The dynamic interplay between sleep and mood: an intensive longitudinal study of individuals with bipolar disorder.

BACKGROUND: Sleep disturbances are important symptoms to monitor in people with bipolar disorder (BD) but the precise longitudinal relationships between sleep and mood remain unclear. We aimed to examine associations between stable and dynamic aspects of sleep and mood in people with BD, and assess individual differences in the strength of these associations. METHODS: Participants (N = 649) with BD-I (N = 400) and BD-II (N = 249) provided weekly self-reports of insomnia, depression and (hypo)mania symptoms using the True Colours online monitoring tool for 21 months. Dynamic structural equation models were used to examine the interplay between weekly reports of insomnia and mood. The effects of clinical and demographic characteristics on associations were also assessed. RESULTS: Increased variability in insomnia symptoms was associated with increased mood variability. In the sample as a whole, we found strong evidence of bidirectional relationships between insomnia and depressive symptoms but only weak support for bidirectional relationships between insomnia and (hypo)manic symptoms. We found substantial variability between participants in the strength of prospective associations between insomnia and mood, which depended on age, gender, bipolar subtype, and a history of rapid cycling. CONCLUSIONS: Our results highlight the importance of monitoring sleep in people with BD. However, researchers and clinicians investigating the association between sleep and mood should consider subgroup differences in this relationship. Advances in digital technology mean that intensive longitudinal data on sleep and mood are becoming increasingly available. Novel methods to analyse these data present an exciting opportunity for furthering our understanding of BD.

Clinical characteristics, attendance outcomes and deaths of homeless persons in the emergency department: implications for primary health care and community prevention programmes.

OBJECTIVES: Persons experiencing homelessness (PEH) are known to be often excluded from primary health care and community prevention programmes leading to high use of hospital emergency departments (EDs). This study aimed to identify demographic features, clinical characteristics and attendance outcomes of PEH presenting to ED. STUDY DESIGN: Analysis of routinely collected data set. METHODS: Clinical presentations and drug prescription data of PEH who presented a major ED in the West Midlands region of England from 2014 to 2019 were extracted and analysed using descriptive and inferential statistics. RESULTS: During the study period, 3271 of 596,198 presentations were made by PEH; 74% PEH attendees were male. Drug- and alcohol-related conditions, as well as pain and injury constituted the most frequent reasons for presentation, contributing to over half of all presentations. A significantly higher proportion of males (n = 481, 20.3%) presented with drug and alcohol problems than females (n = 93, 11.2%) (P ≤ 0.001). However, pain was the primary reason for presentation for twice as many female patients (n = 189, 22.8%) compared with males (n = 305, 12.9%) (P < 0.001). Nearly one in five left the ED before being assessed and a total of 39 patients (1.2%) died in the ED and 785 (24.0%) required in-patient admissions to the same hospital. CONCLUSIONS: Drug, alcohol and pain including the need of opioid analgesics constituted the majority of presentations made by PEH in ED. The observed rate of death of PEH in ED is 12 times higher than the general population. A very high proportion of PEH also leave the ED before being treated. Future research should focus on strengthening community interventions, particularly to improve access to those at risk of dual diagnoses of substance misuse and mental health problems. Interventions involving multisector collaborations are needed to improve seamless discharge from ED and minimise repeat attendance. Gender differences in the nature of presentations and ED outcomes needs to be investigated further.

Actigraphic patterns, impulsivity and mood instability in bipolar disorder, borderline personality disorder and healthy controls.

OBJECTIVES: To differentiate the relation between the structure and timing of rest-activity patterns and symptoms of impulsivity and mood instability in bipolar disorder (BD), borderline personality disorder (BPD) and healthy controls (HC). METHODS: Eighty-seven participants (31 BD, 21 BPD and 35 HC) underwent actigraph monitoring for 28 days as part of the Automated Monitoring of Symptom Severity (AMoSS) study. Impulsivity was assessed at study entry using the BIS-11. Mood instability was subsequently longitudinally monitored using the digital Mood Zoom questionnaire. RESULTS: BPD participants show several robust and significant correlations between non-parametric circadian rest-activity variables and worsened symptoms. Impulsivity was associated with low interdaily stability (r = -0.663) and weak amplitude (r = -0.616). Mood instability was associated with low interdaily stability (r = -0.773), greater rhythm fragmentation (r = 0.662), weak amplitude (r = -0.694) and later onset of daily activity (r = 0.553). These associations were not present for BD or HCs. Classification analysis using actigraphic measures determined that later L5 onset reliably distinguished BPD from BD and HC but did not sufficiently discriminate between BD and HC. CONCLUSIONS: Rest-activity pattern disturbance indicative of perturbed sleep and circadian function is an important predictor of symptom severity in BPD. This appears to validate the greater subjective complaints of BPD individuals that are sometimes regarded as exaggerated by clinicians. We suggest that treatment strategies directed towards improving sleep and circadian entrainment may in the future be investigated in BPD.

