Engineering Clock Transitions in Molecular Lanthanide Complexes.

Molecular lanthanide (Ln) complexes are promising candidates for the development of next-generation quantum technologies. High-symmetry structures incorporating integer spin Ln ions can give rise to well-isolated crystal field quasi-doublet ground states, i.e., quantum two-level systems that may serve as the basis for magnetic qubits. Recent work has shown that symmetry lowering of the coordination environment around the Ln ion can produce an avoided crossing or clock transition within the ground doublet, leading to significantly enhanced coherence. Here, we employ single-crystal high-frequency electron paramagnetic resonance spectroscopy and high-level ab initio calculations to carry out a detailed investigation of the nine-coordinate complexes, [HoIIIL1L2], where L1 = 1,4,7,10-tetrakis(2-pyridylmethyl)-1,4,7,10-tetraaza-cyclododecane and L2 = F- (1) or [MeCN]0 (2). The pseudo-4-fold symmetry imposed by the neutral organic ligand scaffold (L1) and the apical anionic fluoride ion generates a strong axial anisotropy with an mJ = ±8 ground-state quasi-doublet in 1, where mJ denotes the projection of the J = 8 spin-orbital moment onto the ∼C4 axis. Meanwhile, off-diagonal crystal field interactions give rise to a giant 116.4 ± 1.0 GHz clock transition within this doublet. We then demonstrate targeted crystal field engineering of the clock transition by replacing F- with neutral MeCN (2), resulting in an increase in the clock transition frequency by a factor of 2.2. The experimental results are in broad agreement with quantum chemical calculations. This tunability is highly desirable because decoherence caused by second-order sensitivity to magnetic noise scales inversely with the clock transition frequency.

Investigating mental healthcare inequalities associated with forced migration: promise and potential pitfalls of electronic health records.

There is a lack of data on mental health service utilisation and outcomes for people with experience of forced migration living in the UK. Details about migration experiences documented in free-text fields in electronic health records might be harnessed using novel data science methods; however, there are potential limitations and ethical concerns.

Estimating demand for potential disease-modifying therapies for Alzheimer's disease in the UK.

BACKGROUND: Phase three trials of the monoclonal antibodies lecanemab and donanemab, which target brain amyloid, have reported statistically significant differences in clinical end-points in early Alzheimer's disease. These drugs are already in use in some countries and are going through the regulatory approval process for use in the UK. Concerns have been raised about the ability of healthcare systems, including those in the UK, to deliver these treatments, considering the resources required for their administration and monitoring. AIMS: To estimate the scale of real-world demand for monoclonal antibodies for Alzheimer's disease in the UK. METHOD: We used anonymised patient record databases from two National Health Service trusts for the year 2019 to collect clinical, demographic, cognitive and neuroimaging data for these cohorts. Eligibility for treatment was assessed using the inclusion criteria from the clinical trials of donanemab and lecanemab, with consideration given to diagnosis, cognitive performance, cerebrovascular disease and willingness to receive treatment. RESULTS: We examined the records of 82 386 people referred to services covering around 2.2 million people. After applying the trial criteria, we estimate that a maximum of 906 people per year would start treatment with monoclonal antibodies in the two services, equating to 30 200 people if extrapolated nationally. CONCLUSIONS: Monoclonal antibody treatments for Alzheimer's disease are likely to present a significant challenge for healthcare services to deliver in terms of the neuroimaging and treatment delivery. The data provided here allows health services to understand the potential demand and plan accordingly.

An investigation of neuropsychiatric symptoms, contextual factors, and antidepressant treatment as risk factors for dementia development in people with mild cognitive impairment.

BACKGROUND: While some people with mild cognitive impairment (MCI) progress to dementia, many others show no progression. The aim of this study was to identify factors associated with risk of dementia development in this population. METHOD: A large naturalistic retrospective cohort study was assembled from mental healthcare records in a south London catchment. Patients were selected at first recorded diagnosis of MCI and subsequent dementia diagnosis was ascertained from case notes or death certificate, excluding those with dementia diagnoses and deaths within 6 months of MCI diagnosis. A range of demographic and clinical characteristics were ascertained around MCI diagnosis and Cox proportional hazards models were used to investigate independent predictors of dementia, focussing on neuropsychiatric symptoms, contextual factors, and antidepressant treatment. RESULTS: Of 2250 patients with MCI, 236 (10.5%) developed dementia at least 6 months after MCI diagnosis. Aside from older age, lower cognitive function, and activities of daily living impairment, impaired social relationships and recorded loneliness were associated with a higher risk of developing dementia. Patients of Black (compared to White) ethnicity were at a lower risk. For depression and antidepressant receipt, only tricyclic use compared to no antidepressant use was associated with an increased dementia risk. CONCLUSIONS: No evidence was found for co-morbid affective disorders or different antidepressant classes as risk factors for dementia development following MCI diagnosis, but loneliness and social impairment were independent predictors and would be worth evaluating as targets for interventions to delay progression.

