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

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

Knowledge and Behavior of Primary Care Physicians Regarding Utilization of Standardized Tools in Screening and Assessment of Anxiety, Depression, and Mood Disorders at a Large Integrated Health System.

INTRODUCTION: Standardized screening, objective evaluation, and management of behavioral health conditions are major challenges in primary care. The Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire (PHQ-9), and Mood Disorder Questionnaire (MDQ) provide standardized screening and symptom management tools for generalized anxiety disorder (GAD), major depressive disorder (MDD), and Mood Disorders (MD), respectively. This study explores family physicians' knowledge, attitudes, and practices regarding the utilization of GAD-7, PHQ-9, and MDQ in outpatient primary care offices. METHODS: The study method was a cross-sectional electronic and paper survey utilizing a self-administered questionnaire that assessed primary care physicians' demographics, knowledge, attitudes, and practices in rural and urban outpatient clinical settings regarding GAD-7, PHQ-9, and MDQ. Statistical software SAS 9.4 was used for descriptive and Chi-Square statistics. RESULTS: Out of 320 total participants,145 responded (45.3%). Responding family physicians demonstrated a high level of familiarity with the GAD-7 (97.9%), PHQ-9 (97.9%), and MDQ (81.3%) assessment tools. However, the reported utilization rates were relatively lower than knowledge, with 62.7%, 73.1%, and 31.9% extremely likely or likely to utilize the GAD-7, PHQ-9, and MDQ as screening and monitoring tools, respectively. Less than a quarter of the total respondents use the objective score for the future management of GAD, with significantly more residents utilizing the score for GAD-7 compared to attendings (P < .05). There was no statistical significance difference between residents and attendings for the objective evaluation of Major Depressive Disorder (P = .26) and Mood Disorders (P = .05). CONCLUSIONS: Despite being knowledgeable of the utility of GAD-7, PHQ-9, and MDQ, the primary care physicians in a large integrated health system in Central Pennsylvania and Northern Maryland report inconsistent utilization in their practice. Further studies are needed to determine the underlying factors contributing to the suboptimal usage of these screening tools and ways to increase it.

Omega-3 polyunsaturated fatty acids supplementation improves memory in first-diagnosed, drug-naïve patients with depression: Secondary analysis of data from a randomized controlled trial.

INTRODUCTION: Cognitive impairments are found in most patients with major depressive disorder (MDD). It is believed that low Omega-3 polyunsaturated fatty acids (n-3 PUFAs) level raise the risk of anxiety, depressive symptoms and cognition dysfunction. Since our previous research has found n-3 PUFAs supplementation improves anxiety in MDD, this study was to further explore the effectiveness on cognitive impairment among depressed patients. METHODS: A total of 72 venlafaxine treated outpatients with first-diagnosed, drug-naïve depression were enrolled. Daily n-3 PUFAs supplementation (2.4 g/d of fish oil, including 1440 mg eicosapentaenoic acid and 960 mg of docosahexaenoic acid) or placebo was used for 12 weeks. Cognitive function, measure by repeatable battery for the assessment of neuropsychological status ([RBANS]) scores, was compared over time. RESULTS: Immediate memory, delayed memory and RBANS total scores were significant higher in both groups at week 4 and week 12 compared with baseline. Both groups exhibited improvement on attention scores at week 12. No significant differences were observed comparing n-3 PUFAs with placebo groups in the improvement of total RBANS scores and other subscales except in the change of immediate memory at both week 4 and week 12 (p < 0.05). LIMITATIONS: Sample size was relatively low. Moreover, multiple ethnic populations and the income of patients should be considered. Lastly, we used raw scores instead of the standardized scores of RBANS. CONCLUSION: N-3 PUFAs supplementation yielded a small but statistically significant improvement on immediate memory in first-diagnosed, drug-naïve depressed patients. While, antidepressant treatment resulted in significant improvement of cognitive function.

Increased functional connectivity between the midbrain and frontal cortex following bright light therapy in subthreshold depression: A randomized clinical trial.

