Acta Psychiatrica Scandinavica最新文献

Background: Previous research has shown that females who use hormonal contraception are at increased risk of developing depression, and that the risk is highest among adolescents. While this finding could reflect age-specific effects of exogenous hormones on mental health, genetic liability for mental disorders could be confounding the association. Our goal was to test the plausibility of this hypothesis by determining whether polygenic liabilities for major depressive disorder (MDD), bipolar disorder (BD), schizophrenia (SCZ), and attention deficit hyperactivity disorder (ADHD) are associated with younger age at hormonal contraception initiation.

Methods: We conducted a cohort study using data from the Danish iPSYCH2015 sub-cohort, a representative sample of people born in Denmark between May 1981 and December 2008. Polygenic scores (PGSs) for MDD, BD, SCZ, and ADHD were created using the most recent genome-wide association study meta-analyses from the Psychiatric Genomics Consortium. Associations between PGSs and hormonal contraception initiation in the following age categories: 10-14, 15-19, 20-24, and 25+ were examined via Cox regression. We examined any hormonal contraception, oral contraception, and non-oral contraception.

Results: PGS-MDD and PGS-ADHD showed the strongest associations with hormonal contraception initiation at age 10-14 (PGS-ADHD: HR = 1.21 [95% CI = 1.16-1.27], p = 6.16 x 10^-18; PGS-MDD: 1.21 [1.16-1.27], p = 1.22 x 10^-17). The associations then steadily decreased as age at hormonal contraception initiation increased. Both PGS-MDD and PGS-ADHD were also associated with initiation at ages 15-19, but not at 20-24 or 25+. PGS-BD and PGS-SCZ were also associated, albeit not as strongly, with initiation at age 10-14 only (PGS-BD: 1.07 [1.02-1.13], p = 6.87 × 10^-3; PGS-SCZ: 1.09 [1.04-1.14], p = 8.61 × 10^-4).

Conclusions and relevance: These results suggest that genetic confounding could explain some of the association between early hormonal contraception use and depression. Where possible, researchers studying this important topic should account for possible confounding by genetic liability for mental disorders.

Background: Studies have shown associations between polygenic risk scores for educational attainment (PRS_EA), cognitive reserve (CR), cognition, negative symptoms (NS), and psychosocial functioning in first-episode psychosis (FEP). However, their specific interactions remain unclear. This study aimed to investigate the mediating roles of CR, cognition, and NS in the relationship between PRS_EA and psychosocial functioning one year after a FEP. Additionally, we sought to explore the impact of two NS subtypes on this relationship: diminished Expression (EXP-NS) and Motivation and Pleasure (MAP-NS).

Methods: A total of 138 FEP participants, predominantly male (70%), with a mean age of 24.77 years (SD = 5.29), underwent genetic, clinical, and cognitive assessments two months after study enrollment. Functioning evaluation followed at one-year follow-up. To investigate the mediating role of CR, cognition, and NS in the relationship between PRS_EA and functioning, a serial mediation model was employed. Two further mediation models were tested to explore the differential impact of EXP-NS and MAP-NS. Mediation analysis was performed using the PROCESS macro version 4.1 within SPSS version 26.

Results: The serial mediation model revealed a causal chain for PRS_EA > CR > cognition > NS > Functioning (β = -3.08, 95%CI [-5.73, -0.43], p = 0.023). When differentiating by type of NS, only EXP-NS were significantly associated in the casual chain (β = -0.17, 95% CI [-0.39, -0.01], p < 0.05).

Conclusions: CR, cognition and NS -specifically EXP-NS- mediate the association between PRS_EA and psychosocial functioning at one-year follow-up in FEP patients. These results highlight the potential for personalized interventions based on genetic predisposition.

Objective: The aim of this umbrella review is to summarise existing international evidence on means restriction activities for the prevention of suicide, and provide evidence of their success or lack thereof. The consolidated and integrated information can help inform potential public health interventions.

Methods: An overview of published systematic reviews in English was undertaken. There were no time restrictions. Six major repositories of systematic reviews databases were searched for relevant studies and the reference lists of all selected systematic reviews searched for identifying reviews not retrieved within the database searches. Included studies needed to be Cochrane or non-Cochrane systematic reviews (with or without meta-analyses) that explored means restriction activities for suicide prevention.

