Neuroinflammation as measured by positron emission tomography in patients with recent onset and established schizophrenia: implications for immune pathogenesis.

Positron emission tomography (PET) imaging of the 18 kDa translocator protein (TSPO), which is upregulated in activated microglia, is a method for investigating whether immune activation is evident in the brain of adults with schizophrenia. This study aimed to measure TSPO availability in the largest patient group to date, and to compare it between patients with recent onset (ROS) and established (ES) schizophrenia. In total, 20 ROS patients (14 male), 21 ES (13 male), and 21 healthy controls completed the study. Patients were predominantly antipsychotic-medicated. Participants underwent a PET scan using the TSPO-specific radioligand [11C](R)-PK11195. The primary outcome was binding potential (BPND) in the anterior cingulate cortex (ACC). Secondary outcomes were BPND in six other regions. Correlations were investigated between TSPO availability and symptom severity. Data showed that mean BPND was higher in older (ES and controls) compared with younger (ROS and controls) individuals, but did not significantly differ between ROS or ES and their respective age-matched controls (ACC; ANOVA main effect of diagnosis: F1,58 = 0.407, p = 0.526). Compared with controls, BPND was lower in antipsychotic-free (n = 6), but not in medicated, ROS patients. BPND in the ES group was negatively correlated with positive symptoms, and positively correlated with negative symptom score. Our data suggest ageing is associated with higher TSPO but a diagnosis of schizophrenia is not. Rather, subnormal TSPO levels in drug-free recent-onset patients may imply impaired microglial development and/or function, which is counteracted by antipsychotic treatment. The development of novel radioligands for specific immune-mechanisms is needed for further clarification.

Psoriasis and Mental Health Workshop Report: Exploring the Links between Psychosocial Factors, Psoriasis, Neuroinflammation and Cardiovascular Disease Risk.

Psoriasis is a systemic, relapsing, inflammatory disease associated with serious comorbidities including mood problems and/or unhealthy lifestyle behaviours. Cutaneous and systemic abnormalities in innate and acquired immunity play a role in its pathogenesis. The exact pathogenetic mechanism remains elusive. Evidence is accumulating that TNF-alpha, IL-17 and IL-23 signalling are highly relevant as targeting these pathways reduces disease activity. Evidence suggests a strong link between psoriasis and depression in adults. The International Psoriasis Council (IPC) held a roundtable event, "Psoriasis and Mental Health", in Barcelona, Spain which focused on the presence of depression and suicidality, plus the role of neuroinflammation in psoriasis, sleep disruption and the impact of depression on cardiovascular disease outcomes. We summarize here the expert presentations to provide additional insight into the understanding of psychiatric comorbidities of psoriasis and of the impact of chronic, systemic inflammation on neuro- and cardiovascular outcomes. the associations between psoriasis and other psychiatric comorbidities are still controversial and warrant further attention.

Treatment-resistant and multi-therapy-resistant criteria for bipolar depression: consensus definition.