Why Weight? An Analytic Review of Obesity Management, Diabetes Prevention, and Cardiovascular Risk Reduction.

PURPOSE OF REVIEW: In this review, we examine one of the ironies of American health care-that we pay more for disease management than disease prevention. Instead of preventing type 2 diabetes (T2DM) by treating its precursor, obesity, we fail to provide sufficient insurance coverage for weight management only to fund the more costly burden of overt T2DM. RECENT FINDINGS: There is a vital need for expanded insurance coverage to help foster a weight-centric approach to T2DM management. This includes broader coverage of anti-diabetic medications with evidence of cardiovascular risk reduction and mortality benefit, anti-obesity pharmacotherapy, bariatric surgery, weight loss devices, endoscopic bariatric therapies, and lifestyle interventions for the treatment of obesity. The fundamental question to ask is why weight? Why wait to go after obesity until its end-stage sequelae cause intractable conditions? Instead of managing the complications of T2DM, consider preventing them by tackling obesity.

A systematic review of calcium channel antagonists in bipolar disorder and some considerations for their future development.

l-type calcium channel (LTCC) antagonists have been used in bipolar disorder for over 30 years, without becoming an established therapeutic approach. Interest in this class of drugs has been rekindled by the discovery that LTCC genes are part of the genetic aetiology of bipolar disorder and related phenotypes. We have therefore conducted a systematic review of LTCC antagonists in the treatment and prophylaxis of bipolar disorder. We identified 23 eligible studies, with six randomised, double-blind, controlled clinical trials, all of which investigated verapamil in acute mania, and finding no evidence that it is effective. Data for other LTCC antagonists (diltiazem, nimodipine, nifedipine, methyoxyverapamil and isradipine) and for other phases of the illness are limited to observational studies, and therefore no robust conclusions can be drawn. Given the increasingly strong evidence for calcium signalling dysfunction in bipolar disorder, the therapeutic candidacy of this class of drugs has become stronger, and hence we also discuss issues relevant to their future development and evaluation. In particular, we consider how genetic, molecular and pharmacological data can be used to improve the selectivity, efficacy and tolerability of LTCC antagonists. We suggest that a renewed focus on LTCCs as targets, and the development of 'brain-selective' LTCC ligands, could be one fruitful approach to innovative pharmacotherapy for bipolar disorder and related phenotypes.

Metformin: an Old Therapy that Deserves a New Indication for the Treatment of Obesity.

Metformin is not currently used for weight loss or diabetes prevention because it lacks an FDA indication for obesity and/or pre-diabetes treatment. Based on the evidence, metformin has been shown to decrease the incidence of type 2 diabetes, and compares favorably to other weight-loss medications in terms of efficacy as well as safety. Thus, metformin should be considered for a treatment indication in patients with these conditions.

Mood instability: significance, definition and measurement.

Mood instability is common, and an important feature of several psychiatric disorders. We discuss the definition and measurement of mood instability, and review its prevalence, characteristics, neurobiological correlates and clinical implications. We suggest that mood instability has underappreciated transdiagnostic potential as an investigational and therapeutic target.

Borderline personality disorder, but not euthymic bipolar disorder, is associated with a failure to sustain reciprocal cooperative behaviour: implications for spectrum models of mood disorders.

