Publications by authors named "Milev R"

Article Synopsis
  • Current antidepressants show limited effectiveness, prompting research to identify biological targets for new treatments and understand their mechanisms.
  • The study utilized EEG data from two Canadian trials to examine how changes in brain wave patterns (neural oscillations) correlate with symptom improvement in patients undergoing pharmacological and CBT treatments.
  • Findings indicate that early increases in theta waves and late changes in delta and alpha waves are linked to better treatment outcomes, with common patterns observed in both treatment methods, enhancing our understanding of how depression treatments work.
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  • * The research involved examining the relationship between MDD, childhood maltreatment (CM), and eCB levels in blood plasma from 91 adults with MDD and 62 healthy participants.
  • * Findings indicate that while MDD is associated with higher eCB levels, the relationship between CM and hippocampal volume shows that only lower levels of one eCB (AEA) are linked to reduced hippocampal volume, highlighting the complex role of eCBs in stress and depression.
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Current psychotherapeutic treatments for OCD, while effective, have complex outcomes with mixed efficacy. Previous research has observed baseline brain activation patterns in OCD patients, elucidating some of the implications of this disorder. Observing the effects of evidence-based psychotherapeutics for OCD on brain activation (through MRI) may provide a more comprehensive outline of pathology.

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Introduction: Little is known about the interplay between genetics and epigenetics on antidepressant treatment (1) response and remission, (2) side effects, and (3) serum levels. This study explored the relationship among single nucleotide polymorphisms (SNPs), DNA methylation (DNAm), and mRNA levels of four pharmacokinetic genes, , , , and , and its effect on these outcomes.

Methods: The Canadian Biomarker Integration Network for Depression-1 dataset consisted of 177 individuals with major depressive disorder treated for 8 weeks with escitalopram (ESC) followed by 8 weeks with ESC monotherapy or augmentation with aripiprazole.

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Article Synopsis
  • Fibromyalgia causes chronic pain and sleep disturbances, and current treatment options only significantly help 30-60% of patients; therefore, a study will examine the effectiveness of combining melatonin and pregabalin in treating this condition.
  • The trial will involve 54 adults diagnosed with fibromyalgia, assessing pain levels and other health outcomes over 6 weeks while comparing the combination treatment to the individual medications.
  • Ethical approval for the trial has been secured, and it is registered for transparency and adherence to research standards.
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Background: A critical challenge in the study and management of major depressive disorder (MDD) is predicting relapse. We examined the temporal correlation/coupling between depression and anxiety (called Depression-Anxiety Coupling Strength, DACS) as a predictor of relapse in patients with MDD.

Methods: We followed 97 patients with remitted MDD for an average of 394 days.

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Clinical studies of major depression (MD) generally focus on group effects, yet interindividual differences in brain function are increasingly recognized as important and may even impact effect sizes related to group effects. Here, we examine the magnitude of individual differences in relation to group differences that are commonly investigated (e.g.

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Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults.

Methods: CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners.

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Article Synopsis
  • - The study investigates how major depressive disorder (MDD) affects brain structure and cognitive function, particularly looking at how these changes relate to normal brain development and aging in adolescents and adults.
  • - Researchers analyzed brain data from 304 participants with MDD and 236 without, finding that individuals with MDD had lower brain centile scores, indicating atypical brain aging, and those scores were linked to working memory only in the control group.
  • - The findings suggest that MDD is associated with unusual brain development and aging, but severity of depression and childhood maltreatment did not significantly influence brain measurements or treatment responses.
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  • Pain management for chronic pain patients with depression is difficult and the effectiveness of intermittent theta-burst stimulation (iTBS) is being studied.
  • A retrospective review of 104 patients treated with iTBS showed significant reductions in depression and pain scores after treatment.
  • The findings indicate potential benefits of iTBS for patients experiencing both chronic pain and depression, warranting further research into this treatment modality.
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Background: The COVID-19 pandemic has brought significant mental health challenges, particularly for vulnerable populations, including non-binary gender individuals. The COMET international study aimed to investigate specific risk factors for clinical depression or distress during the pandemic, also in these special populations.

Methods: Chi-square tests were used for initial screening to select only those variables which would show an initial significance.

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Neural network-level changes underlying symptom remission in major depressive disorder (MDD) are often studied from a single perspective. Multimodal approaches to assess neuropsychiatric disorders are evolving, as they offer richer information about brain networks. A pipeline was developed to integrate a computationally intense data fusion method with a toolbox, to produce a faster and more intuitive pipeline for combining functional connectivity with structural connectivity (denoted as anatomically weighted functional connectivity ()).

