Acta Psychiatrica Scandinavica最新文献

Introduction: Depression with a history of trauma often responds poorly to conventional antidepressants and has a poor prognosis. Prazosin, an α1-adrenoceptor blocker, has shown promise in treating post-traumatic stress disorder symptoms, particularly nightmares. Its potential in treating depression with trauma history warrants investigation.

Aims of the study: This randomised, double-blind, placebo-controlled study aimed to investigate the efficacy and tolerability of low-dose prazosin (0.5-1 mg/day) as an augmentation strategy in patients with depression and a history of trauma. We sought to determine if prazosin could provide rapid symptom improvement and enhance overall treatment response compared to placebo in this difficult-to-treat patient population.

Methods: This randomised, double-blind, placebo-controlled clinical study included 59 patients with first-episode or recurrent unipolar or bipolar depression. After basic antidepressant treatment, they were randomly assigned to a prazosin (0.5-1 mg/day) or placebo group for a 6-week double-blind controlled study. The Montgomery-Åsberg Depression Rating Scale, 17-item Hamilton Depression Scale (HAMD-17), and Hamilton Anxiety Scale (HAMA) were used to evaluate efficacy.

Results: There were no significant differences in the results of the demographic and clinical symptom assessment between the two groups (p > 0.05). The difference between the HAMD-17 and HAMA scores was statistically significant after 3 days of treatment (p < 0.05). The difference in response rate between the two groups was statistically significant after week 4 of treatment (end of week 4, 56.7% vs. 24.1%, p = 0.011; end of week 6, 80.0% vs. 48.3%, p = 0.011). The incidence of adverse reactions in the prazosin and placebo groups was 20.0% and 24.1%, respectively, with no statistically significant differences (p > 0.05); however, the prazosin group had a lower incidence of sleeplessness or nightmares (3.3% vs. 20.7%, p = 0.039) but a higher incidence of orthostatic hypotension (16.7% vs. 0%, p = 0.007). The severity of orthostatic hypotension was mild to moderate.

Conclusion: Low-dose prazosin can effectively improve the emotional symptoms of patients with depression and a history of trauma, and the common adverse reaction is mild-to-moderate orthostatic hypotension.

Clinical trial registration: ChiCTR2200063642.

Introduction: There is a "traditional belief" that antidepressant side effect complaints improve with medication persistence; however, support for this theory has remained inconclusive. We aimed to examine if side effect complaints improved over time by modeling the relationship between side effect complaints and time at dropout for patients receiving citalopram during the first level of acute treatment in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.

Methods: We categorized the 2833 patients into five patterns by week of dropout. We used pattern-mixture modeling to model change in side effect complaints (frequency, intensity, and burden) over the 12-week course of treatment, while accounting for attrition and depressive severity. Using post-hoc linear contrasts, we compared the attrition patterns with the completers' pattern for severity of side effect complaints at each respective last visit prior to dropout as well as averaged side effect complaints across the duration of treatment. We also reported frequencies and tolerability of side effects for nine organ/function systems over the course of treatment.

Results: Patients who dropped out early exhibited worsening side effect burden and patients who dropped out later showed improvements in side effect frequency and intensity. Treatment completers improved in all side effect complaints over the course of treatment. Early attrition patterns had more severe side effect complaints for both tests of post-hoc linear contrasts than later attrition patterns and completers.

Conclusions: Side effect complaints from antidepressant treatment improve over time, but only for some types of patients. As a precaution for early dropout, clinicians should monitor patients who exhibit worsening and more severe side effect complaints-especially in the first 6 weeks of antidepressant treatment. In addition, clinicians may want to consider changing the type of treatment early on for these patients, rather than encouraging them to persist with their current medication.

Introduction: Early-onset psychotic disorders include the prodromal phase and the first-episode psychosis (FEP). They constitute a high-risk period for suicidal behavior. Early intervention for psychosis (EIP) consists of intervening as early as possible. The effectiveness of early intervention on overall prognosis has been reported in numerous studies, and EIP services are emerging worldwide. Several authors report an improvement in suicidal behavior, but no study has looked at all the data.

Aims of the study: The aim of work is to study whether early intervention for psychosis has an impact on deaths by suicide and suicide attempts, and study which intervention methods have an impact on suicidal behavior.

Methodology: By respecting the PRISMA criteria, previously declared on PROSPERO, by exploring 5 medical databases (PubMed, Cochrane, PsycINFO, Scopus, Embase), from their creation dates, published until 20/02/2023, in English, we carried out a meta-analysis. The articles selected had to deal with the EIP and deaths by suicide or suicide attempts. Our primary outcome is the deaths by suicide and the secondary outcome the suicide attempt.

Results: The exhaustive search identified a total of 2310 references. Nine articles were included. Their intervention modalities were pharmacotherapy, psychotherapy, case-management, or related services, and psycho-social therapies. Our meta-analysis shows that early intervention for early-onset psychotic disorders is associated with a statistically significant reduction by a third in deaths by suicide (ORa = 0.66 (0.49-0.88), p = 0.005) and by a third in suicide attempts (ORa = 0.66 (0.50-0.86), p = 0.002), with non-significant heterogeneity. Sensitivity analyses excluding the study with statistical difficulties due to the absence of an event and studies with a high risk of bias point in the same direction, that is a statistically significant reduction and non-significant heterogeneity.

