Georgian Scientists/ . 4 N 3, 2022 261 Georgian Scientists Vol. 4 Issue 4, 2022 https://doi.org/10.52340/gs.2022.04.04.29 The association of atopic dermatitis (AD) with anxiety and depression Z. Telia1, K. Machavariani2, A. Telia2 1 MD PhD student of the Department of Allergology and Clinical Immunology of Tbilisi State Medical University 2 Department of Allergology and Clinical Immunology of Tbilisi State Medical University Abstract Atopic dermatitis (AD), a common chronic inflammatory skin disease that may persist into adulthood, is associated with intense itching and a high incidence of sleep disturbances [1, 2]. The worldwide prevalence of AD is 15-20% among children [3] and 1-3% among adults. Psychological distress is a common comorbidity associated with atopic dermatitis and can negatively impact the quality of life [4]. Previous large-scale population-based studies have identified an association between AD and psychiatric illness [5–8]. Children with AD in the United States had a significantly higher prevalence of attention-deficit/hyperactivity disorder (ADHD, depression, anxiety, behavioral disorders, and autism) than children without AD [5]. Other authors [6] found that Taiwanese patients with AD had an increased risk of developing the major depressive disorder (MDD) and anxiety disorders. And also, depressive symptoms were significantly higher in patients with AD than in the control group [7, 8]. This study aimed to evaluate the association of AD with anxiety and depression using a data mining approach to match patients with AD with controls by sex and age. Materials and methods Patients with atopic dermatitis were interviewed at the Allergology and Clinical Immunology Department of the Tbilisi State Medical University clinics. Their medical records (2018-2021 years) were analyzed to determine the coexistence of this disease with anxiety and depression. The study was conducted according to the case-control protocol and included 315 people aged 18 to 69. The "case" and "control" groups consisted of 154 people with chronic atopic dermatitis and 161 randomly selected Georgian Scientists/ . 4 N 3, 2022 262 healthy individuals (including medical students, their family members, and teaching staff without the presence of asthma, rhinitis, urticaria, seborrheic dermatitis, psoriasis and contact dermatitis). We classified patients by age: 18-29 years old, 30-49 years old, and 50-69 years old. Since the severity of AD is difficult to classify, we assess the severity of the disease based on the drugs used by patients: mild AD (patients used only moisturisers and topical therapy - topical corticosteroids (TCS) short course and topical calcineurin inhibitors (TCIs), moderate AD (patients who received additional oral antihistamines), and severe AD (patients who received other oral immunosuppressants). Anxiety and depression were identified through appropriate questionnaires GAD-7 (Generalized Anxiety Disorder) and PHQ-9 (Patient Health Questionnaire) by allergists, dermatologists, and general practitioners. Statistical analysis was performed using software version 25 SPSS and Review Manager 5.4.1. The study was carried out in 4 subgroups according to demographic and clinical characteristics. Odds ratios (ORs) utilised a 95% confidence interval, with a p-value lower than 0.05 considered significant. Results Demographic and clinical parameters of the study population are presented in Table. 1. There were no significant differences in gender; the mean age of patients with AD was 44.26 (SD = 14.76), and the control group was 46.38 (SD = 15.91). The percentage ratio between patients with AD and control was 45.4% vs 46.6% in men and 54.5% vs 53.4% in women. There were no significant differences in the overall number of participants in AD and control (OR = 1.09, 95% CI 0.80-1.49) and gender groups (Case vs Control in male, OR=1.05, 95% CI 0.67-1.63; Case vs Control in female, OR=0.96, 95% CI 0.61-1.49). Significant differences were found in the prevalence of only three (out of six) clinical variables studied (asthma, allergic rhinitis, urticaria, respectively: OR = 0.25, 95% CI 0.07- 0.90; OR = 0.18, 95% CI 0.04-0.84; OR = 0.30, 95% CI 0.10-0.96), but not in seborrheic dermatitis, psoriasis, and contact dermatitis. Table 1. Demographic and clinical parameters of the study population Georgian Scientists/ . 