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Background: The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders.

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Background: Identifying neuroimaging biomarkers of antidepressant response may help guide treatment decisions and advance precision medicine.

Aims: To examine the relationship between anhedonia and functional neurocircuitry in key reward processing brain regions in people with major depressive disorder receiving aripiprazole adjunct therapy with escitalopram.

Method: Data were collected as part of the CAN-BIND-1 study.

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Preclinical research implicates stress-induced upregulation of the enzyme, serum- and glucocorticoid-regulated kinase 1 (SGK1), in reduced hippocampal volume. In the current study, we tested the hypothesis that greater SGK1 mRNA expression in humans would be associated with lower hippocampal volume, but only among those with a history of prolonged stress exposure, operationalized as childhood maltreatment (physical, sexual, and/or emotional abuse). Further, we examined whether baseline levels of SGK1 and hippocampal volume, or changes in these markers over the course of antidepressant treatment, would predict treatment outcomes in adults with major depression [MDD].

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Identifying clinically relevant predictors of depressive recurrence following treatment for Major Depressive Disorder (MDD) is critical for relapse prevention. Implicit self-depressed associations (SDAs), defined as implicit cognitive associations between elements of depression (e.g.

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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. 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.

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Childhood maltreatment (CM) is a strong transdiagnostic risk factor for future psychopathology. This risk is theorized to emerge partly because of glucocorticoid-mediated atrophy in the hippocampus, which leaves this area sensitive to further volume loss even through adulthood in the face of future stress and the emergence of psychopathology. This proof-of-principle study examines which specific dimensions of internalizing psychopathology in the context of a CM history are associated with decreases in hippocampal volume over a 6-month period.

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Objectives: Treatment-emergent sexual dysfunction is frequently reported by individuals with major depressive disorder (MDD) on antidepressants, which negatively impacts treatment adherence and efficacy. We investigated the association of polymorphisms in pharmacokinetic genes encoding cytochrome-P450 drug-metabolizing enzymes, and , and the transmembrane efflux pump, P-glycoprotein (i.e.

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Importance: Untreated depression is a growing public health concern, with patients often facing a prolonged trial-and-error process in search of effective treatment. Developing a predictive model for treatment response in clinical practice remains challenging.

Objective: To establish a model based on electroencephalography (EEG) to predict response to 2 distinct selective serotonin reuptake inhibitor (SSRI) medications.

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Monitoring sleep and activity through wearable devices such as wrist-worn actigraphs has the potential for long-term measurement in the individual's own environment. Long periods of data collection require a complex approach, including standardized pre-processing and data trimming, and robust algorithms to address non-wear and missing data. In this study, we used a data-driven approach to quality control, pre-processing and analysis of longitudinal actigraphy data collected over the course of 1 year in a sample of 95 participants.

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Article Synopsis
  • A study was conducted comparing the effectiveness of alpha-lipoic acid (ALA), pregabalin, and their combination for treating neuropathic pain in peripheral neuropathies over a 6-week period in a randomized, double-blind trial.
  • Results showed that pregabalin significantly reduced mean pain intensity more than ALA, with scores of 3.96 for pregabalin and 5.32 for ALA, while the combination provided no additional benefits.
  • Quality of life assessments indicated that while ALA and pregabalin improved scores, the combination treatment did not show significant advantages, and there were no notable differences in adverse effects between the treatments.
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Objective: There is limited data about the impact of mood disorders treatment guidelines on clinical outcomes. The objective of this study was to investigate the impact of prescribers' adherence to the 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) treatment guidelines recommendations on the readmission rates of patients hospitalized for mania.

Method: A retrospective cohort of all individuals admitted due to acute mania to Kingston General Hospital, Kingston, ON, from January 2018 to July 2021 was included in this study.

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Background: Antidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has not been well studied.

Methods: We conducted a multisite, double-blind, randomized, placebo-controlled trial of maintenance of treatment with adjunctive escitalopram or bupropion XL as compared with discontinuation of antidepressant therapy in patients with bipolar I disorder who had recently had remission of a depressive episode. Patients were randomly assigned in a 1:1 ratio to continue treatment with antidepressants for 52 weeks after remission or to switch to placebo at 8 weeks.

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