1/8 REVIEW ARTICLE Psoriasis and Mental Health Workshop Report: Exploring the Links ActaDV between Psychosocial Factors, Psoriasis, Neuroinflammation and Cardiovascular Disease Risk C. Elise KLEYN1, Peter S. TALBOT2, Nehal N. MEHTA3, Francesca SAMPOGNA4, Chris BUNDY5, Darren M. ASHCROFT6, Alexa B. KIMBALL7, Peter VAN DE KERKHOF8, Christopher E. M. GRIFFITHS1,9, Fernando VALENZUELA10, Joelle M. VAN DER WALT8, Tsion ABERRA3 and Lluís PUIG11 1 Dermatology Centre, Salford Royal NHS Foundation Trust, 2Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK, Acta Dermato-Venereologica 3 National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, USA, 4Clinical Epidemiology Unit, IDI-IRCCS, Rome, Italy, 5School of Healthcare Sciences, College of Biomedical & Life Sciences, Cardiff University, Cardiff, 6School of Health Sciences, NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester, UK, 7Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, 8International Psoriasis Council, St. Louis, USA, 9Dermatology Centre, University of Manchester, NIHR Manchester Biomedical Research Centre, Manchester, UK, 10Dermatology Department, University of Chile and Probity Medical Research, Santiago, Chile, and 11Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain Psoriasis is a systemic, relapsing, inflammatory di- sease associated with serious comorbidities including SIGNIFICANCE mood problems and/or unhealthy lifestyle behaviours. Psoriasis is a chronic, systemic disease which is marked by Cutaneous and systemic abnormalities in innate and a significant psychosocial burden. In recent years, multiple acquired immunity play a role in its pathogenesis. The lines of evidence support the strong association between exact pathogenetic mechanism remains elusive. Evi- psoriasis and psychosocial comorbidities. The role of neuro­ dence is accumulating that TNF-alpha, IL-17 and IL- inflammation in psoriasis pathology, sleep disruption and the 23 signalling are highly relevant as targeting these impact of depression on cardiovascular outcomes was explo­ pathways reduces disease activity. Evidence suggests red in a workshop convened by the International Psoriasis a strong link between psoriasis and depression in Council. The workshop was assembled to increase the under­ adults. The International Psoriasis Council (IPC) held standing of depression as an important comorbidity of pso­ a roundtable event, “Psoriasis and Mental Health”, in riasis and elevate awareness of the impact of chronic, sys­ ActaDV Barcelona, Spain which focused on the presence of de- temic inflammation on neuro- and cardiovascular outcomes. pression and suicidality, plus the role of neuroinflam- Studies discussed at this workshop suggest that depression mation in psoriasis, sleep disruption and the impact is consistently associated with psoriasis, while suicidal idea­ of depression on cardiovascular disease outcomes. We tion is not. Increased awareness of and concern about effec­ summarize here the expert presentations to provide tive depression management in patients with psoriasis will additional insight into the understanding of psychiatric undoubtedly improve overall disease management. comorbidities of psoriasis and of the impact of chro- nic, systemic inflammation on neuro- and cardiovascu- lar outcomes. the associations between psoriasis and Psoriasis provides an ideal model within which to Advances in dermatology and venereology other psychiatric comorbidities are still controversial study relationships between chronic inflammation and and warrant further attention. depression and other psychiatric co-morbidities. For clinical practice, greater awareness of the association Key words: psoriasis; depression; cardiovascular mental health; sleep; neuroinflammation. between psoriasis and depression is important (6). The term ‘depression’ covers a range of experiences, Accepted Nov 19, 2019; Epub ahead of print Nov 19, 2019 from low mood symptoms that may be a transient reac- Acta Derm Venereol 2020; 100: adv00020. tion to adverse life events to the enduring and potentially Corr: Luís Puig, Department of Dermatology, Hospital de la Santa Creu i life threatening disorder. The latter is more accurately Sant Pau, Sant Antoni Maria Claret 167, ES-08025 Barcelona, Spain. E- mail: LPuig@santpau.cat called Depressive Disorder (International Classification of Diseases [ICD-10]) or Major Depressive Disorder (MDD; Diagnostic and Statistical Manual of Mental P soriasis is a chronic inflammatory skin