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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 -
Psychiatria Danubina Oct 2023There is a lot of evidence for a bidirectional communication between the gut and brain. Dysbiosis and increase intestinal permeability may lead to a systemic low-grade... (Review)
Review
BACKGROUND
There is a lot of evidence for a bidirectional communication between the gut and brain. Dysbiosis and increase intestinal permeability may lead to a systemic low-grade inflammatory response or various neuroactive bacterial metabolite may cross gut barrier. Pro-inflammatory cytokines or bacterial metabolites such as short-chain fatty acid (SCFA) are known to pass through blood brain barrier and altered neurotransmitter metabolism or increase production of neurotoxic pathways. In this review we hypothesized that restoring the gut microbiota ecosystem could improve mental disorders. We reviewed literature for human evidence proving clinical relevance of probiotics intake in mental disorders.
SUBJECTS AND METHODS
We searched literature with keywords "depression" or "major depressive disorder" and "probiotic". We selected randomized control trial and we considered having both outcomes concerning impact on depressive symptoms but also on inflammation biomarkers, microbiota composition, cerebral nervous system or cognition.
RESULTS
Seven out of fourteen randomized control trial reported significant improvement on depressive symptoms in patients taking probiotics. Besides improvement in depressive symptoms, we found decrease in inflammatory markers such as IL-6, decrease in serum kynurenine level, changes in microbiota diversity and abundance of species correlated to depressive disorder and higher cognitive performance.
CONCLUSIONS
Probiotic seems to be secure and more effective on depression when used in supplement to usual antidepressant and in mild to moderate depression. We highlighted positive impact on vulnerability factors prevent further worsening. Probiotics could have anti-inflammatory effect acting on inflammatory markers well known to have a role on pathogenesis of depression. A strong correlation between neuroactive metabolites and a relative abundance of microbiota bacterial species underlined importance to consider the gut-brain axis in mental disorders.
Topics: Humans; Depressive Disorder, Major; Probiotics; Microbiota; Inflammation; Brain
PubMed: 37800206
DOI: No ID Found -
MMW Fortschritte Der Medizin Jun 2024
Topics: Humans; Depressive Disorder; Diabetes Mellitus, Type 2
PubMed: 38806899
DOI: 10.1007/s15006-024-4001-5 -
Psychiatry and Clinical Neurosciences Sep 2023To evaluate the efficacy and safety of an oral, once-daily, 14-day treatment course of zuranolone in Japanese patients with major depressive disorder (MDD). (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
To evaluate the efficacy and safety of an oral, once-daily, 14-day treatment course of zuranolone in Japanese patients with major depressive disorder (MDD).
METHODS
This multicenter, randomized, double-blind, placebo-controlled study randomized eligible patients (1:1:1) to receive oral zuranolone 20 mg, zuranolone 30 mg, or placebo once daily for 14 days (treatment-period), followed by two 6-week follow-up periods. The primary endpoint was change from baseline in the 17-item Hamilton Depression Rating Scale (HAMD-17) total score on Day 15.
RESULTS
Overall, 250 patients (enrolled: 07/07/2020-05/26/2021) were randomized to receive placebo (n = 83), zuranolone 20 mg (n = 85), or zuranolone 30 mg (n = 82). The demographic and baseline characteristics were balanced between groups. The adjusted mean (standard error) change from baseline in the HAMD-17 total score on Day 15 was -6.22 (0.62), -8.14 (0.62), and - 8.31 (0.63) in the placebo, zuranolone 20-mg, and zuranolone 30-mg groups, respectively. Significant differences in the adjusted mean (95% confidence interval [CI]) for zuranolone 20 mg versus placebo (-1.92; [-3.65, -0.19]; P = 0.0296) and zuranolone 30 mg versus placebo (-2.09; [-3.83, -0.35]; P = 0.0190) groups were observed on Day 15, and also as early as Day 3. A nonsignificant yet distinct drug-placebo separation was observed during follow-up. Somnolence (placebo [3.7%], zuranolone 20 mg [10.6%], and zuranolone 30 mg [20.7%]) and dizziness (3.7%, 9.4%, and 9.8%, respectively) were more common with zuranolone.
