Cortisol is a well-established biomarker of stress, assessed through salivary or blood samples, which are intrusive and time-consuming. Speech, influenced by physiological stress responses, offers a promising non-invasive, real-time alternative for stress detection. This study examined relationships between speech features, state anger, and salivary cortisol using a validated stress-induction paradigm.

Participants (N=82) were assigned to cold (n=43) or warm water (n=39) groups. Saliva samples and speech recordings were collected before and 20 minutes after the Socially Evaluated Cold Pressor Test (SECPT), alongside State-Trait Anger Expression Inventory (STAXI) ratings. Acoustic features from frequency, energy, spectral, and temporal domains were analyzed. Statistical analyses included Wilcoxon tests, correlations, linear mixed models (LMMs), and machine learning (ML) models, adjusting for covariates.

Post-intervention, the cold group showed significantly higher cortisol and state anger. Stress-related speech changes occurred across domains. Alpha ratio decreased and MFCC3 increased post-stress in the cold group, associated with cortisol and robust to sex and baseline levels. Cortisol–speech correlations were significant in the cold group, including sex-specific patterns. LMMs indicated baseline cortisol influenced feature changes, differing by sex. ML models modestly predicted SECPT group membership (AUC = 0.55) and showed moderate accuracy estimating cortisol and STAXI scores, with mean absolute errors corresponding to ∼24–38% and ∼16–28% of observed ranges, respectively.

This study demonstrates the potential of speech features as objective stress markers, revealing associations with cortisol and state anger. Speech analysis may offer a valuable, non-invasive tool for assessing stress responses, with notable sex differences in vocal biomarkers.

Major depressive disorder (MDD) is a significant public health concern, and current treatments often have limitations in effectiveness and adherence. Psilocybin, a psychedelic compound found in certain mushrooms, is being explored as a potential treatment for depression. It primarily acts through the serotonin 5-HT2A receptor but interacts with 5-HT1A and 5-HT2C receptors. Its precise mechanisms remain under investigation.

(1) To consolidate evidence on psilocybin’s efficacy and safety for depression, (2) to identify limitations in the literature, and (3) to highlight areas needing further research.

This systematic review follows PRISMA guidelines and analyzes 20 studies, including randomized controlled trials (RCTs) and open-label studies. The studies cover various populations, including individuals with treatment-resistant depression, different dosing regimens, and adjunctive therapies.

Psilocybin therapy shows substantial and rapid antidepressant effects, often after one or two sessions with psychological support. Improvements are sustained for weeks or months in many cases. Psilocybin is generally well-tolerated, with mild adverse effects such as anxiety during administration and transient headaches, which are manageable in controlled settings .

Psilocybin demonstrates promise as a novel treatment for depression, especially for individuals unresponsive to conventional antidepressants. Further research is needed to refine dosing, explore long-term effects, and understand its mechanisms of action.

There are differences in IgA responses to tryptophan catabolites (TRYCATs) in major neurocognitive psychosis (MNP) versus simple neurocognitive psychosis (SNP) and normal controls. MNP and SNP are distinct schizophrenia classes which are differentiated by neurocognitive deficits, phenome features, and biomarker pathways. Nevertheless, there is no data on serum concentrations of those TRYCATs in MNP and SNP. The aim of the present study is to examine serum concentrations of tryptophan and TRYCATs in MNP versus SNP and controls.

This case-control study examines serum levels of tryptophan and TRYCATs in 52 MNP patients, 68 SNP patients and 60 controls in association with overall severity of schizophrenia (OSOS).

MNP patients show lower tryptophan, kynurenic acid (KA), 3-OH-anthranilic acid (3HAA), and higher anthranilic acid (AA) and quinolinic acid (QA) than SNP patients and controls. There were no differences between SNP and controls in these TRYCATs. Kynurenine (KYN) was lower in MNP+SNP than in controls. We found that 36.5% of the variance in OSOS was explained by the combined effects of lowered tryptophan, KA, and 3-HK, and increased QA and AA. The most important biomarkers of MNP and OSOS were the QA/KA ratio followed by the QA/3HAA ratio.

The alterations in serum TRYCAT levels further emphasize that MNP and SNP represent two biologically distinct subtypes of schizophrenia. The reductions in TRYCATs diminish the antioxidant and immunoregulatory functions of the TRYCAT pathway. Elevated QA levels may exacerbate the disruption of the blood-brain barrier and the immune-related and oxidative neurotoxicity in MNP.

Patient-Initiated Brief Admission (PIBA) is an intervention designed to provide constructive crisis management for patients. The purpose of this study was to evaluate outcomes in healthcare utilisation and self-inflicted injuries at one Swedish Hospital where PIBA was implemented in late 2017.

