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The Journal of Clinical Psychiatry Nov 2023To systematically review the literature to identify and categorize the predictors and risk factors for treatment-resistant depression (TRD). Online databases (PubMed,...
To systematically review the literature to identify and categorize the predictors and risk factors for treatment-resistant depression (TRD). Online databases (PubMed, MEDLINE, Embase, and APA PsycNet) and relevant conference sources were searched from inception up to January 24, 2022. The following keywords were used: , , , , and . All studies that included a definition of TRD were included. A total of 1,686 abstracts were screened, and 57 studies were included in the final data synthesis. Data were extracted using a data extraction form developed for this study. The most frequently reported mental predictors/risk factors were greater symptom severity (9 studies), suicidality (8 studies), and recurrent depression (6 studies). Cardiovascular disease (4 studies), pain (3 studies), and thyroid dysfunction (3 studies) were the most common physical predictors/risk factors, while younger age (7 studies) and female gender (6 studies) were the most common demographic predictors/risk factors. Higher levels of neuroticism appeared twice in the literature. Several articles reported on genetic, biological, and imaging variables, but results were too heterogenous to identify common predictors/risk factors. TRD is a complex disorder with many contributing factors that need to be identified and addressed earlier in the disease course to prevent its development or facilitate better treatment outcomes. Future work should focus on replicating the key predictors/risk factors identified in this review.
Topics: Humans; Female; Antidepressive Agents; Depression; Treatment Outcome; Depressive Disorder, Treatment-Resistant; Pain
PubMed: 37967334
DOI: 10.4088/JCP.23r14885 -
Der Nervenarzt May 2024Treatment-resistant depression (TRD) is a complex disorder. Although no standardized definition has been established to date, there are promising and well-established... (Review)
Review
Treatment-resistant depression (TRD) is a complex disorder. Although no standardized definition has been established to date, there are promising and well-established treatment options for the condition. Looking at the current pharmacological and neuromodulatory strategies, there is an urgent need for fast-acting and well-tolerated treatment options. The search for new mechanisms of action goes beyond the monoamine hypothesis. For example, esketamine is already an established treatment method that is fast-acting and well tolerated, while psychedelics or esmethadone are currently still undergoing clinical trials. Compounds that can be used off-label, such as dextromethorphan or anti-inflammatory strategies are also presented. Pharmacological approaches that focus on the modulation of the glutamatergic system or belong to the class of psychedelics, appear to be of particular importance for current research and development. These particularly include substances that rapidly exert clinical effects and have a favorable side-effect profile.
Topics: Humans; Depressive Disorder, Treatment-Resistant; Antidepressive Agents; Hallucinogens; Ketamine
PubMed: 38568318
DOI: 10.1007/s00115-024-01647-z -
Translational Psychiatry Jul 2023Here, we investigated the brain functional connectivity (FC) changes following a novel accelerated theta burst stimulation protocol known as Stanford Neuromodulation... (Randomized Controlled Trial)
Randomized Controlled Trial
Here, we investigated the brain functional connectivity (FC) changes following a novel accelerated theta burst stimulation protocol known as Stanford Neuromodulation Therapy (SNT) which demonstrated significant antidepressant efficacy in treatment-resistant depression (TRD). In a sample of 24 patients (12 active and 12 sham), active stimulation was associated with significant pre- and post-treatment modulation of three FC pairs, involving the default mode network (DMN), amygdala, salience network (SN) and striatum. The most robust finding was the SNT effect on amygdala-DMN FC (group*time interaction F(1,22) = 14.89, p < 0.001). This FC change correlated with improvement in depressive symptoms (rho (Spearman) = -0.45, df = 22, p = 0.026). The post-treatment FC pattern showed a change in the direction of the healthy control group and was sustained at the one-month follow-up. These results are consistent with amygdala-DMN connectivity dysfunction as an underlying mechanism of TRD and bring us closer to the goal of developing imaging biomarkers for TMS treatment optimization.Trial registration: ClinicalTrials.gov NCT03068715.