disorder with a broad and variable range of phenotypes, treatments, and associated comorbidities including metabolic syn- Disorders [DSM-5]) (7, 8). Although these disorders are not identical constructs, they overlap to a consider­ able extent and represent a common clinical syndrome drome (1), liver disease (2), respiratory disease (3), characterized by sustained depressed mood and/or psoriatic arthritis (4), cardiovascular disease (5) and anhedonia (reduced motivation for or pleasure from psychosocial disorders (6). It has been proposed that in previously enjoyable activities) and impairing somatic psoriasis its cutaneous and specific systemic manifes- (sleep, energy, sensorimotor, appetites) and cognitive tations are driven by a shared pathogenic inflammatory (self-esteem, concentration) functioning as well as the mechanism. will to live (suicidal thinking and actions). This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta doi: 10.2340/00015555-3375 Journal Compilation © 2020 Acta Dermato-Venereologica. Acta Derm Venereol 2020; 100: adv00020 2/8 C. E. Klein et al. DEPRESSION AND NEUROINFLAMMATION ActaDV An influential current hypothesis of the neurobio- logy of MDD emphasizes a complex and interacting dysregulation of endocrine, immune, and monoami- ne neurotransmitter systems, often triggered initially by environmental stress but gradually becoming self-sustaining and resulting in impaired regional brain structure and function (9, 10). Thus, chronic stress activates the hypothalamic-pi- tuitary-adrenal (HPA) axis resulting in increased rele- Acta Dermato-Venereologica ase of glucocorticoids from the adrenal cortex which, in turn, dysregulates amygdala function (Fig. 1) (10). The elevated adrenal activity and associated increase in sympathetic tone causes the release of proinflammatory cytokines which, along with the Fig. 1. Hypothalamic-pituitary-adrenal (HPA) axis and depression. BDNF: increased glucocorticoids, increase the activity of brain-derived neurotrophic factor; CRH: corticotropin-releasing hormone; DA: the enzyme monoamine oxidase (MAO) which in dopamine; 5HT: serotonin; NE: noradrenaline. turn causes reduced levels of the monoamine neu- rotransmitters serotonin (5-HT), noradrenaline, and stimuli (18), suggesting a neural basis for the negative dopamine. The elevated cytokines and glucocorticoids cognitive bias in MDD which is the therapeutic target also depress neurotrophic factors such as brain-derived of cognitive behavioural therapy. neurotrophic factor (BDNF) resulting in decreased neuro­ Increasing evidence suggests involvement of inflam- genesis in the hippocampus and reduced hippocampal mation in MDD in a proportion of individuals (19–22). volume. Amygdala and hippocampus dysregulation then Inflammatory disorders such as psoriasis are associated maintains abnormal glucocorticoids, BDNF and cytoki- with a high prevalence of depression (23, 24). Similarly, nes, and increased proinflammatory cytokines give rise to symptoms of depression develop in a high proportion of physical illness symptoms and increased risk of inflam- patients administered pro-inflammatory cytokines for ActaDV matory disorders such as cardiovascular disease (CVD). therapeutic reasons (25–27) and in healthy volunteers fol- Stress has been shown to trigger psoriasis onset and lowing peripheral immune challenges, such as vaccination contribute to psoriasis flares in patients (6). The role of or bacterial endotoxin injection, which result in a mild the HPA axis activity dysregulation and the link to the immune activation (28, 29). In MDD, several peripheral modulation of immune response in psoriasis have been pro-inflammatory cytokines are elevated (30–33) and explored (11, 12). Verhoeven et al. (13) demonstrated polymorphisms in inflammatory cytokine genes are as- that flares of psoriasis are characterised by high activity sociated with MDD and treatment response (34). Several of daily stressors and low cortisol levels. Furthermore, PET studies have now investigated whether MDD is also patients with persistently high levels of stressors have associated with evidence for central neuroinflammation Advances in dermatology and venereology related lowered cortisol levels and may be particularly using tracers specific for the 18 kDA translocator protein vulnerable to the influence of stressors on their psoriasis. (TSPO), a mitochondrial membrane protein which is over- expressed on activated microglia and, to a lesser extent, astrocytes. One study