Patients who signed a PIBA-contract between 2017 and 2023 were included in the study. Data on inpatient care, contacts with the psychiatric emergency department and self-inflicted injuries that resulted in contact with medical care were collected from patients’ medical records. Effects of PIBA were assessed using paired t-tests, comparing pre-post changes 0.5, 1 and 2 years, from initiation of PIBA-contract, respectively.

Data from a total of 38 patients were analysed. There was a marked decrease in inpatient care from voluntary admissions in the first six months after initiation of PIBA. There was also a significant decrease in number of contacts with the psychiatric emergency department (for all patients) in the 1-year pre-post comparison, but not for the 0.5- and 2-year pre-post comparisons. There were no significant reductions in compulsory inpatient care or self-inflicted injuries in our cohort. Patients with contracts extending over several years appeared stable, on average, in their use of care and prevalence of intoxications.

The main effect on inpatient care after initiation of PIBA was a reduction in voluntary admissions, coinciding with a shift from voluntary admissions in favour of PIBA. The results support a more widespread utilisation of PIBA from a health-economic perspective.

Metabolic syndrome (MetS) is highly prevalent among adults and is frequently accompanied by depressive symptoms. While high-sensitivity C-reactive protein (hsCRP) has been proposed as a potential indicator of depression, existing evidence remains inconclusive.

This study aimed to determine whether increased serum hsCRP or other immune-metabolic biomarkers are associated with depressive symptoms in drug-naïve individuals with obesity and MetS.

A total of 88 drug-naïve patients with obesity and MetS but without coronary-artery disease were enrolled and serum levels of neuro-immune and metabolic biomarkers were assessed.

In MetS, the severity of depression, as assessed using the von Zerssen Depression Rating (VZDR) scale was significantly associated with interleukin (IL)-6, leukocyte numbers, triglyceride x glucose (Tyg) index, low-density lipoprotein cholesterol, Apolipoprotein B (all positively) and mean platelet volume (MPV), visfatin and adiponectin (all negatively). There were no significant associations between hsCRP and severity of depression. In MetS patients, hsCRP is strongly associated with increased leukocyte numbers, alkaline phosphatase, γ-glutamyl transferase, uric acid, platelet numbers and MPV, thereby shaping a distinct subtype of MetS, which is not related to depression.

Our findings indicate that depressive symptoms in MetS patients are associated with immune–metabolic biomarkers indicating immune activation, atherogenicity and insulin resistance, but not with hsCRP. The reason is that hsCRP in MetS is a biomarker of a specific MetS subtype that is characterized by megakaryopoiesis, hepatocyte activation, and uric acid production, which were not associated with depression.

By synthesising findings from both clinical and preclinical research, this review aims to provide an understanding of the interplay between 5-HT2A receptor psychedelics and the immune system and considers how their immunomodulatory effects associate with neuronal and behavioural changes.

A PubMed literature search covering the past 30 years was conducted using keywords such as ‘5-HT2A receptor’, ‘psychedelics’, ‘immune system’, and ‘HPA axis’. Studies were included if they addressed the effects of 5-HT2AR psychedelics on immune function, neuroimmune interactions, or HPA axis involvement. This narrative review synthesises evidence highlighting the bi-directional effects of 5-HT2AR psychedelics between the immune and nervous systems, identified through this search process.

Preclinical and clinical studies report that 5-HT2AR psychedelics have some direct immunomodulatory properties with downregulation of gene regulators like NF-κB, and reduced cytokine expression such as TNF-α, IL-6, and IL-1β at a central and peripheral level, accompanied by modulation of corticotrophin releasing hormone (CRH), adrenocorticotrophic hormone (ACTH), and cortisol. Direct immunomodulatory effects are mediated by pathways involving serotonin receptors, the Sigma-1 receptor, and the TrkB receptor. Immunomodulation is further mediated indirectly via the HPA axis.

Further studies will determine the molecular and cellular mechanisms underlying these immunomodulatory effects. There is growing interest in the potential of 5-HT2AR psychedelics for treating a range of mental health and brain disorders. In keeping with their immunomodulatory actions, the likely modulation of brain glia and glial-neuronal interaction remains to be determined, representing a promising direction of further research on the therapeutic potential of 5-HT2AR psychedelics.

This study aimed to examine the relationship between fibroblast growth factor 19 (FGF19) and depressive symptoms, measured by Beck’s Depression Inventory (BDI) scores and investigate the moderating role of smoking.

