European Psychiatry最新文献

Current evidence points to a research-practice gap in mental health. There is a specific unmet need to identify novel strategies to improve diagnostic criteria, especially when clinical manifestations overlap as in the case of bipolar (BD) and major depressive disorder (MDD). Based on the rapidly evolving notion that affective disorders are characterized by disrupted brain-body communication, current efforts of neuropsychiatric research are converging towards the identification of specific clusters of peripheral interconnected biomarkers. We argue that these can capture the complexity of the disease as they are linked to the fundamental pathophysiological mechanisms underlying BD or MDD, and can thus deliver an unbiased biosignature. Here we provide a critical viewpoint on the promises and challenges of biomarkers to identify reliable biosignatures of affective disorders. Novel methodological insight and relevant biomarkers are discussed with a main focus on immunometabolic derangements and disrupted redox balance. Major advancements are reviewed taking into consideration that an unbiased diagnosis can only derive from a deep understanding of how biological, psychological, and social factors interact ultimately affecting the clinical manifestation of affective disorders.

The dissociative effects of ketamine and psychedelics might be associated with their rapid antidepressant properties, raising questions about whether these effects are necessary for their therapeutic action. Additionally, the distinct dissociative experiences often reported by patients in clinical trials may reveal whether they receive an active treatment or a placebo, potentially introducing bias into the results. In this viewpoint, we propose administering ketamine/psychedelics to patients during sleep, offering a novel approach to address and explore these challenges.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used due to their profound efficacy in glycemic control and weight management. Real-world observations have revealed potential neuropsychiatric adverse events (AEs) associated with GLP-1RAs. This study aimed to comprehensively investigate and characterize these neuropsychiatric AEs with GLP-1RAs.

Methods: We analyzed GLP-1RA adverse reaction reports using the FDA Adverse Event Reporting System database. Disproportionality analysis using reporting odds ratio (ROR) identified eight categories of neuropsychiatric AEs associated with GLP-1RAs. We conducted descriptive and time-to-onset (TTO) analyses and explored neuropsychiatric AE signals among individual GLP-1RAs for weight loss and diabetes mellitus (DM) indications.

Results: We identified 25,110 cases of GLP-1RA-related neuropsychiatric AEs. GLP-1RAs showed an association with headache (ROR 1.74, 95% confidence interval [CI] 1.65-1.84), migraine (ROR 1.28, 95%CI 1.06-1.55), and olfactory and sensory nerve abnormalities (ROR 2.44, 95%CI 1.83-3.25; ROR 1.69, 95%CI 1.54-1.85). Semaglutide showed a moderate suicide-related AEs signal in the weight loss population (ROR 2.55, 95%CI 1.97-3.31). The median TTO was 16 days (interquartile range: 3-66 days).

Conclusions: In this study, we identified eight potential neuropsychiatric adverse events (AEs) associated with GLP-1RAs and, for the first time, detected positive signals for migraine, olfactory abnormalities, and sensory abnormalities. We also observed positive suicide-related signals of semaglutide, in weight loss population. This study provides a reliable basis for further investigation of GLP-1RA-related neuropsychiatric AEs. However, as an exploratory study, our findings require confirmation through large-scale prospective studies.

Background: Despite uncertain benefits, antidepressants are used in the management of personality disorders (PDs). We investigated the association between antidepressants and two adverse outcomes - suicidal behaviour and violent crimes - in individuals with PDs.

Methods: We used nationwide Danish healthcare registries to identify all individuals with a diagnosed PD aged 18-64 years from 2007 to 2016. Antidepressant use was identified using dispensed prescriptions. Individuals were followed up for healthcare presentations of suicidal behaviour and separately for police-recorded charges of violent crimes. We applied a within-individual design comparing rates of suicidal behaviour and violent crimes during time periods of antidepressant treatment with periods without treatment. Subgroup analyses were performed according to PD clusters, individual antidepressants, specific PDs, psychiatric comorbidities, and history of suicidal behaviour and violent crime.

Results: The cohort included 167,319 individuals with a diagnosed PD, 19,519 (12%) of whom were prescribed antidepressants and presented at least one outcome event during follow-up, making them eligible for within-individual analyses. Overall, we found an association with lower rates of suicidal behavior during periods of antidepressant treatment, compared with periods when individuals were not on antidepressants (incidence rate ratio 0.86, 95% CI 0.84-0.89). However, this association was modified by specific PDs, individual antidepressants, comorbidities, and past history. For violent crimes, we did not observe consistent associations in any direction.

Conclusions: Antidepressants were associated with lower rates of suicidal behaviour, but less clearly in violent crimes. Types of PDs, individual antidepressants, and comorbidities modified these associations.