The underlying mechanisms of bright light therapy (BLT) in the prevention of individuals with subthreshold depression symptoms are yet to be elucidated. The goal of the study was to assess the correlation between midbrain monoamine-producing nuclei treatment-related functional connectivity (FC) changes and depressive symptom improvements in subthreshold depression. This double-blind, randomized, placebo-controlled clinical trial was conducted between March 2020 and June 2022. A total of 74 young adults with subthreshold depression were randomly assigned to receive 8-week BLT (N = 38) or placebo (N = 36). Depression severity was measured using the Hamilton Depression Rating Scale (HDRS). The participants underwent resting-state functional magnetic resonance imaging at baseline and after treatment. The dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and habenula seed-based whole-brain FC were analyzed. A multivariate regression model examined whether baseline brain FC was associated with changes in scores on HDRS during BLT treatment. BLT group displayed significantly decreased HDRS scores from pre- to posttreatment compared to the placebo group. BLT increased the FC between the DRN and medial prefrontal cortex (mPFC) and between the left VTA and right superior frontal gyrus (SFG). Altered VTA-SFG connectivity was associated with HDRS changes in the BLT group. Moreover, the baseline FC between DRN and mPFC could predict HDRS changes in BLT. These results suggested that BLT improves depressive symptoms and increases midbrain monoamine-producing nuclei and frontal cortex connectivity in subthreshold depression, which raises the possibility that pretreatment FC of DRN-mPFC could be used as a biomarker for improved BLT treatment in depression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Prospectively assessed summer mood status in major depression, recurrent with seasonal pattern: Evidence for SAD's construct validity.

OBJECTIVE: Seasonal patterns are often undetectable in population-based depression studies, calling into question the existence of winter seasonal affective disorder (SAD). If SAD has construct validity, individuals with SAD should show spontaneous depression remission in the summer. Data are sparse on prospectively assessed summer mood status in confirmed SAD patients. METHOD: We conducted prospective summer followup of community adults who, the winter before, were diagnosed with Major Depression, Recurrent with Seasonal Pattern on the Structured Clinical Interview for DSM-IV Axis I Disorders, developed a current SAD episode on the Structured Interview Guide for the Hamilton Rating Scale for Depression-Seasonal Affective Disorder Version (SIGH-SAD), and enrolled in a clinical trial comparing group cognitive-behavioral therapy for SAD and light therapy. In July/August after treatment, 143/153 (93.5 %) participants provided data on the SIGH-SAD, the Beck Depression Inventory-Second Edition, and the Longitudinal Interval Followup Evaluation (LIFE). RESULTS: Summer mean depression scores were in the normal range, with the substantial majority in remission across different measures. On the LIFE, 113/143 (79.0 %) experienced complete summer remission, 19/143 (13.3 %) experienced partial summer remission, and 11/143 (7.7 %) had major depression in the summer. Depression scores were significantly lower at summer than post-treatment in both treatments, indicating incomplete treatment response. LIMITATIONS: This was a single-site study with a relatively homogeneous sample. CONCLUSIONS: Supporting construct validity for SAD, the substantial majority experienced complete summer remission, with a minority in partial remission and a very small minority in episode. Both treatments left residual symptoms at treatment endpoint compared to summer.

Machine Learning Prediction of Quality of Life Improvement During Antidepressant Treatment of Patients With Major Depressive Disorder: A STAR*D and CAN-BIND-1 Report.

Background: Quality of life (QoL) is an important patient-centric outcome to evaluate in treatment of major depressive disorder (MDD). This work sought to investigate the performance of several machine learning methods to predict a return to normative QoL in patients with MDD after antidepressant treatment.Methods: Several binary classification algorithms were trained on data from the first 2 weeks of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (n = 651, conducted from 2001 to 2006) to predict week 9 normative QoL (score ≥ 67, based on a community normative sample, on the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form [Q-LES-Q-SF]) after treatment with citalopram. Internal validation was performed using a STAR*D holdout dataset, and external validation was performed using the Canadian Biomarker Integration Network in Depression-1 (CAN-BIND-1) dataset (n = 175, study conducted from 2012 to 2017) after treatment with escitalopram. Feature importance was calculated using SHapley Additive exPlanations (SHAP).Results: Random Forest performed most consistently on internal and external validation, with balanced accuracy (area under the receiver operator curve) of 71% (0.81) on the STAR*D dataset and 69% (0.75) on the CAN-BIND-1 dataset. Random Forest Classifiers trained on Q-LES-Q-SF and Quick Inventory of Depressive Symptomatology-Self-Rated variables had similar performance on both internal and external validation. Important predictive variables came from psychological, physical, and socioeconomic domains.Conclusions: Machine learning can predict normative QoL after antidepressant treatment with similar performance to that of prior work predicting depressive symptom response and remission. These results suggest that QoL outcomes in MDD patients can be predicted with simple patient-rated measures and provide a foundation to further improve performance and demonstrate clinical utility.Trial Registration: ClinicalTrials.gov identifiers NCT00021528 and NCT01655706.

