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.

Individuals who die by suicide tend to share more characteristics with those who attempt suicide using violent methods than with those who employ nonviolent means. To date, limited research has been published on the demographic characteristics of individuals who engage in violent suicide attempts.

This study aimed to examine trends in the characteristics of violent suicidal behavior in comparison to nonviolent suicidal behavior.

Patients included in the study were consecutively admitted between 2016 and 2021 to the Dr. Manninger Jenő National Trauma Center and the Psychiatric and Toxicology Wards of Péterfy Sándor Hospital in Budapest, Hungary, for medical treatment following violent or nonviolent suicide attempts. Differences in demographic characteristics, risk factors associated with violent suicidal behavior, and methods of attempt were analyzed using Chi-square tests and logistic regression models.

A total of 298 inpatients (46.1% male, 53.9% female), aged between 18 and 65 – representing the economically active population – were included in the study. The sample comprised 145 individuals who attempted suicide using nonviolent methods (73% female, 27% male) and 153 who used violent methods (64.7% male, 35.3% female). Of the total sample, 22 individuals (12.1%) died during treatment due to severe medical complications. Among male attempters, the highest proportion fell within the economically active age range of 18–55 years, whereas among female attempters, the 18–35 age group represented the highest proportion. The most common violent methods, in descending order of frequency, were stabbing (49.7%), jumping from a height (29.8%), and jumping in front of a train (7.7%). The most frequently diagnosed psychiatric disorders among the sample were major depressive disorder (42.2%), anxiety disorders (44.9%), and bipolar disorder (12%). The leading reported motives for violent suicide attempts, in decreasing order of frequency, were marital conflict (32.4%), divorce/separation/break-up (30.2%), and severe or chronic somatic illnesses (12%). When comparing the two subgroups, the strongest risk factors associated with violent suicide methods included male gender, older age, and residence in the capital city.

Previous studies suggest that risk factors are largely indistinguishable between individuals who engage in violent versus nonviolent suicide attempts. However, individuals who attempted suicide using violent methods exhibited characteristics more closely aligned with those who died by suicide than with the remainder of the sample. The majority of data in this study were collected during the COVID-19 pandemic – a period marked by multiple overlapping crises – which may have played a disproportionately large role in the emergence of suicide risk.

Limited studies have examined the association between the whole range of parental psychopathology and offspring major depression (MD). No previous study has examined this association by age of onset of offspring MD, or restricting to parental psychiatric diagnoses before offspring birth.

This nested case–control study included 37,677 cases of MD and 145,068 controls, identified from Finnish national registers. Conditional logistic regression models examined the association between parental psychopathology and MD, adjusting for potential confounders.

Increased risk of MD, expressed as adjusted odds ratio and 95% confidence interval (aOR [95% CI]) were most strongly observed for maternal diagnoses of schizophrenia and schizoaffective disorders (2.51 [2.24–2.82]) and depression (2.19 [2.11–2.28]), and paternal diagnoses of schizophrenia and schizoaffective disorders (2.0 [1.75–2.29]) and conduct disorders (1.90 [1.40–2.59]). The aORs for any psychiatric diagnosis were (2.66 [2.54–2.78]) for mothers, (1.95 [1.86–2.04]) for fathers, and (4.50 [4.24–4.79]) for both parents. When both parents had any psychiatric diagnosis, the highest risk was for MD diagnosed at the age of 5–12 years (7.66 [6.60–8.89]); versus at 13–18 years (4.13 [3.85–4.44]) or 19–25 years (3.37 [2.78–4.07]). A stronger association with parental psychopathology and offspring MD was seen among boys than girls, especially among 13–19 years and 19–25 years.

Parental psychiatric disorders, including those diagnosed before offspring birth, were associated with offspring MD, indicating potential genetic and environmental factors in the development of the disorder.

Recent years show an exponential increased interest (“renaissance”) in the use of psychedelics for the treatment of mental disorders and broader. Some of these treatments, such as psilocybin for depression, are in the process of formal regulation by regulatory bodies in the US (FDA) and Europe (EMA), and as such on the brink of real-world implementation. In the slipstream of these developments increasing commercial initiatives are taking shape. The European Psychiatric Association (EPA) acknowledges both the therapeutic potential of psychedelic substances and the challenges for both research and clinical implementation. Steps need to be taken toward a well-balanced policy based upon sound scientific evidence and research, aiming at safe, ethical responsible integration of psychedelic therapy available for all patients who can potentially benefit.

In this EPA policy paper, we highlight the potential benefits, and also the challenges of psychedelic treatments, which can be relevant for the future real-world implementation of these treatments.