Conclusion: The literature shows that early intervention programs are associated with positive impact on deaths by suicide and suicide attempt. This is the first meta-analysis of early intervention in early psychotic disorders and its impact on suicidal risk. The deployment of EIP should be supported worldwide in order to intervene as early as possible and prevent the risk of suicide.

Trial registration: PROSPERO CRD42022366976.

Background: Egsgaard et al. (2024) highlight the temporal patterns of postpartum depression (PPD) risk in twin parents versus singleton parents. However, additional factors such as social support systems, delivery mode, and cultural influences require exploration.

Purpose: To discuss the role of structured postpartum care, cesarean sections, and mother-infant bonding in moderating PPD risk, especially within cultural contexts.

Conclusion: These factors may explain the gender-specific temporal patterns observed by Egsgaard et al. Future research should integrate sociocultural and clinical variables to inform interventions for twin parents at risk of PPD.

Background: Parents of twins appear to be at increased risk of postpartum depression (PPD), yet little is known about the magnitude and timing of onset in the postpartum period compared to singleton parents.

Methods: We conducted a cohort study using the Danish nationwide health registers. We defined a study population of parents that is, mothers and fathers of all twin and singleton livebirths between 1997 and 2019. Postpartum depression was defined as incident depression diagnosis or a redeemed antidepressant prescription from childbirth through 365 days postpartum. We performed a parametric time-to-event analysis based on Poisson regression. The time scale was time since birth, modeled using restricted cubic splines. From this we estimated the hazard ratio (HR) representing the momentary risk, and the cumulative risk ratio (RR) over the first year postpartum, in twin compared to singleton parents.

Results: The study population was based on 27,095 twin and 1,350,046 singleton births. In adjusted analyses, the HR of twins compared to singletons was highest around 2 months postpartum (HR 1.28, 95% CI 1.10-1.49) for mothers, and around 6 months (1.20, 95% CI 1.02-1.42) for fathers. The 6 months adjusted cumulative RR of PPD in twins compared to singletons was 1.24 (95% CI 1.10-1.40) for mothers and 1.11 (95% CI 0.95-1.30) for fathers.

Conclusions: Twin mothers had increased risk of PPD compared to singleton mothers, which was driven by an immediate increase after childbirth. The risk among twin fathers was not increased immediately after childbirth, but we found slightly elevated risk around 6 months postpartum. This could suggest diverse patterns of PPD symptomatology in twin parents compared to singleton parents and between mothers and fathers. Our findings underline parents of twins as a potentially vulnerable group to PPD and emphasize the need for increased awareness of their mental health.

Background: The neurobiological basis of impulsivity and its role in suicide attempt (SA) in BD remains underexplored. This study aimed to examine the functional connectivity (FC) within the prefrontal cortex (PFC) in BD patients with and without a history of SA, focusing on the role of trait impulsivity.

Methods: Seventy-two euthymic BD patients (34 with a history of SA, BDSA; and 38 without, BDNS) and 55 age- and sex-matched healthy controls underwent resting-state functional MRI. FC analyses were conducted on four PFC regions: superior frontal gyrus (SFG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG), and orbitofrontal cortex (OFC). Trait impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11), and its association with FC was analyzed using a general linear model, adjusting for demographic and clinical variables.

Results: BDSA had higher trait impulsivity than BDNS and the controls. BDSA exhibited reduced FC between the PFC and sensorimotor (postcentral and precentral gyri) and thalamic regions compared to BDNS. These reductions in FC of the fronto-thalamic and fronto-sensorimotor circuits were significantly associated with higher trait impulsivity scores.

Conclusion: The findings highlight specific PFC-based FC alterations associated with suicide attempts and trait impulsivity in BD, offering potential neurobiological markers for suicide risk in this population.

Objective: The study aimed to estimate 5-year recurrence rates of first-episode major depressive disorder (MDD) and assess the impact of adolescence on recurrence likelihood after the first episode, compared to adults.

Methods: A pre-registered retrospective cohort study that utilized epidemiological data from the Stockholm MDD Cohort (1997-2018), including all individuals registered with a depression diagnosis in Region Stockholm from 2010 to 2018. This dataset combines longitudinal information from primary and secondary care, socioeconomic data, drug dispensations, psychotherapy sessions, brain stimulation treatments, and inpatient treatment. The study included 9124 individuals (1727 adolescents aged 13-17 and 7397 adults aged 18-40) who experienced their first MDD episode between 2011 and 2012, with at least three months of remission. Propensity score weighting balanced cohorts for biological sex, socioeconomic status, depression severity, psychiatric comorbidities, and treatments.

Results: The 5-year recurrence rates were 46.1% for adolescents and 49.0% for adults. The study had over 80% power to detect a minimum absolute difference in recurrence rates of approximately 5.5 percentage points. No significant difference in recurrence likelihood (p = 0.364) or time from remission to recurrence (median 379 days for adolescents, 326 days for adults, p = 0.836) was found between groups. Findings were consistent across bootstrap replicates and sensitivity analyses with extended remission periods.

Conclusions: Approximately half of individuals with a first MDD episode experience recurrence within five years. Recurrence rates were higher than expected for adults but consistent with expectations for adolescents. The study underscores the need for relapse prevention from adolescence through adulthood and indicates a similar clinical course of MDD across age groups.

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.