Kaiser Permanente Southern California and Henry Ford Health. Cohorts of patients diagnosed from 2007 to 2019 with BPI or schizophrenia were matched 1:1 by age at analysis, age at diagnosis (if applicable), sex, race and ethnicity, and Medicaid status to (1) an active comparison group with diagnoses of major depressive disorder (MDD) and (2) a general health (GH) cohort without diagnoses of BPI, schizophrenia, or MDD. Patients with diagnoses of BPI or schizophrenia and their respective comparison cohorts were matched to public records data aggregated by a consumer credit reporting agency (98% match rate). Analysis took place between November 2020 and December 2022. The differences in the occurrence of disruptive life events among patients with BPI or schizophrenia and their comparison groups. Of 46 167 patients, 30 008 (65%) had BPI (mean [SD] age, 42.6 [14.2] years) and 16 159 (35%) had schizophrenia (mean [SD], 41.4 [15.1] years). The majoriy of patients were White (30 167 [65%]). In addition, 18 500 patients with BPI (62%) and 6552 patients with schizophrenia (41%) were female. Patients with BPI were more likely to change addresses than patients in either comparison cohort (with the incidence ratio being as high as 1.25 [95% CI, 1.23-1.28]) when compared with GH cohort. Patients with BPI were also more likely to experience any of the financial disruptive life events with odds ratio ranging from 1.15 [95% CI, 1.07-1.24] to 1.50 [95% CI, 1.42-1.58]). The largest differences in disruptive life events were seen in arrests of patients with either BPI or schizophrenia compared with GH peers (3.27 [95% CI, 2.84-3.78] and 3.04 [95% CI, 2.57-3.59], respectively). Patients with schizophrenia had fewer address changes and were less likely to experience a financial event than their matched comparison cohorts. This study demonstrated that data aggregated by a consumer credit reporting agency can support population-level studies on disruptive life events among patients with BPI or schizophrenia.

Association between programmed death-1 pathway and major depression

Objectives Major depression (MD) may be associated with inflammation and immunity. PD-1 (programmed death-1), PD-L1 (programmed death-ligand 1) and PD-L2 (programmed death-ligand 2) are among the inhibitory immune mediators on the PD-1 pathway. However, previous data regarding the association between MD and PD-1 pathway were still scarce; therefore, we investigated the association of PD-1 pathway with MD. Methods During a period of 2 years, patients with MD and healthy controls were recruited from a medical centre in this study. The diagnosis of MD was established according to the DSM-5 criteria. The severity of MD was assessed with 17-item Hamilton Depression Rating Scale. PD-1, PD-L1 and PD-L2 were detected in peripheral blood from MD patients after 4 weeks of treatment with antidepressant drugs. Results A total of 54 patients with MD and 38 healthy controls were recruited. According to the analyses, there is a significantly higher PD-L2 level in MD than in healthy controls and lower PD-1 level after age and BMI adjustment. Besides, moderately positive correlation between HAM-D scores and PD-L2 level was found. Conclusions It was found that PD-1 pathway might play an important role in MD. We need a large sample to prove these results in the future.

Differences in Selective Attention and Inhibitory Control in Patients with Major Depressive Disorder and Healthy Controls Who Do Not Engage in Sufficient Physical Activity.

Patients with major depressive disorder (MDD) are characterized by neurocognitive impairments and show deficits in various cognitive performance indicators, including executive function. We examined whether sustained attention and inhibitory control differ between patients with MDD and healthy controls, and whether differences exist between patients with mild, moderate, and severe depression. Clinical in-patients (N = 212) aged 18-65 years with a current diagnosis of MDD and 128 healthy controls were recruited. Depression severity was assessed using the Beck Depression Inventory, and sustained attention and inhibitory control were assessed using the oddball and flanker tasks. The use of these tasks promises insights into executive function in depressive patients that are not biased by verbal skills. Group differences were tested via analyses of covariance. Patients with MDD showed slower reaction times in both the oddball and flanker task, independent of the executive demands of the trial types. Younger participants achieved shorter reaction times in both inhibitory control tasks. After correcting for age, education, smoking, BMI, and nationality, only differences in reaction times in the oddball task were statistically significant. In contrast, reaction times were not sensitive to the symptom severity of depression. Our results corroborate deficits in basic information processing and specific impairments in higher-order cognitive processes in MDD patients. As difficulties in executive function underlie problems in planning, initiating, and completing goal-directed activities, they may jeopardize in-patient treatment and contribute to the recurrent nature of depression.

Balancing the beautiful and the good in pursuit of biomarkers for depression.

Balancing the beautiful and the good in pursuit of biomarkers for depression.

The curse and opportunity of heterogeneity in the pursuit of psychiatric biomarkers.

The curse and opportunity of heterogeneity in the pursuit of psychiatric biomarkers.

Sleep disorders in veterans with serious mental illnesses: prevalence in Veterans Affairs health record data.

This study aimed to estimate the 12-month prevalence of diagnosed sleep disorders among veterans with and without serious mental illnesses (SMI) in Veterans Affairs health record data in 2019. We also examined diagnosed sleep disorders across a 9-year period and explored associations with demographic and health factors. This study used health record data from VISN 4 of the Veterans Health Administration from 2011 to 2019. SMI diagnoses included schizophrenia and bipolar spectrum diagnoses as well as major depression with psychosis. Sleep diagnoses included insomnias, hypersomnias, sleep-related breathing disorders, circadian rhythm sleep-wake disorders, and sleep-related movement disorders. Demographic and health-related factors were also collected from the record. In 2019, 21.8% of veterans with SMI were diagnosed with a sleep disorder. This is a significantly higher proportion than for veterans without SMI, 15.1% of whom were diagnosed with a sleep disorder. Sleep disorder rates were highest in veterans with a chart diagnosis of major depression with psychosis. From 2011 to 2019, the overall prevalence of sleep disorders in veterans with SMI more than doubled (10.2%-21.8%), suggesting improvements in the detection and diagnosis of sleep concerns for this group. Our findings suggest that identification and diagnosis of sleep disorders for veterans with SMI has improved over the past decade, though diagnoses still likely underrepresent actual prevalence of clinically relevant sleep concerns. Sleep concerns may be at particularly high risk of going untreated in veterans with schizophrenia-spectrum disorders. Bonfils KA, Longenecker JM, Soreca I, etal. Sleep disorders in veterans with serious mental illnesses: prevalence in Veterans Affairs health record data. J Clin Sleep Med. 2023;19(9):1651-1660.