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Journal of Affective Disorders Apr 2024Association between depression and aneurysm has been implicated but the specific role of depression in aneurysm remains unclear. We aimed to comprehensively characterize...
BACKGROUND
Association between depression and aneurysm has been implicated but the specific role of depression in aneurysm remains unclear. We aimed to comprehensively characterize the relation of major depressive disorder (MDD) with aneurysm by subtype.
METHODS
Harnessing summary statistics from genome-wide association studies (N/N = 7603/317,899 for aortic aneurysm; 7321/317,899 for thoracic aortic aneurysm; 3201/317,899 for abdominal aortic aneurysm; 1788/317,899 for cerebral aneurysm; and 246,363/561,190 for major depressive disorder), we estimated the genetic correlation between MDD and each of four aneurysm subtypes via LD Score Regression and tested the causality via various estimators under the bi-directional Mendelian randomization (MR) framework.
RESULTS
Positive genetic correlation of statistical significance, ranging between 0.15 (with thoracic aortic aneurysm, P = 0.005) and 0.25 (with abdominal aortic aneurysm, P = 0.001), was consistently observed for MDD with each aneurysm subtype. In the MR analysis of MDD as an exposure, genetic liability to MDD causally increased the risk of cerebral (odds ratio: 1.71; 95 % confidence interval: 1.26-2.34) but not aortic aneurysm. Replication analysis of an independent dataset (N/N = 6242/59,418) corroborated this signal. In contrast, causal effect was not evident for any neurysm subtype on susceptibility to MDD.
LIMITATIONS
Aneurysm could have been underdiagnosed if asymptomatic, leading to an underestimated causal impact on MDD. Non-linearity of the causal effect was not tested due to the lack of individual-level data.
CONCLUSIONS
Depression and aneurysm may share common pathomechanisms. Screening depressed population and improving the clinical management for depression may benefit the primary prevention of cerebral aneurysm.
Topics: Humans; Depressive Disorder, Major; Genome-Wide Association Study; Intracranial Aneurysm; Mendelian Randomization Analysis; Aortic Aneurysm, Thoracic; Aortic Aneurysm, Abdominal; Polymorphism, Single Nucleotide
PubMed: 38237871
DOI: 10.1016/j.jad.2024.01.128 -
JAMA Psychiatry Jan 2024Antidepressants are increasingly prescribed to pediatric patients with unipolar depression, but little is known about the risk of treatment-emergent mania. Previous...
IMPORTANCE
Antidepressants are increasingly prescribed to pediatric patients with unipolar depression, but little is known about the risk of treatment-emergent mania. Previous research suggests pediatric patients may be particularly vulnerable to this adverse outcome.
OBJECTIVE
To estimate whether pediatric patients treated with antidepressants have an increased incidence of mania/hypomania compared with patients not treated with antidepressants and to identify patient characteristics associated with the risk of mania/hypomania.
DESIGN, SETTING, AND PARTICIPANTS
In a cohort study applying the target trial emulation framework, nationwide inpatient and outpatient care in Sweden from July 1, 2006, to December 31, 2019, was evaluated. Follow-up was conducted for 12 and 52 weeks after treatment initiation, with administrative follow-up ending December 31, 2020. Data were analyzed between May 1, 2022, and June 28, 2023. Individuals aged 4 to 17 years with a diagnosis of depression, but without a prior diagnosis of mania/hypomania, bipolar disorder, or psychosis or treatment with mood stabilizer (lithium, valproate, or carbamazepine), prescriptions were included.
EXPOSURES
The treatment group included patients who initiated any antidepressant medication within 90 days of diagnosis. The control group included patients who did not initiate antidepressants within 90 days.
MAIN OUTCOMES AND MEASURES
Diagnosis of mania/hypomania or initiation of mood stabilizer therapy. Incidences were estimated with Kaplan-Meier estimator, and inverse probability of treatment weighting was used to adjust for group differences at baseline.