Developing Advanced AI Ecosystems to Enhance Diagnosis and Care for Patients with Depression.

Major Depressive Disorder (MDD) has a significant impact on the daily lives of those affected. This concept paper presents a project that aims at addressing MDD challenges through innovative therapy systems. The project consists of two use cases: a multimodal neurofeedback (NFB) therapy and an AI-based virtual therapy assistant (VTA). The multimodal NFB integrates EEG and fNIRS to comprehensively assess brain function. The goal is to develop an open-source NFB toolbox for EEG-fNIRS integration, augmented by the VTA for optimized efficacy. The VTA will be able to collect behavioral data, provide personalized feedback and support MDD patients in their daily lives. This project aims to improve depression treatment by bringing together digital therapy, AI and mobile apps to potentially improve outcomes and accessibility for people living with depression.

The role of the communicated treatment rationale on treatment outcome: study protocol for a randomized controlled trial.

BACKGROUND: Placebo effects are a well-established phenomenon in the treatment of depression. However, the mechanism underlying these effects are not fully understood. Treatment expectations are considered one explanation for why placebos work. Treatment expectations are likely to be affected by clinician-patient interactions. This study aims to investigate the role of the communicated treatment rationale in modulating treatment expectations and its effects on the treatment outcomes of a pharmacological and a psychological active placebo intervention for depression. In this study, treatment expectations are modulated by presenting illness models that are either congruent or incongruent with the treatment intervention that follows. METHODS: This 2 × 2 randomized controlled trial will involve patients with major depression. Participants will either receive a biological or a psychological illness model from a clinician. Following this, they are randomly assigned to receive either a pharmacological or a psychological active placebo intervention. The illness model and the treatment are either congruent or incongruent with each other, resulting in four groups. In addition, a natural course control group will be included. DISCUSSION: This study will provide insights into the mechanism of expectation modulation in active placebo treatments for major depression. The results may provide insights for clinicians to improve their communication with patients by focusing on treatment expectations. By identifying the factors that contribute to placebo effects, this study has the potential to improve the effectiveness of existing depression treatments and reduce the burden of this highly prevalent mental health condition. TRIAL REGISTRATION: This trial has been registered prospectively at ClinicalTrials.gov under the identifier: NCT04719663. Registered on January 22, 2021.

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

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Main Outcomes and Measures: The differences in the occurrence of disruptive life events among patients with BPI or schizophrenia and their comparison groups. Results: 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. Conclusions and Relevance: 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.

Effect of 25-hydroxyvitamin D levels on the internalising dimension as a transdiagnostic risk factor: Mendelian randomisation study.

BACKGROUND: Observational studies indicate a relationship between vitamin D (25-hydroxyvitamin D; 25OHD) deficiency and the development of internalising disorders, especially depression. However, causal inference approaches (e.g. Mendelian randomisation) did not confirm this relationship. Findings from biobehavioural research suggests that new insights are revealed when focusing on psychopathological dimensions rather than on clinical diagnoses. This study provides further evidence on the relationship between 25OHD and the internalising dimension. AIMS: This investigation aimed at examining the causality between 25OHD and internalising disorders including a common internalising factor. METHOD: We performed a two-sample Mendelian randomisation using genome-wide association study (GWAS) summary data for 25OHD (417 580 participants), major depressive disorder (45 591 cases; 97 674 controls), anxiety (5580 cases; 11 730 controls), post-traumatic stress disorder (12 080 cases; 33 446 controls), panic disorder (2248 cases; 7992 controls), obsessive-compulsive disorder (2688 cases; 7037 controls) and anorexia nervosa (16 992 cases; 55 525 controls). GWAS results of the internalising phenotypes were combined to a common factor representing the internalising dimension. We performed several complementary analyses to reduce the risk of pleiotropy and used a second 25OHD GWAS for replication. RESULTS: We found no causal relationship between 25OHD and any of the internalising phenotypes studied, nor with the common internalising factor. Several pleiotropy-robust methods corroborated the null association. CONCLUSIONS: Following current transdiagnostic approaches to investigate mental disorders, our results focused on the shared genetic basis between different internalising phenotypes and provide no evidence for an effect of 25OHD on the internalising dimension.