Results: A total of 670 records were identified across the searches; 11 reviews were eligible for inclusion. Three further reviews were identified through list searches with one eligible for inclusion. Thus, 12 systematic reviews were included in this umbrella review. Activities undertaken around the world were implemented for the prevention of suicide by firearms, jumping from heights and in front of a moving object, and suicide by hazardous agents. A variety of factors associated with the success and/or failure of mean restriction activities were identified, including the prevalence of method and presence or lack of a substitution effect. Most reviews found means restriction activities successful in the prevention of suicide.

Conclusions: Means restriction is an empirically proven strategy that should be considered for the prevention of suicide. Priority should be given to the most prevalent methods of suicide and implementation of locally relevant solutions, including the cultural context of the targeted population. Other important factors such as minimisation of any substitution effect need to be considered when implementing means restriction activities for suicide prevention.

Background: Although repetitive transcranial magnetic stimulation (rTMS) is an effective and commonly used treatment option for treatment-resistant depression, its cost-effectiveness remains much less studied. In particular, the comparative cost-effectiveness of rTMS and other treatment options, such as antidepressant medication, has not been investigated.

Methods: An economic evaluation with 12 months follow-up was conducted in the Dutch care setting as part of a pragmatic multicenter randomized controlled trial, in which patients with treatment-resistant depression were randomized to treatment with rTMS or treatment with the next pharmacological step according to the treatment algorithm. Missing data were handled with single imputations using predictive mean matching (PMM) nested in bootstraps. Incremental cost-effectiveness and cost-utility ratios (ICERs/ICURs) were calculated, as well as cost-effectiveness planes and cost-effectiveness acceptability curves (CEACs).

Results: Higher QALYs, response, and remission rates were found for lower costs when comparing the rTMS group to the medication group. After 12 months, QALYs were 0.618 in the rTMS group and 0.545 in the medication group. The response was 27.1% and 24.4% and remission was 25.0% and 17.1%, respectively. Incremental costs for rTMS were -€2.280, resulting in a dominant ICUR for QALYs and ICER for response and remission.

Conclusion: rTMS appears to be a cost-effective treatment option for treatment-resistant depression when compared to the next pharmacological treatment step. The results support the implementation of rTMS as a step in the treatment algorithm for depression.

Trial registration: The trial is registered within the Netherlands Trial Register (code: NL7628, date: March 29, 2019).

Introduction: There is growing interest in the use of psychedelic-assisted therapy (PAT) for major depressive disorder (MDD), including treatment-resistant depression. We used randomized controlled trial (RCT) data to compare summary estimates of change in depression ratings with PAT versus comparator treatments in MDD. We also compared response and remission rates, and adverse effects.

Methods: We searched MEDLINE, EMBASE, Cochrane Central Register for Controlled Trials (CENTRAL), and SCOPUS from inception till April 2024. Our primary efficacy outcome was 1-week (or nearest) between-group change in depression ratings. Secondary efficacy outcomes were changes in depression ratings at days 2, 14, and 42 (or nearest) and study-defined response and remission rates at week 1 (or nearest). Safety outcomes were reported adverse effects. We pooled outcomes in random-effects meta-analyses using standardized mean difference (SMD; Hedges g) for continuous outcomes and risk ratio (RR) for categorical outcomes.

Results: We found 6 eligible RCTs (pooled N = 427), all on psilocybin. The pooled SMD for 1-week between-group change in depression ratings was -0.72 [95% CI, -0.95 to -0.49; I2 = 17%; 5 RCTs; n = 403], favouring PAT; results were similar at days 2, 14, and 42. The response [RR = 3.42; 95% CI, 2.35-4.97; I2 = 0%; 4 RCTs; n = 373] and remission [RR = 3.66; 95% CI, 2.26-5.92; I2 = 0%; 4 RCTs; n = 373] rates also favored PAT. The PAT group had a small but significantly increased risk of developing any adverse event [RR = 1.20; 95% CI, 1.01-1.42; I2 = 43%; 4 RCTs; n = 373] and a significantly higher risk of experiencing headache [RR = 1.78; 95% CI, 1.10-2.86; I2 = 52%; 4 RCTs; n = 373] and dizziness [RR = 6.52; 95% CI, 1.19-35.87; I2 = 0%; 3 RCTs; n = 269]. Low heterogeneity characterized most analyses and findings were similar in sensitivity analyses.

Conclusion: Antidepressant effects of psilocybin-assisted therapy are superior (with at least medium effect sizes) to comparator interventions for at least up to 6 weeks postintervention.