CONCLUSION
Oral zuranolone was safe and demonstrated significant improvements in depressive symptoms, as assessed by HAMD-17 total score change from baseline over 14 days in Japanese patients with MDD.
Topics: Humans; Adult; Depressive Disorder, Major; East Asian People; Double-Blind Method; Treatment Outcome
PubMed: 37252829
DOI: 10.1111/pcn.13569 -
PloS One 2023Identifying modifiable risk factors early on is essential to prevent major depressive disorder (MDD). This study systematically investigated the causal relationship...
Identifying modifiable risk factors early on is essential to prevent major depressive disorder (MDD). This study systematically investigated the causal relationship between 19 modifiable risk factors and MDD. Single-nucleotide polymorphisms (SNPs) associated with 19 potentially modifiable risk factors were screened via the genome-wide association study (GWAS) enrolling individuals of European descent. Summary-level data for MDD (59,851 cases and 113,154 controls) were extracted from the UK Biobank. The inverse-variance-weighted (IVW) method was utilized as the primary analysis. Sensitivity analyses were performed using the MR-Egger method, the Maximum likelihood method, the MR-pleiotropy residual sum outlier (MR-PRESSO) method, and MR-robust adjusted profile score (MR-RAPS) method. MR-Egger regression, heterogeneity tests, pleiotropy tests, and leave-one-out tests were also performed to analyze sensitivity. The MR Steiger test was used to verify the directionality of the exposure to the outcome. Genetically predicted smoking initiation increased the risk of MDD (P = 6.00E-09), while smoking status: never and past tobacco smoking decreased the risk of MDD (all P < 0.01). In addition, education level was inversely associated with MDD risk (all P < 0.01). Genetically instrumented sleeplessness/insomnia, daytime naps, and nap during the day were positively related to the risk of MDD (all P < 0.01). Personal feelings, including guilt, hurt, tension, and worry too long after an embarrassing experience, had a suggestive increased risk for MDD (all P < 0.000). The remaining five modifiable risk factors were all causally associated with the risk of MDD, including neuroticism, neuroticism scores, body mass index (BMI), average total household income before tax, and types of physical activity in the last 4 weeks (all P < 0.01). All 19 potentially modifiable risk factors were causally associated with the risk of MDD. The main hypothesis of this MR study was that identifying and intervening in these 19 potentially modifiable risk factors could be beneficial to the prevention and treatment of MDD and further reduce mortality and economic burden.
Topics: Humans; Depressive Disorder, Major; Genome-Wide Association Study; Mendelian Randomization Analysis; Risk Factors; Smoking
PubMed: 37535610
DOI: 10.1371/journal.pone.0289419 -
Psychopharmacology Bulletin Aug 2023Transcranial magnetic stimulation (TMS) is effective in the management of treatment resistant major depressive disorder (MDD) and has recently become widely available.... (Review)
Review
BACKGROUND
Transcranial magnetic stimulation (TMS) is effective in the management of treatment resistant major depressive disorder (MDD) and has recently become widely available. Our aim was to explore the literature for evidence of the mechanism of action.
METHOD
We examined our own accumulating TMS library, the reference lists of all available papers and used a search engine to collect information. We collated and examined this information under relevant heading.
RESULTS
TMS produces a large number of physiological changes including site of stimulation neurochemical, brain wave and blood flow effects, and distant structure effects including neurotransmitter effects and volume increase. TMS also corrects generalized and local functional connectivity (FC) abnormalities which are a feature of MDD.
CONCLUSION
TMS produces a range of physiological changes. It is unclear which of these underpin its antidepressant. It is likely more than one work synergistically to this end-almost certainly the capacity to correct MDD induced FC abnormalities makes a strong antidepressant contribution.
Topics: Humans; Depressive Disorder, Major; Transcranial Magnetic Stimulation; Depressive Disorder, Treatment-Resistant
PubMed: 37601083
DOI: No ID Found -
Journal of Affective Disorders Sep 2023Parental depression is a common and potent risk factor for depression in offspring. However, the developmental course of depression from childhood to early-adulthood has...