Eye movement desensitization and processing for adolescents with major depressive disorder: study protocol for a multi-site randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is one of the most common mental disorders in adolescence carrying a serious risk of adverse development later in life. Extant treatments are limited in effectiveness and have high drop-out and relapse rates. A body of literature has been published on the association between distressing/ traumatic experiences and development and maintenance of MDD, but the effectiveness of a trauma-focused treatment approach for MDD has hardly been studied. This study aims to determine the effectiveness of eye movement desensitization and reprocessing (EMDR) therapy as stand-alone intervention in adolescents diagnosed with MDD. METHODS: This study will be a randomized controlled trial with two conditions: (1) EMDR treatment (6 sessions) and (2) waiting list condition (WL: 6 weeks, followed by EMDR treatment). First, participants receive a baseline measure after which they will be randomized. Participants will be assessed post-intervention after which the WL participants will also receive six EMDR sessions. Follow-up assessments will be conducted at 3 and 6 months follow-up. STUDY POPULATION: In total, 64 adolescents (aged 12-18) diagnosed with a major depressive disorder (DSM-5) and identified memories of at least one distressing or traumatic event related to the depressive symptomatology will be included. Main study parameters/endpoints: Primary outcome variables will be the percentage of patients meeting criteria for MDD classification, and level of depressive symptoms. Secondary outcome measures include symptoms of PTSD, anxiety, and general social-emotional problems. At baseline, family functioning and having experienced emotional abuse or neglect will be assessed to explore whether these factors predict post-treatment outcome. DISCUSSION: With the present study, we aim to investigate whether EMDR as a trauma-focussed brief intervention may be effective for adolescents with a primary diagnosis of MDD. EMDR has been proven an effective treatment for traumatic memories in other disorders. It is hypothesized that traumatic memories play a role in the onset and maintenance of depressive disorders. Particularly in adolescence, early treatment of these traumatic memories is warranted to prevent a more chronic or recurrent course of the disorder. TRIAL REGISTRATION: International Clinical Trial Registry Platform (ICTRP): NL9008 (30-10-2020).

Neurophysiological markers of depression detection and severity prediction in first-episode major depressive disorder.

OBJECTIVE: Deviant γ auditory steady-state responses (γ-ASSRs) have been documented in some psychiatric disorders. Nevertheless, the role of γ-ASSR in drug-naïve first-episode major depressive disorder (FEMD) patients remains equivocal. This study aimed to examine whether γ-ASSRs are impaired in FEMD patients and predict depression severity. METHODS: Cortical reactivity was assessed in a cohort of 28 FEMD patients relative to 30 healthy control (HC) subjects during an ASSR paradigm randomly presented at 40 and 60 Hz. Event-related spectral perturbation and inter-trial phase coherence (ITC) were calculated to quantify dynamic changes of the γ-ASSR. Receiver operating characteristic curve combined with binary logistic regression were then employed to summarize ASSR variables that maximally differentiated groups. RESULTS: FEMD patients exhibited significantly inferior 40 Hz-ASSR-ITC in the right hemisphere versus HC subjects (p = 0.007), along with attenuated θ-ITC that reflected underlying impairments in θ responses during 60 Hz clicks (p < 0.05). Moreover, the 40 Hz-ASSR-ITC and θ-ITC in the right hemisphere can be used as a combinational marker to detect FEMD patients with 84.0 % sensitivity and 81.5 % specificity (area under the curve was 0.868, 95 % CI: 0.768-0.968). Pearson's correlations between the depression severity and ASSR variables were further conducted. The symptom severity of FEMD patients was negatively correlated with 60 Hz-ASSR-ITC in the midline and right hemisphere, possibly indicating that depression severity mediated high γ neural synchrony. CONCLUSIONS: Our findings provide critical insight into the pathological mechanism of FEMD, suggesting first that 40 Hz-ASSR-ITC and θ-ITC in right hemisphere constitute potential neurophysiological markers for early depression detection, and second, that high γ entrainment deficits may contribute to underlying symptom severity in FEMD patients.