BACKGROUND: Most people with bipolar disorder spend a significant percentage of their lifetime experiencing either subsyndromal depressive symptoms or major depressive episodes, which contribute greatly to the high levels of disability and mortality associated with the disorder. Despite the importance of bipolar depression, there are only a small number of recognised treatment options available. Consecutive treatment failures can quickly exhaust these options leading to treatment-resistant bipolar depression (TRBD). Remarkably few studies have evaluated TRBD and those available lack a comprehensive definition of multi-therapy-resistant bipolar depression (MTRBD).AimsTo reach consensus regarding threshold definitions criteria for TRBD and MTRBD. METHOD: Based on the evidence of standard treatments available in the latest bipolar disorder treatment guidelines, TRBD and MTRBD criteria were agreed by a representative panel of bipolar disorder experts using a modified Delphi method. RESULTS: TRBD criteria in bipolar depression was defined as failure to reach sustained symptomatic remission for 8 consecutive weeks after two different treatment trials, at adequate therapeutic doses, with at least two recommended monotherapy treatments or at least one monotherapy treatment and another combination treatment. MTRBD included the same initial definition as TRBD, with the addition of failure of at least one trial with an antidepressant, a psychological treatment and a course of electroconvulsive therapy. CONCLUSIONS: The proposed TRBD and MTRBD criteria may provide an important signpost to help clinicians, researchers and stakeholders in judging how and when to consider new non-standard treatments. However, some challenging diagnostic and therapeutic issues were identified in the consensus process that need further evaluation and research.Declaration of interestIn the past 3 years, M.B. has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Eli Lilly, Grunbiotics, Glaxo SmithKline, Janssen Cilag, LivaNova, Lundbeck, Merck, Mylan, Otsuka, Pfizer and Servier. A.C. has received fees for lecturing from pharmaceutical companies namely Lundbeck and Sunovion. A.J.C. has in the past 3 years received honoraria for speaking from Astra Zeneca and Lundbeck, honoraria for consulting from Allergan, Janssen, Lundbeck and LivaNova and research grant support from Lundbeck. G.M.G. holds shares in P1Vital and has served as consultant, advisor or CME speaker for Allergan, Angelini, Compass pathways, MSD, Lundbeck, Otsuka, Takeda, Medscape, Minervra, P1Vital, Pfizer, Servier, Shire and Sun Pharma. J.G. has received research funding from National Institute for Health Research, Medical Research Council, Stanley Medical Research Institute and Wellcome. H.G. received grants/research support, consulting fees or honoraria from Gedeon Richter, Genericon, Janssen Cilag, Lundbeck, Otsuka, Pfizer and Servier. R.H.M.-W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, Liva Nova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion. R.M. has received research support from Big White Wall, Electromedical Products, Johnson and Johnson, Magstim and P1Vital. S.N. received honoraria from Lundbeck, Jensen and Otsuka. J.C.S. has received funds for research from Alkermes, Pfizer, Allergan, J&J, BMS and been a speaker or consultant for Astellas, Abbott, Sunovion, Sanofi. S.W has, within the past 3 years, attended advisory boards for Sunovion and LivaNova and has undertaken paid lectures for Lundbeck. D.J.S. has received honoraria from Lundbeck. T.S. has reported grants from Pathway Genomics, Stanley Medical Research Institute and Palo Alto Health Sciences; consulting fees from Sunovion Pharamaceuticals Inc.; honoraria from Medscape Education, Global Medical Education and CMEology; and royalties from Jones and Bartlett, UpToDate and Hogrefe Publishing. S.P. has served as a consultant or speaker for Janssen, and Sunovion. P.T. has received consultancy fees as an advisory board member from the following companies: Galen Limited, Sunovion Pharmaceuticals Europe Ltd, myTomorrows and LivaNova. E.V. received grants/ research support, consulting fees or honoraria from Abbott, AB-Biotics, Allergan, Angelini, Dainippon Sumitomo, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka and Sunovion. L.N.Y. has received grants/research support, consulting fees or honoraria from Allergan, Alkermes, Dainippon Sumitomo, Janssen, Lundbeck, Otsuka, Sanofi, Servier, Sunovion, Teva and Valeant. A.H.Y. has undertaken paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders and LivaNova. He has also previously received funding for investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth. P.R.A.S. has received research funding support from Corcept Therapeutics Inc. Corcept Therapeutics Inc fully funded attendance at their internal conference in California USA and all related expenses. He has received grant funding from the Medical Research Council UK for a collaborative study with Janssen Research and Development LLC. Janssen Research and Development LLC are providing non-financial contributions to support this study. P.R.A.S. has received a presentation fee from Indivior and an advisory board fee from LivaNova.

Deep brain stimulation of the periaqueductal gray releases endogenous opioids in humans.