4 N 3, 2022 263 Odds ratios for the association between atopic dermatitis (AD), anxiety, and depression stratified by age and sex, are demonstrated in Table 2. Anxiety was nearly 1.5 times more prevalent in the AD group than in the controls (33.7% vs 21.7%; OR 1.84, 95% CI 1.11–3.03, p < 0.001). Anxiety prevalence also was higher in women (OR = 2.27, 95% CI 1.02–5.07, p < 0.001) and two age groups: 30-49 y, 50- 60 y (respectively OR = 3.93, 95% CI 1.04–14.90, p < 0.001; OR = 3.44, 95% CI 1.04–11.39, p < 0.001). There was no difference between the prevalence of depression in men and women. (31.2% vs 39.7%; OR 0.69, 95% CI 1.11–3.03, p<0.001). However, depression was more prevalent in the following age groups (30-49 y, 50-69 y; OR = 2.78, 95% CI 1.09–7.06, OR = 3.99, 95% CI 1.71–9.28 respectively) of both sexes. Table 2. Association between Atopic Dermatitis (AD), anxiety and depression Discussion Previous research on the relationship between anxiety/depression and atopic dermatitis has been inconsistent. Several studies have reported no significant difference in anxiety levels between AD patients and controls [1, 2] and no significant correlation between AD severity and anxiety [10]. However, other studies have shown that AD patients are more likely to experience anxiety than healthy individuals [5, 6]. A recent large population-based study showed that moderate to severe AD is significantly associated with an increased risk of using anxiolytics and antidepressants [11]. Anxiety and depression are the primary disorders associated with chronic skin diseases. This disease can contribute significantly to psychological distress and is often associated with other atopic conditions such as allergic rhinitis (AR) and asthma. Our study confirmed the association between AD and some mental illnesses (depression and anxiety) in the 30-69 age group compared to healthy individuals; It was also revealed that patients with atopic dermatitis suffer more often from diseases such as bronchial asthma, allergic rhinitis and urticaria. Many authors failed to confirm the hypothesis that the severity and duration of dermatitis affect depression because they couldn't find a correlation, probably due to the shortage of observed individuals in the respective groups. Some publications claim that depressive symptoms in Georgian Scientists/ . 4 N 3, 2022 264 dermatological patients are associated with cosmetic malformations and body image problems [12, 13] and that most pruritic depressive skin diseases include psoriasis and chronic idiopathic urticaria [14]. The mechanisms underlying mental illness and AD are unknown. One theoretical tool is that mental illness may be a common consequence of many chronic illnesses, including AD. Blackman et al. [15] found that children with chronic illnesses are at increased risk of emotional and behavioural problems. The link between mental illness and AD can be explained by elevated levels of pro- inflammatory cytokines in AD, which can lead to depression, anxiety, and autism [15,16]. Schmitt et al. [17] suggested that sustained overexpression of inflammatory mediators released during atopic reactions may influence brain circuits. Several candidate genes encoding significant elements of the immune system and proteins involved in regulating Th1/Th2 cell differentiation and effector function for atopic traits have been identi ed [18]. In particular, genetic variants in the gene encoding signal transducer and activator of transcription 6 (Stat6), a key regulatory element of Th2 immune response, have been associated with atopy-related traits [19]. Activator of transcription 6 (Stat 6) is also highly expressed in the central nervous system and is suggested to play a significant role in Attention deficit hyperactivity disorder (ADHD) pathogenesis [19]. In addition, previous research on the association between atopy and behavioural symptoms in twins has supported the hypothesis of shared genetic factors in uencing the risk for atopic and behavioural disorders [18]. Conclusion Our study has shown that concomitant diseases (bronchial asthma, allergic rhinitis and urticarial) were more often observed in patients with atopic dermatitis; Depression and anxiety are also more common in this condition in the 30-69 age group. The association of depression and anxiety with chronic AD is not well understood. Future studies recommend exploring the inverse relationship between atopic dermatitis and psychiatric disorders (depression and anxiety). Reference 1. Silverberg JI, Garg NK, Paller AS, Fishbein AB, Zee PC. According to a US population-based study, sleep disturbances in adults with eczema are associated with impaired overall health. J Invest Dermatol. 2015; 135:56–66. doi:10.1038/jid.2014.325; 2. Kim JP, Chao LX, Simpson EL, Silverberg JI. Persistence of atopic dermatitis (AD): a systematic review and meta-analysis. J Am Acad Dermatol. 2016; 75:681–7.e11. doi:10.1016/j.jaad.2016.05.028; 3. Asher MI, Montfort S, Bjorksten B, et al. 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(AD) . 1, . 2, . 2 1 2 (AD), , . . . ( ) . 18- 69 315 . 154 161 . ( , , , , ) . 25 SPSS Review Manager 5.4.1 . (ORs) 95% , 0.05- . 4 . , (30-69 ) , , . , , , . , .