did not find elevated TSPO during NEUROIMAGING a mild-to-moderate MDE (35). However, a subsequent A number of changes in the HPA axis have been identified study in more severely symptomatic patients (moderate- by neuroimaging. Molecular positron emission tomo- to-severe MDE) found significantly elevated TSPO, graphy (PET) studies during major depressive episodes most prominent in prefrontal cortex, anterior cingulate (MDE), have found significantly elevated density of cortex (ACC), and insula, and positively correlated with MAO-A – which could result in chronically low synaptic symptom severity (36). More recent data from a clinically 5-HT levels through increased metabolism in a range of and demographically comparable cohort of patients in a brain regions. Further evidence from PET studies demon- moderate-to-severe MDE replicates the TSPO elevation strates that 5-HT1A receptors (14) and 5-HT2A receptors in the ACC, but suggests that microglial activation may be (15, 16) are upregulated in MDD, suggesting an adaptive more strong­ly associated with the presence of suicidality response to reduced 5-HT transmission, and that higher than the diagnosis of MDD itself (37). These studies in levels of 5-HT1A receptors predict higher suicidal ideation working age adults with MDD are supported by the finding and attempts of greater lethality and intent (17). of elevated ACC TSPO in a recent small PET study in pa- Functional magnetic resonance imaging (fMRI) shows tients with late-life depression who had largely recovered the amygdala is overly active in people with MDD when from a depression episode but who had remaining evidence shown sad stimuli, but under-active when shown positive of peripheral inflammation (38). Thus, PET evidence for www.medicaljournals.se/acta Mental health in psoriasis 3/8 neuroinflammation in MDD, and potentially suicidality, Prospective cohort Systematic review Systematic review Systematic review and meta analysis Meta-analysis and 1,174,612 healthy controls were pooled. systematic review Type of study seems to be converging on the ACC, a brain region playing ActaDV an important role in regulating cognitive and emotional processing (39). Interestingly, no PET evidence for neuro­ study inflammation was found in non-depressed patients with moderate-to-severe plaque psoriasis and raised peripheral 35,001 patients with mild psoriasis and cytokines (40). However, a comparable study in depres- sed psoriasis patients has not yet been conducted, and the 264,568 psoriasis patients and neurobiological mechanism underlying the increased inci- 7,510 with severe psoriasis dence of depression in psoriasis remains to be elucidated. 607 psoriasis patients Hamilton Anxiety and Depression scale 626 psoriasis patients Acta Dermato-Venereologica More recently increased TSPO binding has been shown in the brains of patients with MDD and post hoc Sample Size analysis extended these findings by demonstrating that 330,207 this abnormality is significant in unmedicated but not in 36,214 medicated MDD subjects (41). Moreover, in drug-naïve patients in a moderate-severe MDE, improvement in de- pressive symptoms following successful psychotherapy Diagnostic and Statistical Manual of has been shown to be associated with a normalisation of Classification of Diseases codes elevated TSPO (42). Patient Health Questionnaire Mental Disorders IV Assessment tool DEPRESSION AND PSORIASIS Depression Scale Questionnaires Depending on the screening method used, depression SMD: standard mean differences; OR: odds ratio; CI: confidence interval; IRR: incidence rate ratios; MDD: Major Depressive Disorder. prevalence estimates vary between 9 and 55% of people with psoriasis (43, 44). One meta-analysis and systema- tic review estimated rates of clinical depression at 28% suicides (pooled OR,1.26; 95% CI, 1.13–1.40) RR 1.13; 95% CI 0.87–1.46), suicide attempt Psoriasis more likely to attempt and complete (RR 1.26; 95% CI 0.97–1.64) among people using questionnaires while estimates were 12% using (RR 1.25; 95% CI 0.89–1.75), or suicidality Suicidal ideation estimates for psoriasis International Classification of Diseases codes, 19% using ActaDV 35% of patients diagnosed with MDD Diagnostic and Statistical Manual of Mental Disorders IV, and 9% for antidepressant use (24). Psoriasis patients OR = 1.94, 95% CI 1.33–2.82 IRR 1.01; 95%CI 0.85–1.20 in this study had significantly more depressive symptoms (standardized mean differences 1.16; 95% confidence interval (CI) 