RESULTS
The cohort included 43 677 patients (28 885 [66%] girls); 24 573 in the treatment group and 19 104 in the control group. The median age was 15 (IQR, 14-16) years. The outcome occurred in 96 individuals by 12 weeks and in 291 by 52 weeks. The cumulative incidence of mania was 0.26% (95% CI, 0.19%-0.33%) in the treatment group and 0.20% (95% CI, 0.13%-0.27%) in the control group at 12 weeks, with a risk difference of 0.06% (95% CI, -0.04% to 0.16%). At 52 weeks, the cumulative incidence was 0.79% (95% CI, 0.68%-0.91%) in the treatment group and 0.52% (95% CI, 0.40%-0.63%) in the control group (risk difference, 0.28%; 95% CI, 0.12%-0.44%). Hospitalizations, parental bipolar disorder, and use of antipsychotics and antiepileptics were the most important predictors of mania/hypomania by 12 weeks.
CONCLUSION
This cohort study found no evidence of treatment-emergent mania/hypomania by 12 weeks in children and adolescents. This corresponds to the time frame for antidepressants to exert their psychotropic effect. A small risk difference was found only with longer follow-up. Certain patient characteristics were associated with mania/hypomania, which warrants clinical attention.
Topics: Female; Humans; Adolescent; Child; Male; Mania; Cohort Studies; Depression; Antidepressive Agents; Depressive Disorder; Antipsychotic Agents
PubMed: 37755835
DOI: 10.1001/jamapsychiatry.2023.3555 -
BMJ (Clinical Research Ed.) May 2024
Topics: Humans; Psilocybin; Hallucinogens; Depressive Disorder
PubMed: 38692675
DOI: 10.1136/bmj.q798 -
The Journal of Clinical Psychiatry Dec 2023Zuranolone is a positive allosteric modulator of both synaptic and extrasynaptic γ-aminobutyric acid (GABA) type A receptors and a neuroactive steroid approved in the...
Long-Term Safety and Efficacy of Initial and Repeat Treatment Courses With Zuranolone in Adult Patients With Major Depressive Disorder: Interim Results From the Open-Label, Phase 3 SHORELINE Study.
Zuranolone is a positive allosteric modulator of both synaptic and extrasynaptic γ-aminobutyric acid (GABA) type A receptors and a neuroactive steroid approved in the United States as an oral, once-daily, 14-day treatment course for adults with postpartum depression and under investigation for adults with major depressive disorder (MDD). Interim results from the open-label, longitudinal, phase 3 SHORELINE Study (NCT03864614) that evaluated the long-term safety and efficacy of zuranolone in adults with MDD are reported. This interim report includes patients who were enrolled and had the opportunity to be on study for up to 1 year between February 2019 and September 2021. Adults aged 18-75 years with MDD diagnosed per criteria and a 17-item Hamilton Rating Scale for Depression (HAMD-17) total score ≥ 20 received an initial 30-mg or 50-mg 14-day zuranolone course. HAMD-17 responders (≥ 50% reduction from baseline) at Day (D)15 of the initial treatment period were allowed to continue in the study beyond D28 and were followed up for ≤ 1 year, during which repeat treatment courses were permitted. The primary endpoint was safety and tolerability of the initial and repeat treatment courses through 1 year. Secondary endpoints included change from baseline (CFB) in HAMD-17 total score and need for repeat treatment course(s). As of September 2021, among patients in the 30-mg (n = 725) and 50-mg (n = 199) Cohorts who received a zuranolone dose, 493 (68.0%) and 137 (68.8%), respectively, reported a treatment-emergent adverse event (TEAE); most patients who experienced TEAEs reported mild/moderate events (30-mg Cohort, 90.9% [448/493]; 50-mg Cohort, 85.4% [117/137]). Mean (standard deviation) CFB HAMD-17 total score at D15 of the initial treatment period was -15.2 (7.1) and -16.0 (6.0) for the 30-mg and 50-mg Cohorts, respectively; similar improvements were observed after repeat treatment courses. The proportion of patients who received only 1 treatment course during their time on study was 42.9% (210/489) in the 30-mg Cohort and 54.8% (80/146) in the 50-mg Cohort; 57.1% (279/489) and 45.2% (66/146) patients, respectively, received 2-5 total treatment courses. The majority of patients who initially responded to zuranolone received ≤ 2 total treatment courses (30-mg Cohort, 68.5% [335/489]; 50-mg Cohort, 79.5% [116/146]). Of patients who experienced TEAEs, most reported mild or moderately severe events, and responders to zuranolone experienced improvements in depressive symptoms with initial and repeat treatment courses. ClinicalTrials.gov identifier: NCT03864614.
