Address for correspondence: Luiza Marek-Józefowicz PhD, Department of Dermatology and Venerology, Faculty of Medicine, Ludwik Rydygier Medical College, Nicolaus Copernicus University, Bydgoszcz, Poland, phone: +48 600 494 367, e-mail: lui06@interia.pl Received: 22.05.2020, accepted: 12.06.2020.
Affective temperament, depressive symptoms and interleukins in patients with psoriasis
Luiza Marek-Józefowicz1, Marcin Jaracz2, Alina Borkowska2
1Department of Dermatology and Venerology, Faculty of Medicine, Ludwik Rydygier Medical College in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
2Chair of Clinical Neuropsychology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
Adv Dermatol Allergol 2021; XXXVIII (1): 137–143 DOI: https://doi.org/10.5114/ada.2021.104289
A b s t r a c t
Introduction: Psoriasis is a chronic inflammatory skin disease, in which psychological factors play an important role. In the studies of common markers of psoriasis and depression, the abnormal function of the stress axis in both diseases is highlighted, whereas interleukin-6 (IL-6) and interleukin-1 are indicated as particularly important.
Aim: To evaluate the relationship between the affective temperament traits and the intensity of depressive symp- toms in patients with psoriasis in the context of immunoenzymatic markers.
Material and methods: The study included 208 subjects. Severity of psoriasis was assessed by PASI. TEMPS-A was applied for the evaluation of affective temperament and BDI was used for the assessment of the intensity of depres- sive symptoms. The level of cytokines was determined by means of the immunoenzymatic method.
Results: Patients presented a specific profile of affective temperament, with higher scores on depressive, anxious and irritable dimensions. The severity of depressive symptoms correlated positively with the severity of psoriasis.
A significant correlation was found between IL-6 and the severity of psoriasis in patients with depressive disorders and psoriasis. No similar correlation was found in patients without depressive disorder.
Conclusions: Results of the present study show common mechanisms for psoriasis and depression. Specific traits of affective temperament may play an important role in the clinical picture of both diseases. Higher levels of IL-6 in patients with psoriasis predispose to more frequent occurrence of depressive disorders and the depressive dimen- sion of affective temperament.
Key words: affective temperament, psoriasis, interleukins.
Introduction
Psoriasis is a chronic disease significantly impairing psychosocial functioning of patients and is also recog- nized as a serious psychosomatic disease. Distress re- lated to the disease may lead to a significant decrease in the quality of life, and in extreme cases this may be a cause of depression, or even suicide [1–4]. Psoriasis also co-occurs with mental disorders, depression being the most frequent. The studies carried out in recent years also indicate the possibility of the existence of common etiopathogenetic factors in psoriasis and depression. In the studies of common markers for both disorders, the abnormal function of the stress axis is emphasised, with special significance being attributed to interleukin (espe- cially interleukin-1 (IL-1), interleukin-6 (IL-6)) and cortisol.
Several studies have shown that inflammatory-immuno- logical processes play a significant role in the course of depression and it is likely that they are important for hy- pothalamic-pituitary-adrenal (HPA) axis regulation [5–7].
The function of nervous, immune and endocrine systems is disrupted both in depression and psoriasis [1, 8, 9].
The results of up-to-date studies indicate the exis- tence of specific personality and temperamental traits related to a higher risk of occurrence of psoriasis, which are also significant for its further course and treatment [10–13]. The studies of significance of affective tempera- ment traits in etiopathogenesis and clinical picture of somatic diseases in general, have been undertaken in recent years. The study of a large population of 9937 sub- jects indicate that individuals with dysphoric, cyclothy- mic and depressive temperaments and those who adopt-
ed displacement, somatization and passive aggression as their predominant defence mechanisms presented high somatic symptom severity [14]. This indicates the plausibility of affective temperament evaluation in pa- tients suffering from various somatic diseases. Stressful life events were more frequently associated with anx- ious and depressive temperaments in female psoriasis patients [13].
Aim
In the present study we hypothesized that affective temperament dimensions measured by the Polish ver- sion of Temperament Evaluation of Pisa, Paris and San Diego Autoquestionnaire may be related to the severity of depressive symptoms and the levels of IL-1 and IL-6, which are associated with immune system activity, in pa- tients with psoriasis.
