Psychiatric syndromes can be caused by underlying autoimmune encephalitis (AE). This represents a diagnostic challenge at the interface of psychiatry and neurology. While AE mostly manifests with a combined, complex neuropsychiatric syndrome, some patients with AE may (initially) present with predominant or isolated psychiatric symptoms. These cases can be difficult to classify, and diagnostic approaches vary considerably across clinical settings. This paper from the GErman NEtwork for Research on AuToimmune Encephalitis (GENERATE) provides interdisciplinary expert recommendations from psychiatry and neurology for the diagnostic evaluation of patients with suspected AE as the cause of psychiatric syndromes for psychiatric care settings. It integrates current scientific evidence with practical, empirical considerations from routine clinical care in different healthcare settings. The proposed diagnostic approach to detect psychiatric manifestations of AE emphasizes a rational, stepwise evaluation incorporating clinical assessment, magnetic resonance imaging, electroencephalography, blood testing, cerebrospinal fluid (CSF) analysis, and neuronal/glial antibody testing in serum and CSF. In diagnostically ambiguous individuals, [¹⁸F]fluorodeoxyglucose positron-emission-tomography and advanced antibody testing (e.g., live-cell-based assays) or neuroimaging techniques (e.g., volumetric analysis) may provide additional supportive information. Typical findings and limitations of diagnostic modalities are discussed to facilitate appropriate interpretation and to avoid under-recognition or overdiagnosis. Importantly, these recommendations do not aim to define new disease entities or diagnostic criteria, but rather to support a harmonized and pragmatic diagnostic approach to patients presenting with psychiatric syndromes suspected to be caused by underlying AE. Finally, key unresolved issues in this evolving field of immunopsychiatry are outlined, and promising research strategies are described.

Socially Interactive Agents (SIAs) in mental health are of great promise for psychiatry, but currently lack validated instruments to evaluate both technological acceptance and clinical alliance. In the Human-Computer Interface (HCI) community, SIAs are broadly evaluated using the Artificial Social Agent Questionnaire (ASAQ), to evaluate how users perceive and interact with SIAs. Despite its importance in the SIA community, this questionnaire is unknown in psychiatry and has never been validated in French. Furthermore, doubts remain about the constructs measured by it.

Our objective is threefold: (i) validate the short version of ASAQ in French (24 items); (ii) analyse through Exploratory Graphical Analysis (EGA) the underlying dimensions of the short ASAQ; (iii) discuss an interdisciplinary conceptual analysis of the socio-technical imaginaries and cosmology (the way to inhabit the world) promoted by the SIA community.

After a rigorous translation process, we recruited 203 French-speaking participants to evaluate 14 videos of SIA/human interactions using the ASAQ. We validated the short ASAQ using both usual psychometric methods and EGA.

The French version of the short ASAQ had satisfactory psychometrics properties. The EGA revealed three underlying dimensions, expertly named 'instrumental' (items related to technological acceptance of the SIAs), 'affective' (items related to affective aspects of the interaction with SIAs) and 'relational' (items related to relational aspects of the interaction with SIAs).

The interdisciplinary conceptual analysis identified the tension between instrumental and the relational dimensions - mediated by the affective one - as part of a naturalistic cosmology that traditionally contrasts nature and culture.

This study contributes to bridging the gap between the evaluation frameworks of HCI and the clinical frameworks of psychiatry, toward a more integrated understanding of digital relationality. Recognizing and interrogating the underlying socio-technical imaginaries and cosmology beyond the ASAQ is essential for any future adaptation of the ASAQ within mental health contexts.