Associations between recorded loneliness and adverse mental health outcomes among patients receiving mental healthcare in South London: a retrospective cohort study.

PURPOSE: Loneliness disproportionately affects people with mental disorders, but associations with mental health outcomes in groups affected remain less well understood. METHOD: A cohort of patients receiving mental healthcare on 30th June 2012 was assembled from a large mental health records database covering a south London catchment area. Recorded loneliness within the preceding 2 years was extracted using natural language processing and outcomes were measured between 30th June 2012 until 30th December 2019, except for survival which applied a censoring point of 6th December 2020 according to data available at the time of extraction. The following mental healthcare outcomes: (i) time to first crisis episode; (ii) time to first emergency presentation; (iii) all-cause mortality; (iv) days active to service per year; and (v) face-to-face contacts per year. RESULTS: Loneliness was recorded in 4,483 (16.7%) patients in the study population and fully adjusted models showed associations with subsequent crisis episode (HR 1.17, 95% CI 1.07-1.29), emergency presentation (HR 1.30, 1.21-1.40), days active per year (IRR 1.04, 1.03-1.05), and face-to-face contacts per year (IRR 1.28, 1.27-1.30). Recorded loneliness in patients with substance misuse problems was particularly strongly associated with adverse outcomes, including risk of emergency presentation (HR 1.68, 1.29-2.18) and mortality (HR 1.29, 1.01-1.65). CONCLUSION: Patients receiving mental healthcare who are recorded as lonely have a higher risk of several adverse outcomes which may require a need for higher service input.

Understanding social and clinical associations with unemployment for people with schizophrenia and bipolar disorders: large-scale health records study.

PURPOSE: People with severe mental illness (SMI) experience high levels of unemployment. We aimed to better understand the associations between clinical, social, and demographic inequality indicators and unemployment. METHODS: Data were extracted from de-identified health records of people with SMI in contact with secondary mental health services in south London, UK. A Natural Language Processing text-mining application was applied to extract information on unemployment in the health records. Multivariable logistic regression was used to assess associations with unemployment, in people with SMI. RESULTS: Records from 19,768 service users were used for analysis, 84.9% (n = 16,778) had experienced unemployment. In fully adjusted models, Black Caribbean and Black African service users were more likely to experience unemployment compared with White British service users (Black Caribbean: aOR 1.62, 95% CI 1.45-1.80; Black African: 1.32, 1.15-1.51). Although men were more likely to have experienced unemployment relative to women in unadjusted models (OR 1.36, 95% CI 1.26-1.47), differences were no longer apparent in the fully adjusted models (aOR 1.05, 95% CI 0.97-1.15). The presence of a non-affective (compared to affective) diagnosis (1.24, 1.13-1.35), comorbid substance use (2.02, 1.76-2.33), previous inpatient admissions (4.18, 3.71-4.70), longer inpatient stays (78 + days: 7.78, 6.34-9.54), and compulsory admissions (3.45, 3.04-3.92) were associated with unemployment, in fully adjusted models. CONCLUSION: People with SMI experience high levels of unemployment, and we found that unemployment was associated with several clinical and social factors. Interventions to address low employment may need to also address these broader inequalities.

Maternal asthma and asthma exacerbation during pregnancy and attention-deficit/hyperactivity disorder in offspring: a population-based cohort study.

The link between inflammatory disorders, such as asthma, and attention deficit hyperactivity disorder (ADHD) is attracting increasing attention but few studies have examined cross-generational associations. We sought to examine associations of maternal asthma and asthma exacerbation during pregnancy, as well as paternal asthma, with the risk of ADHD in children. This population-based cohort study used data from the Taiwan National Health Insurance Research Database from 2004 to 2017. Cox regression models compared the risk of ADHD in children of parents with and without asthma, adjusting for parental sociodemographic, physical, and mental health conditions, as well as the child's birth weight, and number of births. A sibling control approach was employed to compensate for unmeasured confounders of asthma exacerbation during pregnancy. In the fully adjusted models, maternal and paternal asthma were both significantly associated with an increased risk of ADHD in offspring, with hazard ratios (HRs) of 1.36 (1.31-1.40) and 1.10 (1.05-1.14), respectively. Acute asthma exacerbation during pregnancy was not associated with the risk of further offspring ADHD (adjusted HR 1.00, 95% CI: 0.75-1.34). Both maternal and paternal asthma are associated with an increased risk of ADHD in offspring. The risk was higher from maternal asthma. However, no such association was found with maternal asthma exacerbation during pregnancy of sibling comparison.

