Treatment Of Major Depressive Disorder Research Articles

Feasibility and preliminary efficacy of a theory-informed resistance exercise training single-arm intervention for major depression

Many adults with major depressive disorder (MDD) do not receive effective treatment. The potential benefits of resistance exercise training (RET) are understudied and may be mechanistically related to cerebral blood flow changes. PurposeTo assess feasibility, acceptability, and preliminary efficacy of a 16-week, theory-informed RET trial for the treatment of MDD and explore changes in cerebral blood flow. MethodsTen adults with DSM-5-diagnosed MDD were enrolled in a single-arm, 16-week, twice-weekly, whole-body RET intervention, consistent with US and WHO Physical Activity resistance exercise guidelines. To build intrinsic motivation and develop exercise-preparatory habits, motivators and commitment were discussed weekly. Screening, enrollment, and intervention attendance and compliance rates documented feasibility. At baseline and weeks 8, 16, and 26, current MDD diagnosis, clinician-rated, and self-reported symptom severity were evaluated along with cerebral blood flow which was assessed as middle cerebral artery (MCA) mean blood velocity, conductance, and pulsatility. ResultsNine participants completed the intervention. Strong feasibility and acceptability (98 % adherence, 93 % compliance, and 90 % retention) were found. MDD remission was reached by 8/9 participants at week 16 and persisted through week 26. There were large decreases in clinician-rated and self-reported symptoms at each assessment (Hedges’ g = 0.84–2.13). There were small-to-moderate increases in MCA velocity (g = 0.32–0.57) and conductance (g = 0.20–0.76) across time, with minimal changes in pulsatility (all g < 0.21). ConclusionsPreliminary results suggest RET for MDD treatment is feasible and plausibly efficacious, finding large antidepressant effects. A sufficiently powered randomized controlled trial to assess RET’s efficacy for treating MDD via potential cerebrovascular mechanisms is warranted.

Validation of the predictive value of BDNF -87 methylation for antidepressant treatment success in severely depressed patients—a randomized rater-blinded trial

BackgroundBrain-derived neurotrophic factor (BDNF) is essential for antidepressant treatment of major depressive disorder (MDD). Our repeated studies suggest that DNA methylation of a specific CpG site in the promoter region of exon IV of the BDNF gene (CpG -87) might be predictive of the efficacy of monoaminergic antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others. This trial aims to evaluate whether knowing the biomarker is non-inferior to treatment-as-usual (TAU) regarding remission rates while exhibiting significantly fewer adverse events (AE).MethodsThe BDNF trial is a prospective, randomized, rater-blinded diagnostic study conducted at five university hospitals in Germany. The study’s main hypothesis is that {1} knowing the methylation status of CpG -87 is non-inferior to not knowing it with respect to the remission rate while it significantly reduces the AE rate in patients experiencing at least one AE. The baseline assessment will occur upon hospitalization and a follow-up assessment on day 49 (± 3). A telephone follow-up will be conducted on day 70 (± 3). A total of 256 patients will be recruited, and methylation will be evaluated in all participants. They will be randomly assigned to either the marker or the TAU group. In the marker group, the methylation results will be shared with both the patient and their treating physician. In the TAU group, neither the patients nor their treating physicians will receive the marker status. The primary endpoints include the rate of patients achieving remission on day 49 (± 3), defined as a score of ≤ 10 on the Hamilton Depression Rating Scale (HDRS-24), and the occurrence of AE.Ethics and disseminationThe trial protocol has received approval from the Institutional Review Boards at the five participating universities. This trial holds significance in generating valuable data on a predictive biomarker for antidepressant treatment in patients with MDD. The findings will be shared with study participants, disseminated through professional society meetings, and published in peer-reviewed journals.Trial registrationGerman Clinical Trial Register DRKS00032503. Registered on 17 August 2023.

Ketamine's mechanism of action with an emphasis on neuroimmune regulation: can the complement system complement ketamine's antidepressant effects?