Deep brain stimulation (DBS) of the periaqueductal gray (PAG) is used in the treatment of severe refractory neuropathic pain. We tested the hypothesis that DBS releases endogenous opioids to exert its analgesic effect using [11C]diprenorphine (DPN) positron emission tomography (PET). Patients with de-afferentation pain (phantom limb pain or Anaesthesia Dolorosa (n=5)) who obtained long-lasting analgesic benefit from DBS were recruited. [11C]DPN and [15O]water PET scanning was performed in consecutive sessions; first without, and then with PAG stimulation. The regional cerebral tracer distribution and kinetics were quantified for the whole brain and brainstem. Analysis was performed on a voxel-wise basis using statistical parametric mapping (SPM) and also within brainstem regions of interest and correlated to the DBS-induced improvement in pain score and mood. Brain-wide analysis identified a single cluster of reduced [11C]DPN binding (15.5% reduction) in the caudal, dorsal PAG following DBS from effective electrodes located in rostral dorsal/lateral PAG. There was no evidence for an accompanying focal change in blood flow within the PAG. No correlation was found between the change in PAG [11C]DPN binding and the analgesic effect or the effect on mood (POMSSV) of DBS. The analgesic effect of DBS in these subjects was not altered by systemic administration of the opioid antagonist naloxone (400ug). These findings indicate that DBS of the PAG does indeed release endogenous opioid peptides focally within the midbrain of these neuropathic pain patients but we are unable to further resolve the question of whether this release is responsible for the observed analgesic benefit.

Evaluation of patient quality of life and satisfaction with home enteral feeding and oral nutrition support services: a cross-sectional study.

Objective The aims of the present study, in home enteral nutrition (HEN) patients, were to assess patient satisfaction with the service and quality of life (QOL) scores, and to compare QOL scores in HEN patients with general Australian population values. Methods Self-administered voluntary questionnaires for the present cross-sectional study were mailed out to 322 eligible participants registered with HEN for >5 months. The questionnaires used included a patient satisfaction survey and a validated QOL questionnaire. Data analysis consisted of cross-tabulation, Chi-squared tests and t-tests. Results There were 112 participants. Patients reported satisfaction with information received before discharge (86%), support received after discharge (74%), expertise of the health professional (87%), access to health professionals experienced with HEN (74%), communication between health professionals (74%), costs of HEN supplies (52%) and delivery of HEN supplies (88%). QOL scores related to physical, psychological, social and environment domains were significantly lower in HEN patients than in the Australian reference population (P<0.001). There was no significant difference in QOL and health satisfaction across different clinical areas (0.737 and 0.316, respectively). Conclusion Overall, participants were satisfied with HEN services. Participants had lower QOL scores compared with the Australian general population. Improvements to the HEN service were suggested, including sooner follow-up after hospital discharge; more frequent reviews for long-term patients; and the availability of a multidisciplinary team to manage HEN patients. What is known about the topic? Malnutrition is a common problem in Australian hospitals. Many patients require nutrition support to maintain or improve their nutrition status because of inadequate oral intake, malabsorption of nutrients or because of a disease process. Nutrition support is commonly started in the in-patient setting and, because of faster patient discharge from hospital, HEN is a cost-effective and reliable way of treating patients who continue to need nutrition support after hospital discharge. Inconsistencies exist in service provision of HEN because there is no national or state-wide standardisation of services. Australian studies that have evaluated patient satisfaction with HEN services are lacking. This is of particular importance because HEN service use is increasing. What does this paper add? This study reveals that patients receiving HEN therapy are mostly satisfied with the service provided. Patients surveyed have expressed important aspects of the HEN service include follow-up and advice from health care professionals, low price and home delivery of supplies, emphasising the importance of adequate clinical services, supply and delivery of HEN. QOL is poorer in the HEN patient population compared with the general Australian population. What are the implications for practitioners? Standardisation of HEN services is important to ensure uniformity in service provision to HEN patients. Health services adhering to best practice guidelines for HEN will result in the provision of adequate quality of care, and subsequently improved patient satisfaction and adherence to HEN therapy. Adequate service provision and appropriate monitoring and review of HEN patients in the community may also contribute to better health outcomes and better QOL for patients.