Material and methods Study subjects
One hundred and ten patients with psoriasis (62 men and 48 women) were enrolled in the present study. The patients’ age ranged from 18 to 60 years (mean: 44.1
±13.0). The control group consisted of 98 healthy individ- uals aged 22–65 years (mean: 41.0 ±10.7). The exclusion criteria were: age above 65 and under 18 years, history of head injuries, comorbid severe neurological and auto- immune diseases, addiction to drugs or alcohol, intake of immunosuppressive drugs in the past 3 months. Ex- amination and assessment of severity of dermatological lesions PASI was conducted by one physician.
Psychological assessment
Affective temperament was assessed by means of the Temperament Assessment of Pisa, Paris and San Di- ego Autoquestionnaire (TEMPS-A). The TEMPS-A is a 110- item yes-or-no self-report autoquestionnaire, designed to assess affective temperament in psychiatric and healthy subjects. It consists of five sub-scales: depressive, cyclo- thymic, irritable, hyperthymic and anxious. In the present study, we used the Polish version of TEMPS-A.
Beck Depression Inventory
Beck Depression Inventory is a self-rated scale con- sisting of 21 items relating to the various symptoms of depression. The minimum overall score is 0 points, and maximum is 63 points. The threshold for the recognition of depression was adopted as 12 points.
Dermatological assessment
PASI (Psoriasis Area and Severity Index). The maxi- mum PASI value is 72, and the minimum is 0. Higher scores indicate greater severity of the clinical lesions.
Immunological assessment
In order to determine the cytokine levels in the se- rum, ELISA method was applied.
Statistical analysis
The normality of distribution of variables was as- sessed by means of the Shapiro Wilk test. As the distri- bution of variables did not meet the normality criterion, nonparametric tests were applied. For comparison of the significance of differences between groups, U-Mann Whitney test was applied and an analysis of correla- tions between variables was performed by means of the Spearman’s rho coefficient. Homogeneity of variance was evaluated using the Levene test. Internal consis- tency of affective temperament subscales was evalu- ated with Cronbach-a coefficient. For exploratory factor analysis, the Principal Component Analysis (PCA) with a Varimax rotation was applied.
Results
Sociodemographical and clinical data including age, duration of psoriasis and of its current episode, the PASI score, the BDI score, and the level of interleukins in psoriasis patients (with and without depression) and in healthy controls are presented in Table 1. Healthy sub- jects were younger than psoriasis patients and scored lower in BDI. The level of interleukins did not differ be- tween patients and healthy subjects. Psoriasis patients with depression showed significantly greater intensity of psoriasis symptoms and shorter duration of the current acute illness episode compared to patients without de- pression. The prevalence of depression among psoriasis patients was high with more than 50% of patients ob- taining results higher than 12 points in BDI.
Results of correlations between subscales of TEMPS-A in psoriasis patients are displayed in Table 2. Highest pos- itive correlations were obtained between depressive and anxious, and between cyclothymic and irritable domains (correlation coefficients 0.68 and 0.65, respectively).
The reliability analysis results based on the Cronbach-a coefficient show high internal consistency of the five subscales measuring five domains of affective tempera- ment (Table 3). These results indicate the usefulness of TEMPS-A autoquestionnaire in the evaluation of affective temperament in psoriasis.
The results of TEMPS-A in psoriasis patients with and without depression and in healthy controls are shown in Table 4. Psoriasis patients present significantly higher scores on depressive, cyclothymic, irritable and anxious scales compared to the healthy subjects. No between- group differences were observed with respect to the hy- perthymic temperament. Psoriasis patients with depres- sion (BDI ≥ 12) showed higher levels of depressive and anxious temperaments compared to patients without
depression. They also scored somewhat lower on the hy- perthymic scale, however the difference was not statisti- cally significant.
The results of correlations between duration of ill- ness, duration of the current acute episode, PASI and BDI scores, the level of interleukins in psoriasis patients, and between BDI scores, interleukins in healthy controls are presented in Table 5. Bonferroni correction was ap- plied to all correlations. Severity of psoriasis was posi- tively correlated with BDI score in the whole group of psoriasis patients. Duration of the current acute episode of psoriasis correlated negatively with PASI score in the whole group of psoriasis patients and in patients with depression, while such relationship was not observed in patients without depression. With regard to other param- eters evaluated, a significant correlation between levels of IL-6 and the intensity of psoriasis in the whole group of psoriasis patients as well as in patients with depres- sion were noted. Such correlation was not found in pa- tients without depression.