BACKGROUND
Parental depression is a common and potent risk factor for depression in offspring. However, the developmental course of depression from childhood to early-adulthood has not been characterized in this high-risk group.
METHODS
Using longitudinal data from 337 young people who had a parent with a history of recurrent major depressive disorder (MDD), we characterized trajectories of broadly defined depressive disorder using latent class growth analysis. We used clinical descriptions to further characterise trajectory classes.
RESULTS
Two trajectory classes were identified: childhood-emerging (25 %) and adulthood-emerging (75 %). The childhood-emerging class showed high rates of depressive disorder from age 12.5, which persisted through the study period. The adulthood-emerging class showed low rates of depressive disorder until age 26. Individual factors (IQ and ADHD symptoms) and parent depression severity (comorbidity, persistence and impairment) differentiated the classes but there were no differences in family history score or polygenic scores associated with psychiatric disorder. Clinical descriptions indicated functional impairment in both classes, but more severe symptomatology and impairment in the childhood-emerging class.
LIMITATIONS
Attrition particularly affected participation in young adulthood. Factors associated with attrition were low family income, single parent household status and low parental education.
CONCLUSIONS
The developmental course of depressive disorder in children of depressed parents is variable. When followed up to adult life, most individuals exhibited some functional impairment. An earlier age-of-onset was associated with a more persistent and impairing course of depression. Access to effective prevention strategies is particularly warranted for at-risk young people showing early-onsetting and persistent depressive symptoms.
Topics: Adult; Child; Humans; Young Adult; Adolescent; Depression; Depressive Disorder, Major; Genetic Predisposition to Disease; Comorbidity; Parents; Risk Factors; Longitudinal Studies
PubMed: 37224886
DOI: 10.1016/j.jad.2023.05.063 -
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 -
Journal of Affective Disorders Nov 2023Adjustment disorder has three main subtypes: adjustment disorder with depressed mood, adjustment disorder with anxiety, and adjustment disorder with disturbance of...
Adjustment disorder has three main subtypes: adjustment disorder with depressed mood, adjustment disorder with anxiety, and adjustment disorder with disturbance of conduct. The disorder is moderately heritable and has lifetime comorbidities with major depressive disorder (MDD), anxiety disorders, or risk-tolerant personality. However, it remains unclear whether the degrees of genetic correlations between adjustment disorder and other psychiatric disorders and intermediate phenotypes are similar or different to those between MDD, anxiety disorders or risk-tolerant personality and these other psychiatric disorders and intermediate phenotypes. To compare patterns of genetic correlations, we utilized large-scale genome-wide association study summary statistics for adjustment disorder-related disorders and personality trait, eleven other psychiatric disorders and fifteen intermediate phenotypes. Adjustment disorder had highly positive genetic correlations with MDD, anxiety disorders, and risk-tolerant personality. Among other psychiatric disorders, adjustment disorder, MDD, anxiety disorders and risk-tolerant personality were positively correlated with risks for schizophrenia (SCZ), bipolar disorder (BD), SCZ + BD, attention-deficit/hyperactivity disorder, and cross disorders. In contrast, adjustment disorder was not significantly correlated with risks for obsessive-compulsive disorder, Tourette syndrome, or posttraumatic stress disorder despite significant genetic correlations of MDD or anxiety disorders with these disorders. Among intermediate phenotypes, adjustment disorder, MDD, anxiety disorders, and risk-tolerant personality commonly had a younger age at first sexual intercourse, first birth, and menopause, lower cognitive ability, and higher rate of smoking initiation. Adjustment disorder was not genetically correlated with extraversion, although the related disorder and personality were correlated with extraversion. Only adjustment disorder was correlated with a higher smoking quantity. These findings suggest that adjustment disorder could share a genetic etiology with MDD, anxiety disorders and risk-tolerant personality trait, as well as have a disorder-specific genetic etiology.
Topics: Female; Humans; Depressive Disorder, Major; Adjustment Disorders; Genome-Wide Association Study; Depression; Anxiety; Anxiety Disorders; Personality
PubMed: 37557993
DOI: 10.1016/j.jad.2023.08.019