Topics: Adult; Female; Humans; Depressive Disorder, Major; Double-Blind Method; Treatment Outcome; Longitudinal Studies
PubMed: 38153320
DOI: 10.4088/JCP.23m14845 -
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 -
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 -
Acta Psychiatrica Scandinavica May 2024Long-term studies comparing nonresponse to antidepressants for major depressive disorder (MDD) are lacking. (Comparative Study)
Comparative Study
Comparative responses to 17 different antidepressants in major depressive disorder: Results from a 2-year long-term nation-wide population-based study emulating a randomized trial.
BACKGROUND
Long-term studies comparing nonresponse to antidepressants for major depressive disorder (MDD) are lacking.
AIMS
To present systematic population-based nation-wide register data on comparative 2-year non-response within six antidepressant drug classes and 17 different antidepressants in patients with MDD.
METHOD
The study included all 106,920 patients in Denmark with a first main index diagnosis of MDD at a psychiatric hospital inpatient or outpatient contact and who subsequently had a purchase of an antidepressant in the period from 1995 to 2018. Non-response to first antidepressant within a 2-year study period was defined as switch to or add-on of another antidepressant, antipsychotic medication, lithium, or hospitalization. Analyses emulated a targeted trial in populations standardized according to age, sex, socioeconomic status, and comorbidity with psychiatric and physical disorders.
RESULTS
Compared with sertraline, there was no difference for citalopram (RR: 1.00 [95% CI: 0.98-1.02]) but fluoxetine (1.13 [95% CI: 1.10-1.17]), paroxetine (1.06 [95% CI: 1.01-1.10]) and escitalopram (1.22 [95% CI: 1.18-1.25]) were associated with higher risk ratio of non-responses. Within selective noradrenaline reuptake inhibitors, sertraline outperformed reboxetine; within serotonin-norepinephrine reuptake inhibitors, venlafaxine outperformed duloxetine; within noradrenergic and specific serotonergic antidepressants, mirtazapine outperformed mianserin and within the class of other antidepressants, sertraline outperformed agomelatine and vortioxetine. Within tricyclic antidepressants, compared to amitriptyline, nortriptyline, dosulepin, and clomipramine had higher non-response, whereas there was no difference for imipramine.
CONCLUSIONS
These analyses emulating a randomized trial of "real world" observational register-based data show that 2-year long-term non-responses to some antidepressants within six different drug classes are increased over others.
Topics: Humans; Antidepressive Agents; Depressive Disorder, Major; Fluoxetine; Selective Serotonin Reuptake Inhibitors; Sertraline
PubMed: 38379028
DOI: 10.1111/acps.13673 -
Child: Care, Health and Development Mar 2024This meta-analysis evaluated the relationship between overweight/obesity and depressive disorders in children and adolescents. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This meta-analysis evaluated the relationship between overweight/obesity and depressive disorders in children and adolescents.
METHODS
We examined the databases of PubMed, Embase and Web of Science for pertinent observational studies released up until 20 February 2022. The pooled relative risks (RRs) and 95% confidence intervals (CIs) of obesity and overweight with depressive disorder were calculated by means of random-effects models. The Newcastle-Ottawa Quality Assessment Scale and Agency for Healthcare Research and Quality scale were adopted to evaluate the study quality.
RESULTS
Finally, for this meta-analysis, we evaluated 22 observational publications covering 175 135 participants (5 cohort study articles, 1 case-control study article and 16 cross-sectional study articles). A significant positive association was found between obesity and the risk of depression (RR 1.32, 95% CI 1.09-1.60, I = 79.90%, P < 0.001) and in the association between obesity and depressive symptoms (RR 1.16, 95% CI: 1.00-1.35, I = 25.0%, P = 0.247). On sensitivity analysis, the pooled RRs remained robust. Subgroup analysis indicated that obese children and teenagers in western countries were more prone to depression.
CONCLUSION
Evidence from this meta-analysis, based on observational studies, supported the idea that obese children and adolescents are more likely to experience depression and depressive symptoms.