Table 6 presents the correlations between five af- fective temperaments and the results obtained in PASI, BDI, and the level of interleukins in investigated groups.
Bonferroni correction was applied to all correlations. All correlations were corrected. In the whole group of pso- riasis patients, the intensity of depressive and anxious temperaments correlated with the intensity of depres-
sive symptoms. Similar results were observed in patients with depression and healthy controls, but not in psoriasis patients without depression. In healthy controls, the level of depressive symptoms was additionally correlated with rates of irritable temperament. No correlations between cytokine levels and scores in TEMPS-A were observed in other groups.
Discussion
The results of the present study revealed a consider- able prevalence of depressive symptoms in psoriasis pa- tients. More than 50% of subjects from this group pres- ent moderate to severe depression. This clearly indicates that psoriasis and depression may co-occur, and consid- erable worsening of symptoms of depression in some Table 1. Sociodemographic and clinical data of psoriasis patients (with and without depression) and healthy controls.
Median value: 25–75%
Parameter Psoriasis patients Control group
N = 98 Whole group
n = 110
BDI ≥ 12 n = 65
BDI < 12 n = 45
Age (mean ± SD) 44.1 ±13.1 44.2 ±12.6 44.0 ±14.0 36.8 ±10.4*
Illness duration [years] 16.0; 8.0–30.0 16.0; 6.0–30.0 16.0; 10.0–23.0 –
Duration of the current acute psoriasis episode [weeks] 12.0; 6.0–16.0 8.0; 4.0–14.0 12.0; 8.0–16.0#
PASI 19.6; 15.5–26.1 22.8; 16.8–29.5 17.4; 14.8–21.0# –
BDI 13.0; 9.0–18.0 23.0; 16.5–23.0 8.0; 5.0–10.0# 4,0; 2.0–8.0**
IL-1 [pg/ml] 0.9; 0.6–1.4 0.8; 0.5–1.3 0.9; 0.6–1.6 0.9; 0.6–1.3
IL-6 [pg/ml] 1.6; 0.9–4.1 1.8; 1.1–6.4 1.6; 0.9–2.0 1.3; 0.6–2.3
Difference between psoriasis patients and healthy controls significant at: *p < 0.05; **p < 0.001. Difference between psoriasis patients with and without depres- sion significant at #p < 0.001. Mann-Whitney U test.
Table 2. Correlations between subscales of TEMPS-A in psoriasis patients (Spearman’s rho)
TEMPS-A Depressive Cyclothymic Hyperthymic Irritable Anxious
Depressive – 0.45* –0.40* 0.53* 0.68*
Cyclothymic 0.45* – –0.26* 0.65* 0.58*
Hyperthymic –0.40* –0.26* – –0.32* –0.39*
Irritable 0.53* 0.65* –0.32* – 0.57*
Anxious 0.68* 0.58* –0.39* 0.57* –
*Correlation statistically significant at p < 0.05.
Table 3. Reliability analysis of TEMPS-A scales results based on the Cronbach-a
Temperament Cronbach-a
Depressive 0.79
Cyclothymic 0.80
Hyperthymic 0.55
Irritable 0.79
Anxious 0.83
Table 4. TEMPS-A results in psoriasis patients (with and without depression) and in healthy controls. Median value:
25–75%
TEMPS-A Psoriasis patients Control group
n = 98 Whole group
n = 110
BDI ≥ 12 n = 65
BDI < 12 n = 45
Depressive 0.43; 0.33–0.62 0.52; 0.38–0.67 0.33; 0.29–0.43# 0.36; 0.24–0.48*
Cyclothymic 0.38; 0.24–0.52 0.43; 0.24–0.57 0.33; 0.24–0.48 0.24; 0.14–0.33**
Hyperthymic 0.38; 0.19–0.57 0.38; 0.19–0.57 0.48; 0.33–0.57 0.43; 0.33–0.57
Irritable 0.20; 0.10–0.35 0.24; 0.14–0.40 0.20; 0.10–0.25 0.14; 0.10–0.20**
Anxious 0.39; 0.23–0.65 0.48; 0.27–0.69 0.31; 0.19–0.50# 0.21; 0.08–0.35**
Difference between psoriasis patients and healthy controls significant at: *p < 0.05; **p < 0.001. Difference between psoriasis patients with and without depres- sion significant at #p < 0.001. U Mann-Whitney test.