An evaluation of current home enteral nutrition services at principal referral hospitals in New South Wales, Australia.

OBJECTIVE: This cross-sectional study investigates the home enteral nutrition (HEN) services of public principal referral hospitals in NSW, Australia, comparing their services to best practice guidelines for HEN. METHODS: HEN service processes were investigated using an online questionnaire and telephone interview with the dietitian primarily working with HEN at each hospital. RESULTS: Participating hospitals reported a total of approximately 3200 HEN patients, 76% required oral nutrition support. Only 69% of hospitals had a dietitian allocated to their HEN service and no hospitals had established multidisciplinary teams to manage HEN patients. Post-discharge follow-up, as recommended for tube fed and oral patients, was achieved by 8% and 15% of hospitals respectively. Forty-six per cent of dietitians were satisfied and 46% of dietitians were dissatisfied with current HEN services provided, and reported the following improvements were required: increased clinical resources allocated to HEN dietitian/coordinator; increased outpatient services (home visits, outpatient clinic, multidisciplinary clinic); and an efficient registration process and database. CONCLUSIONS: HEN services among participating hospitals are inconsistent, demonstrating gaps in service provision. Baseline assessment scores varied, with an average of 61% of recommendations currently in use. Best practice guidelines are not firmly adhered to due to limited funding and allocated resources for HEN.

Managing inadequate antidepressant response in depressive illness.

INTRODUCTION OR BACKGROUND: Depression frequently fails to respond to initial treatment. SOURCES OF DATA: Predominantly meta-analyses and RCTs but supplemented where necessary by additional data and the authors' clinical experience. AREAS OF AGREEMENT: A systematic assessment to identify remedial causes of poor response should be followed by planned sequential treatment trials. Joint decision making by the patient and clinician is essential. Strategies with the strongest support are antidepressant augmentation with lithium or second generation antipsychotics and adding cognitive behavioural treatment. Electroconvulsive therapy is highly effective in resistant depression but there is a high relapse rate when treatment ends. AREAS OF CONTROVERSY: Some pharmacological strategies have inconsistent data (e.g. antidepressant combinations, T3 augmentation) or limited preliminary data (e.g. ketamine, antidepressant augmentation with pramipexole). The efficacy of vagus nerve stimulation, deep brain stimulation and repetitive transcranial magnetic stimulation is unclear. GROWING POINTS: A greater understanding of the causes of depression may assist the development of more effective treatments. AREAS TIMELY FOR DEVELOPING RESEARCH: Role of glutamate antagonists and psychological treatments, other than cognitive behavioural therapy, as adjunctive treatments.

Phonon anomalies predict superconducting T(c) for AlB2-type structures.

We show that the well-known Kohn anomaly predicts Tc for ordered AlB2-type structures. We use ab initio density functional theory to calculate phonon dispersions for Mg1-xAlxB2 compositions and identify a phonon anomaly with magnitude that predicts experimental values of Tc for all x. Key features of these anomalies correlate with the electronic structure of Mg1-xAlxB2. This approach predicts Tc for other known AlB2-type structures as well as new compositions. We predict that Mg0.5Ba0.5B2 will show Tc = 63.6 ± 6.6 K. Other forms of the Mg1-xBaxB2 series will also be superconductors when successfully synthesised. Our calculations predict that the end-member composition, BaB2, is likely to show a Tc significantly higher than currently achieved by other diborides although an applied pressure ∼16 GPa may be required to stabilise the structure.

Coherent phonon decay and the boron isotope effect for MgB2.

