Severe Major Depressive Disorder Research Articles

Vitamin B12 and homocysteine in patients with major depressive disorder

ABSTRACT Background: Alterations in the level of neurotransmitters are evident in patients with major depressive disorder (MDD). Vitamin B12 mediates the synthesis of neurotransmitters, and hence, vitamin B12 deficiency could be associated with depression. Aims and Objectives: To assess the levels of serum vitamin B12, homocysteine (Hcy), and haematological profiles in patients of MDD. Materials and Methods: Fifty-nine patients with MDD were recruited based on ICD-10 criteria. Severity of depression was assessed by HAM-D scale. Vitamin B12, Hcy levels, and haematological profiles were analysed. Results: Vitamin B12 was deficient or depleted in all patients with MDD. The median level of vitamin B12 in serum was 164.2 pg./ml and significantly lower in patients with severe MDD. The mean value of Hcy was 18.34 μmol/L, which was high compared to the normal reference range. The red cell distribution width (RDW-CV) varied significantly between the three groups of MDD patients. Patients consuming non-vegetarian food had a significantly higher median value of serum vitamin B12. Conclusion: Vitamin B12 deficiency is found in patients with MDD and varies inversely with severity of MDD. Hcy is found to be higher in patients with MDD. The manifestation of depressive symptoms precedes the more commonly known haematological manifestations of vitamin B12 deficiency in this study.

Altered Serotonin 1B Receptor Binding After Escitalopram for Depression Is Correlated With Treatment Effect.

Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT), but the downstream antidepressant mechanism of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI administration in primates and rodents, respectively. The effect of SSRI treatment on 5-HT1B receptor binding in patients with MDD has not been examined previously. This positron emission tomography (PET) study aimed to quantify brain 5-HT1B receptor binding changes in vivo after SSRI treatment for MDD in relation to treatment effect. Eight unmedicated patients with moderate to severe MDD underwent PET with the 5-HT1B receptor radioligand [11C]AZ10419369 before and after 3 to 4 weeks of treatment with the SSRI escitalopram 10mg daily. Depression severity was assessed at time of PET and after 6 to 7 weeks of treatment with the Montgomery-Åsberg Depression Rating Scale. We observed a significant reduction in [11C]AZ10419369 binding in a dorsal brainstem (DBS) region containing the median and dorsal raphe nuclei after escitalopram treatment (P = .036). Change in DBS [11C]AZ10419369 binding correlated with Montgomery-Åsberg Depression Rating Scale reduction after 3-4 (r = 0.78, P = .021) and 6-7 (r = 0.94, P < .001) weeks' treatment. Our findings align with the previously reported reduction of 5-HT1B receptor binding in the raphe nuclei after SSRI administration and support future studies testing change in DBS 5-HT1B receptor binding as an SSRI treatment response marker.

Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial

Several phase II studies have demonstrated that psilocybin-assisted therapy shows therapeutic potential across a spectrum of neuropsychiatric conditions, including major depressive disorder (MDD). However, the mechanisms underlying its often persisting beneficial effects remain unclear. Observational research suggests that improvements in psychological flexibility may mediate therapeutic effects. However, no psychedelic trials to date have substantiated this finding in a clinical sample. In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe MDD were administered placebo (n = 19) followed by psilocybin (0.3 mg/kg) (n = 15) 4 weeks later. Dosing sessions were embedded within a manualized psychotherapy that incorporated principles of Acceptance and Commitment Therapy. Depression severity, psychological flexibility, mindfulness, and values-congruent living were measured over a 16-weeks study period. Psychological flexibility, several facets of mindfulness, and values-congruent living significantly improved following psilocybin and were maintained through week 16. Additionally, improvements in psychological flexibility and experiential acceptance were strongly associated with reductions in depression severity following psilocybin. These findings support the theoretical premise of integrating psilocybin treatment with psychotherapeutic platforms that target psychological flexibility and add to emerging evidence that increasing psychological flexibility may be an important putative mechanism of change in psilocybin-assisted therapy for MDD and potentially, other mental health conditions.