Over 300 million people worldwide suffer from major depressive disorder (MDD). Unfortunately, only 30-40% of patients with MDD achieve complete remission after conventional monoamine antidepressant therapy. In recent years, ketamine has revolutionized the treatment of MDD, with its rapid antidepressant effects manifesting within a few hours as opposed to weeks with conventional antidepressants. Many research endeavors have sought to identify ketamine's mechanism of action in mood disorders; while many studies have focused on ketamine's role in glutamatergic modulation, several studies have implicated its role in regulating neuroinflammation. The complement system is an important component of the innate immune response vital for synaptic plasticity. The complement system has been implicated in the pathophysiology of depression, and studies have shown increases in complement component 3 (C3) expression in the prefrontal cortex of suicidal individuals with depression. Given the role of the complement system in depression, ketamine and the complement system's abilities to modulate glutamatergic transmission, and our current understanding of ketamine's anti-inflammatory properties, there is reason to suspect a common link between the complement system and ketamine's mechanism of action. This review will summarize ketamine's anti- inflammatory roles in the periphery and central nervous system, with an emphasis on complement system regulation.

A Study of Prevalence of Major Depressive Disorder in Patients with Hypertension Attending a Medical Clinic

Abstract Objectives: In this study, we intended to assess the prevalence of major depressive disorder (MDD) in hypertensive patients who were attending a medical clinic. We also assessed various sociodemographic and other factors related to MDD in patients with hypertension. Methods: We did a cross-sectional study at the medical clinic of Pandit Dindayal Upadhyay Medical College and Hospital, Rajkot, Gujarat, India. The study included 256 hypertensive patients from September 2020 to May 2021. Patients were evaluated in detail for demographic and clinical histories and mental status examination. Diagnosis of MDD was made using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Their severity of MDD was assessed using the Hamilton Rating Scale for Depression (HAM-D). Results: Out of 256 hypertensive patients, 60 (23.43%) patients were found to have MDD. With HAM-D assessment, we found that out of 60 patients with MDD, 25 (9.76%) patients had mild depression, 21 (8.20%) moderate depression, 12 (4.68%) severe depression, and 2 (0.78%) very severe depression. A significant association existed between depression and sociodemographic variables of hypertensive patients in domicile (p &lt; 0.05), marital status (p &lt; 0.05), as well as educational level (p &lt; 0.05). A significant association was also found between depression and other medical comorbidities in hypertensive patients (p &lt; 0.05). Conclusion: Our study results showed that the prevalence of MDD was 23.43% among hypertensive patients who attended the medical clinic. Physicians and mental health professionals should work together to prompt diagnosis and timely referral to a psychiatric facility for proper evaluation and treatment of MDD among those hypertensive patients.

Working mechanisms of Cognitive Behavioral Therapy and Acceptance and Commitment Therapy: a dynamic network approach

IntroductionCognitive Behavioral Therapy (CBT) and Acceptance and Commitment Therapy (ACT) seem be similarly effective for the treatment of major depressive disorder (MDD). However, much remains unknown about the differences in underlying psychological mechanisms of change. Assessing dynamic change of depressive symptoms and treatment-specific psychological constructs over time may yield important insights.ObjectivesThe current study will be the first to compare dynamic symptom networks in randomized groups of two psychotherapies by using dynamic time-warp (DTW) analyses.MethodsWe reanalyzed data from a randomized controlled trail of 82 patients suffering from MDD. Three depressive symptom subscales (mood, sleep, appetite/weight) and three treatment-related constructs (dysfunctional attitudes, decentering, and experiential avoidance) were collected at 7 time-points before, during, after treatment, and at up to 12 months follow-up. The DTW-analysis modeled the temporal dynamics of depressive symptoms and treatment-related constructs within each individual after which the findings were aggregated on the group-level. Undirected and directed networks were constructed, of which the latter yielded in- and out-strength for each node, that were compared between treatment arms.ResultsNetworks based on symptom and construct dynamics markedly differed between treatment arms. Within the CBT-arm a decrease of experiential avoidance was related to a decrease in dysfunctional attitudes (d = 0.059, p = 0.008). Within the ACT-arm a decrease of mood symptoms was related to a decrease of experiential avoidance (d = 0.051, p = 0.04) and an increase of decentering was related to a decrease in sleep symptoms (d = 0.038, p = 0.02) and appetite/weight symptoms (d = 0.049, p = 0.03).ConclusionsDTW offers a promising alternative approach to study and compare working mechanisms of different treatment interventions. Comparing CBT and ACT revealed a decrease in experiential avoidance within CBT and an increase in the ability to decenter within ACT. However, within both treatments a change in other constructs, suggesting that a first alleviation of mood symptoms is important to activate underlying psychological change.Disclosure of InterestNone Declared

Non MRI Guided Accelerated Intermittent Theta Burst Stimulation is Effective in Patients with Treatment Resistant Depression and Suicidality