Topics: Humans; Depressive Disorder, Major; Brain Mapping; Magnetic Resonance Imaging; Brain; Depressive Disorder, Treatment-Resistant
PubMed: 37400432
DOI: 10.1038/s41398-023-02537-9 -
Molecules (Basel, Switzerland) Nov 2023Major depressive disorder (MDD) is a serious mental illness with a heavy social burden, but its underlying molecular mechanisms remain unclear. Mass spectrometry... (Review)
Review
Major depressive disorder (MDD) is a serious mental illness with a heavy social burden, but its underlying molecular mechanisms remain unclear. Mass spectrometry (MS)-based metabolomics is providing new insights into the heterogeneous pathophysiology, diagnosis, treatment, and prognosis of MDD by revealing multi-parametric biomarker signatures at the metabolite level. In this comprehensive review, recent developments of MS-based metabolomics in MDD research are summarized from the perspective of analytical platforms (liquid chromatography-MS, gas chromatography-MS, supercritical fluid chromatography-MS, etc.), strategies (untargeted, targeted, and pseudotargeted metabolomics), key metabolite changes (monoamine neurotransmitters, amino acids, lipids, etc.), and antidepressant treatments (both western and traditional Chinese medicines). Depression sub-phenotypes, comorbid depression, and multi-omics approaches are also highlighted to stimulate further advances in MS-based metabolomics in the field of MDD research.
Topics: Humans; Depressive Disorder, Major; Mass Spectrometry; Gas Chromatography-Mass Spectrometry; Metabolomics; Chromatography, Liquid
PubMed: 37959849
DOI: 10.3390/molecules28217430 -
BMC Psychiatry Dec 2023Insomnia symptoms in patients with major depressive disorder (MDD) are common and deleterious. Childhood trauma, personality traits, interpersonal distress, and social...
BACKGROUND
Insomnia symptoms in patients with major depressive disorder (MDD) are common and deleterious. Childhood trauma, personality traits, interpersonal distress, and social support contribute to insomnia, but how they interact to affect insomnia remains uncertain.
METHODS
A total of 791 patients with MDD completed the Insomnia Severity Index, Eysenck Personality Questionnaire, Interpersonal Relationship Comprehensive Diagnostic Scale, Childhood Trauma Questionnaire, Social Support Rating Scale and Hamilton Depression Scale-17. This study utilized network analyses to identify the central symptoms of insomnia and their associations with psychosocial factors.
RESULTS
Worrying about sleep was identified as the central symptom in the insomnia network, insomnia and associated personality network, insomnia and associated interpersonal disturbance network, insomnia and associated childhood trauma network, insomnia and associated social support network, and the integrated network of insomnia symptoms and associated psychosocial factors. In the networks of insomnia symptoms and individual psychosocial factors, most psychosocial factors (other than childhood trauma) were directly or indirectly related to insomnia symptoms; however, neuroticism was the only factor directly associated with insomnia symptoms before and after controlling for covariates. In the final integrated network of insomnia symptoms and psychosocial factors, neuroticism was a bridge node and mediated the relationships of social support and interpersonal disturbances with insomnia symptoms, which is clearly presented in the shortest pathways.
CONCLUSIONS
Worrying about sleep and neuroticism were prominent in the integrated network of insomnia symptoms and associated psychosocial factors, and the edge between them connected psychosocial factors and insomnia symptoms in MDD patients.
Topics: Humans; Depression; Sleep Initiation and Maintenance Disorders; Depressive Disorder, Major; Personality
PubMed: 38104061
DOI: 10.1186/s12888-023-05454-9 -
Bipolar Disorders May 2024The perinatal period is an extremely delicate phase that can involve a high risk for onset of depressive disorders. The Edinburgh Postnatal Depression Scale (EPDS) is a... (Review)
Review
The perinatal period is an extremely delicate phase that can involve a high risk for onset of depressive disorders. The Edinburgh Postnatal Depression Scale (EPDS) is a widely validated instrument for assessing perinatal depressive symptoms, including the dimension of anhedonia. There are studies suggesting that the neural mechanism underlying the occurrence of anhedonia in patients with major depressive disorder (MDD) and bipolar depression (BD) might be distinct. Anhedonia seems to represent a more stable and frequent symptom in women with postpartum bipolar relative to unipolar depressive disorder and is associated with significantly higher depressive symptom severity. Perinatal medicine is an important component of women's health. Treatment of anhedonia can be challenging, and the most effective treatment can be a combination of psychotherapy and medication, but the screening of anhedonia in peripartum women can prevent the development of other psychiatric disorders and maladaptive behaviors.