0.67–1.66), and population-based studies showed that they were at least one and a half times more with psoriasis likely to experience depression (odds ratio [OR] 1.57; 95% CI 1.40–1.76) and used more antidepressant medi- 17.35% Advances in dermatology and venereology cation than did controls (OR 4.24, 95% CI 1.53–11.76) (Table I). In a multicentre study (45), 13.8% of patients OR 1.57; 95% CI 1.53–1.76) odds of depression IRR 1.08 (1.04–1.12) in mild and 1.36 (1.27– with psoriasis reported depression symptoms using the OR 4.24; 95% CI 1.53–11.76 odds of use of SMD 1.16; 95% CI 0.67–1.66) depressive IRR: psoriasis, 1.14 [95% CI, 1.11–1.17] Hospital Anxiety and Depression scale (HADS) versus Depression estimates for psoriasis 4.3% in controls (OR 2.40, 95% CI 1.67–3.47)). Table I. Psoriasis and psycho-comorbidity studies Furthermore, in a study including 607 patients with OR 3.02 (95% CI 1.86–4.90) psoriasis, 9.9% (95% CI: 7.5–12.3%) screened positive 28% depressive symptoms 1.46) in severe psoriasis. for MDD, measured using the (Patient Health Question­ 12% clinical depression 19% clinical depression 9% antidepressant use naire -9 items) PHQ-9 (46). Of these, 42% reported 13.8% depression severe symptoms and 25% met criteria for urgent mental antidepressants health specialist referral. Interestingly, in the 71% of 9.9% MDD symptoms patients from the cohort that identified with severe de- pression, this clinical finding was de novo. In the patient group diagnosed with MDD, 39% had a Dermatology Dalgard et al. 2015 (45) Dowlatshahi et al. 2014 Life Quality Index (DLQI) score <10 indicating low to Jensen et al. 2016 (48) Singh et al. 2017 (54) Lamb et al. 2017 (46) Chi et al. 2017 (53) Wu et al. 2017 (52) medium impact of psoriasis on quality of life. Therefore, using the DLQI alone would potentially miss important depression symptoms that were detected by the PHQ-9. Severity of psoriasis, as determined by a code for syste- Study (24) mic medications, was found to be associated with higher Acta Derm Venereol 2020 4/8 C. E. Klein et al. risk of receiving a clinical diagnosis of depression, and suicidal ideation tend to be more frequent in patients as evidenced by a hazard ratio of 1.72 (CI 1.57–1.88) with severe disease. Although depression is consistently ActaDV in severe psoriasis compared to a hazard ratio of 1.38 associated with psoriasis, suicidal ideation is not (52, 53). (CI 1.35–1.40) in mild psoriasis (47). Depression may One cross-sectional multicentre study found that suicidal act as a trigger or exacerbating factor for psoriasis and ideation was significantly associated with psoriasis (45) may also be a consequence of the disease. Jensen et and some studies indicate that psoriasis is significantly al. (48) examined the risk of new-onset depression in linked to all 3 measures of suicidality (54), but the avail­ patients with psoriasis in a nationwide Danish cohort able data on suicide attempts and death by suicide is of 5 million people in the timeframe 2001–2011. In a limited and less consistent. Younger patients and patients total of 35,001 patients with mild psoriasis and 7,510 with more severe psoriasis are at significantly higher Acta Dermato-Venereologica with severe psoriasis, incidence rates for depression risk of suicidality (54). Higher levels of psoriasis-related were 20.0% (95% CI:19.9–20.0), 23.9% (23.1–24.7) stressors and reduced QoL were significantly associated and 31.6% (29.5–33.8) for the reference population, with suicidality in people with psoriasis. mild, and severe psoriasis, respectively. This finding A large population-based study utilizing a primary care indicates that in patients with severe disease new onset database in the United Kingdom with linked hospital depression is more frequent. and mortality records indicated that the prevalence of In a Brazilian study, PASI (Psoriasis Area Severity depression was raised in patients with psoriasis and this Index), DLQI, State-Trait Anxiety Inventory (STAI) may lead to a greater risk of self-harm. Nevertheless, the questionnaire, PHQ-9 and Holmes and Rahe Life Events risk of suicide was lower in patients with psoriasis com- scale were used to assess the total “load” of stressful pared with those without psoriasis, and it was postulated life events in 119 psoriasis patients having experienced that increased contacts with healthcare professionals for psoriasis for 3 years or more years and moderate severity treatment of skin and coexistent depression may have (49). Salivary cortisol was assessed. The DLQI and stress ameliorated suicide risk (55). questionnaire results demonstrated 20% of patients with depression, and nearly 20% of patients reported severe or very severe impact on QoL. The biometric study sho- DEPRESSION AND ALEXITHYMIA IN PSORIASIS wed a positive correlation (r = 0.39, p < 0.001) between Alexithymia, the difficulty in recognising and describing salivary cortisol values at bedtime and the PASI score. emotions as measured by the Toronto Alexithymia Scale ActaDV The association of psoriasis with anxiety and psycho- (TAS-20), has been linked to psoriasis. The observed logical stress is well established. In order to evaluate prevalence of alexithymia in patients with psoriasis psycho­logical impact, it is important to use instruments ranges between approximately 15.6% and 33%, which such as the HADS and PHQ-9, which are validated is significantly higher than found among the general measures of anxiety and depressive symptomatology. public (56–59). In a multicentre study which included Studies have demonstrated that using the DLQI to mea- 670 patients with psoriasis, the prevalence of alexithymia sure impact on life is not sufficient to identify depression was 24.8% (95% CI: 21.7–28.2) (59). Some studies have as about one in 3 patients with MDD or major anxiety shown that alexithymia is stable over time in the general reported low to medium DLQI scores (46). Advances in dermatology and venereology population (60). However, it may be partly modifiable Effective biologic psoriasis treatments reduce signs with therapeutic interventions, and reversal of alexithy- and symptoms of psoriasis, lower disease impact (DLQI) mia improves QoL, anxiety and depression (61, 62). It and may also improve mental health outcomes (50, 51). is likely that “trait alexithymia” and “state alexithymia” Examination of depression through a prospective, longi- exist – the latter may be modified by therapeutic inter- tudinal psoriasis registry (PSOLAR) demonstrated that vention or change in psychological status. It is important treatment with biologics in moderate-to-severe psoriasis to identify alexithymic patients with psoriasis in clinical patients may reduce the risk of depressive symptoms practice as they suffer from a higher disease burden, (50). Similarly, a large cross-sectional study consisting including significant impairment of QoL, higher levels of over 2 million patients with moderate-to-severe pso- of anxiety and depression, higher risk of alcohol depen- riasis demonstrated reduction of psychological stress and dency and impairment of work productivity, compared depression, in patients treated with biologics compared to patients without alexithymia (63). to those treated with oral therapies as measured by the Kessler Psychological Distress Scale- 6 (K6) and Patient Health Questionnaire-2 (PHQ2) tools (51). SLEEP DISRUPTION, DEPRESSION AND PSORIASIS Sleep is a complex behavioural and physiological pro- DEPRESSION AND SUICIDALITY IN PSORIASIS cess necessary for healthy functioning of the immune The association between psoriasis, depression and suici- and metabolic systems, neuro-cognitive activity and dal ideation has been summarized in Table I. Depression emotional regulation. There is a large body of evidence www.medicaljournals.se/acta Mental health in psoriasis 5/8 demonstrating the vital role sleep has in maintaining for age, gender, socio-economic status, medication health (64–66) and optimal physiological (67) and and comorbidity were estimated by Poisson regression ActaDV psychological functioning (68, 69). Persistent sleep models. Risk of myocardial infarction (MI) (IRR 1.57, disturbance is related to a number of medical illnesses 95% confidence interval (95% CI) 1.07–2.29), stroke including diabetes (70) and has established relationships (IRR 1.95, 95% CI 1.43–2.66), and death from CVD with depression (71, 72). (IRR 2.24, 95% CI 1.53–3.26) were increased signifi- Sleep disturbance is associated with a range of adverse cantly during acute depression, and risk of stroke (IRR health outcomes including elevated risk for a range of 1.51, 95% CI 1.19–1.90) was increased significantly in physical diseases, several of which people with psoriasis chronic depression. During remission from depression, are already more susceptible to (e.g. diabetes (73), hyper­ only the risk of stroke was increased. In patients with Acta Dermato-Venereologica tension (74), CVD (75). Moreover, sleep disturbance