BACKGROUND: Borderline personality disorder (BPD) and bipolar disorder (BD) have overlapping clinical presentations and symptoms - sources of persistent clinical confusion. Game-theory can characterize how social function might be sub-optimal in the two disorders and move the field beyond the anecdotal description of clinical history. Here, we tested the hypothesis that BPD and BD can be distinguished on the basis of diminished reciprocal altruism in iterated Prisoner's Dilemma (PD) games. METHOD: Twenty females with BPD, 20 females with euthymic BD and 20 healthy (non-clinical) females, matched for age and cognitive ability, were assessed for Axis-I and personality disorders, and completed psychometric measures of state affect, impulsivity and hostility. Participants completed two iterated PD games and a test of gaze-cueing. RESULTS: In the PD games, BPD participants failed to show statistically stable preferences to cooperate with social partners (playing tit-for-tat) and made significantly fewer cooperative responses compared to BD or controls (ANOVA main effect p = 0.03, post-hoc Tukey p < 0.05 for both comparisons). BPD participants were also less likely to sustain cooperation following experiences involving mutual cooperation than the other groups. Neither BPD nor BD participants demonstrated impairments in shifting visual attention on the basis of other peoples' gaze. CONCLUSIONS: These data indicate that BPD is (selectively) associated with difficulties in establishing, and then maintaining, reciprocal cooperation, involving altruism. These difficulties are not seen in euthymic BD. Our data support the differentiation of BPD from BD and offer fresh insights into the social difficulties experienced by individuals with diagnoses of BPD.

A lack of vision: evidence for poor communication of visual problems and support needs in education statements/plans for children with SEN.

OBJECTIVE: Visual dysfunction is more common in children with neurological impairments and previous studies have recommended such children receive visual and refractive assessment. In the UK, children with neurological impairment often have educational statementing for Special Educational Needs (SEN) and the statement should detail all health care and support needs to ensure the child's needs are met during school life. STUDY DESIGN: This study examined the representation of visual information in statements of SEN and compared this to orthoptic visual information from school visual assessments for children in a special school in Northern Ireland, UK. METHODS: The parents of 115 school children in a special school were informed about the study via written information. Participation involved parents permitting the researchers to access their child's SEN educational statement and orthoptic clinical records. RESULTS: Statement information was accessed for 28 participants aged between four and 19 years; 25 contained visual information. Two participants were identified in their statements as having a certification of visual impairment. An additional 10 children had visual acuity ≥ 0.3 logMAR. This visual deficit was not reported in statements in eight out of these 12 cases (67%). 11 participants had significant refractive error and wore spectacles, but only five (45%) had this requirement recorded in their statement. Overall, 10 participants (55%) had either reduced visual acuity or significant refractive error which was not recorded in their statement. CONCLUSIONS: Despite additional visual needs being common, and described in clinical records, the majority of those with reduced vision and/or spectacle requirements did not have this information included in their statement. If visual limitations are not recognized by educational services, the child's needs may not be met during school life. More comprehensive eye care services, embedded with stakeholder communication and links to education are necessary to improve understanding of vision for children with neurological impairments.

Mental health and academic outcomes over the first year at university in international compared to domestic Canadian students.

OBJECTIVE: To compare risk factors and associated mental health and academic outcomes between international and domestic students. PARTICIPANTS: Canadian university undergraduate students. METHODS: Electronic surveys were completed at university entry and the end of first year. Surveys assessed demographics, risk factors, symptoms of mental disorders, and access to support. Academic outcomes were obtained from university databases. RESULTS: International students had comparable or lower rates of clinically significant anxiety, depression, and insomnia. Domestic female students reported the highest screening rates for common mental disorders. However, international students were more likely to report having attempted suicide. International students felt less connected to the university community and had lower academic performance. Psychosocial risk factor profiles and proportions accessing mental health services were similar. CONCLUSIONS: The scope of mental health need appears more similar than different between international and domestic students; however, international students may benefit from targeted academic and social support initiatives.

The impacts of intensive mining on terrestrial and aquatic ecosystems: A case of sediment pollution and calcium decline in cool temperate Tasmania, Australia.

