Psychotic depression (PD) is a severe form of depression that can occur in both major depressive disorder (MDD) and bipolar disorder (BD). Although relatively prevalent, the prognostic impact of psychotic symptoms in depression remains controversial.

To systematically review the available evidence comparing PD and non-psychotic depression (NPD) in terms of clinical course, functional outcomes, and treatment outcomes.

A systematic search of electronic databases (PubMed, Cochrane Library and Web of Science) following PRISMA guidelines was conducted from inception to 31st January 2025 to integrate current evidence about the impact of psychotic symptoms in both unipolar and bipolar depressed patients. This study was registered in PROSPERO (CRD42024563172).

Fourty-one studies met inclusion criteria. Compared to NPD, PD was associated with greater clinical severity, longer hospitalizations, and higher inpatient treatment rates. Several studies showed lower remission rates and greater chronicity in PD. Relapse, readmission, or shorter time to recurrence were also more common in PD. Evidence indicated a higher risk of suicide and poorer functional outcomes in PD. Treatment patterns showed more frequent use of ECT and pharmacological combinations in PD, although no consistent drug-specific differences emerged. Overall, heterogeneity across designs and outcome measures was substantial.

Despite heterogeneity, evidence across 41 studies indicates that PD is a higher-risk depressive subtype, characterized by greater service use, higher relapse liability, lower sustained remission, increased suicidality, and poorer functioning. These findings support the need for intensified assessment and management and highlight the importance of large, standardized prospective studies, especially in BD.

To determine the epidemiology of ranger injuries, risk factors for injury, and health support needs among members of the Game Rangers Association of Africa (GRAA).

We employed a retrospective cross-sectional design to collect data online using a questionnaire developed specifically for this study. We used convenience sampling to include 120 rangers aged 18 years or older who were actively working in Africa.

Our findings showed a career injury prevalence of 52 % and period prevalence (past 12 months) of 33 %. The lower limb was the most frequently injured anatomical region (38 %), followed by the upper limb (31 %) and trunk (19 %), specifically affecting the hand (19 %), ankle (14 %), and foot (13 %). The most common injury types included skin lacerations (29 %), followed by muscle injuries (23 %), and fractures (10 %). Working for more than 15 years as a ranger is associated with an increased risk for career injury (OR=2.63) compared to working for 10 years or less. Injuries resulted in a median of 7 days (IQR=0-20 days) lost from work, with most injuries requiring either emergency medical care (31 %) or consultation with a medical doctor (26 %). Rangers need better equipment, cardiovascular fitness training programs, safety training, and mental health support.

One in every two rangers associated with the GRAA sustains an injury across their careers, with a third of rangers reporting being injured in the past 12 months. Working more than 15 years as a ranger was associated with an increased risk for career injury. Our findings should be used in conjunction with sound clinical reasoning to aid in the development of future injury prevention strategies for rangers working in Africa.

This systematic review and meta-analysis aimed to quantify the magnitude of placebo and nocebo effects in pharmacological trials for OCRDs and identify clinical and methodological moderators influencing these effects.

A comprehensive literature search was conducted across multiple databases and clinical trial registries up to May 2025. Randomized, placebo-controlled trials involving pharmacological interventions for OCRDs were included. The primary outcomes were placebo effect size and placebo response rate; secondary outcomes included nocebo response rate and side effect profile. Data were extracted independently and meta-analysed using random-effects models. Meta-regression was performed to assess moderators of placebo response.

Fifteen eligible trials (N = 640; placebo N = 341) were included. The pooled placebo effect size was moderate (SMC = -0.63; 95% CI -0.77 to -0.48), with low heterogeneity (I² = 4.73%). The placebo response rate was 21%, and the nocebo response rate was 18%. Despite testing a broad range of potential moderators, including clinical characteristics, methodological design, and medication class, no significant predictors of placebo effect size were identified. Side effects were reported in nearly one-third of placebo recipients, underscoring the relevance of nocebo effects.

Placebo and nocebo responses are noteworthy in trials for OCRDs and may influence perceived treatment efficacy. Variability in placebo responses is not well explained by currently measurable moderators. Further research is needed to explore neurobiological, psychological, and methodological contributors to expectancy effects in OCRD pharmacotherapy trials.

Psychosis is characterized by both genetic and neurostructural abnormalities. However, the mechanisms linking genetic risk to brain structural alterations remain unclear. This study investigates associations between polygenic risk scores (PRS) and brain structural measures in individuals experiencing a first-episode psychosis (FEP) and healthy controls (HC).