The human cortex is organized around primary sensory-motor landmarks, but the way these distances shape large-scale functional organization remains unclear. Using geodesic measures in males and females, we show that global minimum distance to sensory-motor landmarks aligns with the principal gradient of intrinsic connectivity, reflecting the shift from unimodal to heteromodal cortex, while equidistance between landmarks captures complementary organizational patterns. Heteromodal networks, including default mode, control, and limbic systems, occupy cortical regions that are both distant from primary systems and relatively balanced between them. Subsystems within these networks exhibit distinctive spatial embeddings: core default mode regions sit equidistant between visual and somatomotor cortex, frontotemporal default mode regions favour auditory cortex but remain relatively balanced, and medial temporal regions are biased toward visual cortex. Control network subsystems also vary: the control-DMN subsystem occupies the most distant and equidistant positions, core control is closer to motor regions, and medial control is closer to visual cortex, reflecting their different functional specializations. At the parcel level, greater equidistance predicts stronger task-evoked activation, particularly in heteromodal border zones. These findings highlight two complementary spatial principles -- proximity and balance -- that structure the cortex, shaping both the location and functional profile of heteromodal networks.Significance statement Distance from unimodal cortex has been proposed as a structural constraint on functional organisation. However, it remains unclear how relative position with respect to multiple sensory-motor landmarks contributes to functional specialisation. Here, we show that both absolute distance from primary landmarks and their relative balance (equidistance) shape the organisation of heteromodal networks. Equidistance between specific sensory-motor landmarks differentiates heteromodal subsystems and predicts task-evoked activation during story comprehension and mathematical reasoning. These results demonstrate that cortical geometry is linked to cognitive function, and highlight two complementary spatial principles - proximity and balance - that structure the cortex and shape the functional profile of heteromodal networks.

Sleep disruption is a common hallmark of posttraumatic stress disorder (PTSD), causing significant distress and often persisting after remission of other symptoms. Autonomic dysregulation is commonly comorbid and has been implicated in the underlying pathophysiology of both wake- and sleep-related symptoms following trauma. However, existing self-report tools for nightmares and trauma-related sleep disruption place relatively little emphasis on autonomic symptoms such as palpitations and sweating, limiting our ability to gauge these features quantitatively, assess their impact on sleep, and track their response to treatment. Here, we describe the initial validation of a novel exploratory 11-item self-report measure, the Seattle Trauma and Autonomic Related Sleep Symptoms (STARSS) Scale, developed to assess trauma-related sleep disruption including nightmares and autonomic hyperarousal symptoms. Psychometric validation of the STARSS was assessed in a sample of 830 healthcare workers and first responders working during the COVID-19 pandemic. The full scale (STARSS-11) positively correlated with self-report measures of symptom domains often associated with nightmares and commonly elevated following trauma exposure including PTSD (PCL-5; r = 0.76), anxiety (GAD7; r = 0.65), depression (PHQ9; r = 0.63), and insomnia (ISI; r = 0.56), and displayed strong internal consistency (α = 0.89; ω = 0.93). The STARSS-11 is well-fit by a 4-factor model: hyperarousal upon waking, trauma dream intensity, and self- and partner-reported excessive physical activity during sleep. An item-reduced STARSS-9 with 3 factors is also described. These outcomes suggest STARSS is a promising tool for the assessment of sleep disturbance related to trauma and dysautonomia in research settings.

In Australia, early implementation of headspace Early Psychosis (hEP) services was supported by fidelity assessments using the Early Psychosis Prevention and Intervention Centre (EPPIC) Model Integrity Tool (EMIT). Its suitability became limited by ceiling effects and limited sensitivity to evolving service contexts. This paper describes the redevelopment of EMIT into the Revised-EMIT (REMIT) and testing implementation of the tool.

A multi-phase mixed-methods, human-centred design approach was used. Phases included reviewing international fidelity frameworks, stakeholder co-design and iterative redevelopment of fidelity items, scoring and data sources. Testing of the REMIT occurred over 2 years via face-to-face visits to hEP clusters, using semi-structured interviews, review of organisational documents and clinical file audits. Routine data reporting via Tableau embedded Learning Health System principles within the process. National fidelity trends across fidelity item outcomes for all six hEP service clusters were descriptively analysed.

The REMIT was found to reduce ceiling effects and improve sensitivity. National mean REMIT score increased from 3.99 (2023) to 4.19 (2024), with notable gains in caseload management, physical health monitoring and measuring key outcomes. Relational domains (such as continuous engagement and family involvement) remained persistently low across services and years.