This study involved 156 Chinese adult males (78 smokers and 78 non-smokers) from September 2014 to January 2016. The severity of depressive symptoms was evaluated using the BDI scores. Spearman rank correlation analyses were used to investigate the relationship between cerebrospinal fluid (CSF) FGF19 levels and BDI scores. Additionally, moderation and simple slope analyses were applied to assess the moderating effect of smoking on the relationship between the two.

FGF19 levels were significantly associated with BDI scores across all participants (r = 0.26, p < 0.001). Smokers had higher CSF FGF19 levels and BDI scores compared to non-smokers (445.9 ± 272.7 pg/ml vs 229.6 ± 162.7 pg/ml, p < 0.001; 2.7 ± 3.0 vs 1.3 ± 2.4, p < 0.001). CSF FGF19 levels were positively associated with BDI scores in non-smokers (r = 0.27, p = 0.015), but no similar association was found among smokers (r = −0.11, p = 0.32). Linear regression revealed a positive correlation between FGF19 and BDI scores (β = 0.173, t = 2.161, 95% CI: 0.015–0.331, p < 0.05), which was negatively impacted by smoking (β = −0.873, t = −4.644, 95% CI: −1.244 to −0.501, p < 0.001).

These results highlight the potential role of FGF19 in individuals at risk for presence of or further development of depressive symptoms and underscore the importance of considering smoking status when examining this association.

To investigate the effect of physical exercise intensity on state anxiety symptoms and affective responses.

Twenty-one healthy women (mean age: 23.6 ± 5.4 years) participated in three sessions: self-selected intensity exercise, moderate-intensity prescribed exercise, and a nonexercise control session. Before each session, participants were exposed to unpleasant stimuli. State anxiety symptoms and affective responses were assessed pre- and post-stimulus exposure and pre- and post-sessions. A two-way repeated measures ANOVA tested state anxiety, while the Friedman test analysed affective responses.

Time significantly affected state anxiety symptoms [F (2,0) = 25.977; P < 0.001; η2p = 0.565]. Anxiety increased post-stimulus (P < 0.001) and decreased after all sessions. No significant differences were found between exercise and control conditions. Time also significantly influenced affective responses [χ2 (8.0) = 62.953; P < 0.001; Kendall’s W: 0.375]. Affective responses decreased post-stimulus (P = 0.029) and significantly increased after both exercise sessions (P < 0.001) but remained unchanged in the control session (P = 0.183).

Although state anxiety increased after unpleasant stimuli in all conditions, reductions following exercise sessions were comparable to the nonexercise session. However, both exercise sessions uniquely improved affective responses, highlighting their potential for emotional recovery after unpleasant stimuli.

Although social anxiety remains prevalent, conventional exposure therapy faces limitations such as limited accessibility, high cost, and low ecological validity. These barriers highlight the need for alternative, scalable methods that can effectively simulate social evaluative contexts.

This study aims to evaluate the anxiety-inducing effects of videoconferencing exposure, measured through heart rate variability (HRV), using a fully online-based methodology.

A total of 31 participants who reported social anxiety were recruited online and engaged in a simulated videoconference task, where they interacted with multiple audience members’ emotional faces on a 3 × 3 split screen. Their video recordings were analysed using imaging photoplethysmography to obtain HRV data. Baseline anxiety levels were assessed using validated self-report questionnaires, including the State Anxiety Scale (STAI-X1), Trait Anxiety Scale (STAI-X2), Social Interaction Anxiety Scale, and Social Phobia Scale.

Pearson correlation analysis revealed that STAI-X1 scores negatively correlated with high-frequency normalised units (HFnu) changes and positively correlated with low-frequency high-frequency (LF–HF) ratio and low-frequency normalised units (LFnu) changes. Similar patterns were observed for STAI-X2. These findings suggest that higher levels of trait and state anxiety are associated with greater reductions in parasympathetic activity and increased sympathetic activation during online videoconferencing.

This study underscores the clinical potential of online videoconferencing as a scalable and accessible exposure therapy for the digital era, eliminating spatial and logistical constraints associated with traditional in-person exposure therapy.

The COVID-19 pandemic and associated restrictive measures affected the mental health and well-being of individuals globally. We assessed non-modifiable and modifiable factors associated with the change in well-being and mental health from before to during the COVID-19 pandemic in South Africa.

A cross-sectional online survey was conducted from 26 April, 2020, to 22 April, 2021. Paired samples t-tests were conducted to assess change in well-being (measured on The World Health Organization-Five Well-Being Index (WHO-5)) and mental health (a validated composite psychopathology p-score). Sociodemographic, environmental, clinical, and behavioural factors associated with change in outcomes were examined.