3D VSP Imaging Using DAS Recording of P- and S-Waves in Vertical and Lateral Well Sections in West Texas.

A 3D vertical seismic profiling (VSP) survey was acquired using a distributed acoustic sensing (DAS) system in the Permian Basin, West Texas. In total, 682 shot points from a pair of vibroseis units were recorded using optical fibers installed in a 9000 ft (2743 m) vertical part and 5000 ft (1524 m) horizontal reach of a well. Transmitted and reflected P, S, and converted waves were evident in the DAS data. From first-break P and S arrivals, we found average P-wave velocities of approximately 14,000 ft/s (4570 m/s) and S-wave velocities of 8800 ft/s (3000 m/s) in the deep section. We modified the conventional geophone VSP processing workflow and produced P-P reflection and P-S volumes derived from the well's vertical section. The Wolfcamp formation can be seen in two 3D volumes (P-P and P-S) from the vertical section of the well. They cover an area of 3000 ft (914 m) in the north-south direction and 1500 ft (460 m) in the west-east direction. Time slices showed coherent reflections, especially at 1.7 s (~11,000 ft), which was interpreted as the bottom of the Wolfcamp formation. Vp/Vs values from 2300 ft (701 m) -8800 ft (2682 m) interval range were between 1.7 and 2.0. These first data provide baseline images to compare to follow-up surveys after hydraulic fracturing as well as potential usefulness in extracting elastic properties and providing further indications of fractured volumes.

Identifying Mentions of Pain in Mental Health Records Text: A Natural Language Processing Approach.

Pain is a common reason for accessing healthcare resources and is a growing area of research, especially in its overlap with mental health. Mental health electronic health records are a good data source to study this overlap. However, much information on pain is held in the free text of these records, where mentions of pain present a unique natural language processing problem due to its ambiguous nature. This project uses data from an anonymised mental health electronic health records database. A machine learning based classification algorithm is trained to classify sentences as discussing patient pain or not. This will facilitate the extraction of relevant pain information from large databases. 1,985 documents were manually triple-annotated for creation of gold standard training data, which was used to train four classification algorithms. The best performing model achieved an F1-score of 0.98 (95% CI 0.98-0.99).

Distributions of recorded pain in mental health records: a natural language processing based study.

OBJECTIVE: The objective of this study is to determine demographic and diagnostic distributions of physical pain recorded in clinical notes of a mental health electronic health records database by using natural language processing and examine the overlap in recorded physical pain between primary and secondary care. DESIGN, SETTING AND PARTICIPANTS: The data were extracted from an anonymised version of the electronic health records of a large secondary mental healthcare provider serving a catchment of 1.3 million residents in south London. These included patients under active referral, aged 18+ at the index date of 1 July 2018 and having at least one clinical document (≥30 characters) between 1 July 2017 and 1 July 2019. This cohort was compared with linked primary care records from one of the four local government areas. OUTCOME: The primary outcome of interest was the presence of recorded physical pain within the clinical notes of the patients, not including psychological or metaphorical pain. RESULTS: A total of 27 211 patients were retrieved. Of these, 52% (14,202) had narrative text containing relevant mentions of physical pain. Older patients (OR 1.17, 95% CI 1.15 to 1.19), females (OR 1.42, 95% CI 1.35 to 1.49), Asians (OR 1.30, 95% CI 1.16 to 1.45) or black (OR 1.49, 95% CI 1.40 to 1.59) ethnicities, living in deprived neighbourhoods (OR 1.64, 95% CI 1.55 to 1.73) showed higher odds of recorded pain. Patients with severe mental illnesses were found to be less likely to report pain (OR 0.43, 95% CI 0.41 to 0.46, p<0.001). 17% of the cohort from secondary care also had records from primary care. CONCLUSION: The findings of this study show sociodemographic and diagnostic differences in recorded pain. Specifically, lower documentation across certain groups indicates the need for better screening protocols and training on recognising varied pain presentations. Additionally, targeting improved detection of pain for minority and disadvantaged groups by care providers can promote health equity.