Zuranolone and its role in treating major depressive disorder: a narrative review.

Major Depressive Disorder (MDD) is a mood disorder classified as a persistent depressive mood and loss of interest lasting for more than two weeks and accompanied by a list of symptoms outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic criteria. MDD affects approximately 264 million people worldwide and is the most prevailing form of neuropsychiatric disorder. Owing to the probable hypothesized pathophysiology of MDD being an outcome of abnormalities in the amino acid neurotransmitter system, including glutamate (the primary excitatory neurotransmitter) and γ-aminobutyric acid (GABA), SAGE-217 (Zuranolone) is being evaluated as a possible therapeutic treatment for MDD. Zuranolone is a synthetic, neuroactive steroid (NAS) and positive allosteric modulator (PMA) of GABAA receptors, regulating both synaptic and extra-synaptic release of GABA. It is administered as a once-daily oral dose for 2 weeks due to its low-moderate clearance. A change in total HAM-D score from baseline was the primary end-point of all the trials. A phase II trial conducted to evaluate the efficacy and safety of Zuranolone (30 mg, once-daily dose), described a significant reduction in total HAM-D score at day 14 and reported the drug to be well tolerated with headache, dizziness, nausea, and somnolence as the most common adverse events (AE). Additional phase III trials were also conducted to evaluate similar outcomes, the interim topline results of which have been released. Consequently, this article attempts to briefly analyze the pharmacology of Zuranolone, review the available clinical data and outcomes regarding its use, and evaluate its place as a prospective novel therapy in the effective management of MDD.

A randomised controlled trial to investigate the clinical effectiveness and cost effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) for depressed non-responders to Increasing Access to Psychological Therapies (IAPT) high-intensity therapies: study protocol.

BACKGROUND: Major depression represents a pressing challenge for health care. In England, Increasing Access to Psychological Therapies (IAPT) services provide evidence-based psychological therapies in a stepped-care approach to patients with depression. While introduction of these services has successfully increased access to therapy, estimates suggest that about 50% of depressed patients who have come to the end of the IAPT pathway still show significant levels of symptoms. This study will investigate whether Mindfulness-Based Cognitive Therapy (MBCT), a group intervention combining training in mindfulness meditation and elements from cognitive therapy, can have beneficial effects in depressed patients who have not responded to high-intensity therapy in IAPT. It will seek to establish the effectiveness and cost-effectiveness of MBCT as compared to the treatment these patients would usually receive. METHODS: In a 2-arm randomised controlled trial, patients who currently meet the criteria for major depressive disorder and who have not sufficiently responded to at least 12 sessions of IAPT high-intensity therapy will be allocated, at a ratio of 1:1, to receive either MBCT (in addition to treatment as usual [TAU]) or continue with TAU only. Assessments will take place at baseline, 10 weeks and 34 weeks post-randomisation. The primary outcome will be reduction in depression symptomatology 34 weeks post-randomisation as assessed using the Public Health Questionnaire-9 (PHQ-9). Secondary outcomes will include depressive symptomatology at 10 weeks post-randomisation and other clinical outcomes measured at 10-week and 34-week follow-up, along with a series of binarised outcomes to indicate clinically significant and reliable change. Evaluations of cost-effectiveness will be based on assessments of service use costs collected using the Adult Service Use Schedule and health utilities derived from the EQ-5D. DISCUSSION: This trial will add to the evidence base for the use of MBCT in depressed treatment non-responders. It will constitute the first trial to test MBCT following non-response to psychological therapy, with results providing a direct estimate of efficacy within the IAPT pathway. As such, its results will offer an important basis for decisions regarding the adoption of MBCT for non-responders within IAPT. TRIAL REGISTRATION: ClinicalTrials.gov NCT05236959. Registered on 11 February 2022. ISRCTN 17755571. Registered on 2 February 2021.

An Insight through Various Models being used for Assessment of Depression and its Management at Primary Level in Current Scenario.