The sample comprised of 1866 adults (M age = 44.26 ± 17.36 years, female = 78.9%). Results indicated a significant decrease in well-being (p < 0.001) and increase in p-score (p < 0.001) from before to during the pandemic. Having a prior mental health condition was associated with a worsening well-being score, while being female was associated with a worsening p-score. Being of Black African descent was associated with improved p-score and higher socio-economic status (SES) was associated with improved well-being. Factors associated with worsening of both well-being and the p-score included adulthood adversity, financial loss since COVID-19, and placing greater importance on direct contact/interactions and substance use as coping strategies. Higher education level and endorsing studying/learning something new as a very important coping strategy were associated with improved well-being and p-score.

Findings inform the need for targeted interventions to reduce and prevent adverse well-being and mental health outcomes during a pandemic, especially among vulnerable groups.

A previous analysis of 200,000 exome-sequenced UK Biobank participants using weighted burden analysis of rare, damaging variants failed to identify any genes associated with risk of affective disorder requiring specialist treatment. Exome-sequence data has now been made available for the remaining 270,000 participants and a two-stage process was applied in order to test for association in this second sample using only genes showing suggestive evidence for association in the first sample.

Cases were defined as participants who reported having seen a psychiatrist for ‘nerves, anxiety, tension or depression’. Exhaustive testing of the first sample was carried out using rare variant analyses informed by 45 different predictors of impact of nonsynonymous variants. The 100 genes showing the strongest evidence for association were then analysed in the second sample using the same predictor as had been most statistically significant in the first sample.

The results for the 100 nominated genes conformed closely with the null hypothesis, with none approaching statistical significance after correction for multiple testing.

Risk of common affective disorder, even if severe enough to warrant specialist referral, is not sufficiently impacted by effects of rare variants in a small enough number of genes that effects can be detected even with large sample sizes. Actionable results might be obtained with a more extreme phenotype but very significant resources would be required to achieve adequate power. This research has been conducted using the UK Biobank Resource.

This study presents the most recent data on the incidence, prevalence, and years lived with disability (YLDs) due to anxiety disorders across the Middle East and North Africa (MENA) region from 1990–2021, analysed by sex, age, and sociodemographic index (SDI).

We reported the burden of anxiety disorders using data sourced from the Global Burden of Disease 2021 study. The estimates of prevalence, DALYs, and YLDs are provided as numbers and age-standardised rates, accompanied by their 95% uncertainty intervals (UIs).

In 2021, the age-standardised point prevalence of anxiety disorders in the region was 5.95 thousand, with an incidence rate of 883.4 per 100,000. The number of YLDs in 2021 reached 4.5 million. From 1990 to 2021, the burden of anxiety disorders increased significantly. Lebanon had the highest burden in 2021. Among both sexes, the 10–14 age group had the highest incidence rate, while the 15–19 age group had the highest prevalence and YLD rates. In 2021, most age groups in the MENA region had YLD rates that were higher than the global average.

This study highlights the urgent need for a multidisciplinary approach to prevent and manage anxiety disorders. Ensuring accessible and affordable treatment options for all affected individuals is crucial. Governments should prioritise supporting programmes to effectively address mental health issues, given the unique socioeconomic and geopolitical challenges in the MENA region. By including effective preventive methods alongside treatment in healthcare strategies, the burden of anxiety disorders can be significantly reduced.

Psychosocial wellbeing is increasingly recognised as a key outcome in dementia research and care, reflecting a shift towards person-centred care and patient-reported outcome measures. However, progress is hindered by a lack of a clear and consistent definition. The present systematic review aimed to establish how previous dementia research has defined the term and how existing definitions may be unified.

A systematic literature review was conducted in PubMed, Embase, and Web of Science using only the term ‘psychosocial’ as well as terms related to dementia in the search string. Two blinded reviewers independently conducted the abstract screening and full-text screening. Definitions used in included records were extracted and their content grouped into categories and domains. For papers presenting empirical findings, quality screening was performed using Critical Appraisal Skills Programme (CASP) checklists and findings were narratively summarised.

A total of n = 36 records were identified that provided a definition for psychosocial wellbeing. Conceptualizations most commonly (86 %) included emotional wellbeing, social health (64%), behavioural symptoms (44%), and subjective lived wellbeing (42%). A total of n = 23 records also contained empirical data, which indicated that psychosocial wellbeing may be improved by several interventions such as tailored activities and validation group therapies, among others.

The construct of ‘psychosocial wellbeing’ as currently used in dementia research predominantly incorporates emotional and subjective lived wellbeing, social health, and behavioural symptoms. This indicates an emerging consensus. To progress dementia research and care practice, it is essential that future studies use a common operationalisation.