In addition to an overview of the current evidence and hypotheses of working mechanisms of psychedelic treatment, this policy paper specifically highlights the importance of the psychosocial components of the treatment as well as the ethical and professional aspects playing a role in real-world implementation.

Four recommendations are formulated for further research and clinical implementation.

Assessing the risk of subsequent self-harm after hospitalisation for COVID-19 is critical for mental health care planning during and after the pandemic.

This study aims to compare the risk of admission to hospital for self-harm within 12 months following a COVID-19 hospitalisation during the first half of 2020, with the risk following hospitalisations for other reasons.

Using the French administrative healthcare database, logistic regression models were employed to analyse data from patients admitted to hospitals in metropolitan France between January and June 2020. The analysis included adjustments for sociodemographic factors, psychiatric history and the level of care received during the initial hospital stay.

Of the 96 313 patients hospitalised for COVID-19, 336 (0.35%) were subsequently admitted for self-harm within 12 months, compared to 20 135 (0.72%) of 2 797 775 patients admitted for other reasons. This difference remained significant after adjusting for sociodemographic factors (adjusted odds ratio (aOR) = 0.66, 95% CI: 0.59–0.73), psychiatric disorder history (aOR = 0.65, 95% CI: 0.58–0.73) and the level of care received during the initial hospital stay (aOR = 0.70, 95% CI: 0.63–0.78). History of psychiatric disorders and intensive care were strongly correlated with increased risk, while older age was inversely associated with self-harm admissions.

Hospitalisation for COVID-19 during the early pandemic was linked to a lower risk of subsequent self-harm than hospitalisation for other reasons. Clinicians should consider psychiatric history and intensive care factors in evaluating the risk of future suicide.

The differential diagnosis of psychiatric disorders is relatively challenging for several reasons. In this context, we believe that task-based magnetic resonance imaging (MRI) can serve as a tool for differential diagnosis. The aim of this study was to explore the commonalities in brain activities among individuals with psychiatric disorders and to identify the key brain regions that can distinguish between these disorders.

The PubMed, MEDLINE, EMBASE, Web of Science, Scopus, PsycINFO, and Google Scholar databases were searched for whole-brain functional MRI studies that compared psychiatric patients and normal controls. The psychiatric disorders included schizophrenia (SCZ), bipolar disorder (BD), major depressive disorder (MDD), obsessive–compulsive disorder, attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). Studies using go–nogo paradigms were selected, we then conducted activation likelihood estimation (ALE) meta-analysis, factor analysis, and regression analysis on these studies subsequently.

A total of 152 studies (108 with patients) were selected and a consistent pattern was found, that is, decreased activities in the same brain regions across six disorders. Factor analysis clustered six disorders into three pairs: SCZ and ASD, MDD and BD, and ADHD and BD. Furthermore, the heterogeneity of SCZ and ASD was located in the left and right thalamus; and the heterogeneity of MDD and BD was located in the thalamus, insula, and superior frontal gyrus.

The results can lead to a new classification method for psychiatric disorders, benefit the differential diagnosis at an early stage, and help to understand the biobasis of psychiatric disorders.

This systematic review aimed to review therapeutic patient education (TPE) programmes in managing psychiatric disorders, considering the diversity in delivering agents, intervention formats, targeted skills, and therapeutic outcomes.

Comprehensive database searches, including Web of Science, PubMed, and COCHRANE, were conducted from September 2019 to January 2023, yielding 514 unique records, with 33 making it through rigorous evaluation for full-text review. Eleven studies met the inclusion criteria, focusing on various psychiatric disorders such as depression, bipolar disorder, psychosis, and multiple serious mental illnesses. A total of 38 studies were included from our previous review to supplement the current database search.

TPE programmes exhibited diversity in delivering agents and intervention formats, with a notable presence of multidisciplinary teams and various professionals. The interventions prioritized coping strategies and disease management techniques, though the extent varied based on the disorder. Effectiveness was heterogeneous across studies; some interventions showed significant benefits in areas such as symptom management, coping, and functional improvement, while others reported no significant outcomes.

The findings underscore the potential of TPE in psychiatric care, revealing its multifaceted nature and varied impact. TPE not only addresses deficits but also leverages patients’ existing strengths and capabilities. Despite the reported benefits, a portion of the interventions lacked statistical significance, indicating the necessity for continuous refinement and evaluation.

Previous pandemics have had negative effects on mental health, but there are few data on children and adolescents who were receiving ongoing psychiatric treatment.

To study changes in emotions and clinical state, and their predictors, during the COVID-19 pandemic in France.

We administered (by interview) the baseline Youth Self-Report version of the CoRonavIruS Health Impact Survey v0.3 (CRISIS, French translation) to 123 adolescent patients and the Parent/Caregiver version to evaluate 99 child patients before and during the first ‘lockdown’. For 139 of these patients who received ongoing treatment in our centre, treating physicians retrospectively completed longitudinal global ratings for five time periods, masked to CRISIS ratings.

