Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2024;14(2):e2024104 1 Correlation of Specific Inflammatory Markers With the Occurrence of Depression in Patients With Psoriasis and Their Use as Biomarkers for the Diagnosis of Depression Eleni Mitsiou1, Aikaterini Kyriakou1, Eleni Parlapani2, Anastasia Trigoni1, Myrto Trakatelli1, Zoe Apalla1, Dimitrios Sotiriadis1, Elizabeth Lazaridou1, Aikaterini Patsatsi1 1 2nd Dermatology Department, Aristotle University School of Medicine, Papageorgiou Hospital, Thessaloniki, Greece 2 1st Department of Psychiatry, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece Key words: psoriasis, depression, , inflammation, CRP, ESR Citation: Mitsiou E, Kyriakou A, Parlapani E, et al. Correlation of Specific Inflammatory Markers With the Occurrence of Depression in Patients With Psoriasis and Their Use as Biomarkers for the Diagnosis Of Depression. Dermatol Pract Concept. 2024;14(2):e2024104. DOI: https://doi.org/10.5826/dpc.1402a104 Accepted: December 12, 2023; Published: April 2024 Copyright: ©2024 Mitsiou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing Interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding Author: Eleni Mitsiou, 2nd Dermatology Department, Aristotle University School of Medicine, Elias 6, GR-59132, Veroia (Greece), Tel. +30 6973032982, E-Mail: mitsiou_elena@yahoo.gr Introduction: Psoriasis is a systemic disease of the skin and nails associated with a wide range of comorbidities such as depression, psoriatic arthritis and metabolic syndrome. Objectives: The study aimed to examine a potential association between inflammatory markers (C- reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and depression in patients with psoriasis. Methods: A total of 80 individuals were enrolled in the study. Case participants included 28 patients diagnosed with Psoriasis (Beck Depression Inventory-II: :0-13) and 24 patients diagnosed with Pso- riasis and Depression (Beck Depression Inventory-II:14-63). Twenty-eight (28) healthy participants comprised the control group. Psoriasis severity was evaluated by using Psoriasis Area and Severity Index, Physician Global Assess- ment, Body Surface Area and Dermatology Life Quality Index. Written approval was obtained for its use in this study: Cardiff University (09/2015). Other factors considered in the study were obesity using the Body Mass Index, the levels of stress using the Beck Anxiety Inventory, and the presence of insomnia using the Athens Insomnia Scale. Blood draws and inflammatory markers measurements were performed for all participants. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2024;14(2):e2024104 Introduction According to the World Health Organization, psoriasis is de- fined as “a chronic, non-communicable, painful, disfiguring and disabling disease for which there is no cure and with great negative impact on patients quality of life (QoL). Pso- riasis involves the skin and nails and is associated with a number of comorbidities. [1]”. The etiology of psoriasis is complex and has not yet been fully elucidated. In patients with genetic predisposition, in- flammation initiation is triggered by an exogenous or en- dogenous stimulus, leading to the appearance of psoriatic plaque. Several evidence underline the interaction between host genetics and environmental factors in stimulating T-cell-mediated inflammatory processes against self-antigens in psoriasis [2]. Various other cells including dermal den- dritic cells, keratinocytes and neutrophils are involved in the immunopathology of psoriasis. The interplay between these cells creates the development of a self-sustained cycle of in- flammation around the IL-23/ IL-17 axis. Lately, research has been focused on the role of Tissue Resident Memory (TRM) T-cells in the course of lesions for- mation in psoriasis. TRM T-cells, a subset of T-memory cells, appear to produce the proinflammatory cytokines IL-17, in- terferon-γ and IL-22. Interestingly, even after the remission of psoriatic lesions following treatment, inflammation re- mains in the apparently healthy tissue in the form of resident TRM cells, as trace of immunological memory [3]. Depression in psoriasis has a substantial effect on the quality of everyday life and the emotional state of patients with psoriasis [4,5]. The association of psoriasis with sleep deprivation, ner- vousness, and inability to relax have also been shown to neg- atively affect concentration and daily performance [6,7]. Psoriasis patients are often stigmatized in their daily lives by their visible lesions, which negatively affects their mental health state, causing anxiety and depression [8-11]. The sever- ity of the depressive symptoms is not proportional to the sever- ity of the disease. Psoriasis can be mild, even a small spot may affect the mental sphere of the person with psoriasis [12]. It seems that the onset of depression is more common in women compared to men and in those younger than 31 years [13]. Overall, depression, which very often accompanies pso- riasis, is characterized by depressed mood, anhedonia and loss of interest, social withdrawal, sleep, and appetite distur- bances. Many times, patients suffering from psoriasis are pos- sessed by feelings of shame, not feeling comfortable in their interpersonal relationships, and do not want to be touched (sexual dysfunction often coexists). There