Table 5. The correlation between clinical variables, intensity of psoriasis and depressive symptoms and the level of interleukins in psoriasis patients and between depression and interleukins in healthy controls
Parameter Psoriasis patients Healthy
controls n = 98 Whole group
n = 110
BDI ≥ 12 n = 65
BDI < 12 n = 45
PASI BDI PASI BDI PASI BDI BDI
Illness duration [years] 0.06 –0.01 0.13 –0.03 –0.17 –0.23 –
Duration of the current episode [weeks] –0.40* –0.31 –0.45* –0.22 –0.14 –0.05 –
IL-1 –0.15 0.04 –0.23 0.05 –0.04 0.28 0.07
IL-6 0.49* 0.22 0.61* 0.26 0.15 –0.09 –0.08
PASI – 0.35* – 0.35 – 0.21 –
BDI 0.35* – 0.35 – 0.21 – –
*Correlation statistically significant at p < 0.004, after Bonferroni correction for multiple correlations.
Table 6. Results of correlations between affective temperament dimensions and the intensity of psoriasis and depressed symptoms, the level of interleukins in psoriasis patients and healthy controls (Spearman’s rho)
Parameter Depressive Cyclothymic Hyperthymic Irritable Anxious
Psoriasis patients – whole group:
PASI 0.19 0.16 –0.16 0.19 0.11
BDI 0.51* 0.21 –0.29 0.31 0.47*
IL-1 0.02 –0.01 0.02 0.01 –0.08
IL-6 0.05 0.03 –0.18 0.00 0.01
Psoriasis patients with depression BDI ≥ 12:
PASI 0.20 0.10 –0.11 0.03 –0.05
BDI 0.49* 0.33 –0.37 0.29 0.47*
IL-1 0.08 –0.00 –0.02 0.05 –0.06
IL-6 0.08 0.06 –0.12 –0.15 –0.04
Psoriasis patients without depression BDI < 12:
PASI –0.10 0.19 –0.07 0.29 0.08
BDI –0.02 0.01 0.07 0.19 0.06
IL-1 –0.11 –0.04 0.08 –0.06 –0.10
IL-6 0.19 –0.06 –0.24 –0.11 –0.18
Healthy controls:
BDI 0.83* 0.54* –0.36 0.45* 0.62*
IL-1 –0.18 –0.18 –0.11 0.24 0.24
patients indicates the need for better recognition and desirability of implementation of antidepressant treat- ment in these patients. These results are concordant with those obtained by other researchers who have observed a greater incidence of depression in dermatological dis- orders including psoriasis [15–19]. Devrimci-Ozguven et al. in a study covering 50 patients with psoriasis and a 50-subject control group found a much higher sever- ity of depressive symptoms in psoriasis patients than in the control group. In addition, the severity of depressive symptoms in BDI correlated positively with the intensity of the symptoms of psoriasis, while negatively with dis- ease duration, which may be the result of development of adaptive mechanisms in a situation of chronic disease.
It was also observed that the risk of occurrence of psoria- sis is significantly increased in patients with moderate or severe depression, which may indicate common etiologi- cal mechanisms in these two disorders [20].
As indicated by other authors, severity of depression is associated with worse quality of life in dermatologi- cal patients. In a study by Gupta and Gupta conducted in a group of 217 patients with psoriasis, 7.2% reported to show the desire to die, and 5.5% had increased sui- cidal thoughts [21]. It is now believed that psoriasis is a risk factor for depression and anxiety disorders as well as disorders of the sexual domain. On the other hand, depression can contribute to the occurrence of psoriasis [17, 22, 23].
In the present paper, the Polish version of TEMPS-A was used to evaluate the affective temperament [15].
