Although three dual orexin receptor antagonists (DORAs), suvorexant, lemborexant, and daridorexant, are currently available and widely used to treat insomnia, the differences in their elimination half-lives are not sufficient. As a result, clinicians have limited ability to tailor therapy to individual sleep complaints. The emergence of vornorexant, with a notably short half-life comparable to that of zolpidem, may substantially expand the clinical utility of DORAs. This broader spectrum of pharmacokinetic profiles enables more individualized treatment strategies that align with patients' specific sleep complaints. This approach, in turn, potentially reshapes the therapeutic paradigm of insomnia management. However, several challenges remain to be addressed in order to fully realize the clinical potential of DORAs. This review identifies four key challenges requiring resolution to advance their optimal use in clinical practice.

Psilocybin, a psychedelic prodrug, has gained renewed interest for its potential to treat various psychiatric disorders, including depression, anxiety, and substance use disorders. While promising, concerns remain regarding its safety profile and the management of potential adverse events (AEs). This systematic review aimed to evaluate the incidence, nature, and severity of adverse events and serious adverse events (SAEs) associated with psilocybin use across diverse clinical populations. A comprehensive search was conducted across MEDLINE, Embase, and APA PsycInfo via the OVID platform, from database inception to May 6, 2024. A total of 42 clinical studies (N = 1068 participants) met inclusion criteria, all of which reported on AEs and/or SAEs following psilocybin administration. All studies were determined as high risk of bias due to concerns regarding blinding. We synthesized information on common, uncommon, and serious adverse events, instances of suicidal ideation, ways of measuring AEs, and AEs requiring medical intervention. Reported AEs included headache, transient increases in blood pressure, and nausea, which typically resolved on their own. In rare instances, medical intervention was required. Serious adverse events were reported infrequently in 2 of 42 studies and were limited to participants with underlying depressive disorders (e.g., suicidal behaviour, hospitalization). Overall, psilocybin appears to have a favorable safety profile when administered in controlled settings. Based on our findings, we provide an outline of commonly reported AEs, uncommon AEs, SAEs, and considerations for future clinical and research protocols 1.

The increasing scale and complexity of neuroimaging datasets aggregated from multiple study sites present substantial analytic challenges, as existing statistical analysis tools struggle to handle missing voxel-data, suffer from limited computational speed and inefficient memory allocation, and are restricted in the types of statistical designs they are able to model. We introduce Image-Based Meta- & Mega-Analysis (IBMMA), a novel software package implemented in R and Python that provides a unified framework for analyzing diverse neuroimaging features, efficiently handles large-scale datasets through parallel processing, offers flexible statistical modeling options, and properly manages missing voxel-data commonly encountered in multi-site studies. IBMMA successfully analyzed a large-n dataset of several thousand participants and revealed findings in brain regions that some traditional software overlooked due to missing voxel-data resulting in gaps in brain coverage. IBMMA has the potential to accelerate discoveries in neuroscience and enhance the clinical utility of neuroimaging findings.

Major depressive disorder (MDD) is a prevalent mental illness with unclear underlying pathophysiology that is often linked to childhood trauma. Emerging evidence suggests a potential association between myelin abnormalities and depression, highlighting the need for further understanding of these neurobiological connections in MDD patients. This study investigated the mediating role of abnormal myelin in the pathophysiology of MDD induced by childhood trauma via quantitative Synthetic Magnetic Resonance Imaging (SyMRI) technique.

MDD patients and healthy controls underwent SyMRI scanning to assess myelin content, T1, T2 and proton density (PD) values in the brain. Statistical analyses compared these values between groups and correlated them with clinical symptom scores. Mediation analysis was used to determine the role of myelin content in the relationship between childhood trauma and clinical symptoms.

Thirty-five MDD patients (median age, 23[18-34] years, 7 men) and forty-nine healthy controls (median age, 24[21-35] years, 18 men) were included. Compared with healthy controls, MDD patients presented significantly lower myelin content (FDR-corrected p < 0.05; Cohen's d = -0.85 - -0.75) and higher PD values (FDR-corrected p < 0.05; Cohen's d = 0.71-0.94) in the left inferior frontal sulcus, left caudal area 45, left medial area 14, left rostral area 7, left lateral area 5, left ventral dysgranular and granular insula, and left nucleus accumbens. The T1 and T2 values were not significantly different (FDR-corrected p > 0.05). A lower myelin content was significantly correlated with higher depression and anxiety scores (p < 0.05; R = 0.1309-0.2550). A myelin reduction in the left lateral area 5 and left ventral dysgranular and granular insula mediated the association between childhood trauma and MDD symptoms (p < 0.05; β = 0.0643-0.0807).

Our findings suggest that reduced myelin content in the left lateral area 5 and left ventral dysgranular and granular insula, due to childhood trauma, mediated 6.4% to 8.1% of the variance of MDD. However, the cross-sectional design limits causal inference, and the influence of comorbid anxiety was not controlled.

Emerging evidence indicates that obstructive sleep apnea (OSA) is highly prevalent in major depressive disorder (MDD) and exacerbates cognitive dysfunction. However, the potential functional brain alterations in MDD patients with comorbid OSA remain underexplored in neuroimaging research. This investigation focused on functional brain modifications related to comorbid OSA in MDD, as well as to explore potential correlations with cognitive dysfunction.