A cross-sectional investigation on remote working, loneliness, workplace isolation, well-being and perceived social support in healthcare workers.

BACKGROUND: Following the onset of the COVID-19 pandemic, healthcare trusts began to implement remote working arrangements, with little knowledge of their impact on staff well-being. AIMS: To investigate how remote working of healthcare workers during the pandemic may have been associated with stress, productivity and work satisfaction at that time, and associations between loneliness, workplace isolation, perceived social support and well-being. METHOD: A questionnaire was developed to explore remote working and productivity, stress and work satisfaction during time spent working remotely. Associations between current loneliness, workplace isolation and well-being, and the influence of perceived social support, were explored with perceived social support as a potential moderator. RESULTS: A total of 520 participants responded to the study, of whom 112 were men (21.5%) and 406 were women (78.1%), with an age range of 21-77 years (mean 40.0, s.d. = 12.1). Very few (3.1%) worked remotely before the COVID-19 pandemic, and this had increased significantly (96.9%). Those who worked ≥31 h a week remotely reported higher stress and lower workplace satisfaction at that time, compared with office work, yet also felt more productive. Current loneliness, workplace isolation and perceived social support were cross-sectionally associated with lower current well-being. CONCLUSIONS: Those who worked more hours a week remotely during the pandemic reported increased stress, which may be related to the lack of resources in place to support this change in work.

Rates of venous thromboembolism associated with acute psychiatric admission: A retrospective cohort study.

The present study aimed to identify rates of venous thromboembolism (VTE) amongst patients treated in inpatient mental health units using linked primary care and mental health care records. Patients resident in the London Borough of Lambeth admitted to mental health units in Southeast London between January 2008 and March 2019 were included, as well as a control group of patients being treated in the community for mental illness. The primary outcome measure was a diagnosis of VTE being recorded in GP records during or within 3 months of an admission to a mental health unit. For 7,198 psychiatric inpatient admissions, 11 episodes of VTE (1.5/1,000 admissions) were identified, with no VTE cases identified in 4,561 patients being treated in the community for mental illness during an equivalent window. This finding indicates that VTE rates following psychiatric inpatient admission might be similar to those following unselected acute medical admission. Larger scale studies are required to confirm the estimated incidence of VTE in patients with mental health conditions and the contribution of acute psychiatry hospitalisation to VTE risk.

Social media users' attitudes toward cyberbullying during the COVID-19 pandemic: associations with gender and verification status.

Introduction: Social media platforms such as Twitter and Weibo facilitate both positive and negative communication, including cyberbullying. Empirical evidence has revealed that cyberbullying increases when public crises occur, that such behavior is gendered, and that social media user account verification may deter it. However, the association of gender and verification status with cyberbullying is underexplored. This study aims to address this gap by examining how Weibo users' gender, verification status, and expression of affect and anger in posts influence cyberbullying attitudes. Specifically, it investigates how these factors differ between posts pro- and anti-cyberbullying of COVID-19 cases during the pandemic. Methods: This study utilized social role theory, the Barlett and Gentile Cyberbullying Model, and general strain theory as theoretical frameworks. We applied text classification techniques to identify pro-cyberbullying and anti-cyberbullying posts on Weibo. Subsequently, we used a standardized mean difference method to compare the emotional content of these posts. Our analysis focused on the prevalence of affective and anger-related expressions, particularly examining variations across gender and verification status of the users. Results: Our text classification identified distinct pro-cyberbullying and anti-cyberbullying posts. The standardized mean difference analysis revealed that pro-cyberbullying posts contained significantly more emotional content compared to anti-cyberbullying posts. Further, within the pro-cyberbullying category, posts by verified female users exhibited a higher frequency of anger-related words than those by other users. Discussion: The findings from this study can enhance researchers' algorithms for identifying cyberbullying attitudes, refine the characterization of cyberbullying behavior using real-world social media data through the integration of the mentioned theories, and help government bodies improve their cyberbullying monitoring especially in the context of public health crises.

Distinct cellular expression and subcellular localization of Kv2 voltage-gated K+ channel subtypes in dorsal root ganglion neurons conserved between mice and humans.