A total of 241 participants (130 FEP, 111 HC, mean age = 24.8 years, 34.9% females) underwent structural magnetic resonance imaging (MRI) and genotyping. PRS for schizophrenia, educational attainment, brain cortical thickness, and surface area were computed using PRS continuous shrinkage (PRS-CS). MRI data provided measures of cortical thickness, surface area, subcortical volumes, and hippocampal subfields. Associations between PRS and brain measures were assessed using generalized linear models within each group.

FEP participants had significantly higher PRS for schizophrenia (p.adj = 1.56e^-6) and lower PRS for educational attainment (p.adj = 0.006) compared to HC, but groups did not differ in neurostructural PRS. Neuroimaging revealed trend-level reductions in left hippocampal volume (p = 0.040, p.adj = 0.280) and significant reductions in specific hippocampal subfields in FEP. In PRS-brain structure analyses, significant associations were observed only in HC, while in FEP, educational attainment PRS showed nominal associations with multiple hippocampal subfields.

By incorporating polygenic scores for brain structural traits, our study shows that neurostructural genetic risk does not differ between FEP and HC, even as FEP participants exhibit significant reductions in specific hippocampal subfields. Genetic influences on brain structure in early psychosis appear subtle and region-specific, underscoring the complex interplay between distinct genetic domains and neurodevelopment in psychosis.

The clinical high-risk for psychosis (CHR-P) paradigm has been widely applied in youth mental health, yet its prognostic validity in minors remains debated. This study aimed to provide an updated meta-analysis of transition rates to psychosis in children and adolescents at CHR-P, and to assess the influence of baseline antipsychotic (AP) exposure on transition outcomes.

We conducted a systematic review and meta-analysis following PRISMA guidelines (PROSPERO CRD420251064505). PubMed/MEDLINE and the Cochrane Library were searched through August 30, 2025. Eligible studies included participants ≤18 years or samples with mean age <18 years, defined CHR-P status with validated instruments, and reported longitudinal data on transition to psychosis. Transition prevalences were pooled using random-effects models. Subgroup analyses evaluated the impact of baseline AP exposure.

Thirty-two independent cohorts were included, comprising 2951 CHR-P individuals, almost all in adolescence. Across studies restricted to minors, overall transition converged at ∼16-17%, while broader samples with mean age <18 years but including young adults reached ∼23%, approximating adult CHR-P estimates (∼25%). Baseline AP exposure was consistently associated with a higher risk of transition (risk ratio ≈1.5), supporting its role as a negative prognostic factor.

CHR-P criteria demonstrate prognostic validity in developmental populations, with transition rates in adolescents comparable to young adult cohorts and significantly higher than in CHR-P negative adolescents. In line with previous research in adult CHR-P, the need of AP at baseline is substantially associated with an increased risk for transition. Future research should broaden prognostic focus beyond transition alone to capture remission, persistence, and functional outcomes in this vulnerable group.

This study aimed to identify metabolomic profiles associated with type 2 diabetes and insulin resistance (HOMA-IR) and relate them to the risk of total mortality.

A longitudinal study was conducted in a subset of participants from a diabetes case-cohort study (mean age, 66.5 years; 62% women; 176/699 with incident T2D) within the PREDIMED trial. Plasma metabolites were analyzed using LC-MS/MS methods at baseline (discovery sample) and 1-year follow-up (validation sample). Multi-metabolite profile scores for type 2 diabetes and HOMA-IR, respectively, were derived using elastic net regression. Cox proportional hazards were fitted to assess the association between metabolomic profiles and total mortality, adjusting for potential confounders. External validation was performed in the NHS/HPFS cohorts.

A total of 31 metabolites were associated with type 2 diabetes and 105 with HOMA-IR. Both metabolomic profiles were significantly associated with a higher risk of total mortality (type 2 diabetes HR = 1.52, 95%CI: 1.04-2.25; HOMA-IR HR = 1.33, 95%CI: 1.00-1.75) in the PREDIMED cohort. Shared metabolites between both metabolomic signatures, including glycine, SDMA, DMGV, and phosphocreatine, were associated with mortality. These associations were replicated in a pooled analysis of three independent American cohorts (type 2 diabetes HR = 1.09, 95%CI: 1.05-1.13; HOMA-IR HR = 1.04, 95%CI: 1.00-1.09).

In an older population at high cardiometabolic risk, metabolomic scores of type 2 diabetes and insulin resistance were associated with total mortality risk, potentially explaining some mechanisms behind the increased risk of mortality observed in epidemiological studies for individuals with glycemic dysregulations.