The main outcome measure was the sum of eight mood state items, which formed a single factor in each age group. Overall, this score improved for each age group during the first lockdown. Clinician ratings modestly supported this result in patients without intellectual disability or autism spectrum disorder. Improvement of mood states was significantly associated with perceived improvement in family relationships in both age groups.

Consistent with previous studies of clinical cohorts, our patients had diverse responses during the pandemic. Several factors may have contributed to the finding of improvement in some individuals during the first lockdown, including the degree of family support or conflict, stress reduction owing to isolation, limitations of the outcome measures and/or possible selection bias. Ongoing treatment may have had a protective effect. Clinically, during crises additional support may be needed by families who experience increased conflict or who care for children with intellectual disability.

Psychiatric disorders may be a risk factor for long COVID, broadly defined as COVID-19 conditions continuing three months post-acute infection. In US Veterans with high psychiatric burden, we examined associations between psychiatric disorders and clinical diagnosis of long COVID.

We conducted a retrospective cohort study using health records from VA patients with a positive SARS-CoV-2 test from February 2020 to February 2023. Generalized linear models estimated associations between any psychiatric disorder and likelihood of subsequent diagnosis with long COVID (i.e. two or more long COVID clinical codes). Models were adjusted for socio-demographic, medical, and behavioral factors. Secondary models examined individual psychiatric disorders and age-stratified associations.

Among 660 217 VA patients with positive SARS-CoV-2 tests, 56.3% had at least one psychiatric disorder diagnosis and 1.4% were diagnosed with long COVID. Individuals with any psychiatric disorder had higher risk for long COVID diagnosis in models adjusted for socio-demographic factors, vaccination status, smoking, and medical comorbidities (relative risk, RR = 1.28, 95% CI 1.21–1.35), with the strongest associations in younger individuals. Considering specific disorders, depressive, anxiety, and stress-related disorders were associated with increased risk for long COVID diagnoses (RRs = 1.36–1.48), but associations were in the opposite direction for substance use and psychotic disorders (RRs = 0.78–0.88).

Psychiatric disorder diagnoses were associated with increased long COVID diagnosis risk in VA patients, with the strongest associations observed in younger individuals. Improved surveillance, treatment, and prevention for COVID-19 and its long-term sequelae should be considered for individuals with psychiatric conditions.

Convergent evidence has suggested atypical relationships between brain structure and function in major psychiatric disorders, yet how the abnormal patterns coincide and/or differ across different disorders remains largely unknown. Here, we aim to investigate the common and/or unique dynamic structure–function coupling patterns across major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ).

We quantified the dynamic structure–function coupling in 452 patients with psychiatric disorders (MDD/BD/SZ = 166/168/118) and 205 unaffected controls at three distinct brain network levels, such as global, meso-, and local levels. We also correlated dynamic structure–function coupling with the topological features of functional networks to examine how the structure–function relationship facilitates brain information communication over time.

The dynamic structure–function coupling is preserved for the three disorders at the global network level. Similar abnormalities in the rich-club organization are found in two distinct functional configuration states at the meso-level and are associated with the disease severity of MDD, BD, and SZ. At the local level, shared and unique alterations are observed in the brain regions involving the visual, cognitive control, and default mode networks. In addition, the relationships between structure–function coupling and the topological features of functional networks are altered in a manner indicative of state specificity.

These findings suggest both transdiagnostic and illness-specific alterations in the dynamic structure–function relationship of large-scale brain networks across MDD, BD, and SZ, providing new insights and potential biomarkers into the neurodevelopmental basis underlying the behavioral and cognitive deficits observed in these disorders.

Performance validity (PVTs) and symptom validity tests (SVTs) are necessary components of neuropsychological testing to identify suboptimal performances and response bias that may impact diagnosis and treatment. The current study examined the clinical and functional characteristics of veterans who failed PVTs and the relationship between PVT and SVT failures.

Five hundred and sixteen post-9/11 veterans participated in clinical interviews, neuropsychological testing, and several validity measures.

Veterans who failed 2+ PVTs performed significantly worse than veterans who failed one PVT in verbal memory (Cohen’s d = .60–.69), processing speed (Cohen’s d = .68), working memory (Cohen’s d = .98), and visual memory (Cohen’s d = .88–1.10). Individuals with 2+ PVT failures had greater posttraumatic stress (PTS; β = 0.16; p = .0002), and worse self-reported depression (β = 0.17; p = .0001), anxiety (β = 0.15; p = .0007), sleep (β = 0.10; p = .0233), and functional outcomes (β = 0.15; p = .0009) compared to veterans who passed PVTs. 7.8% veterans failed the SVT (Validity-10; ≥19 cutoff); Multiple PVT failures were significantly associated with Validity-10 failure at the ≥19 and ≥23 cutoffs (p’s < .0012). The Validity-10 had moderate correspondence in predicting 2+ PVTs failures (AUC = 0.83; 95% CI = 0.76, 0.91).