is a mutual rela- tionship between psoriasis and depression, patients with pso- riasis show a higher degree of depression than healthy people, and patients with depression show more psoriasis [14]. Although still relatively unknown, it has been postulated that psoriasis in younger adults may have even greater psy- chological impact as they are more prone to addictive behav- iors, such as alcohol, experience loneliness, stigmatization, and low self-esteem, while, suicidal ideations are also more intense, COVID-19 – related stress as well as the continued economic pressure experienced by humanity in the recent years have triggered the occurrence of psoriasis and have greatly increased the incidence of disease relapses, and de- pressive illness. [15-17]. The immunological background in the pathophysiology of depression has been illustrated by several studies. Further- more, it has been shown that there are common pathogenetic mechanisms in psoriasis and depression. These two facts can justify the occurrence of increased pro-inflammatory cyto- kines such as C- reactive protein (CRP), TNF-a, IL-17, and IL-6 in both diseases [18-26] while the brain barrier has been shown to be affected, as well. Stress may also play a role in the exacerbation of psoriasis, by dysregulation of the hypothalamic– pituitary–adrenal (HPA) axis, sympathetic– adrenal–medullary axis, peripheral nervous system, and im- mune system [27]. Stress-related increased cortisol levels (due to increased ACTH production) have also been associated with psoriasis exacerbation [28]. An important role in the appearance of depression on Brain skin axis, has been shown [28] with the release of the ACTH hormone and the release of inflammatory factors: IFN-a. IL-2, IL-6, IL1β and TNF-α. Methods Participants All participants were recruited from the Psoriasis Outpatient Clinic of the 2nd Department of Dermatology and Venereol- ogy, Aristotle University of Thessaloniki. The study was approved by the Scientific Committee of Papageorgiou General Hospital after permission from the Results: Both CRP and ESR levels were higher in the case group (ie Psoriasis and Depression and Psoriasis) compared to healthy controls. Furthermore, psoriatic patients with depression showed in- creased CRP and ESR levels compared to those of psoriatic patients without depression. Conclusions: The evaluation of both CRP and ESR and their use to detect the presence of depression in patients with psoriasis can be an important tool for their holistic treatment of theirs. Original Article | Dermatol Pract Concept. 2024;14(2):e2024104 3 Hellenic Data Protection Authority. All the participants were thoroughly informed about the scope of the study and were provided with written informed consent, without receiving any financial benefits. A total number of 52 patients (ie, case participants) was enrolled in the study of whom 28 were diagnosed with Pso- riasis (Beck Depression Inventory-II: :0-13), and 24 were diagnosed with Psoriasis and Depression (Beck Depression Inventory-II:14-63). Twenty-eight (28) controls (ie, healthy participants) were also included in the study. The final diag- nosis of depression was made by a psychiatrist. As a result, two of our patients with psoriasis and depression were ex- cluded from the second blood sampling because they needed to receive systemic antidepressant treatment. Blood samples were taken from all participants for the identification and measurement of CRP and erythrocyte sed- imentation rate (ESR), as markers of inflammation. The following inclusion criteria were applied: (a) The pa- tient suffers from moderate to severe psoriasis (body surface area [BSA] > 10 or Psoriasis Area and Severity Index [PASI] > 10 and Dermatology Life Quality Index [DLQI] > 10). (b) The patient suffers from moderate to severe depression. (c) The patient should not follow systemic treatment for pso- riasis or depression at the time of joining the study. (d) If a patient was taking systemic treatment for psoriasis or for depression, the period stopped for the respective treatment should not be shorter than the period calculated according to the formula: t1/2 (half-life time of the drug he was taking x 5, according to drugs SPC (summary of product characteristics) [68]. (e) Initiation after admission to study systemic therapy for psoriasis. (f) Greek as a native language. (g) Healthy at the time/ not fever / not infection. Specific conditions that were considered as exclusion cri- teria were: (a) Adults over 65 years of age. (b) Under 18 years of age. (c) Pregnancy/breastfeeding. (d) Mild psoriasis: BSA ≤ 10, PASI ≤ 10 and DLQI ≤ 10 [19]. (e) Diagnosed psoriatic ar- thritis. (f) Coexistence of another autoimmune disease. (g) Immunosuppression. (h) Malignancy. (i) PUVA. (j) Patients with Erythrodermic Psoriasis. (k) Patients with Pustular pso- riasis. (l) Patients with Palmoplantar psoriasis. (m) Patients receiving systemic treatment for psoriasis or depression over a shorter period calculated according to the formula: t1/2 (drug half-life) x 5 according to drugs SPC (summary of product characteristics) [68]. (n) Psychiatric disorders other than depression included substance dependence disorder. (o) Fever or any type of infection. (p) Crohn disease (q) Anemia. Time Points Selection a. For healthy controls (i) Day 0: taking informed consent and history of the