IntroductionThe U.S. Food &amp; Drug Administration (FDA) has cleared SNT (Stanford Neuromodulation Therapy) for treatment of major depressive disorder (MDD) in adults who have failed to achieve improvement from at least two prior trials of antidepressants. SNT protocol requires both structural and functional connectivity MRIs which is limited by high cost and lack of availability, its use without neuronavigation is still considered an off label use and need more investigation.Objectives1-To investigate efficacy of SNT like accelerated off-label protocol without Neuronavigation in treating patients with TRD and suicidality.2-To investigate durabiliy ( up to one month ) of SNT like accelerated off-label protocol without Neuronavigation in treating patients with TRD and suicidalityMethods Two cases diagnosed as treatment resistant unipolar depression with suicidal ideations received accelerated intermittent theta burst stimulation (a iTBS); with figure of eight coil administered to the left dorsolateral prefrontal cortex (DL-PFC) determined using Beam method. Stimulation was at 90% MT for 1800 pulses with an intersession interval of fifty minutes. Patients received ten sessions every day for five consecutive days for a total of fifty sessions (90,000 pulses). The following scales were applied at the baseline and at the end of each day of five treatment days:The Montgomery and Asberg Depression Rating Scale (MADRS) The Beck Depression Inventory, Columbia Suicide Severity Rating Scale (C-SSRS) and Young Mania Rating Scale (YMRS).ResultsThe two cases at the end of the fifth day were completely improved regarding both suicidal ideations and depression without emerging of hypomania. Follow up was done weekly for one month with durable results.ConclusionsSNT protocol without neuronavigation needs to be well investigated in suppressing both suicidality and depression in patients with TRD.Disclosure of InterestNone Declared

Combination of CBT and rTMS: what are the advantages?

IntroductionObsessive-Compulsive Disorder (OCD) and Major Depressive Disorder (MDD) are among the ten most disabling disorders, yet only 30-40% of people with the condition seek specialist care (WHO). Considered a relatively new tool in the treatment of OCD and MDD, repetitive transcranial magnetic stimulation (rTMS) was first used by our team 1 year ago. Based on current literature cognitive behavioural therapy (CBT) is effective in 60% of OCD cases, with MDD also having a good response rate of 50-60%. The efficacy of SSRI’s has been demonstrated, but side effects can have a negative impact on adherence in the long term. Prolonged use of certain drugs has adverse reactions that lead specifically to memory impairment, which compromises suitability for psychotherapy. The same problem applies to the use of electroconvulsive therapy (ECT) in a major depressive episode.ObjectivesOur aim was to study the efficacy of combining rTMS with CBT, to gather clinical experience on how these two different methods work in practice when combined.MethodsPatients diagnosed with therapy resistant MDD received rTMS treatment using 50Hz theta burst over 10 sessions. Therapy resistant OCD patients were treated by a 15 sessions rTMS using 1Hz single pulse. These rTMS sessions were combined with CBT, of which we would like to highlight two cases: one of them is a 34 years old woman, who has wide range of sexual, checking and contamination-related OCD symptoms and only received SSRI treatment so far. The other one is a 29 years old man, who suffers from religious obsessions, cleaning compulsions and other repetitive behaviours.Results The positive effects of rTMS treatment on working memory functions, attentional capacity and cooperative skills without significant additive effects suggest exciting possibilities for combining the two treatments, thus the combined treatment has been tested in clinical practice. In our own patient care, an important experience was that patients were committed to the therapy, felt safe and, unlike with medications, did not have to worry about side effects. While medication and ECT can make psychotherapy more difficult in the long term - mainly because of memory problems - rTMS facilitates it. Patients appreciate that we approach their problems in a complex way, and they perceive that the combination of the two very different methods reflects professionalism. Our poster attempts to present the experience of combining rTMS and CBT from the therapist’s perspective through two case studies.ConclusionsBased on our experiences it is an effective approach to combine rTMS with CBT in therapy resistant MDD and OCD patients. In the light of these results the revision of the existing guidelines are considerable.AcknowledgementsThis study has been supported by the Human Resource Development Operating Programme 5.2.6 grant.Disclosure of InterestNone Declared

Altered functional brain activity in first-episode major depressive disorder treated with electro-acupuncture: A resting-state functional magnetic resonance imaging study