PVT failures are associated with psychiatric factors, but not traumatic brain injury (TBI). PVT failures predict SVT failure and vice versa. Standard care should include SVTs and PVTs in all clinical assessments, not just neuropsychological assessments, particularly in clinically complex populations.

Cloninger’s temperament dimensions have been studied widely in relation to genetics. In this study, we examined Cloninger’s temperament dimensions grouped with cluster analyses and their association with single nucleotide polymorphisms (SNPs). This study included 212 genotyped Finnish patients from the Ostrobothnia Depression Study.

The temperament clusters were analysed at baseline and at six weeks from the beginning of the depression intervention study. We selected depression-related catecholamine and serotonin genes based on a literature search, and 59 SNPs from ten different genes were analysed. The associations of single SNPs with temperament clusters were studied. Using the selected genes, genetic risk score (GRS) analyses were conducted considering appropriate confounding factors.

No single SNP had a significant association with the temperament clusters. Associations between GRSs and temperament clusters were observed in multivariate models that were significant after permutation analyses. Two SNPs from the DRD3 gene, two SNPs from the SLC6A2 gene, one SNP from the SLC6A4 gene, and one SNP from the HTR2A gene associated with the HHA/LRD/LP (high harm avoidance, low reward dependence, low persistence) cluster at baseline. Two SNPs from the HTR2A gene were associated with the HHA/LRD/LP cluster at six weeks. Two SNPs from the HTR2A gene and two SNPs from the COMT gene were associated with the HP (high persistence) cluster at six weeks.

GRSs seem to associate with an individual’s temperament profile, which can be observed in the clusters used. Further research needs to be conducted on these types of clusters and their clinical applicability.

The corpus callosum (CC) is a brain structure with a high heritability and potential role in psychiatric disorders. However, the genetic architecture of the CC and the genetic link with psychiatric disorders remain largely unclear. We investigated the genetic architectures of the volume of the CC and its subregions and the genetic overlap with psychiatric disorders.

We applied multivariate genome-wide association study (GWAS) to genetic and T1-weighted magnetic resonance imaging (MRI) data of 40,894 individuals from the UK Biobank, aiming to boost genetic discovery and to assess the pleiotropic effects across volumes of the five subregions of the CC (posterior, mid-posterior, central, mid-anterior and anterior) obtained by FreeSurfer 7.1. Multivariate GWAS was run combining all subregions, co-varying for relevant variables. Gene-set enrichment analyses were performed using MAGMA. Linkage disequilibrium score regression (LDSC) was used to determine Single nucleotide polymorphism (SNP)-based heritability of total CC volume and volumes of its subregions as well as their genetic correlations with relevant psychiatric traits.

We identified 70 independent loci with distributed effects across the five subregions of the CC (p < 5 × 10−8). Additionally, we identified 33 significant loci in the anterior subregion, 23 in the mid-anterior, 29 in the central, 7 in the mid-posterior and 56 in the posterior subregion. Gene-set analysis revealed 156 significant genes contributing to volume of the CC subregions (p < 2.6 × 10−6). LDSC estimated the heritability of CC to (h2SNP = 0.38, SE = 0.03) and subregions ranging from 0.22 (SE = 0.02) to 0.37 (SE = 0.03). We found significant genetic correlations of total CC volume with bipolar disorder (BD, rg = −0.09, SE = 0.03; p = 5.9 × 10−3) and drinks consumed per week (rg = −0.09, SE = 0.02; p = 4.8 × 10−4), and volume of the mid-anterior subregion with BD (rg = −0.12, SE = 0.02; p = 2.5 × 10−4), major depressive disorder (MDD) (rg = −0.12, SE = 0.04; p = 3.6 × 10−3), drinks consumed per week (rg = −0.13, SE = 0.04; p = 1.8 × 10−3) and cannabis use (rg = −0.09, SE = 0.03; p = 8.4 × 10−3).

Our results demonstrate that the CC has a polygenic architecture implicating multiple genes and show that CC subregion volumes are heritable. We found that distinct genetic factors are involved in the development of anterior and posterior subregions, consistent with their divergent functional specialisation. Significant genetic correlation between volumes of the CC and BD, drinks per week, MDD and cannabis consumption subregion volumes with psychiatric traits is noteworthy and deserving of further investigation.