Topics: Humans; Female; Anhedonia; Peripartum Period; Pregnancy; Bipolar Disorder; Depressive Disorder, Major; Depression, Postpartum
PubMed: 38302845
DOI: 10.1111/bdi.13408 -
CMAJ : Canadian Medical Association... Nov 2023Pharmacogenomic testing to identify variations in genes that influence metabolism of antidepressant medications can enhance efficacy and reduce adverse effects of...
BACKGROUND
Pharmacogenomic testing to identify variations in genes that influence metabolism of antidepressant medications can enhance efficacy and reduce adverse effects of pharmacotherapy for major depressive disorder. We sought to establish the cost-effectiveness of implementing pharmacogenomic testing to guide prescription of antidepressants.
METHODS
We developed a discrete-time microsimulation model of care pathways for major depressive disorder in British Columbia, Canada, to evaluate the effectiveness and cost-effectiveness of pharmacogenomic testing from the public payer's perspective over 20 years. The model included unique patient characteristics (e.g., metabolizer phenotypes) and used estimates derived from systematic reviews, analyses of administrative data (2015-2020) and expert judgment. We estimated incremental costs, life-years and quality-adjusted life-years (QALYs) for a representative cohort of patients with major depressive disorder in BC.
RESULTS
Pharmacogenomic testing, if implemented in BC for adult patients with moderate-severe major depressive disorder, was predicted to save the health system $956 million ($4926 per patient) and bring health gains of 0.064 life-years and 0.381 QALYs per patient (12 436 life-years and 74 023 QALYs overall over 20 yr). These savings were mainly driven by slowing or avoiding the transition to refractory (treatment-resistant) depression. Pharmacogenomic-guided care was associated with 37% fewer patients with refractory depression over 20 years. Sensitivity analyses estimated that costs of pharmacogenomic testing would be offset within about 2 years of implementation.
INTERPRETATION
Pharmacogenomic testing to guide antidepressant use was estimated to yield population health gains while substantially reducing health system costs. These findings suggest that pharmacogenomic testing offers health systems an opportunity for a major value-promoting investment.
Topics: Adult; Humans; Depressive Disorder, Major; Pharmacogenetics; Depression; Cost-Benefit Analysis; Antidepressive Agents; Quality-Adjusted Life Years; British Columbia
PubMed: 37963621
DOI: 10.1503/cmaj.221785 -
JAMA Network Open Aug 2023Selective serotonin reuptake inhibitors (SSRIs) are considered a first-line pharmacological treatment for adolescent depression with moderate or higher levels of symptom... (Clinical Trial)
Clinical Trial
Measures of Connectivity and Dorsolateral Prefrontal Cortex Volumes and Depressive Symptoms Following Treatment With Selective Serotonin Reuptake Inhibitors in Adolescents.
IMPORTANCE
Selective serotonin reuptake inhibitors (SSRIs) are considered a first-line pharmacological treatment for adolescent depression with moderate or higher levels of symptom severity. Thus, it is important to understand neurobiological changes related to SSRIs during the course of treatment for adolescents with depression.
OBJECTIVE
To examine neurobiological changes associated with SSRI treatment in adolescents with major depressive disorder (MDD) by measuring longitudinal changes in volume and resting-state functional connectivity (rsFC) in the dorsolateral prefrontal cortex (DLPFC), a core region of cognitive control.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study was conducted with an open-label design. Adolescents with MDD and healthy controls were recruited at the Seoul National University Hospital (Seoul, South Korea). Adolescents with MDD were treated with escitalopram for 8 weeks. Data analysis was conducted between April 2021 and February 2022.
MAIN OUTCOMES AND MEASURES
Depressive symptoms were assessed using the Children's Depression Rating Scale-Revised. The outcome measure was defined as the change in Children's Depression Rating Scale-Revised scores from week 0 (before treatment) to week 8 (after treatment) or upon termination. Participants completed structural and resting-state functional magnetic resonance imaging (rsfMRI) assessments before (week 0) and after (week 8) SSRI treatment. Repeated measures analysis of variance and liner mixed model analyses were used to examine the longitudinal associations of SSRI treatment with DLPFC volume and rsFC between responders who showed at least a 40% decrease in depressive symptoms and nonresponders who did not.
