Recent reports indicate that sustained interaction with conversational artificial intelligence (AI) systems can, in a small subset of users, contribute to the emergence or stabilisation of delusional experience. Existing accounts typically attribute such cases either to individual vulnerability or to failures of safety engineering. These explanations are incomplete. Drawing on phenomenology, psychiatry, and cognitive neuroscience, this paper argues that the risk arises from the relational and ontological structure of the interaction itself. Conversational AI generates ontological dissonance: a conflict between the appearance of relational presence and the absence of any subject capable of sustaining it. Maintained through a communicative double bind and amplified by attentional asymmetries, this dissonance tends, under conditions of affective vulnerability, to stabilise into a technologically mediated analogue of folie à deux. This account explains why explicit disclaimers often fail to disrupt delusional involvement and clarifies the ethical and clinical implications for the design and use of conversational AI.
Loneliness and social isolation are major public health concerns among older adults and are associated with depression, cognitive decline, frailty, and loss of independence. Companion animals (and dogs in particular) might mitigate these adverse outcomes by fostering emotional support, physical activity, and social interactions. The objective of the present study aimed to evaluate the association between dog ownership and loneliness in community-dwelling older adults. C-KDOG is a multicentre, cross-sectional study conducted between September 2020 and April 2023 at seven investigating centers in France. The participants were aged 75 or over and were living at home. Loneliness was assessed on the 11-item De Jong Gierveld Loneliness Scale. The secondary outcomes included emotional and social loneliness subscores, social isolation (according to the Social Network Index). Associations between dog ownership and loneliness were analyzed using multivariable linear regressions adjusted for sociodemographic, environmental and clinical characteristics. A total of 160 participants were included, of whom 47 were dog owners (mean age: 82 years; females: 116 (73%); living alone: 79 (49%)). The median overall loneliness scores did not differ significantly when comparing dog owners and non-owners. In adjusted models, however, dog ownership was independently associated with lower loneliness. This association was mainly driven by a lower emotional loneliness subscore. Living alone, frailty, depressive symptoms, and sleep problems were independently associated with a greater level of loneliness. Dog ownership was primarily motivated by companionship (81%). Adverse events (such as falls or bites) were rare (5%). Dog ownership was associated with a lower level of emotional loneliness among community-dwelling older adults, independently of living alone frailty and depression. Companion dogs might contribute to emotional well-being in older adults. However, longitudinal studies are needed to confirm causality.
Children with autism spectrum disorder (ASD) frequently exhibit selective eating behaviors characterized by food refusal and limited dietary variety, which can lead to nutritional deficiencies and impaired family functioning. This study evaluated the effectiveness of the Schmetterling Nutritional Behavior Intervention (NBI) Program, a creative behavioral intervention integrating established behavioral strategies with innovative components, including imitation chaining, shaping, and therapist-guided exoskeleton modeling. Three children (YW, RA, and JK) diagnosed with autism spectrum disorder (ASD) participated in a single-case experimental design. The study employed the Childhood Autism Rating Scale, 2nd Edition (CARS-2) assessing autism symptom severity, while the Child Eating Behavior Questionnaire (CEBQ) measured changes in eating behavior. Substantial increases in food acceptance were observed across all participants, with the highest improvements in food responsiveness, enjoyment of food, and food fussiness. Tau-U analysis revealed large and significant intervention effects for both therapist-implemented and parent-implemented sessions. Although CARS-2 scores remained within the 'severe' classification range, notable percentage reductions suggested clinically relevant improvements in core autism symptoms. These findings support the Schmetterling NBI Program as an individualized, evidence-based approach to enhancing dietary diversity and reducing maladaptive feeding behaviors in children with ASD. Children with autism spectrum disorder (ASD) commonly demonstrate selective eating patterns, including food refusal and restricted dietary repertoire, which may contribute to nutritional deficits and compromised family dynamics. This investigation examined the efficacy of the Schmetterling Nutritional Behavior Intervention (NBI) Program, a novel behavioral intervention that synthesizes established behavioral methodologies with innovative components such as imitation, shaping procedures, and therapist-guided training. Utilizing a single-case experimental design, three children diagnosed with ASD (YW, RA, and JK) were assessed with the Childhood Autism Rating Scale, Second Edition (CARS-2) to evaluate autism symptom severity, and the Child Eating Behavior Questionnaire (CEBQ) to measure alterations in feeding behavior. Results indicated substantial improvements in food acceptance across all participants, with pronounced enhancements in food responsiveness, enjoyment of food, and reductions in food fussiness. Tau-U statistical analysis demonstrated large and significant intervention effects for both therapist-administered and parent-implemented sessions. Although CARS-2 scores remained within the severe classification range, notable percentage reductions indicated clinically meaningful improvements in core autism symptomatology. These findings support the Schmetterling NBI Program as an individualized, evidence-based intervention for promoting dietary diversity and reducing maladaptive feeding behavior among children with ASD. Replicating our preliminary findings in a larger sample and finding evidence-based tailored interventions for children with ASD pose important challenges for future research.