AIM: The main aim of present study to assess depression and various neurotransmitters involved in it with their evaluating models. BACKGROUND: Depression is a common ailment that can be recurrent or even become chronic. According to the National Service Framework for Mental Health (released in 1999 by the Department of Health), people with depression should continue to be treated primarily in primary care settings. Despite mounting evidence that general practitioners could do a better job of detecting and treating depression, little research has been done on the perspectives of general practitioners who treat patients who are depressed. Depression (major depressive disorder) is a widespread and significant medical condition that has a negative impact on feeling, thinking, and behaviour. OBJECTIVES: The primary goal of this study was to gather data on depression, as well as to discuss several methods for evaluating antidepressant drug response based on physical activities and neurotransmitters. METHODS: Antidepressant activity of various medications can be tested using two different types of studies, including in vivo and in vitro, according to the review. RESULTS: Depression is characterized by a persistent sense of sadness, insomnia, lack of concentration, slowness in activity, restlessness, social isolation and a loss of interest that prevents you from doing normal things. There are several types of depression, with symptoms ranging from mild to severe. Depression is caused by a combination of factors and conditions, rather than a single factor. Major depression is a mental condition marked by feelings of inadequacy, hopelessness, decreased activity, sadness and mood swings, which seriously disrupt and negatively affect a person's life, sometimes, leading to suicidal thoughts. The quest for a better understanding of the causes of depression and the development of more effective treatments is critical. According to clinical and preclinical research, stress appears to be a crucial mediator in the pathophysiology of depression. Using experimental models, depression may be assessed based on several physical parameters such as locomotor activity, rearing, defecation, and the number of centre square entries (in vivo and in vitro). Biological parameters may also be used to locate it. CONCLUSION: Unhappiness and loss of interest in previously enjoyed activities are the symptoms of depression. It can cause emotional and physical problems, as well as a decrease in the ability to function together at work and at home. Finally it has been concluded that various neurotransmitters are involved in depression at the synaptic cleft which can be controlled using various synthetic and herbal drugs through in vitro and in vivo evaluating models.

Efficacy of eicosapentaenoic acid in inflammatory depression: study protocol for a match-mismatch trial.

BACKGROUND: Most antidepressant treatment studies have included patients strictly based on the Diagnostic and Statistical Manual of Mental Disorders definition of Major Depressive Disorder (MDD). Given the heterogeneity of MDD, this approach may have obscured inter-patient differences and hampered the development of novel and targeted treatment strategies. An alternative strategy is ​​to use biomarkers to delineate endophenotypes of depression and test if these can be targeted via mechanism-based interventions. Several lines of evidence suggest that "inflammatory depression" is a clinically meaningful subtype of depression. Preliminary data indicate that omega-3 fatty acids, with their anti-inflammatory and neuroprotective properties, may be efficacious in this subtype of depression, and this study aims to test this hypothesis. METHOD: We conduct a match-mismatch-trial to test if add-on omega-3 fatty acid eicosapentaenoic acid (EPA) reduces depressive symptoms in patients with MDD and systemic low-grade inflammation. MDD patients on a stable antidepressant treatment are stratified at baseline on high sensitivity-C-reactive protein (hs-CRP) levels to a high-inflammation group (hs-CRP ≥ 3 mg/L) or a low-inflammation group (hs-CRP < 3 mg/L). Both groups receive add-on EPA (2 g per day) for 8 weeks with three study visits, all including blood draws. Patients and raters are blind to inflammation status. Primary outcome measure is change in Hamilton Depression Rating Scale score between baseline and week 8. We hypothesize that the inflammation group has a superior antidepressant response to EPA compared to the non-inflammation group. Secondary outcomes include a composite score of "inflammatory depressive symptoms", quality of life, anxiety, anhedonia, sleep disturbances, fatigue, cognitive performance and change in biomarkers relating to inflammation, oxidative stress, metabolomics and cellular aging. DISCUSSION: In this study we will, for the first time using a match-mismatch trial design, test if omega-3 is an efficacious treatment for inflammatory depression. If our study is successful, it could add to the field of precision psychiatry. TRIAL REGISTRATION: This trial was registered May 8, 2017 on clinicaltrials.gov under the reference number NCT03143075.

Adjunctive Bright Light Therapy for Non-Seasonal Major Depressive Disorder: A Randomized Controlled Trial.