BackgroundPrevious studies have found electroacupuncture could improve the clinical symptoms of first-episode major depressive disorder (MDD), but the exact neural mechanism of action needs to be further elucidated. MethodsTwenty-eight first-episode MDD patients were randomly divided into 14 electro-acupuncture stimulation (EAS) groups and 14 sham-acupuncture stimulation (SAS) groups, and clinical symptoms were assessed and functional magnetic resonance imaging (fMRI) scans were done in both groups. Amplitude of low-frequency fluctuations (ALFF) was used to observe the changes between the pre-treatment and post-treatment in the two groups, and the altered brain areas were selected as region of interest (ROI) to observe the FC changes. Meanwhile, the correlation between the altered clinical symptoms and the altered ALFF and FC of brain regions in the two groups was analyzed. ResultsThe EAS significantly decreased the HAMD-24 and HAMA-14 scores of MDD than SAS group. The imaging results revealed that both groups were able to increase the ALFF of the left middle temporal gyrus and the left cerebellar posterior lobe. When using the left middle temporal gyrus and the left posterior cerebellar lobe as ROIs, EAS group increased the FC between the left middle temporal gyrus with the left superior frontal gyrus, the left middle frontal gyrus, and the left hippocampus, and decreased the FC between the left posterior cerebellar lobe and the left calcarine gyrus, while SAS group only increased the FC between the left middle temporal gyrus with the left superior frontal gyrus. The alternations in clinical symptoms after EAS treatment were positively correlated with the altered ALFF values in the left middle temporal gyrus and the altered FC values in the left middle temporal gyrus and the left middle frontal gyrus. ConclusionEA demonstrates modulation of functional activity in the default mode network (DMN), sensorimotor network (SMN), cognitive control network (CCN), limbic system, and visual network (VN) for the treatment of the first-episode MDD. Our findings contribute to the neuroimaging evidence for the efficacy of EAS.

Adjunctive cariprazine for major depressive disorder: a systematic review and meta-analysis.

Converging evidence has suggested that treatment augmentation with a second-generation atypical antipsychotic (SGA) may improve treatment outcomes in major depressive disorder (MDD) patients after an incomplete response to a first-line antidepressant. Cariprazine is a recently approved SGA for MDD augmentation. Herein, we evaluate both continuous (ie, change in depressive symptom severity scores over time) and categorical (ie, remission and response rates) outcomes. Following a full-text review, four randomized controlled trials (RCTs) were included in our meta-analysis, while five studies were included for a qualitative review. Risk ratios (RRs) were calculated for all included randomized controlled studies to determine the relative response and remission rates of cariprazine compared to placebo augmentation. The RR for all-cause dropout was also determined as a proxy for overall acceptability. Two studies found a statistically significant treatment response using cariprazine augmentation. One study observed depressive symptom remission for cariprazine compared to placebo. Our random-effects model revealed moderate antidepressant effects of cariprazine, with a standardized mean difference (SMD) in Montgomery-Åsberg Depression Rating Scale (MADRS) scores of -1.79 (95% CI): -2.89, -0.69). Our pooled response RR and remission RR were calculated as 1.21 (95% CI: 1.05, 1.39, P=0.008) and 0.99 (95% CI: 0.84, 1.17, P=0.91), respectively. The RR for response was statistically significant (P<0.05). However, the RR for remission was not statistically significant. The findings from our meta-analysis include a variable magnitude of effects. Evidence suggests cariprazine may be an effective treatment for MDD; however, further results are needed to clarify this relation.

The Challenges in Treating Obesity Patients with Major Depressive Disorder (MDD) Treatment: a Case Report

The Challenges in Treating Obesity Patients with Major Depressive Disorder (MDD) Treatment: a Case Report

Principal component analysis on the effect of early morning awakening in major depressive disorder

Sleep disturbance is one of the most prevalent symptoms associated with Major Depressive Disorder (MDD). A recent article (Wu et al., 2022, Journal of Multiscale Neuroscience 1, 133-139) explored the significant relationship between early morning awakening (EMA), a type of sleep disturbance, and recovery in MDD patients. In the paper, the authors examined the relationship between EMA and the treatment of MDD with twelve neuropsychological parameters. The authors employed two univariate statistical techniques, students’ t-test and ANOVA, to analyze their data. While their analysis derived a meaningful conclusion that EMA may result in a statistically and clinically significant delay in recovery, we found that a multivariate statistical technique, principal component analysis (PCA), extracted additional quantitative information from their study. In this paper, we present quantitative features in the interaction between EMA and the treatment of MDD obtained from PCA.