Ab initio DFT calculations for the phonon dispersion (PD) and the phonon density of states (PDOS) of the two isotopic forms ((10)B and (11)B) of MgB2 demonstrate that use of a reduced symmetry super-lattice provides an improved approximation to the dynamical, phonon-distorted P6/mmm crystal structure. Construction of phonon frequency plots using calculated values for these isotopic forms gives linear trends with integer multiples of a base frequency that change in slope in a manner consistent with the isotope effect (IE). Spectral parameters inferred from this method are similar to that determined experimentally for the pure isotopic forms of MgB2. Comparison with AlB2 demonstrates that a coherent phonon decay down to acoustic modes is not possible for this metal. Coherent acoustic phonon decay may be an important contributor to superconductivity for MgB2.

Phonon modes of MgB2: super-lattice structures and spectral response.

Micrometre-sized MgB2 crystals of varying quality, synthesized at low temperature and autogenous pressure, are compared using a combination of Raman and infra-red (IR) spectroscopy. These data, which include new peak positions in both spectroscopies for high quality MgB2, are interpreted using DFT calculations on phonon behaviour for symmetry-related structures. Raman and IR activity additional to that predicted by point group analyses of the P6/mmm symmetry are detected. These additional peaks, as well as the overall shapes of calculated phonon dispersion (PD) models are explained by assuming a double super-lattice, consistent with a lower symmetry structure for MgB2. A 2× super-lattice in the c-direction allows a simple correlation of the pair breaking energy and the superconducting gap by activation of corresponding acoustic frequencies. A consistent physical interpretation of these spectra is obtained when the position of a phonon anomaly defines a super-lattice modulation in the a-b plane.

An automatic analysis framework for FDOPA PET neuroimaging.

In this study we evaluate the performance of a fully automated analytical framework for FDOPA PET neuroimaging data, and its sensitivity to demographic and experimental variables and processing parameters. An instance of XNAT imaging platform was used to store the King's College London institutional brain FDOPA PET imaging archive, alongside individual demographics and clinical information. By re-engineering the historical Matlab-based scripts for FDOPA PET analysis, a fully automated analysis pipeline for imaging processing and data quantification was implemented in Python and integrated in XNAT. The final data repository includes 892 FDOPA PET scans organized from 23 different studies. We found good reproducibility of the data analysis by the automated pipeline (in the striatum for the Kicer: for the controls ICC = 0.71, for the psychotic patients ICC = 0.88). From the demographic and experimental variables assessed, gender was found to most influence striatal dopamine synthesis capacity (F = 10.7, p < 0.001), with women showing greater dopamine synthesis capacity than men. Our automated analysis pipeline represents a valid resourse for standardised and robust quantification of dopamine synthesis capacity using FDOPA PET data. Combining information from different neuroimaging studies has allowed us to test it comprehensively and to validate its replicability and reproducibility performances on a large sample size.

Extended characterisation of the serotonin 2A (5-HT2A) receptor-selective PET radiotracer 11C-MDL100907 in humans: quantitative analysis, test-retest reproducibility, and vulnerability to endogenous 5-HT tone.