The relationship between serum resolvin D1, NLRP3, cytokine levels, and adolescents with first-episode medication-naïve major depressive disorder

BackgroundInflammation has become a critical pathological mechanism of Major Depressive Disorder (MDD). NLRP3 is a critical inflammatory pathway to maintain the immune balance. Recently, preclinical evidence showed that Resolvin D1 might potentially offer a new option for antidepressant treatment due to its protective effects through the inhibition of neuroinflammation. However, whether they have clinical value in the diagnosis and treatment evaluation of adolescent depression was unclear.MethodsForty-eight untreated first-episode adolescent patients with moderate to severe major depressive disorder, as well as 30 healthy adolescents (HCs, age and gender-matched), were enrolled for this study. Their ages ranged from 13 to 18 (15.75 ± 1.36) years. The patients were treated with fluoxetine for 6–8 weeks. HDRS-17 was used to evaluate the severity of depressive symptoms. Venous blood samples were collected at baseline for the two groups and at the time-point of post-antidepressant treatment for the patients. Serum concentrations of RvD1, NLRP3, IL-1β, IL-18, and IL-4 were measured by enzyme-linked immunosorbent assays (ELISA) pre- and post-fluoxetine treatment.ResultsSerum levels of RvD1 and anti-inflammatory cytokine IL-4 were significantly elevated in adolescents with MDD compared to healthy adolescents, but no significant difference in NLRP3, IL-1β, and IL-18 between the two groups. Meanwhile, RvD1 (positively) and IL-4 (negatively) were correlated with the severity of symptoms (HDRS-17 scores) after adjusting age, gender, and BMI. Interestingly, fluoxetine treatment significantly reduced the serum levels of RvD1, NLRP3, IL-1β, and IL-18 in MDD adolescents but increased the levels of IL-4 relative to baseline. Furthermore, we observed that serum levels of RvD1 might be an excellent distinguishing indicator for depression and healthy adolescents.ConclusionsOur study is the first to compare RvD1 and NLRP3 between adolescent MDD and HCs. Our findings of reactive increase of RvD1 in adolescent MDD comprised a novel and critical contribution. Our results showed the presence of inflammation resolution unbalanced in adolescents with MDD and indicated that RvD1 might be an ideal biomarker for diagnosing and treating adolescent MDD.

In major dysmood disorder, physiosomatic, chronic fatigue and fibromyalgia symptoms are driven by immune activation and increased immune-associated neurotoxicity

Major depressive disorder (MDD) is accompanied by activated neuro-immune pathways, increased physiosomatic and chronic fatigue-fibromyalgia (FF) symptoms. The most severe MDD phenotype, namely major dysmood disorder (MDMD), is associated with adverse childhood experiences (ACEs) and negative life events (NLEs) which induce cytokines/chemokines/growth factors. To delineate the impact of ACE + NLEs on physiosomatic and FF symptoms in first episode (FE)-MDMD, and examine whether these effects are mediated by immune profiles. ACEs, NLEs, physiosomatic and FF symptoms, and 48 cytokines/chemokines/growth factors were measured in 64 FE-MDMD patients and 32 normal controls. Physiosomatic, FF and gastro-intestinal symptoms belong to the same factor as depression, anxiety, melancholia, and insomnia. The first factor extracted from these seven domains is labeled the physio-affective phenome of depression. A part (59.0%) of the variance in physiosomatic symptoms is explained by the independent effects of interleukin (IL)-16 and IL-8 (positively), CCL3 and IL-1 receptor antagonist (inversely correlated). A part (46.5%) of the variance in physiosomatic (59.0%) symptoms is explained by the independent effects of interleukin (IL)-16, TNF-related apoptosis-inducing ligand (TRAIL) (positively) and combined activities of negative immunoregulatory cytokines (inversely associated). Partial least squares analysis shows that ACE + NLEs exert a substantial influence on the physio-affective phenome which are partly mediated by an immune network composed of interleukin-16, CCL27, TRAIL, macrophage-colony stimulating factor, and stem cell growth factor. The physiosomatic and FF symptoms of FE-MDMD are partly caused by immune-associated neurotoxicity due to T helper (Th)-1 polarization and M1 macrophage activation and relative lowered compensatory immunoregulatory protection.