RESULTS
Ninety-five adolescents with MDD and 57 healthy controls were initially recruited. The final analyses of volume included 36 responders (mean [SD] age, 15.0 [1.6] years; 25 girls [69.4%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). Analyses of rsFC included 33 responders (mean [SD] age, 15.2 [1.5] years; 21 girls [63.6%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). The longitudinal associations of SSRI treatment were more evident in responders than in nonresponders. Responders showed significantly increased right DLPFC volume, decreased bilateral DLPFC rsFC with the superior frontal gyri, and decreased left DLPFC rsFC with the ventromedial PFC after treatment compared with before treatment. Furthermore, increased right DLPFC volume was correlated with decreased rsFC between the right DLPFC and superior frontal gyri after SSRI treatment.
CONCLUSIONS AND RELEVANCE
The preliminary results of this cohort study suggest that the DLPFC volumetric and rsFC changes may serve as potential neurobiological treatment markers that are associated with symptom improvement in adolescents with MDD.
Topics: Adolescent; Child; Female; Humans; Cohort Studies; Depression; Depressive Disorder, Major; Dorsolateral Prefrontal Cortex; Selective Serotonin Reuptake Inhibitors
PubMed: 37540512
DOI: 10.1001/jamanetworkopen.2023.27331 -
European Neuropsychopharmacology : the... Nov 2023Major depressive disorder (MDD) presents different clinical features in women and men, with women being more affected and responding differently to antidepressant... (Review)
Review
Major depressive disorder (MDD) presents different clinical features in women and men, with women being more affected and responding differently to antidepressant treatment. Specific molecular mechanisms underlying these differences are not well studied and this narrative review aims at providing an overview of the neurobiological features underlying sex-differences in biological systems involved in MDD pathophysiology and response to antidepressant treatment, focusing on human studies. The majority of the reviewed studies were performed through candidate gene approaches, focusing on biological systems involved in MDD pathophysiology, including the stress response, inflammatory and immune, monoaminergic, neurotrophic, gamma-aminobutyric acid and glutamatergic, and oxytocin systems. The influence of the endocrine system and sex-specific hormone effects are also discussed. Genome, epigenome and transcriptome-wide approaches are less frequently performed and most of these studies do not focus on sex-specific alterations, revealing a paucity of omics studies directed to unravel sex-based differences in MDD. Few studies about sex-related differences in antidepressant treatment response have been conducted, mostly involving the inflammatory system, with less evidence on the monoaminergic system and sparse evidence in omics approaches. Our review covers the importance of accounting for sex-differences in research, optimizing patient stratification for a more precise diagnostic and individualized treatment for women and men.
Topics: Male; Humans; Female; Depressive Disorder, Major; Antidepressive Agents; Biomarkers
PubMed: 37595325
DOI: 10.1016/j.euroneuro.2023.07.012 -
Journal of the American Academy of... Aug 2023Irritability as part of depression has been studied for a long time; it was a cardinal symptom in Burton's concept of melancholia and an underlying mechanism toward...
Irritability as part of depression has been studied for a long time; it was a cardinal symptom in Burton's concept of melancholia and an underlying mechanism toward oneself in Freud's description of melancholia. Today, irritability is considered a cardinal symptom of depression in children and adolescents by DSM-5, along with depressed mood and anhedonia, and is present in about 40% of youth with depression. Longitudinally, irritability has been shown to be a specific predictor of depression across development in several studies. The mechanisms underlying the close relationship between irritability and depression are unclear, but most evidence points to shared risk factors, including genetic risk, family history of depression, early temperament and personality, and parenting styles. However, other plausible shared mechanisms, especially those involving neural circuits, have been undertested.
Topics: Child; Adolescent; Humans; Depression; Depressive Disorder; Temperament; Personality Disorders; Irritable Mood
PubMed: 37169148
DOI: 10.1016/j.jaac.2023.05.001