patient, filling out questionnaires, and blood sampling for the measurement of CRP, ESR. b. For Patients with Psoriasis and Depression and Patients with Psoriasis: (i) Day 0: taking informed consents and history of the patient, filling out questionnaires, blood sampling for the measurement of CRP and ESR, initia- tion of systemic treatment for psoriasis (ii) 3 months later since Day 0 and if the same systemic treatment for psori- asis continues: history taking, filling out questionnaires, blood sampling for the measurement of CRP and ESR. Psoriasis Assessment Tools/Methods Psoriasis area severity index (PASI)[29,30] Physician Global Assessment (PGA): PGA score is a physi- cian-reported measure of psoriasis severity, using a 6-point measure. Lower PGA scores indicate a better skin condition [31,32]. Body Surface Area (BSA): The palming method is used for the calculation, considering that one palm of the hand is about 1% of the body surface [33,34]. Dermatology Life Quality Index (DLQI): All questions refer to the last week before the exam. Higher DLQI scores indicate lower quality of life [35]. Beck Depression Inventory-II (BDI-II): a 21-item self- report instrument, measuring different aspects of depression on a 4-point severity scale during the last two weeks [36,37]. Body Mass Index (BMI): It is calculated based on the formula: BMI = weight(kg)/heigh)2 (m2) and determines the ideal weight of each person based on height and kilograms . Recent data lead to the conclusion that obesity is not just epidemiologically related as a comorbidity with psoriasis but is a causative risk factor for the onset or worsening of psoriasis. Obesity is therefore related to psoriasis with com- mon inflammatory factors while it is mainly characterized by increased leptin, resistin, and chemerin but also decreased adiponectin (adipocytokines) [38,39]. Athens Insomnia Scale (AIS): The Athens Insomnia Scale is an effective and easy sleep analysis tool. There are studies that report that inflammation markers are affected by sleep quality [40,41,42,7,]. Beck Anxiety Inventory (BAI): It is a self-report assess- ment for measuring various stress symptoms by patients during the last week since completing the questionnaire (ie, Day 0). If the symptoms persist, the help of a mental health specialist may be needed [43]. Inflammation Markers CRP CRP belongs to the acute phase proteins and its levels in- crease in the serum immediately after the onset of the in- flammatory reaction. It is produced exclusively in the liver and exhibits both pro-inflammatory and anti-inflammatory properties and plays a role in the non-specific response 4 Original Article | Dermatol Pract Concept. 2024;14(2):e2024104 gender, and treatment.  Statistical significance was set at 0.05 and the analysis was carried out using STATISTICA v 12.0. Results Characteristics of Participants Their baseline characteristics appear in table 1 and other ep- idemiological characteristics in Table 1 below. Other Clinical Characteristics of individuals enrolled in the study appears in Table 2 based on a semi-structured in- terview and patients’ medical records. The study examines the difference observed in CRP and ESR values among the three groups at baseline, as well as the changes observed within a period of three months in the two groups. (psoriasis, psoriasis and depression). Regarding dif- ferences at baseline and ESR, statistically significant differ- ences were observed between groups (F2,76= 6.312 P = 0.03), after adjusting for baseline BMI values. Specifically, patients suffering from Psoriasis and Depression showed higher levels of ESR than patients diagnosed with Psoriasis but no depres- sion (P = 0.032). The difference between patients suffering Psoriasis and Depression vs controls was also statistically significant as the adjusted p value for multiple comparisons was found to be 0.022. No differences were observed be- tween patients with Psoriasis and controls (P = 1.000). The distribution of data is displayed by a boxplot-type of dia- gram in Figure 1. Regarding CRP measurements at baseline, statistically significant differences were observed between healthy con- trols and both groups of patients suffering from Psoriasis, with or without depression (F2,76= 6.937, P = 0.002). Spe- cifically, higher CRP levels were observed in Psoriasis and Depression group compared to controls (P = 0.001) while the Psoriasis group did not differ from the Psoriasis and De- pression group (P = 0.210) or the control group (P = 0129). (innate/ adaptive immunity). It belongs to blood tests. The detection of C-reactive protein levels in the blood is easy, no special procedures were required, and cheap. The mea- surement was carried out with the PETIA method (particle- enhanced turbidimetric immunoassay) [44]. The normal value of CRP levels: is less than 0.3 mg/dL. ESR ESR is the rate at which red blood cells settle in the plasma and is expressed in mm per hour. It is classified in blood tests. No special procedures are required before blood sampling. For blood, the collection is used special closed tubes of vacuum air with sodium citrate (sodium citrate 3.2%), usually black in color. The Wester- gren method measures the distance in millimeters (mm) that red blood cells in anticoagulated whole blood fall to the bot- tom of a standard upright, elongated tube (Westergren tube) over the course