Mining causes extensive damage to aquatic ecosystems via acidification, heavy metal pollution, sediment loading, and Ca decline. Yet little is known about the effects of mining on freshwater systems in the Southern Hemisphere. A case in point is the region of western Tasmania, Australia, an area extensively mined in the 19th century, resulting in severe environmental contamination. In order to assess the impacts of mining on aquatic ecosystems in this region, we present a multiproxy investigation of the lacustrine sediments from Owen Tarn, Tasmania. This study includes a combination of radiometric dating (14C and 210Pb), sediment geochemistry (XRF and ICP-MS), pollen, charcoal and diatoms. Generalised additive mixed models were used to test if changes in the aquatic ecosystem can be explained by other covariates. Results from this record found four key impact phases: (1) Pre-mining, (2) Early mining, (3) Intense mining, and (4) Post-mining. Before mining, low heavy metal concentrations, slow sedimentation, low fire activity, and high biomass indicate pre-impact conditions. The aquatic environment at this time was oligotrophic and dystrophic with sufficient light availability, typical of western Tasmanian lakes during the Holocene. Prosperous mining resulted in increased burning, a decrease in landscape biomass and an increase in sedimentation resulting in decreased light availability of the aquatic environment. Extensive mining at Mount Lyell in the 1930s resulted in peak heavy metal pollutants (Pb, Cu and Co) and a further increase in inorganic inputs resulted in a disturbed low light lake environment (dominated by Hantzschia amphioxys and Pinnularia divergentissima). Following the closure of the Mount Lyell Co. in 1994 CE, Ca declined to below pre-mining levels resulting in a new diatom assemblage and deformed diatom valves. Therefore, the Owen Tarn record demonstrates severe sediment pollution and continued impacts of mining long after mining has stopped at Mt. Lyell Mining Co.

Efficacy of digital cognitive behavioural therapy for symptoms of generalised anxiety disorder: a study protocol for a randomised controlled trial.

BACKGROUND: Generalised anxiety disorder (GAD) is a chronic and disabling condition with considerable personal and economic impact. Cognitive behavioural therapy (CBT) is a recommended psychological therapy for GAD; however, there are substantial barriers to accessing treatment. Digital CBT, in particular smartphone-delivered CBT, has the potential to improve accessibility and increase dissemination of CBT. Despite the emerging evidence of smartphone-based psychological interventions for reducing anxiety, effect size scores are typically smaller than in-person interventions, and there is a lack of research assessing the efficacy of smartphone-delivered digital interventions specifically for GAD. METHODS: In the DeLTA trial (DigitaL Therapy for Anxiety), we plan to conduct a parallel-group superiority randomised controlled trial examining the efficacy of a novel smartphone-based digital CBT intervention for GAD compared to a waitlist control. We aim to recruit 242 adults (aged 18 years or above) with moderate-to-severe symptoms of GAD. This trial will be conducted entirely online and will involve assessments at baseline (week 0; immediately preceding randomisation), mid-intervention (week 3), post-intervention (week 6; primary end point) and follow-up (week 10). The primary objective is to evaluate the efficacy of the intervention on GAD symptom severity compared to a waitlist control at post-intervention. Secondary objectives are to examine between-group effects on GAD at follow-up, and to examine the following secondary outcomes at both post-intervention and follow-up: 1) worry; 2) depressive symptoms; 3) wellbeing; 4) quality of life; and 5) sleep difficulty. DISCUSSION: This trial will report findings on the initial efficacy of a novel digital CBT intervention for GAD. Results have the potential to contribute towards the evidence base for digital CBT for GAD and increase the dissemination of CBT. TRIAL REGISTRATION: ISRCTN, ISRCTN12765810. Registered on 11 January 2019.

Predictors of mental health and academic outcomes in first-year university students: Identifying prevention and early-intervention targets.

BACKGROUND: Although there is growing interest in mental health problems in university students there is limited understanding of the scope of need and determinants to inform intervention efforts. AIMS: To longitudinally examine the extent and persistence of mental health symptoms and the importance of psychosocial and lifestyle factors for student mental health and academic outcomes. METHOD: Undergraduates at a Canadian university were invited to complete electronic surveys at entry and completion of their first year. The baseline survey measured important distal and proximal risk factors and the follow-up assessed mental health and well-being. Surveys were linked to academic grades. Multivariable models of risk factors and mental health and academic outcomes were fit and adjusted for confounders. RESULTS: In 1530 students surveyed at entry to university 28% and 33% screened positive for clinically significant depressive and anxiety symptoms respectively, which increased to 36% and 39% at the completion of first year. Over the academic year, 14% of students reported suicidal thoughts and 1.6% suicide attempts. Moreover, there was persistence and overlap in these mental health outcomes. Modifiable psychosocial and lifestyle factors at entry were associated with positive screens for mental health outcomes at completion of first year, while anxiety and depressive symptoms were associated with lower grades and university well-being. CONCLUSIONS: Clinically significant mental health symptoms are common and persistent among first-year university students and have a negative impact on academic performance and well-being. A comprehensive mental health strategy that includes a whole university approach to prevention and targeted early-intervention measures and associated research is justified.

