Psychiatry and Clinical Neurosciences最新文献

Aim: This study aims to investigate the acute and sustained antidepressant effects of repeated ketamine infusions in patients with treatment-resistant depression (TRD), and to identify early metabolomic changes predictive of treatment outcomes using metabolome analyses.

Methods: This open-label study investigated the effects of four intravenous ketamine infusions (0.5 mg/kg) administered over 2 weeks in 30 patients with TRD. Clinical outcomes, including the Montgomery-Åsberg Depression Rating Scale (MADRS), were evaluated at baseline, 1-2 h after each infusion, and monthly during a 12-month follow-up. Plasma levels of 11 depression-associated metabolites were measured at baseline and 1.5-2 h after the first infusion. A general linear model was employed to analyze the association between metabolite changes after the first infusion and the MADRS score percent improvements after the fourth infusion and at 12 months. Remission was defined as a MADRS score of ≤10.

Results: All participants completed the four infusions. The MADRS score decreased from 30.6 ± 6.1 at baseline to 20.3 ± 11.5 after the fourth infusion, with a remission rate of 26.7%. At 12 months, 13.3% of participants remained in remission. Changes in 3-hydroxybutyrate levels after the first infusion predicted the MADRS score percent improvements after the fourth infusion (β = 1.35, 95% CI: 0.41-2.30, P = 0.005) and at 12 months (β = 1.38, 95% CI: 0.37-2.39, P = 0.007).

Conclusion: While repeated ketamine infusions demonstrated rapid antidepressant effects, sustained remission was achieved in a minority of patients with TRD. 3-Hydroxybutyrate may serve as a biomarker for predicting treatment response. These findings underscore the potential for individualized strategies using ketamine infusions.

Clinical trial registration: jRCTs031210648 (Japan Registry of Clinical Trials).

Aim: Depression and antidepressant drugs may both impact breast cancer incidence, potentially in opposite directions. The few epidemiological studies attempting to disentangle their effects have been inconclusive. We aimed to assess within the same prospective cohort the association between depression, antidepressant use, and breast cancer risk, while controlling for potential confounders.

Methods: The study population included 47,791 women from the E3N (Etude Epidémiologique Auprès de Femmes de la Mutuelle Générale de l'Education Nationale) prospective cohort, born between 1925 and 1950 and followed for breast cancer incidence from 2005 to 2014. Depression was defined by a Center for Epidemiologic Studies-Depression Scale (CES-D) score ≥17. Exposure to antidepressants was identified from drug claims data available from 2004 onwards. Hazard ratios (HRs) and 95% confidence intervals (CIs) for invasive breast cancer were calculated using Cox proportional hazards models adjusted for breast cancer risk factors. Antidepressant exposure was time-varying.

Results: During a mean follow-up of 7.2 years, 1365 breast cancers occurred. Depression was associated with a higher incidence of breast cancer (HR, 1.14 [95% CI, 1.01-1.29]), while exposure to antidepressants was associated with a lower risk (HR, 0.85 [95% CI, 0.74-0.98]). No association was observed for treatment durations <6 months (HR, 1.02 [95% CI, 0.79-1.32]), while antidepressant use for at least 24 months was associated with an HR of 0.80 (95% CI, 0.64-0.99).

Conclusion: These findings from a prospective cohort suggest that depression and antidepressant drugs exert opposing effects on breast cancer incidence. While these results require replication in future studies, they could help promote adherence to antidepressant drugs in women with depression.

Background: Sexual and gender minorities (SGMs) are known to experience mental health disparities. Outing, the non-consensual disclosure of one's sexual orientation or gender identity, has been suggested to exacerbate these issues. This study aimed to investigate the mental health status, outing experiences and their associations among SGMs in Japan.

Methods: This cross-sectional study used data from 'the Japan COVID-19 and Society Internet Survey' conducted in September-October 2022, analyzing SGMs aged 18-79. Outing experiences were assessed across family, friends and school/workplace. Mental health was measured using the Kessler 6-Item Psychological Distress Scale (K6) and self-reported suicidal ideation within the past year. Modified Poisson regression was used to estimate prevalence ratios for mental health outcomes associated with outing experiences and the outing ranges within communities while adjusting for sociodemographic factors.