Divorce, genetic risk, and suicidal thoughts and behaviors in a sample with recurrent major depressive disorder

BackgroundTheories of risk for suicidal thoughts and behaviors (STB) implicate both interpersonal and biological factors. Divorce/separation and aggregate genetic liability are robustly associated with STB, but have seldom been evaluated in conjunction with one another. Furthermore, whether these factors are effective predictors in high-risk populations is not clear. MethodsAnalyses were conducted in a sample of Han Chinese women with severe recurrent major depressive disorder (maximum N = 4380). Logistic regressions were used to evaluate the associations between divorce/separation and polygenic scores (PGS) for suicidal ideation or behavior with STB. Where appropriate, additive interactions between divorce and PGS were tested. ResultsDivorce/separation was significantly associated with increased risk of suicidal ideation, plans, and attempts (odds ratios = 1.28–1.61). PGS for suicidal ideation were not associated with STB, while PGS for suicidal behavior were associated with ideation and plans (odds ratios = 1.08–1.09). There were no significant interactions between divorce/separation and PGS. ConclusionsConsistent with theories of suicidality, the disruption or end of an important interpersonal relationship is an indicator of risk for STB. Aggregate genetic liability for suicidal behavior more modestly contributes to risk, but does not exacerbate the negative impact of divorce. Thus, even within a high-risk sample, interpersonal and biological exposures distinguish between those who do and do not experience STB, and could motivate targeted screening. Further research is necessary to evaluate whether and how the context of divorce contributes to variation in its effect on STB risk.

Bright Light Therapy as Add-On to Inpatient Treatment in Youth With Moderate to Severe Depression

Major depressive disorder is one of the most common mental disorders among adolescents, entailing severe, long-term psychosocial impairment and a high risk of chronicity. In view of the large number of patients requiring treatment, along with insufficient treatment responses with small effect sizes, innovative adjunctive treatment strategies are urgently needed. To investigate whether the effect of adolescent psychiatric inpatient treatment as usual for major depressive disorder can be enhanced by simultaneous use of morning bright light therapy. This was a double-blind, placebo-controlled randomized parallel-group trial with enrollment between March 2018 and November 2020 and follow-up completed in May 2021. The study took place among inpatients at 4 university hospitals for child and adolescent psychiatry across Germany. Of 248 eligible youth aged 12 to 18 years fulfilling ICD-10 criteria for major depressive disorder, 227 were randomized to bright light therapy (n = 116) or placebo red light (n = 111); 151 participants completed the study. Up to 20 sessions of either morning bright light therapy with an intensity of 10 000 lux or placebo red light (100 lux) in addition to multimodal inpatient treatment as usual over 4 weeks. The primary outcome was the change in Beck Depression Inventory-II (BDI-II) score from baseline to posttreatment in the intention-to-treat sample. Among the 224 patients included in the intention-to-treat analyses (192 girls and 32 boys; mean [SD] age, 15.5 [1.4] years), the mean (SD) BDI-II score at baseline was 37.3 (8.7). BDI-II scores were significantly reduced after 4 weeks (postassessment) by a mean of -7.5 (95% CI, -9.0 to -6.0; Hedges g = 0.71). Bright light therapy had no impact on this change (no significant group × time effect). Loss to follow-up was 31% (n = 69) at 16 weeks and 49% (n = 110) at 28 weeks. There were 10 serious adverse events throughout the whole trial, which were not considered related to study treatment. The findings in this study did not indicate superiority of bright light therapy over placebo red light therapy in a large sample of adolescent inpatients with moderate or severe major depressive disorder. Both groups benefited equally from treatment as usual, showing relevant symptom reduction. German Clinical Trials Register: DRKS00013188.

Depression and generalized anxiety and associated factors among adult women and men in Nepal: Results of a national cross-sectional survey in 2022