A role for the epidermal growth factor-like domain of P-selectin in ligand recognition and cell adhesion.

The selectin family of adhesion molecules mediates the initial interactions of leukocytes with endothelium. The extracellular region of each selectin contains an amino-terminal C-type lectin domain, followed by an EGF-like domain and multiple short consensus repeat units (SCR). Previous studies have indirectly suggested a role for each of the extracellular domains of the selectins in cell adhesion. In this study, a panel of chimeric selectins created by exchange of domains between L- and P-selectin was used to directly examine the role of the extracellular domains in cell adhesion. Exchange of only the lectin domains between L- and P-selectin conferred the adhesive and ligand recognition functions of the lectin domain of the parent molecule. However, chimeric selectins which contained both the lectin domain of L-selectin and the EGF-like domain of P-selectin exhibited dual ligand-binding specificity. These chimeric proteins supported adhesion both to myeloid cells and to high endothelial venules (HEV) of lymph nodes and mesenteric venules in vivo. Exchange of the SCR domains had no detectable effect on receptor function or specificity. Thus, the EGF-like domain of P-selectin may play a direct role in ligand recognition and leukocyte adhesion mediated by P-selectin, with the lectin plus EGF-like domains collectively forming a functional ligand recognition unit.

Correction: In-school eyecare in special education settings has measurable benefits for children's vision and behaviour.

[This corrects the article DOI: 10.1371/journal.pone.0220480.].

In-school eyecare in special education settings has measurable benefits for children's vision and behaviour.

OBJECTIVES: To determine whether implementation of comprehensive in-school eyecare results in measurable benefits for children and young people in terms of visual status, classroom behaviours and how well their visual needs are met. DESIGN: School-based observational study. PARTICIPANTS & METHODS: 200 pupils [mean age 10 years 9 months, 70% male, majority moderate (40%) or severe (35%) learning difficulty] of a special education school in the UK. A sector-agreed in-school eyecare framework including full eye examination and cycloplegic refraction, dispensing of spectacles (as appropriate) and written reporting of outcomes to parents/teachers was applied. Classroom behaviours were observed and recorded prior to, and after, the in-school eyecare. Surveys were employed to obtain visual histories from parents/teachers. School records and statutory documents were reviewed for diagnostic and learning disability classifications. Visual function and ocular health were profiled at baseline and significant visual deficits identified. Where such deficits were previously unrecognised, untreated or not compensated for (e.g. correction of refractive error, enlargement of educational material) they were recorded as 'unmet visual need'. At follow-up, 2-5 months after initial (baseline) measures, eye examinations, parent/teacher surveys and behaviour observations were repeated. Follow-up measures were used to determine if measurable improvements were evident in visual function, ocular health, the level of unmet need and classroom behaviour following implementation of in-school eyecare. RESULTS: 199 participants completed baseline and follow-up measures. 122 (61%) participants presented with at least one significant visual or ocular health deficit and 90 (45%) participants had at least one unmet visual need. Younger pupils and those with no previous history of eyecare were more likely to demonstrate unmet visual needs at baseline (OR 1.12 95% CI 1.03 to 1.21) p = 0.012; (OR 4.44 95% CI 1.38 to 14.29 p = 0.007 respectively). On follow-up, the number of pupils with unmet visual needs dropped significantly to 36 (18%) (McNemar's test p<0.001). Visual and behavioural metrics of participants without significant visual deficits or whose visual needs were adequately addressed at baseline remained relatively unchanged between baseline and follow-up (Wilcoxon signed rank p>0.05). Where significant refractive deficits were corrected at follow-up, near visual acuity improved significantly (Wilcoxon signed rank p = 0.013), however, poor spectacle compliance was a persistent cause of unmet visual need. Off-task behaviour reduced significantly after actions to address unmet visual needs were communicated to parents and teachers (Wilcoxon signed rank p = 0.035). CONCLUSIONS: The present study demonstrates for the first time measurable visual and behaviour benefits to children in special education settings when they receive comprehensive in-school eye examinations, on-site spectacle dispensing and jargon-free reporting of outcomes to teachers and parents.

Variability in phase and amplitude of diurnal rhythms is related to variation of mood in bipolar and borderline personality disorder.