of one hour because of gravity [45]. The nor- mal value varies between 10 and 15 mm in the first hour (for women 12-20 mm). The ESR test is not specific for any disease but is used in conjunction with other tests to identify increased inflammatory activity. Statistical Analysis Baseline differences in ESR and CRP levels among groups were analyzed using regression models and adjusting for BMI values. Multiple comparison tests were applied to de- termine statistically significant pairwise differences based on Bonferroni adjusted p- values. Repeated measures gen- eral linear models were applied to examine the differences between the two-time points and between the two groups of patients regarding CRP and ESR levels. The changes were adjusted for baseline values of BMI, PASI score, BGA score,  BSA  score,  DLQI score, BAI score, AIS score, age, Table 1 Baseline Characteristics Group Healthy controls Psoriasis and Depression Psoriasis Mean Deviation Mean Deviation Mean Deviation Age 46.11 11.10 47.96 11.83 49.39 12.72 Age of onset of psoriasis . . 32.21 16.08 32.68 15.21 Group Healthy controls Psoriasis and Depression Psoriasis N % N % N % Gender Male 8.0 28.6% 14.0 58.3% 25.0 89.3% Female 20.0 71.4% 10.0 41.7% 3.0 10.7% Family history of psoriasis Yes .0 0.0% 4.0 16.7% 10.0 35.7% No .0 0.0% 20.0 83.3% 18.0 64.3% Original Article | Dermatol Pract Concept. 2024;14(2):e2024104 5 Comparing the two disease groups, regarding ESR, the ini- tially observed differences at baseline remain statistically significant after adjusting for BMI, PASI score, BGA score, BSA score, DLQI score, BAI score, AIS score, age, gender, and treatment (P = 0.048). The differences, 3 months later, remain statistically significant (P = 0.025). Regarding CRP, The distribution of data is displayed by a boxplot-type of diagram in Figure 2. Differences in ESR and CRP levels were examined be- tween the two-time points (baseline and three months pe- riod) for the two groups of patients (Table 4). No significant changes in ESR or CRP values were observed in either group. Table 2 Summarizes the clinical characteristics of individuals enrolled in the study Group Healthy controls psoriasis+ depression Psoriasis N % N % N % Psoriatric Nails Yes .0 0.0% 16.0 66.7% 16.0 57.1% .0 0.0% 8.0 33.3% 12.0 42.9% TREATMENT FOR PSORIASIS: Treatment Conventional .0 0.0% 5.0 23.8% 5.0 19.2% Biologics .0 0.0% 16.0 76.2% 21.0 80.8% Chemoprophylaxis .0 0.0% 20.0 83.3% 20.0 71.4% Past .0 0.0% 4.0 16.7% 7.0 25.0% Now .0 0.0% .0 0.0% 1.0 3.6% MENTAL HEALTH: Family history of depression Yes 2.0 7.1% 3.0 12.5% 1.0 3.6% No 26.0 92.9% 21.0 87.5% 27.0 96.4% Suicidal ideation Yes .0 0.0% 3.0 12.5% 1.0 3.6% No 28.0 100.0% 21.0 87.5% 27.0 96.4% CO-MORBIDITIES: Hypertension Yes 7.0 25.0% 9.0 37.5% 5.0 17.9% No 21.0 75.0% 15.0 62.5% 23.0 82.1% Cardiovascular disease Yes .0 0.0% 5.0 20.8% 2.0 7.1% No 28.0 100.0% 19.0 79.2% 26.0 92.9% Diabetes Yes 4.0 14.3% 3.0 12.5% 4.0 14.3% No 24.0 85.7% 21.0 87.5% 24.0 85.7% Dyslipidemia Yes 4.0 14.3% 9.0 37.5% 8.0 28.6% No 24.0 85.7% 15.0 62.5% 20.0 71.4% HEALTH HABITS: Smoking Yes 15.0 53.6% 10.0 41.7% 16.0 57.1% No 13.0 46.4% 14.0 58.3% 12.0 42.9% Alcohol Consumption Yes 10.0 35.7% 8.0 33.3% 19.0 67.9% No 18.0 64.3% 16.0 66.7% 9.0 32.1% Drug Use Yes .0 0.0% .0 0.0% 1.0 3.6% No 28.0 100.0% 24.0 100.0% 27.0 96.4% Sports activity Yes 8.0 28.6% 7.0 29.2% 4.0 14.3% No 20.0 71.4% 17.0 70.8% 24.0 85.7% SEX LIFE: Sexual activity Yes 24.0 85.7% 15.0 62.5% 23.0 82.1% No 4.0 14.3% 9.0 37.5% 5.0 17.9% Sexual activity / affected by psoriasis Yes .0 0.0% 14.0 58.3% 7.0 25.0% No .0 0.0% 10.0 41.7% 21.0 75.0% 6 Original Article | Dermatol Pract Concept. 2024;14(2):e2024104 Figure 1. Comparative boxplot of erythrocyte sedimentation rate (ESR) baseline values. Figure 2. Comparative boxplot of C- reactive protein (CRP) base- line values. Table 3. Distribution on erythrocyte sedimentation rate and C- reactive protein values in the three groups across the two time points ESR at baseline CRP at baseline Median Range Median Range Group • Healthy controls 6.00 20.00 .15 .50 • Psoriasis and Depression 12.50a 50.00 .50b 1.73 • Psoriasis 5.00 28.00 .28 b 1.68 a Significantly higher ESR levels versus patients with psoriasis CRP = C- reactive protein; ESR = erythrocyte sedimentation rate. b Significantly higher CRP levels vs healthy controls Table 4. Distribution on erythrocyte sedimentation rate and C- reactive protein values in the two groups across the two time points Group Psoriasis and Depression Psoriasis Median Range Median Range ESR at baseline 12.50a 50.00 5.00 28.00 ESR at 3m 10.00 a 58.00 4.00 28.00 CRP at baseline .50 1.73 .28 1.68 CRP at 3m .31 5.47 .21 1.66 a Significantly higher erythrocyte sedimentation rate levels versus patients with psoriasis no differences were observed between the two groups of pa- tients at either time point. Subgroup analysis indicated significantly higher ESR lev- els in women at 3 months (median=29, range =56), com- pared to men (median=4, range = 39), P = 0.005. The Beck Anxiety score was positively correlated to CRP values at baseline (P = 0.027) and at 3 months as well (P = 0.009). Finally, higher CRP values were observed in patients with higher BMI value at baseline (P < 0.001). Conclusions The aim of the study was to investigate a potential significant difference in the levels of inflammatory markers CRP and ESR between patients with psoriasis and patients with psori- asis and depression. The potential influence of a three-month systematic treatment for psoriasis on the inflammatory Original Article | Dermatol Pract Concept. 