ABSTRACT The aim of this study was to assess the prevalence and correlates of major depressive disorder (MDD) and generalized anxiety disorder (GAD) among adults in a national population-based survey in Nepal in 2022. MDD was assessed with the PHQ-9 and GAD with the GAD-7. Among women, the prevalence of mild and moderate or severe MDD was 16.2% and 5.9%, respectively, and the prevalence of mild and moderate or severe GAD was 20.6% and 8.2%, respectively. Among men, the prevalence of mild and moderate or severe MDD was 9.4% and 1.8%, respectively, and the prevalence of mild and moderate or severe GAD was 14.0% and 2.4%, respectively. Among women, in the multivariable model, poor self-rated health status, genital discharge, barriers to access health care, having two or more control issues with their husband or partner, experiencing one, or two or more forms of emotional violence, and exposure to two or three types of intimate partner violence were positively associated with MDD. Being widowed, divorced or separated, poor self-rated health status, genital discharge, barriers to access health care, having two or more control issues with their husband or partner, experiencing two or more forms of emotional violence, and exposure to two or three types of intimate partner violence were positively associated with GAD. Among men, poor self-rated health status, current tobacco use, genital sore or ulcer, sons and/or daughters had died, younger age and never internet use were positively associated with MDD, and being widowed, divorced or separated, poor self-rated health status, younger age and sons and/or daughters had died were positively associated with GAD. Low rates and several associated factors of MDD and GAD were found in Nepal.

Antidepressants available in Japan for older people with major depressive disorder: A systematic review and meta-analysis.

To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis of double-blind, randomized, placebo-controlled trials of available antidepressants in Japan for older adults with MDD. Outcome measures included response rate (primary), improvement in depressive symptom scale score, remission rate, all-cause discontinuation, discontinuation due to adverse events, and at least one adverse event. A random-effects model was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (95% CI). Nine double-blind, randomized, placebo-controlled trials (n = 2145) were identified. No study has been conducted in Japan. Our meta-analysis included the following antidepressants: duloxetine, escitalopram, imipramine, sertraline, venlafaxine, and vortioxetine. Antidepressants have significantly higher response rates than placebo (RR [95% CI] = 1.38 [1.04, 1.83], p = 0.02). Antidepressants outperformed placebo in terms of improving depressive symptom scale score (SMD [95% CI] = -0.62 [-0.92, -0.33], p < 0.0001). However, antidepressants were associated with a higher discontinuation rate due to adverse events (RR [95% CI] = 1.94 [1.30, 2.88], p = 0.001) and a higher incidence of at least one adverse event (RR [95% CI] = 1.11 [1.02, 1.21], p = 0.02) compared to placebo. The groups did not differ significantly in terms of remission rate or all-cause discontinuation. Our meta-analysis concluded that treatment with antidepressants available in Japan is only weakly recommended for moderate to severe MDD in older adults.

Investigation of Irisin Levels in Patients with Major Depressive Disorder

Objective: Major depressive disorder (MDD) is a common psychiatric disorder. Irisin, produced by proteolysis of FNDC5, is thought to be an exercise-induced hormone that may play a critical role in inducing antidepressant-like effects. Our study aimed to investigate the relationship between irisin and newly diagnosed MDD patients. Methods: This cross-sectional study included 85 first-time diagnosed MDD patients and 81 healthy controls. Patients were diagnosed with MDD using the Structured Clinical Interview Questionnaire for DSM-IV Axis I and II Disorders (SCID-I, II) and the Hamilton Depression Scale (HAM-D). After an overnight fast, 5 ml of peripheral blood was drawn and serum irisin levels were measured. Results: When the effects of age and gender variables were controlled, no statistically significant difference in irisin levels was found between the groups. (F=1.832, p=0.178). When the effects of age, gender and body mass index variables were controlled and a partial correlation was made between irisin and HAMD scores, a significant negative correlation was found between irisin and HAMD scores (p&lt;0.001, r=-0.523). The correlation analysis showed a statistically significant negative relationship between age and irisin levels (p=0.008, r=-0.205). However, when the effects of other variables were controlled and a partial correlation was made, no statistically significant relationship was found (p=0.610, r=-0.207). Conclusion: Our results indicate that irisin levels are associated with the severity of depression. Further studies are needed on the use of irisin as a potential biomarker for predicting clinical course and treatment response in patients with severe MDD.

Efficacy and safety of semaglutide 2.4 mg according to antidepressant use at baseline: A post hoc subgroup analysis.