So far, the questionnaire has been used mainly to de- fine the characteristics of affective temperament among patients with bipolar disorder and their relatives, it also proved to be useful in determining these characteristics among the general population [24–29]. As indicated by the results of our study, it is also a very valuable tool in studies of patients with psoriasis. The results indicate greater intensity of depressive and anxious tempera- ments in patients with psoriasis as compared to the control group. The investigated healthy subjects have obtained results similar to those observed in the popula- tion of Polish healthy individuals, various dimensions of affective temperament occurring with similar frequency, although the anxious and irritable temperaments are somewhat more pronounced [15]. This also pertains to the data from other populations (Spanish, Hungarian, Italian), in which similar results were obtained [30–32].
The results may indicate that depressive and anxious temperaments are enduring personality dispositions and are associated with a predisposition to the disease. This is also indicated by no association between the severity of lesions in the PASI scale, duration of illness and dura- tion of the recent worsening and the various dimensions of affective temperament.
The rates of hyperthymic temperament in psoriasis patients were similar to those observed in the control
group. An analysis of temperamental profiles in both groups shows these rates to be higher compared to other temperaments, which was also observed in other populations [33]. Hyperthymic traits may be helpful in coping with the disease as they usually involve the sense of a better quality of life, a more optimistic assessment of the current situation and one’s ability to function in that situation, more involvement in the tasks of a “chal- lenge character” and perhaps with greater persistence in goal achievement. An over-representation of hyperthymic traits was demonstrated for example among candidates for pilots and military pilots who work in high-risk condi- tions [32].
An increasing number of reports support the immune hypothesis of depression, which emphasizes the im- portance of the immune system in the aetiology of this disease. It indicates the role of cytokines in disruptions of neurotransmission, behaviour and in the observed endocrine changes. The variable course of depressive disorders is explained by the inherent inflammatory mechanisms and immune disorders. Several clinical trials have demonstrated that depression is associated with changes in the concentration of cytokines in plasma [34–36]. Most observations indicate activation of the im- mune system in depression being an increased synthesis and secretion of acute phase proteins and an increase in the synthesis and concentration of pro-inflammatory cytokines. The receptors for IL-1, IL-2, IL-6 and tumor ne- crosis factor-a (TNF-a) are present within the thalamus and hippocampus, and IL-1, IL-6 and TNF-a are continu- ously generated at low concentrations in neurons and glia [7, 36–39].
Somewhat contrary to our expectations, we did not observe differences in cytokine levels between psoriasis patients and controls. This result is best explained by the fact that the skin changes in psoriasis patients occurred many weeks before the admission to hospital. High cy- tokine rates are observed in the acute phase of the dis- ease and exacerbation of skin changes. Admittedly, the patients from our sample showed elevated skin changes, which was indicated by the PASI score, but the disease process itself was in the chronic phase, which might have accounted for the lack of statistically significant differ- ences in cytokine levels.
We found a significant correlation between the sever- ity of psoriasis in the PASI scale and the level of depres- sive symptoms measured with the BDI. The level of IL-6 was positively correlated with BDI and PASI scores, how- ever, for the BDI score, it failed to hold significance after the correction for multiple correlations. This observa- tion warrants further research, as Karanikas et al. found a higher concentration of inflammatory markers such as IL-6 in depressed patients compared to patients without depressive disorder [40]. Furthermore, in the study by Kaur et al. [41], a positive correlation was found between the severity of psoriasis measured by the PASI scale and
the level of IL-6 in serum, which was also confirmed in studies of other authors [42, 43]. In contrast, Takahashi et al. found a positive correlation between the level of TNF-a, IFN-g, but found no correlation with IL-6 [44].
These differences may result from the presence, in pa- tients with various degrees of psoriasis severity, of many cytokines from different cells, at various concentrations, interacting with each other.
Conclusions
Patients with psoriasis present a greater prevalence of depression, which in about half of patients achieved the severity of clinically expressed depressive syndrome.
Patients with psoriasis present a specific profile of af- fective temperament with elevated depressive, anxious and irritable temperaments. The higher level of IL-6 in patients with psoriasis is related to higher severity of depressive symptoms which in turn is associated with overall greater psoriasis severity. This indicates common mechanisms for both disorders. Specific affective tem- perament traits may constitute a predisposition to both diseases.
Conflict of interest
The authors declare no conflict of interest.
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