2024;14(2):e2024104 7 activity has not been studied [60]. An older drug still used against psoriasis is methotrexate. The antidepressant ef- fect of methotrexate has not been studied. Conversely, depressive symptomatology is reported as an adverse drug effect. Αt the end it would be good to inform our patients about their condition and direct them to the appropriate specialist for them (psychiatrist or psychologist or both of them). Regarding pharmacologic treatment, there are studies that evaluated the efficacy of antidepressants, mainly selective serotonin reuptake inhibitors. Nowadays we know the role of the brain-skin axis [28] in psoriasis and depression, which among others leads to decreased serotonin levels. Serotonin is considered the “happiness hormone” because it affects mood and high levels of se- rotonin are associated with elevated mood and feelings of joy. Low levels of serotonin (serotonergic disbalance) are the key to pathophysiological mechanisms in depres- sion [62]. Brain skin axis [28] by the release of the ACTH hormone, which has receptors among others in the skin, leads to the degranulation of mastocytes and the release of inflammatory factors: IFN-a and the IL-2, IL-6, IL1β, TNF-α by increasing the production of the enzyme In- doleamine 2,3-dioxygenase. This enzyme (Indoleamine 2,3- dioxygenase) catalyzes tryptophan into various other products. Serotonin is produced from tryptophan, result- ing in decreased serotonin production due to reduced tryp- tophan and its products [63]. The relationship between the use of antidepressants for the treatment of depression and the reduction of inflammation and specifically the reduc- tion of CRP has also been studied [64]. However, there is also an opinion that although antidepressants may allevi- ate psychiatric symptoms, there is evidence that they may be associated with psoriasis symptoms exacerbation [63]. Concerning other therapeutic approaches, a meta-analy- sis revealed encouraging results with respect to the psy- chotherapeutic interventions effectiveness on psoriasis outcomes [65]. Cognitive behavioral therapy may be a promising complementary approach for psoriasis patients with depressive symptoms [66]. Still, further research is warranted in this field. Positive psychology interventions strive towards consolidating psychological resources and nourishing positive cognitions and feelings [67] . In conclusion, psoriasis is a disease requiring a multidi- mensional therapeutic approach. Our study is based on lim- ited and preliminary data. More studies are needed to help address this important correlation of specific inflammatory markers with the occurrence of depression in patients with psoriasis. The measurement of the values of CRP and ESR and their use to detect the possibility of the presence of de- pression can be an important tool for the holistic treatment of our patients with psoriasis. markers levels was also examined (Conventional systemic therapy, Biologics). We chose to study these specific indicators of inflamma- tion, because they are easy and economical to measure, while no special preparation for the patient is needed and they are done with a simple blood draw. Specific inflammatory marker as CRP, is influenced by other factors such as body weight [46], gender (female gender may be associated with increased prevalence of de- pressive symptoms [48] and levels of anxiety and insomnia [43]. We also know about the immunological background of depression and its relationship with the severity of pso- riasis skin lesions [47,49] which affects different aspects of a patient life, including family and sexual life [50], and has an impact on the patient quality of life [50] and can lead, in more serious cases, to increased suicidal ideation [51]. The results of our study confirm the publications so far as we found significantly higher ESR in women with psoria- sis and depression and higher CRP was observed in patients with higher BMI at baseline. Regarding CRP and ESR, measurements were found higher CRP and ESR levels in patients with Psoriasis and Depression and Psoriasis vs healthy controls and higher CRP and ESR levels in patients with Psoriasis and De- pression vs patients with Psoriasis. Instead, no significant changes in CRP or ESR values were observed between the two-time points (baseline and three months) after systemic therapy for psoriasis for the two groups of patients (Pso- riasis and Depression and Psoriasis). We consider that the 3-month period between the 2 measurements was too short to allow safe conclusions on the possible reduction of CRP and ESR after systemic treatment for psoriasis that patients received. Therefore, based our results of our study, it would be better to measure them at baseline. Their increased values can alert us not only to the possibility of co-morbidities such as psoriatic arthritis [52] or cardiovascular disease [53] or depression. If it is also confirmed the existence of depression with the use of special questionnaires, such as Beck, it is an important help for us, as the treating doctors, of choos- ing the appropriate treatment for our patients suffering from psoriasis. In the literature, there are studies which found an improvement in the depressive symptoms of pa- tients with psoriasis after systematic medication for pso- riasis, and after the administration of specific biological factors [54,61] such as etanercept[55,56], adalimumab [57], ustekinumab [58,], while there are also drugs that can worsen it such as apremilast [59]. From Conventional drugs even though cyclosporine has been shown to in- hibit Th1 and Th17 pathways exhibiting multifactorial and suppressive anti-psoriatic activity, its antidepressant 8 Original Article | Dermatol Pract Concept. 