The distinct organization of Kv2 voltage-gated potassium channels on and near the cell body of brain neurons enables their regulation of action potentials and specialized membrane contact sites. Somatosensory neurons have a pseudounipolar morphology and transmit action potentials from peripheral nerve endings through axons that bifurcate to the spinal cord and the cell body within ganglia including the dorsal root ganglia (DRG). Kv2 channels regulate action potentials in somatosensory neurons, yet little is known about where Kv2 channels are located. Here, we define the cellular and subcellular localization of the Kv2 paralogs, Kv2.1 and Kv2.2, in DRG somatosensory neurons with a panel of antibodies, cell markers, and genetically modified mice. We find that relative to spinal cord neurons, DRG neurons have similar levels of detectable Kv2.1 and higher levels of Kv2.2. In older mice, detectable Kv2.2 remains similar, while detectable Kv2.1 decreases. Both Kv2 subtypes adopt clustered subcellular patterns that are distinct from central neurons. Most DRG neurons co-express Kv2.1 and Kv2.2, although neuron subpopulations show preferential expression of Kv2.1 or Kv2.2. We find that Kv2 protein expression and subcellular localization are similar between mouse and human DRG neurons. We conclude that the organization of both Kv2 channels is consistent with physiological roles in the somata and stem axons of DRG neurons. The general prevalence of Kv2.2 in DRG as compared to central neurons and the enrichment of Kv2.2 relative to detectable Kv2.1 in older mice, proprioceptors, and axons suggest more widespread roles for Kv2.2 in DRG neurons.

Impact of inconsistent ethnicity recordings on estimates of inequality in child health and education data: a data linkage study of Child and Adolescent Mental Health Services in South London.

OBJECTIVES: Ethnicity data are critical for identifying inequalities, but previous studies suggest that ethnicity is not consistently recorded between different administrative datasets. With researchers increasingly leveraging cross-domain data linkages, we investigated the completeness and consistency of ethnicity data in two linked health and education datasets. DESIGN: Cohort study. SETTING: South London and Maudsley NHS Foundation Trust deidentified electronic health records, accessed via Clinical Record Interactive Search (CRIS) and the National Pupil Database (NPD) (2007-2013). PARTICIPANTS: N=30 426 children and adolescents referred to local Child and Adolescent Mental Health Services. PRIMARY AND SECONDARY OUTCOME MEASURES: Ethnicity data were compared between CRIS and the NPD. Associations between ethnicity as recorded from each source and key educational and clinical outcomes were explored with risk ratios. RESULTS: Ethnicity data were available for 79.3% from the NPD, 87.0% from CRIS, 97.3% from either source and 69.0% from both sources. Among those who had ethnicity data from both, the two data sources agreed on 87.0% of aggregate ethnicity categorisations overall, but with high levels of disagreement in Mixed and Other ethnic groups. Strengths of associations between ethnicity, educational attainment and neurodevelopmental disorder varied according to which data source was used to code ethnicity. For example, as compared with White pupils, a significantly higher proportion of Asian pupils achieved expected educational attainment thresholds only if ethnicity was coded from the NPD (RR=1.46, 95% CI 1.29 to 1.64), not if ethnicity was coded from CRIS (RR=1.11, 0.98 to 1.26). CONCLUSIONS: Data linkage has the potential to minimise missing ethnicity data, and overlap in ethnicity categorisations between CRIS and the NPD was generally high. However, choosing which data source to primarily code ethnicity from can have implications for analyses of ethnicity, mental health and educational outcomes. Users of linked data should exercise caution in combining and comparing ethnicity between different data sources.

Piloting a psychosocial intervention for perinatal depression, the Thinking Healthy Programme-Peer delivered (THPP), in a primary care setting in Lilongwe District, Malawi.

Despite the evidence for the effectiveness of psychosocial interventions for perinatal depression, their uptake is low in Low- and Middle-Income Countries. Reasons for this include the lack of contextually adapted interventions and mental health specialists to deliver them. This study aimed to test the acceptability and feasibility of a psychosocial intervention for perinatal depression, the Thinking Healthy Programme-Peer Delivered, adapted for use in rural Malawi. A multi-method evaluation of feasibility and acceptability of the intervention was conducted using a one-group pretest-posttest quasi-experimental design and an exploratory qualitative study. Pre-post intervention change in depression scores (paired t-test) and recruitment, retention and session adherence rates were calculated. Qualitative data were collected through 29 in-depth interviews (22 mothers and 7 peer volunteers) and 1 Focus Group Discussion (18 mothers). Thematic analysis approach was used to analyse qualitative data. Seven (7) out of 8 peer volunteers were successfully trained to deliver the intervention. A total of 31 pregnant women with Edinburgh Postnatal Depression Scale (EPDS) score ≥12 were offered intervention, of whom 24 were enrolled (recruitment rate 77.4%). Out of these 24 women, 22 completed the intervention (retention rate 91.6%). Mean difference between pre- and post-test EPDS scores one week after 8th session was 7.59 (95% CI 4.98 to 10.19), p<0.001. Qualitative evaluation showed that the intervention was acceptable despite some challenges including stigma and issues around incentivization of peer volunteers. The Thinking Healthy Programme-Peer Delivered, adapted for use in Malawi, was feasible to deliver and acceptable to its target population. The intervention may be useful in management of perinatal depression in primary care settings in Malawi. However, definitive trials are needed to evaluate its effectiveness.