To explore the efficacy and safety of semaglutide 2.4 mg in people with overweight/obesity who were also being treated with antidepressants (ADs). Across the Semaglutide Treatment Effect for People with obesity (STEP) 1-3 and 5 trials, adults with overweight/obesity and type 2 diabetes (STEP 2 only) were enrolled. People with severe major depressive disorder within 2 years prior to screening or with a patient health questionnaire-9 score ≥15 at screening were excluded. Participants were categorized into subgroups according to baseline AD status (on/off ADs) in this post hoc exploratory analysis of the STEP trials. Of 3683 participants randomized, 539 were on ADs at baseline. Mean body weight change from baseline to week 68 was greater for semaglutide versus placebo, regardless of baseline AD use. In STEP 1, for participants on ADs at baseline, mean change from baseline was -15.7% with semaglutide versus -0.2% with placebo and -14.7% versus -2.8% for those not on ADs at baseline. Similar patterns were seen in STEP 2, 3, and 5. The prevalence of adverse events (AEs) was generally similar between semaglutide and placebo in participants on ADs at baseline. In adults with overweight/obesity, semaglutide provided clinically meaningful weight loss regardless of baseline AD use, with an AE profile consistent with previous studies.

Treatment outcomes and cognitive function following electroconvulsive therapy in patients with severe depression

BACKGROUND Traditional treatments for major depressive disorder (MDD), including medication and therapy, often fail and have undesirable side effects. Electroconvulsive therapy (ECT) uses electrical currents to induce brief seizures in the brain, resulting in rapid and potent antidepressant effects. However, owing to misconceptions and controversies, ECT is not as widely used as it could and often faces stigmatization. AIM To evaluate the efficacy and safety of ECT compared to those of medication and/or therapy in patients with severe MDD. METHODS This prospective cohort study included 220 individuals with severe MDD who were divided into the ECT and non-ECT groups. The patients in the ECT group underwent bilateral ECT three times a wk until they either achieved remission or reached a maximum of 12 sessions. The non-ECT group received medication and/or therapy according to clinical guidelines for MDD. The primary outcome was the variation in the hamilton depression rating scale (HDRS) score from treatment/ECT initiation to week 12. In addition, patients’ quality of life, cognitive abilities, and biomarkers were measured throughout the study. RESULTS Although both groups showed significant improvements in their HDRS scores over time, the improvement was more pronounced in the ECT group than in the non-ECT group. Additionally, the ECT group exhibited a more substantial improvement in the quality of life and cognitive function than those of the non-ECT group. Compared with the non-ECT group, the ECT group exhibited evi-dently lower variations in the brain-derived neurotrophic factor (BDNF) and cytokine interleukin-6 (IL-6) levels. The side effects were generally mild and comparable between the two groups. ECT is safer and more potent than medication and/or therapy in mitigating depressive symptoms, enhancing well-being, and bolstering cognitive capabilities in individuals with severe MDD. ECT may also affect the levels of BDNF and IL-6, which are indicators of neuroplasticity and inflammation, respectively. CONCLUSION ECT has emerged as a potentially advantageous therapeutic approach for patients with MDD who are unresponsive to alternative treatments.

BRIDGE: A randomized trial of person-centered collaborative care for adults with serious mental illness (SMI) and newly diagnosed cancers.

216 Background: Individuals with SMI experience increased cancer mortality due to inequities in cancer care. Proactive psychiatry care may improve cancer care outcomes for patients with SMI, yet access to mental health care remains inadequate. The BRIDGE trial assessed the impact of person-centered collaborative care vs enhanced usual care (EUC) on cancer care disruptions for adults with SMI and newly diagnosed cancers. Methods: Eligible patients had SMI (schizophrenia spectrum, bipolar, or severe major depressive disorders) and potentially curable head/neck, lung, breast, or gastrointestinal cancers. Patients were randomized 1:1 to BRIDGE (person-centered collaborative care: proactive psychiatry consultation, linkage to a social work/navigator team, and co-management with oncology across care settings) or EUC (proactive identification at cancer diagnosis using an algorithm to inform the oncology team of the SMI diagnosis and patient of psychosocial resources). The primary outcome was clinically significant cancer care disruptions over 24 weeks (delays in treatment initiation, deviations from guideline-concordant care recommended/received, or interruptions in planned cancer treatment). Oncologists blinded to intervention arm determined the presence of disruptions (yes/no) using NCCN guidelines; discrepancies were resolved by a consensus panel. Secondary outcomes included psychiatric illness severity according to the Brief Psychiatric Rating Scale (BPRS), Clinical Global Severity (CGI), and depression/anxiety measures (Patient Health Questionnaire [PHQ] 9, Generalized Anxiety [GAD] 7) at 24 weeks. The rate of disruption was compared using Fisher’s exact test, and secondary outcomes were compared using ANCOVA and logistic regression. Results: From May 2019-December 2021,120 of 141 eligible patients enrolled in the trial. Participants had a mean age of 63 years, were 65% female, 87.5% reported White race, 52.5% had income &lt;25,000, 51.7% had Medicaid, 38.3% were on disability, 39.4% reported current smoking, and 49% reported past/current substance use disorder. Patients assigned to BRIDGE were significantly less likely to experience cancer care disruptions compared to those receiving EUC (17.2% vs 35.1%, p=.035). BRIDGE patients had significantly improved psychiatric illness severity and anxiety (BPRS: 31.91 vs 36.65, p=.02; CGI: 15% vs 25%, p=.02; GAD: 4.86 vs 6.86, p=.02) compared to EUC patients. Differences in PHQ were not significant (6.62 vs 7.72, p=.28). Conclusions: In this randomized trial of person-centered collaborative care for adults with SMI and cancer, the BRIDGE intervention led to significantly fewer disruptions in cancer care and improvement in psychiatric illness severity. Findings support the need for multi-site trials that include community settings to enhance generalizability. Clinical trial information: NCT03360695 .