Characterizing Major Depressive Disorder (MDD) using alpha-band activity in resting-state electroencephalogram (EEG) combined with MATRICS Consensus Cognitive Battery (MCCB)

BackgroundThe diagnosis of major depressive disorder (MDD) is commonly based on the subjective evaluation by experienced psychiatrists using clinical scales. Hence, it is particularly important to find more objective biomarkers to aid in diagnosis and further treatment. Alpha-band activity (7-13 Hz) is the most prominent component in resting electroencephalogram (EEG), which is also thought to be a potential biomarker. Recent studies have shown the existence of multiple sub-oscillations within the alpha band, with distinct neural underpinnings. However, the specific contribution of these alpha sub-oscillations to the diagnosis and treatment of MDD remains unclear. MethodsIn this study, we recorded the resting-state EEG from MDD and HC populations in both open and closed-eye state conditions. We also assessed cognitive processing using the MATRICS Consensus Cognitive Battery (MCCB). ResultsWe found that the MDD group showed significantly higher power in the high alpha range (10.5–11.5 Hz) and lower power in the low alpha range (7–8.5 Hz) compared to the HC group. Notably, high alpha power in the MDD group is negatively correlated with working memory performance in MCCB, whereas no such correlation was found in the HC group. Furthermore, using five established classification algorithms, we discovered that combining alpha oscillations with MCCB scores as features yielded the highest classification accuracy compared to using EEG or MCCB scores alone. ConclusionsOur results demonstrate the potential of sub-oscillations within the alpha frequency band as a potential distinct biomarker. When combined with psychological scales, they may provide guidance relevant for the diagnosis and treatment of MDD.

Intranasal delivery of paroxetine: A preclinical study on pharmacokinetics, depressive-like behaviour, and neurochemical sex differences

Treatment of major depressive disorder remains a major unmet clinical need. Given the advantages of intranasal administration for targeted brain delivery, the present study aimed at investigating the pharmacokinetics of paroxetine, after its intranasal instillation and assessing its potential therapeutic effect on female and male mice subjected to unpredictable chronic mild stress (UCMS) protocol.IN administration revealed direct nose-to-brain paroxetine delivery but dose- and sex-dependent differences. Pharmacokinetics was nonlinear and paroxetine concentrations were consistently higher in plasma and brain of male mice. Additionally, UCMS decreased animal preference for sucrose in both male and female mice following acute (p < 0.01) and chronic stress (p < 0.05), suggesting anhedonia. Both male and female mice exhibited depressive-like behavior in the forced swimming test. UCMS females displayed a significantly longer immobility time and shorter climbing time than the control group (p < 0.05), while no differences were found between male mice. Two weeks of paroxetine intranasal administration reduced immobility time and lengthened climbing and swimming time, approaching values similar to those observed in the healthy control group. The therapeutic effect was stronger on female mice.Importantly, melatonin plasma levels were significantly decreased in female mice following UCMS (p < 0.05), while males exhibited heightened corticosterone levels. On the other hand, treatment with IN paroxetine significantly increased corticosterone and melatonin levels in both sexes compared to healthy mice (p < 0.05).Intranasal paroxetine delivery undoubtedly ameliorated the behavioral despair, characteristic of depressive-like animals. Despite its efficiency in male and female mice subjected to UCMS, females were more prone to this novel therapeutic strategy.

Just a gut feeling: Faecal microbiota transplant for treatment of depression - A mini-review.

The microbiota-gut-brain axis (MGBA) allows bidirectional crosstalk between the brain and gut microbiota (GM) and is believed to contribute to regulating mood/cognition/behaviour/metabolism/health and homeostasis. Manipulation of GM through faecal microbiota transplant (FMT) is a new, exciting and promising treatment for major depressive disorder (MDD). This mini-review examines current research into GM and FMT as a therapy for depression. Original research articles published in Medline/Cochrane Library/PubMed/EMBASE/PsycINFO databases/National Institute of Health website Clinicaltrials.gov/controlled-trials.com were searched. Full articles included in reference lists were evaluated. We summarise current data on GM and depression and discuss communication through the MGBA and the interaction of antidepressants and GM through this. We review compositions of dysbiosis in depressed cohorts, focusing on future directions in the treatment of MDD. Studies have demonstrated significant gut dysbiosis in depressed patients compared to healthy cohorts, with overgrowth of pro-inflammatory microbiota, reduction in anti-inflammatory species and reduced overall stability and taxonomic richness. FMT allows the introduction of healthy microbiota into the gastrointestinal tract, facilitating the restoration of eubiosis. The GM plays an integral role in human health and disease through its communication with the rest of the body via the MGBA. FMT may provide a means to transfer the healthy phenotype into the recipient and this concept in humans is attracting enormous attention as a prospective treatment for psychopathologies, such as MDD, in the future. It may be possible to manipulate the GM in a number of ways, but further research is needed to determine the exact likelihood and profiles involved in the development and amelioration of MDD in humans, as well as the long-term effects and potential risks of this procedure.