Second-generation antipsychotics are widely prescribed for schizophrenia and other psychiatric disorders; however, their potential effects on cerebral white matter (WM) microstructure and associated cognitive changes remain poorly characterized. Diffusion tensor imaging (DTI) was performed in 43 drug-naïve patients with schizophrenia and 44 healthy controls at baseline, and repeated after 8 weeks during which patients received antipsychotic treatment. Tract-based spatial statistics (TBSS) were applied to assess changes in WM microstructural integrity. Cognitive performance was evaluated using selected measures from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), including story recall, line orientation, picture naming, semantic fluency, digit span, coding, and word recall. At baseline, no significant group differences were observed in fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), or mean diffusivity (MD). Following treatment, compared with healthy controls, patients exhibited decreased FA in the body of the corpus callosum; increased MD across nearly all WM regions; and elevated RD in the genu and body of the corpus callosum, bilateral anterior corona radiata, left superior corona radiata, and left superior longitudinal fasciculus. Spearman correlation analyses revealed that RD values in RD_cluster1 and RD_cluster2 were negatively correlated with digit span scores (r = -0.359, p = 0.018; r = -0.35, p = 0.021). Although clinical symptoms improved during this period, changes in FA, MD, and RD were not associated with symptom improvement or antipsychotic dosage. These findings suggest that antipsychotic treatment exerts potential effects on WM microstructure and cognitive function in drug-naïve patients with schizophrenia.
A number of articles have heralded the use of artificial intelligence (AI) agents to serve as a replacement for human psychotherapists. Despite the rapid advancements in the use of both rule-based and generative AI programs in the recent past, an overall review shows only small impacts on certain mental health symptoms, particularly depression, and then only in the short-term. Significant strides forward, both in terms of technology and the development of answers to ethical questions regarding AI's use in psychotherapy, must be seen before the use of such systems becomes widespread or regularly recommended to replace human mental health clinicians.
The sodium leak channel non-selective (NALCN) is a key regulator of resting membrane potential and cellular excitability in neurons and endocrine cells. Gain-of-function de novo pathogenic variants in NALCN cause severe neurodevelopmental disorders with a broad and heterogeneous clinical spectrum. Partial inhibition of NALCN has been proposed as a therapeutic strategy; however, progress has been limited by the absence of selective pharmacological modulators. This gap largely reflects the lack of a robust heterologous expression system suitable for high-throughput screening, as functional NALCN requires multiple ancillary subunits and its constitutive expression is toxic in commonly used cell lines such as HEK293. To address these challenges, we developed a multitransposon-based approach to generate inducible HEK293 cell lines that stably express the complete NALCN channelosome, including wild-type and disease-associated variants. We further demonstrate that NALCN current expression is cell cycle-dependent, enabling the definition of optimized conditions for consistent and reproducible electrophysiological recordings. Using these cell lines, we conducted a systematic pharmacological characterization of the NALCN channelosome by patch-clamp electrophysiology and identified several candidate modulators that are currently under evaluation. Notably, we revisited NALCN modulation by N-benzhydryl quinuclidine compounds and found that these compounds can restore locomotor phenotypes in an animal model of NALCN gain-of-function. Together, this work establishes a foundational platform for the discovery of NALCN-targeting compounds and opens new therapeutic avenues not only for NALCN-associated neurodevelopmental diseases, but also potentially for psychiatric disorders, chronic pain, and cancer.