INTRODUCTION: Scanning properties and analytic methodology of the 5-HT2A receptor-selective positron emission tomography (PET) tracer 11C-MDL100907 have been partially characterised in previous reports. We present an extended characterisation in healthy human subjects. METHODS: 64 11C-MDL100907 PET scans with metabolite-corrected arterial input function were performed in 39 healthy adults (18-55 years). 12 subjects were scanned twice (duration 150 min) to provide data on plasma analysis, model order estimation, and stability and test-retest characteristics of outcome measures. All other scans were 90 min duration. 3 subjects completed scanning at baseline and following 5-HT2A receptor antagonist medication (risperidone or ciproheptadine) to provide definitive data on the suitability of the cerebellum as reference region. 10 subjects were scanned under reduced 5-HT and control conditions using rapid tryptophan depletion to investigate vulnerability to competition with endogenous 5-HT. 13 subjects were scanned as controls in clinical protocols. Pooled data were used to analyse the relationship between tracer injected mass and receptor occupancy, and age-related decline in 5-HT2A receptors. RESULTS: Optimum analytic method was a 2-tissue compartment model with arterial input function. However, basis function implementation of SRTM may be suitable for measuring between-group differences non-invasively and warrants further investigation. Scan duration of 90 min achieved stable outcome measures in all cortical regions except orbitofrontal which required 120 min. Binding potential (BPP and BPND) test-retest variability was very good (7-11%) in neocortical regions other than orbitofrontal, and moderately good (14-20%) in orbitofrontal cortex and medial temporal lobe. Saturation occupancy of 5-HT2A receptors by risperidone validates the use of the cerebellum as a region devoid of specific binding for the purposes of PET. We advocate a mass limit of 4.6 µg to remain below 5% receptor occupancy. 11C-MDL100907 specific binding is not vulnerable to competition with endogenous 5-HT in humans. Paradoxical decreases in BPND were found in right prefrontal cortex following reduced 5-HT, possibly representing receptor internalisation. Mean age-related decline in brain 5-HT2A receptors was 14.0±5.0% per decade, and higher in prefrontal regions. CONCLUSIONS: Our data confirm and extend support for 11C-MDL100907 as a PET tracer with very favourable properties for quantifying 5-HT2A receptors in the human brain.

Depression and Suicidality in Patients With Psoriasis and the Role of Psoriatic Arthritis: A Cross-sectional Study in a Tertiary Setting.

BACKGROUND: Depression is overrepresented in psoriasis. However, it is not clear whether the presence of psoriatic arthritis (PsA) independently increases patients' depressive burden. Furthermore, current evidence regarding suicidality risk of psoriasis populations is conflicting, and the role of PsA in suicidality outcomes of psoriasis is unknown. OBJECTIVES: (i) To test whether PsA is associated with depression and lifetime suicidal ideation among patients with psoriasis; (ii) to capture different suicidal phenomena in these patients; and (iii) to investigate whether suicidality and depressive symptom severity are associated with clinical markers of psoriasis severity and chronicity. METHODS: A cross-sectional survey of tertiary patients (n = 219, aged 18-65 years) with dermatologist-confirmed chronic plaque psoriasis, of whom 84 had rheumatologist-confirmed PsA, was undertaken. The Hospital Anxiety and Depression Scale and Sheehan-Suicidality Tracking Scale were used to assess depression and lifetime suicidality, respectively. RESULTS: PsA presence was associated with depression in patients with psoriasis, independent of other physical comorbidities (adjusted odds ratio 2.92, 95% confidence interval 1.53-5.68). Furthermore, patients with PsA experienced significantly higher levels of anhedonia and anxiety, after controlling for psychiatric history. Of all participants, 48.8% reported lifetime suicidal ideation with or without intent, 21.3% reported suicidal planning, and 9.4% reported suicide attempts. Lifetime suicidality prevalence did not differ between patients with and without PsA. Depressive symptom severity and lifetime suicidality scores were not associated with objective measures of psoriasis severity or treatment group. CONCLUSIONS: These data suggest that joint involvement in psoriasis is associated with higher depressive burden. There is a need for routine depression screening among patients with psoriasis, particularly when PsA is present. Anhedonia appears to be a particularly relevant symptom in the depression phenotype of this population. We did not find a statistically significant association between PsA and suicidality. Nevertheless, suicidality rates in tertiary patients with psoriasis appear to be higher than those in the general population. Suicidality monitoring is recommended to help in reducing future psychiatric morbidity and mortality in patients with psoriasis.

Associations between psoriatic arthritis and mental health among patients with psoriasis: A replication and extension study using the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR).