2024;14(2):e2024104 study. Skin Health Dis. 2022;2(3):e145. DOI: 10.1002/ski2.145. PMID: 36092261. PMCID: PMC9435449. 16. Wang Q, Luo Y, Lv C, et al. Nonadherence to Treatment and Patient-Reported Outcomes of Psoriasis During the COVID-19 Epidemic: A Web-Based Survey. Patient Prefer Adherence. 2020;14:1403-1409. DOI: 10.2147/PPA.S263843. PMID: 32884243. PMCID: PMC7431943. 17. Narang T, Bhandari A, Mehta H, Narang K, Handa S, Dogra S. Effect of Lockdown Due to COVID-19 on Health and Life- style of Psoriasis Patients: A Web-Based Survey. Indian Dermatol Online J. 2022;13(5):625-628. DOI: 10.4103/idoj.idoj_46_22. PMID: 36304639. PMCID: PMC9595162. 18. Postal M, Appenzeller S. The importance of cytokines and au- toantibodies in depression. Autoimmun Rev. 2015;14(1):30-35. DOI: 10.1016/j.autrev.2014.09.001. PMID: 25242344. 19. Bai YM, Su TP, Li CT, et al. Comparison of pro-inflammatory cytokines among patients with bipolar disorder and unipolar depression and normal controls. Bipolar Disord. 2015;17(3): 269-277. DOI: 10.1111/bdi.12259. PMID: 25257835. 20. Audet MC, McQuaid RJ, Merali Z, Anisman H. Cytokine vari- ations and mood disorders: influence of social stressors and so- cial support. Front Neurosci. 2014;8:416. DOI: 10.3389/fnins .2014.00416. PMID: 25565946. PMCID: PMC4267188. 21. Momeni M, Ghorban K, Dadmanesh M, et al. Differential pattern of cytokine production by depressed medical students; evidence for involvement of cytokine network in pathology of depression. Clin Lab. 2014;60(3):435-440. DOI: 10.7754/clin .lab.2013.130238. PMID: 24697120. 22. Dahl J, Ormstad H, Aass HC, et al. The plasma levels of vari- ous cytokines are increased during ongoing depression and are reduced to normal levels after recovery. Psychoneuroendocri- nology. 2014;45:77-86. DOI: 10.1016/j.psyneuen.2014.03.019. PMID: 24845179. 23. Chocano-Bedoya PO, Mirzaei F, O’Reilly EJ, et al. C-reactive protein, interleukin-6, soluble tumor necrosis factor α receptor 2 and incident clinical depression. J Affect Disord. 2014;163: 25-32. DOI: 10.1016/j.jad.2014.03.023. PMID: 24836084. PMCID: PMC4029945. 24. Kannan S, Heller MM, Lee ES, Koo JY. The role of tumor necro- sis factor-alpha and other cytokines in depression: what derma- tologists should know. J Dermatolog Treat. 2013;24(2):148-152. DOI: 10.3109/09546634.2011.619159. PMID: 21888569. 25. Young JJ, Bruno D, Pomara N. A review of the relationship between proinflammatory cytokines and major depressive disorder. J Affect Disord. 2014;169:15-20. DOI: 10.1016/j .jad.2014.07.032. PMID: 25128861. 26. Momeni M, Ghorban K, Dadmanesh M, et al. Differential pattern of cytokine production by depressed medical students; evidence for involvement of cytokine network in pathology of depression. Clin Lab. 2014;60(3):435-440. DOI: 10.7754/clin .lab.2013.130238. PMID: 24697120. 27. Wei TQ, Kramer S, Chu VP, et al. An improved automated immu- noassay for C-reactive protein on the Dimension clinical chemis- try system. J Autom Methods Manag Chem. 2000;22(5):125-131. DOI: 10.1155/S1463924600000195. PMID: 18924698. PMCID: PMC2562849. 28. Marek-Jozefowicz L, Czajkowski R, Borkowska A, et al. The Brain-Skin Axis in Psoriasis-Psychological, Psychiatric, Hormonal, and Dermatological Aspects. Int J Mol Sci. 2022;23(2):669. DOI: 10.3390/ijms23020669. PMID: 35054853. PMCID: PMC8776235. References 1. Global report on psoriasis, World Health Organization 26 October 2016, page 10 2. Pr.C.E.M.Griffiths MD et al, Psoriasis, lancet, vol 397 april3, 2021 3. Chen L, Shen Z. Tissue-resident memory T cells and their bi- ological characteristics in the recurrence of inflammatory skin disorders. Cell Mol Immunol. 2020;17(1):64-75. DOI: 10.1038 /s41423-019-0291-4. PMID: 31595056. PMCID: PMC6952397. 4. Palijan TZ, Kovacević D, Koić E, Ruzić K, Dervinja F. The impact of psoriasis on the quality of life and psychological characteris- tics of persons suffering from psoriasis. Coll Antropol. 2011;35 Suppl 2:81-85. PMID: 22220410. 5. [Han C, Lofland JH, Zhao N, Schenkel B. Increased prevalence of psychiatric disorders and health care-associated costs among patients with moderate-to-severe psoriasis. J Drugs Dermatol. 2011;10(8):843-850. PMID: 21818505. 6. Gowda S, Goldblum OM, McCall WV, Feldman SR. Factors affecting sleep quality in patients with psoriasis. J Am Acad Der- matol. 2010;63(1):114-123. DOI: 10.1016/j.jaad.2009.07.003. PMID: 19944485. 7. Shutty BG, West C, Huang KE, et al. Sleep disturbances in psoria- sis. Dermatol Online J. 2013;19(1):1. PMID: 23374943. 8. Eskin M, Savk E, Uslu M, Küçükaydoğan N. Social problem- solving, perceived stress, negative life events, depression and life satisfaction in psoriasis. J Eur Acad Dermatol Venereol. 2014;28(11):1553-1559. DOI: 10.1111/jdv.12355. PMID: 24404894. 