Treatment of Depression in Huntington's Disease: A Systematic Review.

Depression is a common psychiatric disorder among individuals with Huntington's disease (HD). Depression in HD and major depressive disorder appear to have different pathophysiological mechanisms. Despite the unique pathophysiology, the treatment of depression in HD is based on data from the treatment of major depressive disorder in the general population. The objective of this systematic review was to conduct a comprehensive evaluation of the available evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Studies on the treatment of depression in HD were identified by searching MEDLINE, Embase, and PsycInfo. The initial search yielded 2,771 records, 41 of which were ultimately included. There were 19 case reports, seven case series, three cross-sectional studies, one qualitative study, nine nonrandomized studies, and two randomized trials among the included studies. The most common assessment tools were the Hospital Anxiety and Depression Scale (N=8), the Beck Depression Inventory (N=6), and the Hamilton Depression Rating Scale (N=6). Only 59% of the included studies assessed depressive symptoms with a scoring system. The pharmacological options for the treatment of depression included antidepressants and antipsychotics. Nonpharmacological approaches were multidisciplinary rehabilitation, psychotherapy, and neurostimulation. Limited evidence on the treatment of depression in HD was available, and this literature consisted mainly of case reports and case series. This systematic review highlights the knowledge gap and the pressing need for HD-specific research to determine the efficacy of treatment approaches for depression in HD.

A Canadian Simulation Model for Major Depressive Disorder: Study Protocol.

Major depressive disorder (MDD) is a common, often recurrent condition and a significant driver of healthcare costs. People with MDD often receive pharmacological therapy as the first-line treatment, but the majority of people require more than one medication trial to find one that relieves symptoms without causing intolerable side effects. There is an acute need for more effective interventions to improve patients' remission and quality of life and reduce the condition's economic burden on the healthcare system. Pharmacogenomic (PGx) testing could deliver these objectives, using genomic information to guide prescribing decisions. With an already complex and multifaceted care pathway for MDD, future evaluations of new treatment options require a flexible analytic infrastructure encompassing the entire care pathway. Individual-level simulation models are ideally suited for this purpose. We sought to develop an economic simulation model to assess the effectiveness and cost effectiveness of PGx testing for individuals with major depression. Additionally, the model serves as an analytic infrastructure, simulating the entire patient pathway for those with MDD. Key stakeholders, including patient partners, clinical experts, researchers, and modelers, designed and developed a discrete-time microsimulation model of the clinical pathways of adults with MDD in British Columbia (BC), including all publicly-funded treatment options and multiple treatment steps. The Simulation Model of Major Depression (SiMMDep) was coded with a modular approach to enhance flexibility. The model was populated using multiple original data analyses conducted with BC administrative data, a systematic review, and an expert panel. The model accommodates newly diagnosed and prevalent adult patients with MDD in BC, with and without PGx-guided treatment. SiMMDep comprises over 1500 parameters in eight modules: entry cohort, demographics, disease progression, treatment, adverse events, hospitalization, costs and quality-adjusted life-years (payoff), and mortality. The model predicts health outcomes and estimates costs from a health system perspective. In addition, the model can incorporate interactive decision nodes to address different implementation strategies for PGx testing (or other interventions) along the clinical pathway. We conducted various forms of model validation (face, internal, and cross-validity) to ensure the correct functioning and expected results of SiMMDep. SiMMDep is Canada's first medication-specific, discrete-time microsimulation model for the treatment of MDD. With patientpartner collaboration guiding its development, it incorporates realistic care journeys. SiMMDep synthesizes existing information and incorporates provincially-specific data to predict the benefits and costs associated with PGx testing. These predictions estimate the effectiveness, cost-effectiveness, resource utilization, and health gains of PGx testing compared with the current standard of care. However, the flexible analytic infrastructure can be adapted to support other policy questions and facilitate the rapid synthesis of new data for a broader search for efficiency improvements in the clinical field of depression.