In competing environments, both selective attention and audiovisual interaction can facilitate visual processing, yet whether their influences operate independently or interactively remains debated. Using electroencephalography (EEG), we addressed this issue by instructing participants to selectively attend to one of two lateralized flickering discs, which also changed their shapes either temporally congruent or incongruent with a pitch-changing sound. We found that reaction times for detecting deviants embedded in the attended visual stream were reduced when a temporally congruent sound was concurrently played. Compared to a temporally incongruent auditory stream, a congruent one selectively enhanced steady-state visual evoked potentials (SSVEPs) in response to flickering of the unattended stream. In contrast, the SSVEP and inter-trial phase coherence in response to the shape-modulation for both attended and unattended streams were enhanced at the harmonic frequencies by the temporally congruent sound. The results indicate that the auditory influence on visual processing orthogonal to audiovisual temporal congruency (flicker) interacts with attention, whereas the auditory influence on visual processing relevant to audiovisual temporal congruency (shape-modulation) is largely independent of attention. However, these congruency effects were observed only under rhythmic audiovisual streams: When audiovisual pitch-shape modulation followed unrhythmic temporal structures, these congruency effects totally disappeared. Together, these findings demonstrate that temporally congruent auditory streams can modulate visual processing both independently of and interactively with selective attention, highlighting a flexible and complex interplay between selective attention and audiovisual interaction.

Behavioural therapy (BT) alleviates tic symptoms in patients with Tourette syndrome/chronic tic disorder (TS/CTD). TS/CTD is often associated with emotional dysregulation, anxiety, and depressive symptoms, substantially impairing quality of life. Nevertheless, the specific effects of BT on tic symptoms in children and adolescents with TS/CTD, including persistence and follow-up outcomes, remain unclear. Tic symptoms in children with TS/CTD are often assessed using the Yale Global Tic Severity Scale (YGTSS) and the Parent Tic Questionnaire (PTQ)-when combined, these tools mitigate subjective biases and enhance assessment objectivity. This meta-analysis aimed to systematically review randomised controlled trials evaluating the impact of BT on tic symptoms in children and adolescents with TS/CTD and to examine longitudinal outcomes.

We systematically searched multiple databases for articles published up to May 2025 and screened their reference lists. The standardised mean difference (SMD) served as the primary effect size metric, focusing on YGTSS and PTQ indicators, from baseline to endpoint through follow-up. Subgroups, heterogeneity, risk of bias, and publication bias were analyzed.

The meta-analysis included 11 studies, encompassing 21 datasets and involving 942 participants. Forest plot analysis revealed that BT improved tic symptoms in patients with TS/CTD compared with controls, as confirmed by both the YGTSS and PTQ assessments. The improvements persisted through follow-up.

BT effectively produces sustained improvements in tic symptoms in children and adolescents with TS/CTD. The demonstrated reduction in core tic severity underscores the potential for BT to alleviate secondary emotional burdens and improve overall mental health in this population.

The contribution of patient support to psilocybin's antidepressant effects remains uncertain.

Relationships between therapeutic alliance (Scale to Assess Therapeutic Relationship-Patient version; STAR-P), psychedelic experience (Five-Dimensional Altered States of Consciousness Questionnaire and Emotional Breakthrough Inventory; 5D-ASC and EBI) and clinical outcomes (Montgomery-Åsberg Depression Rating Scale; MADRS) were explored using correlation and path analysis for individuals with treatment-resistant depression receiving 25 mg psilocybin with monitoring and support (N = 79).

Change from Baseline to Week 3 MADRS scores showed weaker correlations with pre-dosing therapeutic alliance (-0.178) than with measures of the psychedelic experience: EBI (-0.637), Oceanic Boundlessness (-0.508), and Visual Restructuralization (-0.516). Path analysis showed no nominally significant direct effects of therapeutic alliance on Week 3 MADRS scores, but there were nominally significant effects of therapeutic alliance on psychedelic experience (Oceanic Boundlessness (β = 0.28), Visual Restructuralization (β = 0.27), and Auditory Alterations (β = 0.25)). Only one indirect effect of therapeutic alliance on clinical outcome reached nominal significance (via Visual Restructuralization; β = -0.15). Stronger effects were seen on clinical outcomes for psychedelic experience (EBI (β = -0.59), Oceanic Boundlessness (β = -0.53), Visual Restructuralization (β = -0.54), and Auditory Alterations (β = -0.24)).

The therapeutic alliance appeared to facilitate the psychedelic experience, and these experiences in turn had stronger nominally significant direct effects on clinical outcomes. The effects of the alliance itself on therapeutic efficacy were either limited or absent.

EudraCT number: 2017-003288-36; Clinicaltrials.gov identifier: NCT03775200.