Resting-state functional magnetic resonance imaging (rs-MRI), polysomnography, event-related potential (ERP), and cognitive function (the prospective memory, the Continuous Performance Task-Identical Pairs, the digital span test) data were obtained from 32 MDD cases with comorbid OSA and 42 well-matched non-OSA MDD controls. We collected brain function metrics, including regional homogeneity (ReHo) and functional connectivity (FC), from all participants.

Relative to non-OSA MDD controls, MDD cases with comorbid OSA manifested worse in sustained attention, working memory, and prospective memory, had longer P300 wave latencies, had significantly higher ReHo in the Cerebellum_Crus1_L and lower ReHo in the Cerebellum_8_R, and had greater FC involving the Cerebellum_Crus1_L and bilateral lingual gyri. In addition, correlation analyses indicated that changes in ReHo and FC were associated with cognitive variables, including sustained attention and P300 latency, only in MDD patients with OSA.

Comorbid OSA in MDD is linked to cerebellar function and cerebellar-cerebral connectivity dysregulation, highlighting its potential role as an independent contributor to attentional and neurophysiological deficits. These findings emphasize the clinical imperative for longitudinal studies investigating the specific neuropathological mechanisms of OSA and for implementing interventions, thereby offering potential management of MDD comorbidities.

not applicable.

Obsessive-compulsive disorder (OCD) is a severe psychiatric illness associated with substantial psychosocial burden. Although evidence-based first- and second-line treatments are often effective, a significant proportion of patients continue to experience treatment-resistant symptoms. In such cases, brain neurostimulation is gaining increasing attention. This study aims to provide a structured overview of national and international clinical guidelines for the management of treatment-resistant OCD, with a particular focus on neurostimulation techniques.

Relevant clinical guidelines were identified and compared with respect to their recommendations on various neurostimulatory procedures. Among the approaches examined were transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), Deep Brain Stimulation (DBS), ablative neurosurgical procedures, and further techniques such as transcranial direct current stimulation (tDCS).

Across guidelines, DBS is regarded as a potentially effective treatment option for carefully selected, severely affected patients. Its use is restricted to specialized centers and requires an interdisciplinary treatment approach. Ablative procedures are endorsed by certain guidelines solely in exceptionally severe cases. The evidence basis for TMS remains inconsistent, though certain stimulation protocols have shown short-term efficacy. For ECT and tDCS, current evidence is insufficient to support their use in targeting core OCD symptoms.

Overall, the reviewed guidelines emphasize the need for clearly defined indications, standardized treatment protocols, and continuous scientific evaluation. Invasive procedures are not considered standard treatment but represent highly specialized therapeutic options within interdisciplinary care frameworks.

Sweden Finns are one of five officially recognized national minority groups in Sweden. As a group, Sweden Finns have been socioeconomically underprivileged in comparison with the Swedish majority population, and tend to be worse off in terms of somatic health. However, the literature on mental health among Sweden Finns has not previously been systematically appraised. The aim of this scoping review was to synthesize the available evidence on mental health among Sweden Finns or, when the minority terminology is not used in the literature, among individuals in Sweden with a Finnish background (including the so-called Finnish war children). Systematic literature searches in MEDLINE, Web of Science, and PsychINFO were performed. A total of 46 publications met the inclusion criteria; however, very few made use of the self-identification principle central to official Swedish minority politics. The synthesized evidence shows that Sweden Finns tend to be worse off in terms of mental health compared with the Swedish-born majority population, even after adjusting for socioeconomic factors. They are more often diagnosed with various serious psychiatric disorders, such as schizophrenia and other psychotic disorders. Alcohol and other substance-use disorders are also more common. Moreover, substantially higher suicide rates are consistently reported in this group, although no recent studies exist. The few published qualitative studies emphasize the importance of cultural competence in the care of elderly Sweden Finns with neurocognitive deficits. More qualitative and ethnographically oriented research is needed to explore causal pathways behind the observed patterns and to guide potential preventive measures.

Despite common bio-behavioural mechanisms underlying maladaptive sleep and eating, little is known about their temporal associations. The present study aimed to assess the longitudinal relationship between weight loss behaviours (age 13) and sleep (age 17/18) in adolescents (N = 5705) from the '98 Growing Up in Ireland cohort.

Using structural equation modelling, regression models were specified and excessive online behaviours (age 17/18) were tested as a moderator, while depressive symptoms (age 13) were tested as a mediator for the prospective association.

Weight loss behaviours significantly predicted falling asleep at inappropriate times (β = 0.16, SE = 0.04, p < 0.001) and shorter sleep duration (β = 0.06, SE = 0.02, p < 0.001), but no other sleep behaviours. Associations with falling asleep at inappropriate times were partially mediated through depressive symptoms. Associations with shorter sleep duration were fully mediated by depressive symptoms. Excessive online behaviours did not moderate the relationship between sleep and weight loss behaviours.

In line with clinical research, this study provides preliminary evidence for the longitudinal relationship between weight loss behaviours and shorter sleep. Further research into the causal and potentially bi-directional relationship between sleep and disordered eating is needed to aid in preventing the exacerbation of both symptom presentations and to inform general health promotion strategies.