Suicide is a leading cause of maternal mortality, yet there are currently no evidence-based perinatal suicide prevention programs. Given the risk of serious outcomes if undetected or inadequately treated, the goal of this study was to further understand the screening and treatment experiences of individuals with perinatal suicidal thoughts and behaviors (STBs). Qualitative data were generated from in-depth interviews with 13 individuals primarily from the United States who experienced perinatal suicidality at least 6 months prior to participation. Thematic analysis was used to examine the experiences of participants with respect to screening and treatment of perinatal STBs. Regarding screening, three major themes were identified: (1) gaps in comprehensive/routine screening for STBs (e.g., infrequent screenings or non-specific to suicide), (2) attitudes toward disclosure of STBs (resulting in omission of symptoms or downplaying of severity), and (3) importance of follow-up after screening. Three themes influenced participants' treatment experiences: (1) providers' engagement in care, (2) shared decision-making between provider and patient, and (3) impact of perinatal-specific treatment programs. Findings from this study highlight critical gaps in screening for and treatment of perinatal STBs. Implementing routine screening and comprehensive follow-up and improving treatment experiences are essential for improving the care of individuals with perinatal STBs and reducing maternal mortality.
Long-acting injectable buprenorphine may be a promising treatment option for adolescents and young adults with opioid use disorder (OUD). However, little is known about its safety, tolerability, and effectiveness in this age group. We conducted a 1-year feasibility study of elective inpatient buprenorphine induction followed by administration of long-acting injectable buprenorphine and linkage to ongoing substance use care in individuals <21 years in a safety-net health system (n = 18). Eighteen of 22 (82%) of patients admitted to an inpatient unit for buprenorphine initiation opted to receive the long-acting injectable formulation upon completion of induction. Of 18 patients who received long-acting injectable buprenorphine, 15 (83%) and 12 (67%) remained in care at one- and two-months post discharge, respectively. Eleven (61%) participants received repeat doses at both one- and two-months post discharge. Fourteen (78%) and 12 (67%) participants had not returned to opioid use at one- and two- months post discharge, respectively. The findings from this study of adolescents and young adults with OUD demonstrated that inpatient initiation of long-acting injectable buprenorphine after a brief induction with short-acting buprenorphine may be safe, well tolerated, and effective in terms of linkage, retention in care, and return to opioid use.
Major Depressive Disorder (MDD) is characterized by heterogeneous pathogenesis that extends beyond traditional monoamine deficits. A paradigm shift is recognizing neuroinflammation as a central, critical driver of both illness onset and resistance to treatment. The CXCL12/CXCR4 system is traditionally associated with immune cell trafficking, but increasing evidence reveals its powerful regulatory role in neuropsychiatric disorders. We performed a comprehensive synthesis demonstrating that CXCL12/CXCR4 axis acts as a direct molecular modulator of neurotransmission, neuroplasticity, and glial cell signaling. Specifically, this axis can modulate a multiple molecular pathways linked with the glutaminergic, GABAergic, and serotonergic systems, and mediating neuroplasticity and glial cell function. Functionally, CXCL12/CXCR4 axis has twofold character - it can strengthen neurotoxic processes through overactivation of NMDAR and excessive Ca2+ influx. On the other hand, it can also play protective role by preventing excitotoxicity, supporting neurogenesis, enhancing GABA synthesis, and dendritic spines stabilization. This review focuses on identifying potential mechanisms across in vitro, animal, and human studies to establish the CXCL12/CXCR4 axis as a powerful biomarker and, critically, an unexploited therapeutic target.
Clark-Baraitser Syndrome (CLABARS) is an autosomal dominant neurodevelopmental disorder caused by pathogenic variants in the TRIP12 gene. Research into the molecular mechanisms of CLABARS has been limited by the lack of suitable human model systems. In this study, we introduce an induced pluripotent stem cell (iPSC) line derived from a CLABARS patient, providing a promising model to investigate mechanisms of altered cell lineage commitment during disease progression.