Improving our understanding of the social determinants of mental health: a data linkage study of mental health records and the 2011 UK census.

OBJECTIVES: To address the lack of individual-level socioeconomic information in electronic healthcare records, we linked the 2011 census of England and Wales to patient records from a large mental healthcare provider. This paper describes the linkage process and methods for mitigating bias due to non-matching. SETTING: South London and Maudsley NHS Foundation Trust (SLaM), a mental healthcare provider in Southeast London. DESIGN: Clinical records from SLaM were supplied to the Office of National Statistics for linkage to the census through a deterministic matching algorithm. We examined clinical (International Classification of Disease-10 diagnosis, history of hospitalisation, frequency of service contact) and socio-demographic (age, gender, ethnicity, deprivation) information recorded in Clinical Record Interactive Search (CRIS) as predictors of linkage success with the 2011 census. To assess and adjust for potential biases caused by non-matching, we evaluated inverse probability weighting for mortality associations. PARTICIPANTS: Individuals of all ages in contact with SLaM up until December 2019 (N=459 374). OUTCOME MEASURES: Likelihood of mental health records' linkage to census. RESULTS: 220 864 (50.4%) records from CRIS linked to the 2011 census. Young adults (prevalence ratio (PR) 0.80, 95% CI 0.80 to 0.81), individuals living in more deprived areas (PR 0.78, 95% CI 0.78 to 0.79) and minority ethnic groups (eg, Black African, PR 0.67, 0.66 to 0.68) were less likely to match to census. After implementing inverse probability weighting, we observed little change in the strength of association between clinical/demographic characteristics and mortality (eg, presence of any psychiatric disorder: unweighted PR 2.66, 95% CI 2.52 to 2.80; weighted PR 2.70, 95% CI 2.56 to 2.84). CONCLUSIONS: Lower response rates to the 2011 census among people with psychiatric disorders may have contributed to lower match rates, a potential concern as the census informs service planning and allocation of resources. Due to its size and unique characteristics, the linked data set will enable novel investigations into the relationship between socioeconomic factors and psychiatric disorders.

Electrically silent KvS subunits associate with native Kv2 channels in brain and impact diverse properties of channel function.

Voltage-gated K+ channels of the Kv2 family are highly expressed in brain and play dual roles in regulating neuronal excitability and in organizing endoplasmic reticulum - plasma membrane (ER-PM) junctions. Studies in heterologous cells suggest that the two pore-forming alpha subunits Kv2.1 and Kv2.2 assemble with "electrically silent" KvS subunits to form heterotetrameric channels with distinct biophysical properties. Here, using mass spectrometry-based proteomics, we identified five KvS subunits as components of native Kv2.1 channels immunopurified from mouse brain, the most abundant being Kv5.1. We found that Kv5.1 co-immunoprecipitates with Kv2.1 and to a lesser extent with Kv2.2 from brain lysates, and that Kv5.1 protein levels are decreased by 70% in Kv2.1 knockout mice and 95% in Kv2.1/2.2 double knockout mice. Multiplex immunofluorescent labelling of rodent brain sections revealed that in neocortex Kv5.1 immunolabeling is apparent in a large percentage of Kv2.1 and Kv2.2-positive layer 2/3 neurons, and in a smaller percentage of layer 5 and 6 neurons. At the subcellular level, Kv5.1 is co-clustered with Kv2.1 and Kv2.2 at ER-PM junctions in cortical neurons, although clustering of Kv5.1-containing channels is reduced relative to homomeric Kv2 channels. We also found that in heterologous cells coexpression with Kv5.1 reduces the clustering and alters the pharmacological properties of Kv2.1 channels. Together, these findings demonstrate that the Kv5.1 electrically silent subunit is a component of a substantial fraction of native brain Kv2 channels, and that its incorporation into heteromeric channels can impact diverse aspects of Kv2 channel function.