This double-blind, randomized controlled trial assessed bright light therapy (BLT) augmentation efficacy compared with placebo light in treating non-seasonal major depressive disorder. The study participants belonged to a subtropical area (24.5°-25.5°N) with extensive daylight and included outpatients who had received stable dosages and various regimens of antidepressive agents for 4 weeks before enrollment. The outcomes were the 17-item Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale, and Patient Health Questionnaire-9, which were assessed at weeks 1, 2, and 4. A total of 43 participants (mean age 45 years, ranging from 22-81) were randomized into the BLT [n = 22] and placebo light groups [n = 21]. After a 4-week administration of morning light therapy (30 min/day), depressive symptoms did not reduce significantly, which might be due to the small sample size. Nonetheless, this study had some strengths because it was conducted in warmer climates, unlike other studies, and examined diverse Asians with depression. Our findings suggest that several factors, such as poor drug response, different antidepressive regimens, duration of BLT, and daylength variability (i.e., natural daylight in the environment) may influence the utility of add-on BLT. Researchers may consider these important factors for future non-seasonal depression studies in subtropical environments.

Omega-3 Fatty Acids for Major Depressive Disorder With High Inflammation: A Randomized Dose-Finding Clinical Trial.

Objective: This study compared the impact of 3 eicosapentaenoic acid (EPA) doses versus placebo on inflammatory biomarkers and depressive symptoms.Methods: Sixty-one unmedicated adults (75% female; 45.5 ± 13.8 years) with DSM-5 major depressive disorder (MDD), body mass index > 25 kg/m2, and plasma high-sensitivity C-reactive protein (hs-CRP) ≥ 3.0 mg/L were randomly assigned to receive EPA 1 g/d, 2 g/d, or 4 g/d or placebo for 12 weeks. Prespecified endpoints were a ≥ 0.40 effect size decrease in plasma interleukin (IL)-6, peripheral blood mononuclear cell (PBMC) cytokines, and lipopolysaccharide-stimulated tumor necrosis factor (TNF) production. Response was defined as a ≥ 50% decrease of Inventory of Depressive Symptomatology, Clinician-Rated version (IDS-C30) scores. We compared outcomes for the 3 EPA doses versus placebo.Results: In 45 completers, only median PBMC TNF decreased at 2 g/d EPA. No EPA dose produced a ≥ 0.35 effect size reduction in plasma IL-6 or mitogen-stimulated TNF. Response rates for EPA 4 g/d were 64%, versus 40% for placebo (odds ratio [OR] = 2.63; Cohen d = 0.53), 38% for EPA 1 g/d, and 36% for EPA 2 g/d (all P > .05). EPA 4 g/d showed a significant correlation between percent decrease in plasma hs-CRP and IDS-C30 symptom reduction at 12 weeks (Spearman ρ = 0.691, P = .019).Conclusions: EPA 4 g/d demonstrated a medium effect size for response rates versus placebo. This dose may alleviate MDD in overweight individuals with elevated inflammatory markers, and change in hs-CRP may be correlated with clinical response.Trial Registration: ClinicalTrials.gov identifier: NCT02553915.

What does "staying well" after depression mean? Chronic low grade symptomatology after treatment for depression is common.

BACKGROUND: Persistent low grade depression symptoms are common and impairing in major depressive disorder (MDD) yet rarely reported in treatment follow-up studies (Judd et al., 1998a; Kennedy et al., 2004), suggesting that extant sustained remission rates may not reflect this important clinical feature. Furthermore, no long-term MDD treatment follow-up study has reported on quality of life ratings across functioning levels and years throughout the follow-up period, thus the severity, breadth, and persistence of functional impairment remain unclear. Accordingly, the current study evaluated the course of MDD with consideration of low grade depressive symptomatology and holistic features (e.g., quality of life). METHODS: We report long-term (9-14 years) follow-up data from individuals with MDD (N = 37) who underwent either Cognitive Therapy (CBT) or a course of selective serotonin reuptake inhibitor (SSRI) treatment. Patients provided retrospective reports of depression symptoms and quality of life in the years following treatment. RESULTS: Chronic depression symptoms (most often mild in severity) and decreased quality of life in multiple domains are frequent and suggest poorer sustained remission rates than previously observed in the literature. LIMITATIONS: Study limitations include small sample size recruited via convenience sampling methods. CONCLUSIONS: Findings support a conceptualization of depression recovery that entails persistent symptoms and vulnerabilities. Clinical recommendations are provided for discussing these features of depression recovery with patients.