Schizophrenia spectrum disorders (SSD) feature deficits in movement intention, predictive mechanisms, and agency. While prior work characterised BOLD amplitude during movement preparation and temporal dynamics across the entire movement period, it remains unknown whether preparatory neural (BOLD) response timing and duration are selectively impaired in SSD. We analysed fMRI data from 20 SSD patients and 20 healthy controls during active and passive hand movements with video feedback (own vs. other hand). Preparatory and executory BOLD responses were modelled separately using the canonical HRF and its temporal (TD) and dispersion (DD) derivatives to evaluate timing and duration. Patients with SSD showed pronounced preparatory abnormalities under own-hand feedback, including delayed responses in right supplementary motor area during active movement preparation. Passive- and active-specific timing was reversed (earlier/later) in the left (caudate, middle temporal gyrus, superior parietal gyrus) and right (postcentral gyrus, right precentral gyrus, anterior cingulate cortex). Response duration showed reduced/reversed modulation (shorter/longer) in the right supplementary motor area, bilateral supramarginal gyrus, left inferior parietal cortex, and bilateral middle temporal gyrus. Earlier response timing in right precentral gyrus during active own-hand were negatively correlated with delusions of being controlled and formal thought disorder. No group differences emerged during execution.
Ketamine may alleviate treatment-resistant depression (TRD) primarily through glutamatergic modulation, with downstream dopaminergic activation. Iron plays an important role in monoaminergic metabolism, that is also implicated in the pathophysiology of TRD. Both Quantitative Susceptibility Mapping (QSM) and Effective Transverse Relaxation Rate (R2*) mapping can determine the extent of iron deposition in the brain. Given that abnormal iron accumulation may reflect dopamine dysfunction, we hypothesized that baseline magnetic substances could predict ketamine's antidepressant effects in patients with TRD. We used data from a double-blind, randomized placebo-controlled trial followed by an extended single-arm open-label study to assess the efficacy of repeated intravenous ketamine in Japanese patients with TRD (jRCTs031210124). This study analyzed the data from the participants who underwent QSM and R2* mapping before receiving ketamine in either phase. Multivariable regression analyses were conducted to explore the association between baseline magnetic susceptibility and R2* with change in MADRS total and subdomain scores. This study included 17 patients with TRD (7 women; mean ± standard deviation age, 42.9 ± 10.6 years). Baseline magnetic susceptibility in the right nucleus accumbens negatively correlated with the change in MADRS retardation symptom scores (β = -0.73, p = 0.003). Moreover, baseline R2* in the left amygdala was negatively associated with the change in MADRS vegetative symptom scores (β = -0.71, p = 0.004). Baseline magnetic substances in the right nucleus accumbens and the left amygdala may be biomarkers to predict the effect of repeated ketamine infusions in patients with TRD.
Post-traumatic stress disorder (PTSD) is a common psychiatric condition, with a global prevalence of 3.9% and a lifetime prevalence of 7.4% in the Netherlands. Although numerous evidence-based treatments are available, their use varies considerably. Understanding patient perspectives and experiences in the decision-making process when choosing a specific treatment is crucial for improving the quality of care. This study aimed to explore the decision-making process from the perspective of patients with PTSD, focusing on their considerations and experiences when choosing a specific psychotherapeutic treatment. In this qualitative study, twelve semi-structured interviews were conducted with patients with PTSD (aged 21-55 years) receiving care at a mental health organisation in the east of the Netherlands. Data were analysed using reflexive thematic analysis, informed by grounded theory-inspired analytic techniques. Analysis was iterative and inductive, focusing on the identification and interpretation of patterns of meaning across patients' accounts. Five themes were identified, connected through an overarching interpretive concept of patient-attunement: (1) the role of treatment characteristics (2), the role of therapeutic factors (3), the role of treatment duration and intensity (4), the role of significant others, and (5) the role of information about trauma-focused treatment. Patients emphasised the importance of personalised information and support from clinicians and significant others. Ongoing responsiveness within the therapeutic relationship, including trust and collaboration, was central to experiencing the decision-making process as supportive and meaningful. For patients with post-traumatic stress disorder, multiple factors play a role in choosing a psychotherapeutic trauma-focused treatment. This study shows that continued attunement to patients' diverse needs is central to the decision-making process. Such attunement may take various forms, including attention to the therapeutic relationship, discussion of treatment characteristics and frequency, and responsiveness to patients' preferences regarding information provision. Involving patients' support systems may further support decision-making. Together, these findings suggest that clinicians should remain attentive to patients' needs at multiple points during the pre-treatment phase. Approaches such as shared decision-making may help facilitate this attunement. Not applicable.