Sertraline versus escitalopram in South Asians with moderate to severe major depressive disorder: (SOUTH-DEP) a double-blind, parallel, randomized controlled trial.

The study design included the double-blind, parallel, randomized controlled trial. The aim of this randomized controlled trial was to compare the efficacy and safety of sertraline and escitalopram in participants with moderate to severe major depressive disorder (MDD). The study was conducted in South Asian participants. A total of 744 participants with moderate to severe MDD were randomly assigned to receive either sertraline or escitalopram for 8 weeks. Drug dosages and titration schedules were based on the recommendations of the prescribing information for each product and according to the judgment of the clinicians involved in the study. The primary outcome measures were changes from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the clinical global impression (CGI) scale as well as the frequency of adverse events in both groups. Baseline MADRS scores in the escitalopram and sertraline groups were 28.2±0.47 (mean±SD) and 29.70±0.46 (mean±SD) respectively, and was no variability in the baseline assessments. Changes in MADRS as well as CGI scales at the end of the study were significant only for the sertraline group whereas they remained statistically nonsignificant for the escitalopram group. Results: The results of the study showed that sertraline was more efficacious than escitalopram in reducing depression rating scales such as MADRS and CGI, and that participants subjectively felt better regarding their symptoms in the sertraline group. Sertraline displays enhanced safety or tolerability than other groups of antidepressants, which frequently cause high levels of drowsiness, dizziness, blurred vision, and other undesirable effects. Adverse events were seen in both groups, but delayed ejaculation was the most frequent adverse event seen in both groups. However, a greater number of participants reported having nausea and insomnia in the sertraline group compared to the escitalopram group. Our study clearly highlights that there is a statistically significant difference in efficacy between sertraline and escitalopram at the doses used in our study. Sertraline was able to significantly lower the depression rating scales like MADRS and CGI in participants with moderate to severe MDD. Participants subjectively felt better regarding their symptoms in the sertraline group. The most frequent adverse event in both groups was delayed ejaculation. From an efficacy standpoint, sertraline was more efficacious than escitalopram. The study indicates that the prevalence of depressive disorders in South Asia is comparable to the global estimate, and Bangladesh and India has higher proportions of people with depressive disorders in South Asia. Additionally, females and older adults (75-79 years) have the highest burden of depressive disorders across all countries in the region. This study's limitation included the absence of a placebo arm. An additional limitation of the current study was the lack of an evaluation of inter-rater reliability and the research sample could not have been uniform in terms of the kind of depressive disorders and bipolarity.

Interventions promoting recovery from depression for patients transitioning from outpatient mental health services to primary care: Protocol for a scoping review.