in- psoriasis, depression is associated with increased risk creases risk of psychological illness (e.g. depression (72), of MI, stroke and death from CVD, especially during anxiety (76)) and, over time, all-cause mortality (77). acute depression (82). These findings suggest that the Sleep disruption, including obstructive sleep apnoea added burden of comorbid depression in patients with (OSA), may contribute significantly to the health outco- psoriasis confers a greater risk of major adverse CVD mes of psoriasis. A recent study (78) (186 respondents; events. mean age 39.2 years) assessed validated measures of To further understand whether the impact of psoriasis sleep [Pittsburgh Sleep; Quality Index (PSQI), Berlin and comorbid depression occurred prior to CVD events, Questionnaire, Pre-Sleep Arousal Scale]; chronotype 36 patients with psoriasis and reported comorbid depres- (Morningness-Eveningness Questionnaire); mood (Hos- sion and 36 age- and sex-matched patients with psoriasis pital Anxiety and Depression Scale); itch (5-D Itch Sca- but no reported history of psychiatric illness were en- le); and psoriasis severity (Simplified Psoriasis Index). rolled in a study for quantifying vascular inflammation The mean PSQI score was 9.2 ± 4.3, with 76.3% scoring and coronary CT angiography using 18-FDG PET/CT above the threshold for poor sleep (≥ 6 on the PSQI) and (83). Patients with psoriasis and comorbid depression 32.5% scoring ‘positive’ for probable OSA. Poor sleep experienced both greater vascular inflammation and and high likelihood of OSA were associated with more greater total and non-calcified coronary plaque burden severe psoriasis (p < 0.05; η = 0.07; η2 = 0.005) (78). The when compared to psoriasis patients without comorbid precise mechanisms explaining the health outcomes and psychiatric illness. These differences remained signifi- ActaDV sleep link are not fully understood but are thought to cant after adjustment for age, sex and Framingham risk include disrupted cortisol and cytokine production and score, suggesting that comorbid depression in psoriasis changes in body temperature control all of which are contributes to CVD risk beyond what can be attributed implicated in psoriasis. to traditional cardiovascular risk factors. Additionally, a prospective cohort study demonstrated that chronic psychological stress increases neural acti- PSORIASIS, DEPRESSION AND vity, as measured by amygdala activity, in patients with CARDIOVASCULAR EVENTS severe psoriasis disease compared to healthy volunteers Advances in dermatology and venereology Not only is psoriasis accompanied by an increased risk of (84). Elevated neural activity was found to significantly psychiatric comorbidities, but in particular when coupled contribute to the risk of subclinical CVD in patients with these comorbidities, such as depression, psoriasis with psoriasis. Skin clearance after one year of treatment promotes a greater risk of CVD events (79). corresponded with reduction of amygdala activity and Due to the complex interaction of psoriasis and co- subclinical CVD factors. Taken together, these studies morbidities, evidence is accumulating that psoriasis highlight the strong link between psychological stress may trigger the metabolic syndrome and cardiovascular and CVD morbidity in psoriasis. comorbidities. This relationship may be multifactorial, Unfortunately, so far no predictive models nor bio- comprising lifestyles and systematic inflammation. Re- markers are available to predict the course of the disease cently it was shown that blockade of IL12/23 reduced and in particular the development of comorbidities. aortic vascular inflammation (80). Several studies however suggest that predictive models On the other hand these comorbidities may aggravate may become available in the near future. For example, psoriasis. Recently, a Mendelian randomization study a genome-wide analysis of the British Association of showed a causal relationship between body mass index Dermatologists Biologics and Immunomodulators Re- (BMI) and psoriasis, whereas there was little support to gister (BADBIR) revealed that HLA-C*06:02-negative a possible causal effect of psoriasis genetic risk (81). patients responded better to adalimumab, whereas HLA- The link between psoriasis, depression and CVD C*06:02-positive patients responded better to treatment was investigated in a nationwide Danish cohort of pa- with ustekinumab (85). Another analysis of this registry tients with psoriasis (n = 