To investigate the current status and dyadic mechanism of maternal and spousal role adaptation for postpartum anxiety and depression. Convenience sampling was employed to select 276 pairs of mothers and their spouses from October 2023 to October 2024 as study participants. Binary analyses were conducted using the actor-partner interdependence model (APIM) and the mediation model. The prevalence rates of anxiety and depression during the first postpartum year were 38.5% and 14.5% among mothers, and 36.9% and 12.9% among their spouses, respectively. The APIM revealed that maternal and spousal role adaptation significantly and negatively predicted their own postpartum anxiety (maternal actor effect: β = -0.120; spousal actor effect: β = -0.081) and depression (maternal actor effect: β = -0.165; spousal actor effect: β = -0.113), and that role adaptation similarly predicted each other's anxiety (maternal partner effect: β = -0.115; spousal partner effect: β = -0.059) and depression (maternal partner effect: β = -0.129, spousal partner effect: β = -0.064). Mediation analyses suggest that future time insight and parenting competence mediate this process. Postpartum anxiety and depression serve as a dyadic phenomenon, where maternal and spousal role adaptation significantly affects mental health outcomes. Future time insights and feelings of parenting competence serve as mediating variables in the relationship. Not applicable.
Spatial transcriptomics extends traditional transcriptomic methods by quantifying gene expression within intact tissues while preserving each cell's precise spatial context. This technology also captures gene expression under physiological conditions, including interactions with the surrounding microenvironment, thereby enhancing our understanding of cellular states in both health and disease. Rapid recent advances have improved throughput, transcript capture, accuracy, and overall data quality. In this review, we summarize the major spatial transcriptomics platforms and outline their strengths and limitations. We also highlight key applications in neuroscience, including brain cell-type identification, structure-function relationships, and developmental processes. Additionally, we examine spatial gene-expression patterns in psychiatric and neurodegenerative disorders such as Alzheimer's disease and depression. Finally, we discuss emerging directions, including spatial multi-omics integration and the potential for artificial intelligence to advance brain research. Collectively, this work provides a foundation for future studies in neuroscience and brain disorders.
Rapid eye movement (REM) sleep behaviour disorder (RBD), particularly its idiopathic/isolated form (iRBD), is a prodromal marker for α-synucleinopathies, including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Machine learning (ML) offers opportunities to improve diagnosis and risk stratification in this high-risk group. We conducted a systematic review of PubMed, Embase (Ovid) and Medline (Ovid) from 2014 to September 2025, following PRISMA guidelines. From 335 records identified, 202 remained after duplicate removal and 75 studies on adult humans with clinically diagnosed RBD or iRBD that applied and validated an ML model were included. Fifty-eight studies addressed diagnosis, four studied RBD phenotypes, and thirteen evaluated prediction of phenoconversion to overt α-synucleinopathy. Across diagnostic studies, reported accuracies ranged from ∼63% to ∼99.7%, with median values around 90%, using polysomnography, EEG, neuroimaging, molecular and behavioural markers. Phenoconversion models (often using dopaminergic imaging or multimodal features) achieved AUCs up to ∼0.94, but frequently relied on small, single-centre cohorts with heterogeneous definitions of phenoconversion and limited external validation. A wide variety of ML algorithms was used (n ~ 30), most commonly support vector machines, random forests and logistic regression. Overall, ML approaches show promise for scalable diagnosis and risk stratification in iRBD, but progress is constrained by methodological bias, inconsistent endpoints, data imbalance and a lack of explainable, externally validated models. We outline methodological priorities to make future ML tools clinically interpretable and translatable.
Iron plays a central role in neurodevelopment and dopaminergic regulation, yet its relationship with schizophrenia remains conceptually unresolved. Research conducted across the life span, from prenatal exposure to postmortem brain tissue, has produced fragmented findings without an integrating physiological framework. We aimed to systematically synthesize this literature and reinterpret prior findings through core principles of iron regulation, with particular attention to the distinction between absolute iron depletion and inflammation-driven functional restriction. We conducted a PROSPERO-registered systematic review (CRD42022382842) following PRISMA guidelines and included 51 studies spanning genetic risk, gestational exposure, peripheral biomarkers, neuroimaging, and postmortem analyses. Genetic studies do not implicate core iron-regulatory pathways in inherited schizophrenia risk. Large population-based cohorts consistently associate maternal iron deficiency during pregnancy with increased schizophrenia risk in offspring. Sixteen studies assessed adult peripheral iron markers; most report lower serum iron, although heterogeneity remains substantial. Few investigations evaluated regulatory markers such as hepcidin, and only one examined the hepcidin-ferroportin pathway directly. Neuroimaging studies in early psychosis report reduced subcortical iron alongside increased dopaminergic activity, whereas postmortem investigations describe cortical iron-ferritin decoupling in chronic stages. Across levels of analysis, apparent inconsistencies converge when iron physiology is considered. Absolute iron depletion and inflammation-driven functional iron restriction represent biologically distinct states that share reduced circulating iron but arise from different mechanisms. Stratifying schizophrenia according to iron phenotype offers a coherent framework to reinterpret prior evidence and guide future mechanistic research.