Variable mood is an important feature of psychiatric disorders. However, its measurement and relationship to objective measureas of physiology and behaviour have rarely been studied. Smart-phones facilitate continuous personalized prospective monitoring of subjective experience and behavioural and physiological signals can be measured through wearable devices. Such passive data streams allow novel estimates of diurnal variability. Phase and amplitude of diurnal rhythms were quantified using new techniques that fitted sinusoids to heart rate (HR) and acceleration signals. We investigated mood and diurnal variation for four days in 20 outpatients with bipolar disorder (BD), 14 with borderline personality disorder (BPD) and 20 healthy controls (HC) using a smart-phone app, portable electrocardiogram (ECG), and actigraphy. Variability in negative affect, positive affect, and irritability was elevated in patient groups compared with HC. The study demonstrated convincing associations between variability in subjective mood and objective variability in diurnal physiology. For BPD there was a pattern of positive correlations between mood variability and variation in activity, sleep and HR. The findings suggest BPD is linked more than currently believed with a disorder of diurnal rhythm; in both BPD and BD reducing the variability of sleep phase may be a way to reduce variability of subjective mood.

The contribution of GJB2 mutations to slight or mild hearing loss in Australian elementary school children.

BACKGROUND: There is a lack of information on prevalence, cause and consequences of slight/mild bilateral sensorineural hearing loss (SNHL) in children. We report the first systematic genetic analysis of the GJB2 gene in a population-derived sample of children with slight/mild bilateral SNHL. METHODS: Hearing tests were conducted in 6240 Australian elementary school children in Grades 1 and 5. 55 children (0.88%) were found to have a slight/mild sensorineural hearing loss. 48 children with slight/mild sensorineural hearing loss and a matched group of 90 children with normal hearing participated in a genetic study investigating mutations in the GJB2 gene, coding for connexin 26, and the presence of the del(GJB6-D13S1830) and del(GJB6-D13S1854) deletions in the GJB6 gene, coding for connexin 30. RESULTS: Four of 48 children with slight/mild sensorineural hearing loss were homozygous for the GJB2 V37I change. The four children with homozygous V37I mutations were all of Asian background and analysis of SNPs in or near the GJB2 gene suggests that the V37I mutation arose from a single mutational event in the Asian population. DISCUSSION: Based on the prevalence of carriers of this change we conclude that V37I can be a causative mutation that is often associated with slight/mild sensorineural hearing loss. No other children in the slight/mild hearing loss group had a hearing loss related to a GJB2 mutation. One child with normal hearing was homozygous for the R127H change and we conclude that this change does not cause hearing loss. Two children of Asian background were carriers of the V37I mutation. Our data indicate that slight/mild sensorineural hearing loss due to the GJB2 V37I mutation is common in people of Asian background.

Clinical, immunophenotypic and functional characterisation of T-cell leukaemia in six horses.

REASON FOR PERFORMING STUDY: Lymphoid leukaemia (LL) is rare in equids. In man, immunophenotypic classification identifies distinct leukaemic types with different treatment strategies. Improved understanding and classification of equine LL may allow similar advances. OBJECTIVES: To document the clinical, immunophenotypic and functional characteristics in 6 cases of equine LL of T-cell origin. METHODS: The clinical records and pathological findings from 6 cases of equine LL were analysed. Immunohistochemistry to identify T or B lymphocytes was performed on paraffin embedded tissues in 4 cases. Peripheral blood mononuclear cells (PBMC) were phenotyped for expression of CD4, CD8, MHC class I and II and B-cell antigens in 4 cases using monoclonal antibodies (mAbs) and flow cytometry. Neoplastic lymphocytes from 4 horses were stimulated with mitogens. RESULTS AND CONCLUSIONS: Six horses of various breeds were identified with LL of T-cell origin. The clinical course and presenting signs varied. Neoplastic lymphocytes were identified in peripheral blood samples from all horses and tissue invasion was confirmed at examination post mortem in 4 horses. Immunophenotyping identified a predominance of CD3+ T-cells in lymphoid tissues and CD4+ T-cells in circulating peripheral blood mononuclear cells (PBMC) in the affected horses. Neoplastic lymphocytes from the 4 cases that were tested failed to proliferate in response to mitogens. POTENTIAL RELEVANCE: Characterisation of the clinical, pathological and immunological findings in 6 horses with LL has added to reports of this rare condition, characterised it in greater detail and therefore provides a starting point for further investigations.