Patients with severe Major Depressive Disorder (MDD) have an increasing risk of new psychiatric hospitalizations following each new episode of depression highlighting the recurrent nature of the disorder. Furthermore, patients are not fully recovered at the end of their treatment in outpatient mental health services, and residual symptoms of depression might explain why patients with MDD have a high risk of relapse. However, evidence of methods to promote recovery after discharge from outpatient mental health services is lacking. The proposed scoping review aims to systematically scope, map and identify the evidence and knowledge gaps on interventions that aims to promote recovery from MDD for patients transitioning from outpatient mental health services to primary care. The proposed scoping review will follow the latest methodological guidance by the Joanna Briggs Institute (JBI) in tandem with the Preferred Reporting Items for Systematic reviews and Meta-Analysis-extension for Scoping Reviews (PRISMA-ScR) checklist. The review is ongoing. Four electronic databases (Medline via PubMed, PsycINFO, CINAHL, and Sociological Abstracts) were systematically searched from 20 January 2022 till 29 March 2022 using keywords and text words. The review team consists of three independent screeners. Two screeners have completed the initial title and abstract screening for all studies retrieved by the search strategy. Currently, we are in the full text screening phase. Reference lists of included studies will be screened, and data will be independently extracted by the review team. Results will be analyzed qualitatively and quantitatively. The chosen methodology is based on the use of publicly available information and does not require ethical approval. Results will be published in an international peer reviewed scientific journal, at national and international conferences and shared with relevant authorities. A pre-print has been registered at the medRxiv preprint server for health sciences (doi.org/10.1101/2022.10.06.22280499).

Rumination symptoms in treatment-resistant major depressive disorder, and outcomes of repetitive Transcranial Magnetic Stimulation (rTMS) treatment

Rumination is a maladaptive style of regulating thoughts and emotions. It is a common symptom of Major Depressive Disorder (MDD), and more severe rumination is associated with poorer medication and psychotherapy treatment outcomes, particularly among women. It is unclear to what extent rumination may influence the outcomes of, or be responsive to, repetitive Transcranial Magnetic Stimulation (rTMS) treatment of MDD. We retrospectively examined data collected during rTMS treatment of 155 patients (age 42.52 ± 14.22, 79 female) with moderately severe treatment-resistant MDD. The severity of rumination and depression was assessed before and during a course of 30 sessions of measurement-based rTMS treatment using the Ruminative Responses Scale (RSS) and the Patient Health Questionnaire (PHQ-9), respectively. Relationships among baseline levels of rumination, depression, and treatment outcome were assessed using a series of repeated measures linear mixed effects models. Both depression and rumination symptoms significantly improved after treatment, but improvement in depression was not a significant mediator of rumination improvement. Higher baseline rumination (but not depression severity) was associated with poorer depression outcomes independently of depression severity. Female gender was a significant predictor of worse outcomes for all RRS subscales. Both depressive and ruminative symptoms in MDD improved following rTMS treatment. These improvements were correlated, but improvement in rumination was not fully explained by reduction in depressive symptoms. These findings suggest that while improvement in rumination and depression severity during rTMS treatment are correlated, they are partly independent processes. Future studies should examine whether rumination symptoms should be specifically targeted with different rTMS treatment parameters.

Major depressive disorder.

Major depressive disorder (MDD) is characterized by persistent depressed mood, loss of interest or pleasure in previously enjoyable activities, recurrent thoughts of death, and physical and cognitive symptoms. People with MDD can have reduced quality of life owing to the disorder itself as well as related medical comorbidities, social factors, and impaired functional outcomes. MDD is a complex disorder that cannot be fully explained by any one single established biological or environmental pathway. Instead, MDD seems to be caused by a combination of genetic, environmental, psychological and biological factors. Treatment for MDD commonlyinvolves pharmacological therapy with antidepressant medications, psychotherapy or a combination of both. In people with severe and/or treatment-resistant MDD, other biological therapies, such as electroconvulsive therapy, may also be offered.

Distorted thoughts as a mediator of depressive symptoms in patients with major depressive disorder: a longitudinal study

BackgroundDistorted thoughts are common in Major Depressive Disorder (MDD), and can impact patients’ perceptions of depression severity, and predict chronicity and treatment response. This study aimed to investigate whether distorted thoughts mediate depressive symptoms in MDD over a 6-month period.MethodThese are secondary results from a study that followed 119 patients diagnosed with moderate to severe MDD for 6 months. Diagnoses were confirmed by the Structured Interview for DSM-IV (SCID-CV). The analysis was composed of results from the Hamilton Depression Rating Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS), the second edition of the Beck Depression Inventory (BDI-II), and the Depression Thoughts Scale (DTS) collected at weeks 1, 8, 12 and 24.ResultsResults showed that the DTS mediated the relationship between depressive symptoms experienced approximately 3 months after starting antidepressant treatment.ConclusionCognitive distortions were linked as a mediator to depressive symptoms, highlighting the importance of early psychological interventions in patients with MDD who exhibit these distortions.Trial registrationNCT02268487.