Topics: Adolescent; Humans; Child; Overweight; Pediatric Obesity; Cohort Studies; Cross-Sectional Studies; Case-Control Studies; Depressive Disorder; Observational Studies as Topic
PubMed: 38410046
DOI: 10.1111/cch.13237 -
Journal of Affective Disorders Jul 2023Early sexual intercourse and a greater number of sexual partners have been proved associated with depression. However, the causality of these associations is not clear.
Identifying causal associations between early sexual intercourse or number of sexual partners and major depressive disorders: A bidirectional two-sample Mendelian randomization analysis.
BACKGROUND
Early sexual intercourse and a greater number of sexual partners have been proved associated with depression. However, the causality of these associations is not clear.
METHODS
To unveil the causal associations between sexual factors and major depression disorder (MDD). The bidirectional, two-sample Mendelian randomization (MR) study was conducted, which used genetic variants associated with two sexual factors (age first had sexual intercourse, n = 406,457; lifetime number of sexual partners, n = 378,882) and MDD (n = 500,199) from the largest genome-wide association studies (GWASs) conducted by the UK biobank and the Psychiatric Genomics Consortium. The two-step MR analysis was applied to assess mediation. The Genetic predictors for five risky behaviors were also obtained from the most up-to-date GWAS conducted by the UK Biobank (ever self-harmed: 117,733; ever attempted suicide: 4933; psychoactive substance abuse, alcohol use, and tobacco use: 463,010).
RESULTS
MR analysis indicated a risky causal effect of age first had sexual intercourse (OR = 0.720, 95 % CI: 0.661-0.784, P = 2.45 × 10) and lifetime number of sexual partners (OR = 1.656, 95 % CI: 1.356-2.022, P = 7.46 × 10) on MDD. Mediation analysis showed the effects were mediated by tobacco use, with a proportion of 34.20 % on age first had sexual intercourse and 22.94 % on lifetime number of sexual partners separately.
LIMITATIONS
The overlap of participants in different traits and unclear gender.
CONCLUSIONS
Robust genetic evidence indicated that premature sexual intercourse and more sexual partners were risks for MDD. Risky behaviors, especially the tobacco use, mediated this effect.
Topics: Humans; Depressive Disorder, Major; Sexual Partners; Mendelian Randomization Analysis; Genome-Wide Association Study; Coitus; Polymorphism, Single Nucleotide
PubMed: 37086791
DOI: 10.1016/j.jad.2023.04.079 -
Blood Advances Sep 2023Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are associated with an increased risk of cardiovascular diseases, including venous... (Meta-Analysis)
Meta-Analysis
Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are associated with an increased risk of cardiovascular diseases, including venous thromboembolism (VTE). The reasons for this are complex and include obesity, smoking, and use of hormones and psychotropic medications. Genetic studies have increasingly provided evidence of the shared genetic risk of psychiatric and cardiometabolic illnesses. This study aimed to determine whether a genetic predisposition to MDD, BD, or SCZ is associated with an increased risk of VTE. Genetic correlations using the largest genome-wide genetic meta-analyses summary statistics for MDD, BD, and SCZ (Psychiatric Genetics Consortium) and a recent genome-wide genetic meta-analysis of VTE (INVENT Consortium) demonstrated a positive association between VTE and MDD but not BD or SCZ. The same summary statistics were used to construct polygenic risk scores for MDD, BD, and SCZ in UK Biobank participants of self-reported White British ancestry. These were assessed for impact on self-reported VTE risk (10 786 cases, 285 124 controls), using logistic regression, in sex-specific and sex-combined analyses. We identified significant positive associations between polygenic risk for MDD and the risk of VTE in men, women, and sex-combined analyses, independent of the known risk factors. Secondary analyses demonstrated that this association was not driven by those with lifetime experience of mental illness. Meta-analyses of individual data from 6 additional independent cohorts replicated the sex-combined association. This report provides evidence for shared biological mechanisms leading to MDD and VTE and suggests that, in the absence of genetic data, a family history of MDD might be considered when assessing the risk of VTE.
Topics: Male; Humans; Female; Depressive Disorder, Major; Venous Thromboembolism; Bipolar Disorder; Schizophrenia; Risk Factors
PubMed: 37399490
DOI: 10.1182/bloodadvances.2023010562