Digital mental health tools-including telehealth, mobile applications, wearable devices, machine learning, and artificial intelligence-are changing the way patients and providers manage mental health care. This review summarizes the current research findings of digital interventions on patient access to care, the factors impacting personalized care, and overall patient engagement. Gaps of knowledge and future considerations are discussed, including careful observation of existing barriers to care. Clinical recommendations are discussed for clinicians who are considering implementing digital mental health tools into practice.
Internalizing disorders have been linked to alterations in default mode network (DMN) resting-state functional connectivity (RSFC). Given the increased risk of internalizing disorders in offspring of parents with a history of internalizing disorders, this study examined associations between parental depression and anxiety severity and adolescent DMN RSFC. Participants were 116 parent-adolescent dyads with youth between ages of 11-17 years. Structured diagnostic interviews and self-report questionnaires were completed by parents and adolescents to assess history and severity of internalizing disorders. Adolescents completed resting-state functional magnetic resonance imaging to determine the RSFC between regions of the DMN including the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and bilateral lateral parietal cortices (LPC). Analyses examined region-of-interest (ROI) to ROI RSFC, with bivariate correlations and linear regressions used to assess whether child age, sex, child internalizing symptoms, and parental internalizing symptoms were associated with child RSFC alterations. After controlling for child age, sex, internalizing symptoms, and in-scanner motion, increased parental depressive severity was associated with increased child RSFC between the PCC and right LPC. Child internalizing symptoms were also linked to decreased RSFC between the right LPC and the mPFC. This study is limited by its modest sample size relative to effect sizes for functional connectivity-phenotype associations, cross-sectional design, and a relatively homogeneous sample in terms of ethnicity, socioeconomic status, and parental sex. Results suggest that, among youth with a parental history of depression or anxiety, increased severity of parental depression is associated with altered offspring DMN RSFC.
Mental health conditions account for 18% of years lived with disability worldwide. 1-in-6 adults are affected in England, with most mental health conditions beginning in childhood and adolescence. Mental distress and ill health are unequally distributed in the UK, with strong associations with wider determinants of health, and higher prevalence among systemically disadvantaged groups. Currently, there is a lack of evidence to inform effective and timely policymaking for primary prevention in the UK. In recognition of these challenges, a national Population Mental Health (PMH) Consortium was established, as part of Population Health Improvement UK (PHIUK). PHIUK is a national research network which works to transform health and reduce inequalities through change at the population level. Our aim is to establish an interdisciplinary PMH Consortium, focussing on upstream determinants and the prevention of risks and onset of mental health conditions through interdisciplinary stakeholder engagement, to create new opportunities for population-based improvement of mental health in the UK.The PMH Consortium brings together leading interdisciplinary representation in population mental health, spanning from sciences to the arts, across the UK. Membership includes six academic institutions, third sector organisations, lived experience expertise, and strong links with national bodies to ensure integrated cross-national and regional policy impact. The PMH Consortium comprises four cross-cutting platforms (Partners in policy, implementation, and lived experience; Data, linkages, and causal inference; Narrowing inequalities; Training and capacity building) and three challenge areas (Children and young people's mental health; Prevention of suicide and self-harm; Multiple long-term conditions) which are highly integrated and interdependent. The work will be underpinned by a Theory of Change across an initial four-year life cycle. This paper describes the aim, objectives, and approach of the PMH Consortium, as well as anticipated challenges and strengths. The goal of the PMH Consortium is to develop a model for population mental health research and policy translation that is both scalable and sustainable. It is critical to ensure continued impact and viability beyond the initial four years, contributing to the prevention of mental health conditions in the UK, with personal, economic, social, and health benefits.