9. Dowlatshahi EA, Wakkee M, Arends LR, Nijsten T. The preva- lence and odds of depressive symptoms and clinical depression in psoriasis patients: a systematic review and meta-analysis. J Invest Dermatol. 2014;134(6):1542-1551. DOI: 10.1038/jid.2013.508. PMID: 24284419. 10. Bangemann K, Schulz W, Wohlleben J, et al. Depression und Angststörung bei Psoriasispatienten: Schutz- und Risikofaktoren [Depression and anxiety disorders among psoriasis patients: protective and exacerbating factors]. Hautarzt. 2014;65(12): 1056-1061. DOI: 10.1007/s00105-014-3513-9. PMID: 25376619. 11. Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM. The risk of depression, anxiety, and suicidality in patients with pso- riasis: a population-based cohort study. Arch Dermatol. 2010;146(8):891-895. DOI: 10.1001/archdermatol.2010.186. PMID: 20713823. PMCID: PMC2928071. 12. Sondermann W, Fiege O, Körber A, Scherbaum N. Psychological burden of psoriatic patients in a German university hospital der- matology department. J Dermatol. 2021;48(6):794-806. DOI: 10.1111/1346-8138.15721. PMID: 33354818. 13. Duvetorp A, Mrowietz U, Nilsson M, Seifert O. Sex and Age Influence the Associated Risk of Depression in Patients with Psoriasis: A Retrospective Population Study Based on Diagno- sis and Drug-Use. Dermatology. 2021;237(4):595-602. DOI: 10.1159/000509732. PMID: 32927456. PMCID: PMC8315676. 14. Min C, Kim M, Oh DJ, Choi HG. Bidirectional association between psoriasis and depression: Two longitudinal follow-up studies us- ing a national sample cohort. J Affect Disord. 2020;262:126-132. DOI: 10.1016/j.jad.2019.10.043. PMID: 31733456. 15. Lada G, Chinoy H, Talbot PS, Warren RB, Kleyn CE. The ef- fect of the Covid-19 pandemic on illness perceptions of psori- asis and the role of depression: Findings from a cross-sectional Original Article | Dermatol Pract Concept. 2024;14(2):e2024104 9 DOI: 10.1155/S1463924600000195. PMID: 18924698. PMCID: PMC2562849. 45. ICSH recommendations for measurement of erythrocyte sedimenta- tion rate. International Council for Standardization in Haematology (Expert Panel on Blood Rheology). J Clin Pathol. 1993;46(3):198- 203. DOI: 10.1136/jcp.46.3.198. PMID: 8463411. PMCID: PMC501169. 46. Ferrante AW Jr. Obesity-induced inflammation: a metabolic dialogue in the language of inflammation. J Intern Med. 2007;262(4):408-414. DOI: 10.1111/j.1365-2796.2007.01852 .x. PMID: 17875176. 47. Ferreira BI, Abreu JL, Reis JP, Figueiredo AM. Psoriasis and Associated Psychiatric Disorders: A Systematic Review on Etio- pathogenesis and Clinical Correlation. J Clin Aesthet Dermatol. 2016;9(6):36-43. PMID: 27386050. PMCID: PMC4928455. 48. Devrimci-Ozguven H, Kundakci TN, Kumbasar H, Boyvat A. The depression, anxiety, life satisfaction and affective expres- sion levels in psoriasis patients. J Eur Acad Dermatol Venereol. 2000;14(4):267-271. DOI: 10.1046/j.1468-3083.2000.00085.x. PMID: 11204514. 49. Moon HS, Mizara A, McBride SR. Psoriasis and psycho- dermatology. Dermatol Ther (Heidelb). 2013;3(2):117-30. DOI: 10.1007/s13555-013-0031-0. Epub 2013 Jul 10. PMID: 24318414; PMCID: PMC3889305. 50. Schmitt JM, Ford DE. Role of depression in quality of life for patients with psoriasis. Dermatology. 2007;215(1):17-27. DOI: 10.1159/000102029. PMID: 17587835. 51. Wu KK, Armstrong AW. Suicidality among psoriasis pa- tients: a critical evidence synthesis. G Ital Dermatol Venereol. 2019;154(1):56-63. DOI: 10.23736/S0392-0488.18.06112 -6PMID: 30019576. 52. Punzi L, Podswiadek M, Oliviero F, et al. Laboratory findings in psoriatic arthritis. Reumatismo. 2007;59 Suppl 1:52-55. DOI: 10.4081/reumatismo.2007.1s.52. PMID: 17828345. 53. Cooksey R, Brophy S, et al. Cardiovascular risk factors predict- ing cardiac events are different in patients with rheumatoid ar- thritis, psoriatic arthritis, and psoriasis. Semin Arthritis Rheum. 2018;48(3):367-373. DOI: 10.1016/j.semarthrit.2018.03.005. PMID: 29656791. 54. Fleming P, Roubille C, Richer V, et al. Effect of biologics on de- pressive symptoms in patients with psoriasis: a systematic review. J Eur Acad Dermatol Venereol. 2015;29(6):1063-1070. DOI: 10.1111/jdv.12909. PMID: 25490866. 55. Bayramgürler D, Karson A, Ozer C, Utkan T. Effects of long- term etanercept treatment on anxiety- and depression-like neu- robehaviors in rats. Physiol Behav. 2013;119:145-148. DOI: 10.1016/j.physbeh.2013.06.010. PMID: 23769689. 56. [Gottlieb AB, Dunn M, Chiou CF, Patel V, Jahreis A. Effects of etanercept therapy on fatigue and symptoms of depression in subjects treated for moderate to severe plaque psoriasis for up to 96 weeks. Br J Dermatol. 2007;157(6):12757 57. Menter A, Augustin M, Signorovitch J, et al. The effect of adalimumab on reducing depression symptoms in patients with moderate to severe psoriasis: a randomized clinical trial. J Am Acad Dermatol. 2010;62(5):812-818. DOI: 10.1016/j .jaad.2009.07.022. PMID: 20219265. 58. Langley RG, Feldman SR, Han C, et al. Ustekinumab significantly improves symptoms of anxiety, depression, and skin- related quality of life in patients with moderate-to-severe psoriasis: Results from a randomized, double-blind, placebo-controlled 29. Fredriksson T, Pettersson U. Severe psoriasis--oral therapy with a new retinoid. Dermatologica. 1978;157(4):238-244. DOI: 10.1159/000250839. PMID: 357213. 30. Bonifati C, Berardesca E. Clinical outcome measures of psoriasis. Reumatismo. 