Long Term Antidepressant Effects of Deep Brain Stimulation for Treatment Resistant Depression – A Research Protocol

Introduction: Individuals with treatment resistant depression (TRD) are those with severe major depressive disorder who fail to respond to conventional pharmacological treatment. As a result, novel technologies in the field of neuromodulation have been investigated to alleviate depressive symptoms in this population. One such neuromodulation therapy is deep brain stimulation (DBS), in which electrodes are neurosurgically implanted into target regions of the brain associated with depression, such as the subgenual anterior cingulate cortex (sgACC). While previous studies have explored the use of DBS as a therapy for TRD, few studies with adequate statistical power have explored the sustained antidepressant effects of DBS when targeting the sgACC of the brain. Methods: This study aims to explore the long-term effects in DBS patients for TRD by measuring changes in cerebral blood flow and cerebral metabolic rate in the sgACC, and its correlation to changes in self-reported depressive symptoms. Forty-five participants will be enlisted into this study. Psychometric evaluation and positron-emission topography imaging will be conducted prior to neurosurgery. Electrodes will be implanted into the sgACC, with extension wires attaching the electrodes to the internal pulse generator. In the six-week blinded phase, progressive increases in stimulation will be administered within the blinded group and sham stimulation in controls. The three-month open label phase will administer the same degree of high-frequency biphasic stimulation to the control and blinded groups and assess depression scores, neuroimaging, and adverse events. After cessation of active stimulation, a one-year, three-year, seven-year, and ten-year follow-up will monitor changes in antidepressant effects of DBS using simple linear contrasts and paired-sample t-tests. Expected Results: This study expects to find a sustained antidepressant response marked by decreases in sgACC metabolism and cerebral blood flow, and a reduction in self-report depression scores. Discussion: The use of DBS shows promise as a successful treatment intervention with sustained long-term effects for individuals with TRD. Additional secondary outcomes to be expected are improved quality of life and health behaviours. Conclusion: Though minor fluctuations are expected due to the presence of comorbidities, this study expects to showcase the long-term efficacy of deep brain stimulation for treatment resistant depression.

The Economic Burden of Adults with Major Depressive Disorder in the United States (2019).

Previous societal burden estimations for major depressive disorder (MDD) often fail to account for several hidden cost components. This study provides a comprehensive evaluation of societal costs for adults with MDD in the United States (USA) in 2019. The potential impact of a more effective, rapid-acting MDD therapy vs standard of care on the economic burden of MDD was estimated to illustrate the utility of such a framework in evaluating new interventions. This study used a prevalence-based human capital approach. Incremental costs (2019 US dollars) per individual with MDD were derived from national survey inputs and published literature and included incremental healthcare costs and indirect costs. For each cost component, the societal costs were extrapolated by multiplying the per-patient costs by the number of individuals with MDD. The impact of a more effective, rapid-acting novel therapy on the economic burden of MDD was then simulated on the basis of these inputs. In 2019, the number of adults with MDD in the USA was estimated at 19.8 million (62.7% female; 32.9% severe MDD), and the incremental societal economic burden of MDD was estimated at $333.7 billion ($382.4 billion in 2023 US dollars), or $16,854 per adult with MDD. The primary cost drivers were healthcare costs ($127.3 billion; 38.1%), household-related costs ($80.1 billion; 24.0%), presenteeism ($43.3 billion; 13.0%), and absenteeism ($38.4 billion; 11.5%). In the simulated scenario, a hypothetical novel therapy with a 50.0% early response rate was associated with a 7.7% reduction in the economic burden of MDD relative to standard of care over 12months. The economic burden of MDD is substantial and extends beyond healthcare costs, underscoring the impact of MDD across multiple aspects of life. Such a broad societal perspective should be considered in assessing the impact of the advent of effective, rapid-acting MDD therapies.