MicroRNAs as Diagnostic Biomarkers and Predictors of Antidepressant Response in Major Depressive Disorder: A Systematic Review.

Despite the hardships of major depressive disorder (MDD), biomarkers for the diagnosis and pharmacological management of this condition are lacking. MicroRNAs are epigenetic mechanisms that could provide promising MDD biomarkers. Our aim was to summarize the findings and provide validation for the selection and use of specific microRNAs as biomarkers in the diagnosis and treatment of MDD. A systematic review was conducted using the PubMed/Medline, Cochrane, PsycINFO, Embase, and LILACS databases from March 2022 to November 2023, with clusters of terms based on "microRNA" and "antidepressant". Studies involving human subjects, animal models, and cell cultures were included, whereas those that evaluated herbal medicines, non-pharmacological therapies, or epigenetic mechanisms other than miRNA were excluded. The review revealed differences in the expression of various microRNAs when considering the time of assessment (before or after antidepressant treatment) and the population studied. However, due to the heterogeneity of the microRNAs investigated, the limited size of the samples, and the wide variety of antidepressants used, few conclusions could be made. Despite the observed heterogeneity, the following microRNAs were determined to be important factors in MDD and the antidepressant response: mir-1202, mir-135, mir-124, and mir-16. The findings indicate the potential for the use of microRNAs as biomarkers for the diagnosis and treatment of MDD; however, more homogeneous studies are needed.

"I can't escape my scars, even if I do get better": A qualitative exploration of how adolescents talk about their self-harm and self-harm scars during cognitive behavioural therapy for depression.

Emerging evidence indicates that perceptions of self-harm behaviours and self-harm scars may thwart recovery from depression, yet limited research has explored adolescent accounts of their self-harm and scars during therapy. This study sought to explore how adolescents describe their self-harm behaviours and scars during Cognitive Behavioural Therapy (CBT) and explore the sociocultural discourses that may influence these descriptions. The participants were six female adolescents (aged 14-17years old) with clinical depression, who were engaging in self-harm. All participants accessed CBT as part of clinical trial evaluating three psychological treatments for major depressive disorder in Child and Adolescent Mental Health Services. Audio-taped CBT sessions were analyzed using discourse analysis. Within CBT sessions, adolescents drew upon stigma discourses in talking about their self-harm. Adolescent also described their self-harm scars as shameful and stigmatizing, and as "proof" of the legitimacy of their depression. It is important for CBT practitioners to understand the context of sociocultural discourses around self-harm behaviours and self-harm scars, which are reflected in how adolescents with depression describe these within therapy and may serve to maintain distress. The study indicates that awareness of use of language and intersecting sociocultural discourses can inform CBT practice.

FDA gives breakthrough designation for psychedelic treatment

A clinical‐stage biopharmaceutical company that officials said is committed to revolutionizing mental health care by developing new and innovative next‐generation psychedelic‐based treatment options, announced last week that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for an adjunctive psychedelic‐based therapy for the treatment of major depressive disorder (MDD), according to the press release news outlet, Businesswire.

The utility of measuring daily hassles and uplifts in understanding outcomes to treatments for major depressive disorder

Little is known about the effects of common daily experiences in patients with major depressive disorder (MDD). The Daily Hassles and Uplifts Scale (HUPS) was assessed in 142 treatment-naïve adult MDD outpatients randomized to 12 weeks of treatment with either antidepressant medication (ADM) or Cognitive Behavior Therapy (CBT). Three HUPS measures were analyzed: hassle frequency (HF), uplift frequency (UF), and the mean hassle intensity to mean uplift intensity ratio (MHI:MUI). Remission after treatment was not predicted by these baseline HUPS measures and did not moderate outcomes by treatment type. In contrast, HUPS measures significantly changed with treatment and were impacted by remission status. Specifically, HF and MHI:MUI decreased and UF increased from baseline to week 12, with remission leading to significantly greater decreases in HF and MHI:MUI compared to non-remission. ADM-treated patients demonstrated significant improvements on all three HUPS measures regardless of remission status. In contrast, remitters to CBT demonstrated significant improvements in HF and MHI:MUI but not UF; among CBT non-remitters the only significant change was a reduction in HF. The changes in HUPS measures are consistent with how affective biases are impacted by treatments and support the potential value of increasing attention to positive events in CBT.