The REMIT offers a pragmatic, sensitive fidelity measure for contemporary hEP services. Findings support the use of REMIT as an active learning system rather than a static compliance mechanism. Psychometric evaluation of the tool is now required, and ongoing iterative refinement will be essential to maintain relevance within Australia's evolving youth mental health system.

Merkel cell polyomavirus (MCPyV) is the established oncogenic driver of Merkel cell carcinoma (MCC), but its role in other malignancies is under investigation. Although MCPyV DNA has been detected in colorectal cancer (CRC) specimens, its biological relevance and contribution to colorectal tumorigenesis remain unclear. In this observational study, we investigated MCPyV prevalence, load and molecular status in 122 CRC specimens and peritumoral tissues. In addition, to extend beyond DNA detection, transcriptional profiling was performed to assess early (LTAg) and late (VP1) transcripts, and viral microRNAs. Furthermore, the mRNA expression levels of key Wnt signaling components, including CTNNB1, MYC and CCND1 were examined. AXIN2 was also used as a surrogate marker of pathway activation. Our findings revealed similar MCPyV prevalence and load between tumor and adjacent healthy tissues, suggesting a wide colonization of the colorectal mucosa. Sequencing analyses showed canonical NCCR and VP1 structures, and full length LTAg, with no evidence of viral integration. These data, combined with the detection of both early and late transcripts, indicate an episomal and transcriptionally active state in colorectal tissues. Notably, virus-positive tissues exhibited an over-expression of CTNNB1and its target genes across all clinical subgroups, regardless of anatomical site or tumor stage. Our results are congruent with the establishment of persistent MCPyV infection in the colorectal mucosa, potentially characterized by transcriptionally active episomal genomes. Furthermore, upregulation of the Wnt/β-catenin cascade in virus-positive tissues suggests that MCPyV may exploit this host pathway to drive cellular proliferation. A limitation of this study is lack of comparison to colorectal mucosa in patients without CRC. Overall, these findings are consistent with widespread viral colonization of the colorectal mucosa in a subset of CRC patients, and raise the hypothesis that MCPyV may modulate host signaling pathways relevant to colorectal biology. Whether MCPyV plays any etiological role in colorectal carcinogenesis, or whether its detection is coincidental, cannot be determined from the present observational data.

Cortical GABAergic interneurons exhibit remarkable diversity of morphological, electrophysiological and molecular features, which underlies their specialized roles in circuit functions. Molecular characteristics have proven to be a reasonable starting point in the past for classification, grouping them into parvalbumin (PV), somatostatin (SST), vasoactive intestinal polypeptide (VIP) and "others" (e.g. LAMP5). While Patch-seq studies provide valuable insight into human cortical interneurons, similar results from non-human primates are lagging behind. This is problematic because the studying of cell types, circuits and behavior in a detailed experimental fashion is still out of reach in the human. Therefore, using the extensive knowledge from the mouse model as a ground truth, we explore how recent studies of GABAergic interneurons in marmoset and macaque add to our understanding of the expanding variety of cell types and subtypes in primates compared to rodents. Our knowledge of which interneuron participates in which basic circuit motif, like feedforward, feedback, local and lateral inhibition as well as disinhibition is still very limited. However, the more diverse molecular, physiological and morphological features of primate interneurons should allow a broader range of circuit motifs, increasing the computational power of prefrontal cortical circuits. This increased complexity likely supports advanced cognitive functions such as working memory but may also heighten vulnerability to neuropsychiatric disorders. We argue that primate-specific interneuron diversity is not merely a quantitative expansion but a functional innovation, with profound implications for understanding cognition and disease.

To investigate the developmental onset and sex-specific nonlinear trajectories of first-recorded episodes of self-harm among children and young people, examining variations across methods and settings.

We conducted a population-based surveillance study using statewide data from Santa Catarina, Southern Brazil, including individuals aged 5-25 years. Generalised additive models and spline-based mixed models were used to estimate continuous age-specific incidence rates. Spatial and contextual risks were assessed using incidence rate ratios (IRRs).