Background: Despite some evidence that psoriatic arthritis (PsA) may increase psychological burden in psoriasis, the mental health of this subpopulation is under-investigated. Objectives: To investigate whether PsA is associated with higher depression and anxiety in moderate-to-severe psoriasis; explore whether pain mediates these associations; and estimate the prevalence of undiagnosed and untreated depression. Methods: Baseline data from British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) participants completing the Hospital Anxiety and Depression Scale (HADS) were analysed. Results: 707 patients (n = 540 with psoriasis only; n = 167 with PsA) were included. Depression prevalence was higher in patients with than without PsA, when a HADS-depression subscale cut-off ≥8 was used (33% vs. 23%, adjusted Odds Ratio [OR] (95% Confidence Intervals [CI]) = 1.64 (1.09-2.45)), but did not differ using the HADS cut-off ≥ 11. Anxiety prevalence was higher among PsA patients, regardless of HADS cut-off (cut-off ≥11: adjusted OR (95% CI) = 1.62 (1.07-2.45)). Pain fully mediated the effect of PsA on depression and anxiety in psoriasis. 53.6% of participants identified as depressed did not have a known psychiatric disorder; two thirds of depressed participants were not treated. Conclusions: PsA comorbidity in psoriasis is associated with higher anxiety; its association with depression appears to be robust when milder depressive syndromes are included, but less consistent for higher-threshold depression definitions. Depression remains unrecognized and untreated in over half of moderately-to-severe psoriasis patients. Routine depression and anxiety screening is recommended in psoriasis and PsA. PsA comorbidity may increase depression and anxiety in psoriasis through pain experience.

Brain structure and connectivity in psoriasis and associations with depression and inflammation; findings from the UK biobank.

Background: Psoriasis is a chronic systemic inflammatory skin disease, coexisting with depression in up to 25% of patients. Little is known about the drivers of comorbidity, including shared neurobiology and depression brain imaging patterns in patients. An immune-mediated crosstalk between the brain and skin has been hypothesized in psoriasis. With the aim of investigating brain structure and connectivity in psoriasis in relation to depression comorbidity, we conducted a brain imaging study including the largest psoriasis patient sample to date (to our knowledge) and the first to investigate the role of depression and systemic inflammation in brain measures. Effects of coexisting psoriatic arthritis (PsA), which represents joint involvement in psoriasis and a higher putative inflammatory state, were further explored. Methods: Brain magnetic resonance imaging (MRI) data of 1,048 UK Biobank participants were used (131 comorbid patients with psoriasis and depression, age-and sex-matched to: 131 non-depressed psoriasis patients; 393 depressed controls; and 393 non-depressed controls). Interaction effects of psoriasis and depression on volume, thickness and surface of a-priori defined regions of interest (ROIs), white matter tracts and 55x55 partial correlation resting-state connectivity matrices were investigated using general linear models. Linear regression was employed to test associations of brain measures with C-reactive protein (CRP) and neutrophil counts. Results: No differences in regional or global brain volumes or white matter integrity were found in patients with psoriasis compared to controls without psoriasis or PsA. Thickness in right precuneus was increased in psoriasis patients compared to controls, only when depression was present (ß = 0.26, 95% CI [Confidence Intervals] 0.08, 0.44; p = 0.02). In further analysis, psoriasis patients who had PsA exhibited fronto-occipital decoupling in resting-state connectivity compared to patients without joint involvement (ß = 0.39, 95% CI 0.13, 0.64; p = 0.005) and controls (ß = 0.49, 95% CI 0.25, 0.74; p < 0.001), which was unrelated to depression comorbidity. Precuneus thickness and fronto-occipital connectivity were not predicted by CRP or neutrophil counts. Precuneus thickening among depressed psoriasis patients showed a marginal correlation with recurrent lifetime suicidality. Conclusions: Our findings provide evidence for a combined effect of psoriasis and depression on the precuneus, which is not directly linked to systemic inflammation, and may relate to suicidality or altered somatosensory processing. The use of the UK Biobank may limit generalizability of results in populations with severe disease.

Compositional and structural control in LLZO solid electrolytes.