2007;59 Suppl 1:64-67. DOI: 10.4081/reumatismo .2007.1s.64. PMID: 17828348. 31. Feldman SR, Krueger GG. Psoriasis assessment tools in clini- cal trials. Ann Rheum Dis. 2005;64 Suppl 2(Suppl 2):ii65-ii68; discussion ii69-73. DOI: 10.1136/ard.2004.031237. PMID: 15708941. PMCID: PMC1766877. 32. Robinson A, Kardos M, Kimball AB. Physician Global As- sessment (PGA) and Psoriasis Area and Severity Index (PASI): why do both? A systematic analysis of randomized controlled trials of biologic agents for moderate to severe plaque psoria- sis. J Am Acad Dermatol. 2012;66(3):369-375. DOI: 10.1016/j .jaad.2011.01.022. PMID: 22041254. 33. Spuls PI, Lecluse LL, Poulsen ML, Bos JD, Stern RS, Nijsten T. How good are clinical severity and outcome measures for pso- riasis?: quantitative evaluation in a systematic review. J Invest Dermatol. 2010;130(4):933-943. DOI: 10.1038/jid.2009.391. PMID: 20043014. 34. Bożek A, Reich A. The reliability of three psoriasis assessment tools: Psoriasis area and severity index, body surface area and physician global assessment. Adv Clin Exp Med. 2017;26(5): 851-856. DOI: 10.17219/acem/69804. PMID: 29068583. 35. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical use. Clin Exp Der- matol. 1994;19(3):210-216. DOI: 10.1111/j.1365-2230.1994 .tb01167.x. PMID: 8033378. 36. Upton, J. (2013). Beck Depression Inventory (BDI). In: Gellman, M.D., Turner, J.R. (eds) Encyclopedia of Behavioral Medicine. Springer, New York, NY. pp 178–179 Available from: https:// DOI.org/10.1007/978-1-4419-1005-9_441 37. Giannakou M, Roussi P, Kosmides ME, Kiosseoglou G, Adamopoulou A, Garyfallos G- Adaptation of the beck de- pression inventory-II to greek population. Hellenic Journal of Psychology. 2013,vol.10(January 2013), p.p120–146. 38. Kyriakou A, Patsatsi A, Sotiriadis, Goulis DG. Adipokines in pso- riasis. , British Journal of Dermatology.  Volume 179, Issue 2, 1 August 2018 ;179(2):e94. https://DOI.org/10.1111/bjd.16948. 39. Buechler C, Feder S, Haberl EM, Aslanidis C. Chemerin Iso- forms and Activity in Obesity. Int J Mol Sci. 2019;20(5):1128. DOI: 10.3390/ijms20051128. PMID: 30841637. PMCID: PMC6429392. 40. ì Soldatos CR, Dikeos DG, Paparrigopoulos TJ. Athens Insom- nia Scale: validation of an instrument based on ICD-10 criteria. J Psychosom Res. 2000;48(6):555-560. DOI: 10.1016/s0022 -3999(00)00095-7. PMID: 11033374. 41. Soldatos CR, Dikeos DG, Paparrigopoulos TJ. The diagnostic validity of the Athens Insomnia Scale. J Psychosom Res. 2003;55(3):263-267. DOI: 10.1016/s0022-3999(02)00604-9. PMID: 12932801. 42. Gowda S, Goldblum OM, McCall WV, Feldman SR. Factors af- fecting sleep quality in patients with psoriasis. J Am Acad Der- matol. 2010;63(1):114-123. DOI: 10.1016/j.jaad.2009.07.003. PMID: 19944485. 43. Aaron T. Beck, BAI, Beck anxiety inventory, manual Publisher, Psychological Corporation, 1990 ; Length, 22 pages 44. Wei TQ, Kramer S, Chu VP, et al. An improved automated immu- noassay for C-reactive protein on the Dimension clinical chemis- try system. J Autom Methods Manag Chem. 2000;22(5):125-131. 10 Original Article | Dermatol Pract Concept. 2024;14(2):e2024104 64. Moon HS, Mizara A, McBride SR. Psoriasis and psycho- dermatology. Dermatol Ther (Heidelb). 2013;3(2):117-130. DOI: 10.1007/s13555-013-0031-0. PMID: 24318414. PMCID: PMC3889305. 65. Lavda AC, Webb TL, Thompson AR. A meta-analysis of the effectiveness of psychological interventions for adults with skin conditions. Br J Dermatol. 2012;167(5):970-979. DOI: 10.1111/j.1365-2133.2012.11183.x. PMID: 22924999. 66. Sin NL, Lyubomirsky S. Enhancing well-being and alleviating de- pressive symptoms with positive psychology interventions: a prac- tice-friendly meta-analysis. J Clin Psychol. 2009;65(5):467-487. DOI: 10.1002/jclp.20593. PMID: 19301241. 67. Bolier L, Haverman M, Westerhof GJ, Riper H, Smit F, Bohlmeijer E. Positive psychology interventions: a meta-analysis of randomized controlled studies. BMC Public Health. 2013 Feb 8; 13:119. DOI: 10.1186/1471-2458-13-119. PMID: 23390882; PMCID: PMC3599475. 68. Greenblatt DJ. Elimination half-life of drugs: value and limitations. Annu Rev Med. 1985;36:421-7. DOI: 10.1146/annurev.me.36 .020185.002225. PMID: 3994325. phase III trial. J Am Acad Dermatol. 2010;63(3):457-465. DOI: 10.1016/j.jaad.2009.09.014. PMID: 20462664. 59. Strober BE. New Therapies for Psoriasis. Semin Cutan Med Surg. 2016;35(4S):S71-S73. DOI: 10.12788/j.sder.2016.020. PMID: 29850660. 60. [Haider AS, Lowes MA, Suárez-Fariñas M, et al. Identification of cellular pathways of “type 1,” Th17 T cells, and TNF- and inducible nitric oxide synthase-producing dendritic cells in au- toimmune inflammation through pharmacogenomic study of cyclosporine A in psoriasis. J Immunol. 2008;180(3):1913-1920. DOI: 10.4049/jimmunol.180.3.1913. PMID: 18209089. 61. Kraus C, Castrén E, Kasper S, Lanzenberger R. Serotonin and neuroplasticity - Links between molecular, functional and struc- tural pathophysiology in depression. Neurosci Biobehav Rev. 2017;77:317-326. DOI: 10.1016/j.neubiorev.2017.03.007. PMID: 28342763. 62. Patel N, Nadkarni A, Cardwell LA, et al. Psoriasis, Depression, and Inflammatory Overlap: A Review. Am J Clin Dermatol. 2017 Oct;18(5):613-620. DOI: 10.1007/s40257-017-0279-8. PMID: 28432649. 63. Crnković D, Buljan D, Karlović D, Krmek M. Connection be- tween inflammatory markers, antidepressants and depression. Acta Clin Croat. 2012;51(1):25-33. PMID: 22919999.