Out of 63,773 notifications, 12,322 first-recorded cases were identified (68.5% female; 81.1% aged 15-25 years). Overall incidence peaked at 16.0 years. Distinct non-linear developmental trajectories emerged by sex: among females, incidence rose abruptly from age 11 and peaked at 14.0 years, whereas males showed a more gradual increase, peaking five years later at 19.0 years. Sex differences temporarily converged between ages 15 and 19. Method-specific analyses revealed a marked female predominance for self-poisoning (peak at 14.7 years) and sharp objects (peak at 14.0 years), whereas hanging was heavily male-predominant, peaking in young adulthood (20.5 years). School-based self-harm showed the earliest and most concentrated developmental peak (13.7 years), disproportionately affecting females (IRR = 1.73; 95% CI: 1.22-2.46). Conversely, sex differences were attenuated and no longer statistically significant in public spaces (IRR = 0.81; 95% CI: 0.40-1.64).

First-recorded episodes of self-harm follow highly distinct, age- and sex-specific trajectories. The early-adolescent peak among females contrasts with the delayed trajectory observed in males, highlighting critical, setting-specific windows of developmental vulnerability that argue against 'one-size-fits-all' prevention and support targeted clinical and school-based strategies.

Electroconvulsive therapy (ECT) is an effective acute treatment for severe major depressive disorder (MDD), but whether two routinely captured acute-course ECT pathway markers-time from admission to first ECT and total acute-course session count-are associated with longer-term readmission is unclear. We examined their associations with same-hospital psychiatric readmission, overall and across baseline suicidality.

This retrospective cohort study included 4004 inpatients with MDD who received modified ECT during the index hospitalization at a tertiary psychiatric hospital in China (2013-2020); each patient contributed only the earliest qualifying hospitalization. Baseline suicidality was classified as none documented, ideation, or behavior. Separate marker-specific Cox models estimated baseline-adjusted associations with same-hospital psychiatric readmission within 180 and 365 days.

Readmission occurred in 449 patients (11.2%) by 180 days and 593 (14.8%) by 365 days. Neither time from admission to first ECT (hazard ratio [HR], 1.002 per day; 95% confidence interval [CI], 0.989-1.016) nor session count (HR, 1.003 per session; 95% CI, 0.970-1.037) was associated with 180-day readmission; findings were similar at 365 days. There was no evidence of effect modification by baseline suicidality. Total psychiatric hospitalizations including the index hospitalization showed a graded association with readmission. Sensitivity analyses were consistent.

This single-center electronic health record study did not capture other-institution readmission, mortality, or continuation ECT, and could not distinguish planned from unplanned readmissions.

Acute-course ECT pathway markers were not detectably associated with same-hospital psychiatric readmission in baseline-adjusted marker-specific models. Findings should not be generalized to symptomatic relapse, other-institution readmission, or all-cause outcomes.

Outer radial glia (oRG) are abundant in the human fetal cortex but rare in rodents, yet their molecular regulation remains poorly understood. Although the homeodomain-only protein X (HOPX) is a well-established oRG marker, its functional role in human cortical development remains undefined. Using CRISPR-Cas9 gene editing in human pluripotent stem cells, we show that HOPX loss impairs the expansion and lineage progression of oRG-like cells in two-dimensional neural cultures and three-dimensional cortical organoids. HOPX knockout precursors exhibit reduced proliferation, diminished neurogenesis, and premature differentiation toward astrocytic and oligodendrocytic lineages. HOPX-deficient organoids display reduced outer subventricular zone size, decreased neuronal output, and early gliogenesis. Mechanistically, HOPX loss impairs PI3K-mTOR signaling. Transcriptomic analysis identifies HOPX-regulated programs governing gliogenic competence, mTOR, and Wnt signaling. Together, these findings identify HOPX as an important regulator of oRG-like cell maintenance and the neurogenic-gliogenic balance, providing insight into the molecular programs governing human neural progenitor expansion.