Garnet-based solid-state electrolytes (SSEs) represent a promising class of materials for next-generation batteries with improved safety and performance. However, lack of control over the composition and crystal structure of the well-known Li7La3Zr2O12 (LLZO) garnet material has led to poor reproducibility with a wide range of ionic conductivities reported in the literature. In this study, the role of precursor homogeneity in controlling the compositional and structural evolution of Al-doped LLZO is explored. A novel solution-based synthesis approach is employed to demonstrate enhanced atomic-scale mixing of the starting materials in comparison to conventional solid-state preparation methods. Through this technique, it is shown that the stability and formation temperature of the highly conductive cubic phase is directly impacted by the spatial distribution of the doping element and reactant species in the precursor mixture. Precursor homogeneity was also an important factor in mitigating the formation of unwanted secondary impurities. These findings can be used to guide the synthesis of SSEs with reproducible material characteristics and enhanced electrolytic performance.

The effect of the Covid-19 pandemic on illness perceptions of psoriasis and the role of depression: Findings from a cross-sectional study.

Background: Illness perceptions in psoriasis have an impact on adherence and disability. Changes in dermatological healthcare provision during the Covid-19 pandemic and distress may have affected illness perceptions in psoriasis patients. Objectives: To test whether illness perceptions about psoriasis changed during the first year of the Covid-19 pandemic compared to pre-pandemic in a tertiary population with psoriasis and whether pandemic effects differed depending on depressive burden, given this population's high depression prevalence. Methods: In a cross-sectional survey of n = 188 tertiary patients with dermatologist-confirmed psoriasis recruited before and during the pandemic, eight illness perceptions domains were assessed using the Brief-Illness Perceptions Questionnaire (BIPQ). Presence of depression was assessed with the Hospital Anxiety and Depression Scale (HADS). Results: Beliefs about treatment control and patients' understanding of psoriasis were significantly worse in patients responding during the pandemic compared to before Covid-19. These differences were greater when depression was absent (treatment control: adjusted p < 0.001; coherence: adjusted p = 0.01). However, participants during the pandemic felt less emotionally affected (adjusted p = 0.02) and concerned (adjusted p = 0.007) about psoriasis, independently of depression. Conclusions: We found diverse pandemic effects on illness perception domains in psoriasis. Uncertainty and reduced healthcare access may drive poorer treatment and coherence beliefs during Covid-19. These beliefs can hinder patients' health-promoting behaviours and may explain the high pandemic non-adherence reported previously in psoriasis. Appropriate interventions are needed to establish positive long-term cognitions and improve psoriasis management, for example, using the PsoWell patient materials. Dermatology services should invest in engaging and educating patients regardless of concurrent psychological distress.

Burning daylight: balancing vitamin D requirements with sensible sun exposure.

OBJECTIVE: To examine the feasibility of balancing sunlight exposure to meet vitamin D requirements with sun protection guidelines. DESIGN AND SETTING: We used standard erythemal dose and Ultraviolet Index (UVI) data for 1 June 1996 to 30 December 2005 for seven Australian cities to estimate duration of sun exposure required for fair-skinned individuals to synthesise 1000 IU (25 µg) of vitamin D, with 11% and 17% body exposure, for each season and hour of the day. Periods were classified according to whether the UVI was < 3 or ≥ 3 (when sun protection measures are recommended), and whether required duration of exposure was ≤ 30 min, 31-60 min, or > 60 min. MAIN OUTCOME MEASURE: Duration of sunlight exposure required to achieve 1000 IU of vitamin D synthesis. RESULTS: Duration of sunlight exposure required to synthesise 1000 IU of vitamin D varied by time of day, season and city. Although peak UVI periods are typically promoted as between 10 am and 3 pm, UVI was often ≥ 3 before 10 am or after 3 pm. When the UVI was < 3, there were few opportunities to synthesise 1000 IU of vitamin D within 30 min, with either 11% or 17% body exposure. CONCLUSION: There is a delicate line between balancing the beneficial effects of sunlight exposure while avoiding its damaging effects. Physiological and geographical factors may reduce vitamin D synthesis, and supplementation may be necessary to achieve adequate vitamin D status for individuals at risk of deficiency.