Results: Of the 2596 SGM participants analyzed, 50.8% exhibited moderate-to-high K6 scores and 9.3% reported experiencing outings, with transgender and gender non-binary individuals being the most affected. Outing experience was significantly associated with moderate-to-high K6 scores (adjusted prevalence ratios [aPR], 1.43; 95% confidence interval [CI], 1.33-1.55), high K6 scores (aPR, 1.36; 95% CI, 1.10-1.68) and suicidal ideation within the past year (aPR, 1.39; 95% CI, 1.17-1.66). Additionally, experiencing outings within broader communities showed a dose-dependent association with higher levels of mental distress (aPR of moderate-to-high K6 for one to three communities: 1.31, 1.52 and 1.58, respectively).

Conclusion: Outings can be a significant minority stressor among SGMs in Japan, contributing to elevated psychological distress and suicidal ideation.

This article relates to Comment on: Is clozapine use a risk of hematological malignancies? Insights from a meta-analysis "Clozapine and Malignancy Risk".

Aim: Long-acting injectable antipsychotics (LAIs) offer several advantages over oral antipsychotic medications for treating schizophrenia. However, whether the benefits of LAIs extend to patients receiving homecare case management (CM) remains unclear.

Methods: This cohort study used Taiwan's National Health Insurance Research Database, enrolling 19,680 nationwide patients with schizophrenia who began homecare CM between January 1, 2000, and December 31, 2019. Each patient was followed for 5 years or to the data censored, with 30-day periods serving as follow-up units. We evaluated LAI and other medication usage during each period and their associations with mortality outcomes. Additionally, we investigated whether consistent users of homecare CM services (maintenance group) receiving specific LAI treatments had better prognoses.

Results: In the cohort (n = 19,680), 6428 received first-generation antipsychotic long-acting injectables (FGA-LAIs) and 4954 received second-generation antipsychotic long-acting injectables (SGA-LAIs). The FGA-LAI group had a mean age of 39.27 years (55.13% male), while the SGA-LAI group had a mean age of 41.25 years (53.75% male). Of 1366 deaths within 5 years, 980 were from natural causes and 254 from suicide. FGA-LAIs reduced natural mortality (HR: 0.67, P = 0.001) but increased suicide risk (HR: 1.52, P = 0.01). SGA-LAIs lowered all-cause (HR: 0.53, P < 0.001) and natural mortality (HR: 0.42, P < 0.001) without affecting suicide mortality (HR: 0.82, P = 0.384). In the maintenance group, FGA-LAIs showed no mortality benefit and increased suicide risk (HR: 2.07, P < 0.001), while SGA-LAIs consistently reduced all-cause (HR: 0.39, P < 0.001), natural (HR: 0.31, P < 0.001), and suicide mortality (HR: 0.54, P = 0.034).

Conclusions: SGA-LAIs could be a preferable treatment for reducing mortality in patients with schizophrenia receiving homecare CM, particularly for those in the maintenance group.

Although COVID-19 was originally considered a respiratory illness, it is now well established that SARS-CoV-2 infection can have far-reaching impacts on the nervous system. Neurological symptoms such as chemosensory dysfunction are frequently observed during acute infection and approximately 10% of COVID-19 cases will go on to develop new or persistent long-term symptoms, a condition known in the literature as post-acute symptoms of COVID-19 (PASC) or by the patient-coined term Long COVID. Common neurological symptoms in Long COVID include new onset cognitive difficulties, dysautonomia, fatigue, and peripheral neuropathy. The emergence of Long COVID has prompted renewed interest in the study of post-acute infection syndromes (PAIS), particularly in the area of neuroimmune interactions. In this review we provide a comprehensive overview of the current body of literature on neurological manifestations of SARS-CoV-2 infection and Long COVID, with an emphasis on neuroimmune mechanisms drawn largely from autopsy studies and animal models. A more complete understanding of neuroimmune crosstalk in Long COVID will not only guide the development of therapies for this highly disabling condition but will also contribute to our general understanding of neuroimmune interactions in health and disease.