29,406). Incidence rates were indicated that various baseline clinical characteristics calculated, and incidence rate ratios (IRRs) adjusted predict response to treatment with biologics (86). Acta Derm Venereol 2020 6/8 C. E. Klein et al. CONCLUSIONS Lilly, Merck-Serono, Novartis, Pfizer, UCB. CEK is supported by the NIHR Manchester Biomedical Research Centre. PST has ActaDV Psoriasis, depression and CVD are associated and are received consulting fees from Galen Limited; Sunovion Phar- probably connected through systemic inflammation; maceuticals Europe Ltd; myTomorrows; LivaNova UK Ltd. TA neuroimaging has provided evidence for the common has no conflicts of interest to declare. NNM is a full-time US government employee and has served as a consultant for Amgen, inflammatory pathway connecting these conditions. Eli Lilly, and Leo Pharma receiving grants/other payments; as a The interaction of psychological stress with the inflam- principal investigator and/or investigator for AbbVie, Celgene, matory state of psoriasis and depression is complex and Janssen Pharmaceuticals, Inc, and Novartis receiving grants and/ poorly understood. Stressful life events can trigger onset, or research funding; and as a principal investigator for the Natio- exacerbate and initiate flares of psoriasis. In addition, nal Institute of Health receiving grants and/or research funding. FS has acted as a consultant for Abbvie, Eli Lilly, Janssen, Pierre social interactions, economic challenges, and negative Acta Dermato-Venereologica Fabre. PvdK received compensation for consultancy services and behaviours (alcohol and smoking) also contribute to the presenteations from Celgene, Allmirall, Abbvie, Lilly, Novartis, complex interactions of these conditions. Janssen, Leo, Bristol Mayer Squibb, Dermavant and UCB. ABKl The association between psoriasis and distress is has received compensation as a consultant and an investigator for broader than depression alone. Psychological stress Novartis, Abbvie, UCB, Lilly, and Janssen and has received fellow- ship funding from Janssen and Abbvie. CB has received funding and anxiety are also well established features in many for research or honoraria from Abbvie; Almiral; Celgene; Janssen; patients with psoriasis and are aggravating or precipi- Lilly; Novartis; Pfizer. CEMG has received grants and/or hono- tating factors of depression. Alexithymia, which is also raria or consultation fees from Abbvie, Almirall, BMS, Celgene, linked to depression, warrants further investigation. Of Galderma, GSK, Janssen, LEO-Pharma, Lilly, Novartis, Pfizer and note, the association between psoriasis and death by UCB Pharma. CEMG is funded in part by the NIHR Manchester Biomedical Research Centre and by MRC grant MR/1011808/1and suicide may be a matter of debate but suicidal ideation is an NIHR Emeritus Senior Investigator. FV has received grants is more frequently associated with psoriasis. and/or honoraria or consultation fees and/or research support and/ The impairment of patient QoL by psoriasis is common or participated in clinical trials sponsored by Abbvie, Amgen, knowledge and is of major importance in the assessment Janssen, Leo-Pharma, Lilly, Novartis, Pfizer. JMvdW has no con- of treatment outcomes. However, awareness of the asso- flicts of interest to declare. DA has received research grants from Abbvie, Almirall, Celgene, Eli Lilly, Novartis, UCB and the Leo ciation of psoriasis with depression, although established Foundation. LP has received grants and/or honoraria or consulta- in epidemiological studies, is less well-recognised and tion fees and/or research support and/or participated in clinical addressed in the clinic. Early diagnosis of depression trials sponsored by Abbvie, Almirall, Amgen, Baxalta, Biogen, ActaDV through validated tools and insight into related psycholo- Boehringer Ingelheim, Celgene, Gebro, Janssen, Leo-Pharma, gical/psychiatric disorders should form important targets Lilly, Merck-Serono, MSD, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB and has participated in speaker’s bureau for in the treatment of patients with psoriasis. Celgene, Janssen, Lilly, MSD, Novartis, Pfizer. Increased awareness of and concern about effective Funding: AbbVie provided an educational grant to the Interna- depression management in patients with psoriasis will tional Psoriasis Council to support the symposium. This sponsor undoubtedly improve overall disease management. 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