Affective temperament, depressive symptoms and interleukins in patients with psoriasis.

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 symptoms 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 depressive 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 dimension of affective temperament.

Introduction

Psoriasis is a chronic disease significantly impairing psychosocial functioning of patients and is also recognized as a serious psychosomatic disease. Distress related 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 (especially interleukin-1 (IL-1), interleukin-6 (IL-6)) and cortisol. Several studies have shown that inflammatory-immunological processes play a significant role in the course of depression and it is likely that they are important for hypothalamic-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 existence 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 temperament 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 subjects indicate that individuals with dysphoric, cyclothymic and depressive temperaments and those who adopted 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 patients suffering from various somatic diseases. Stressful life events were more frequently associated with anxious and depressive temperaments in female psoriasis patients [13].

Aim

In the present study we hypothesized that affective temperament dimensions measured by the Polish version 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 patients 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 individuals 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 autoimmune diseases, addiction to drugs or alcohol, intake of immunosuppressive drugs in the past 3 months. Examination 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 Diego 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, cyclothymic, 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 consisting 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 maximum 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 serum, ELISA method was applied.

Statistical analysis

The normality of distribution of variables was assessed by means of the Shapiro Wilk test. As the distribution 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 correlations between variables was performed by means of the Spearman’s rho coefficient. Homogeneity of variance was evaluated using the Levene test. Internal consistency of affective temperament subscales was evaluated with Cronbach-α 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 subjects were younger than psoriasis patients and scored lower in BDI. The level of interleukins did not differ between 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 depression. The prevalence of depression among psoriasis patients was high with more than 50% of patients obtaining results higher than 12 points in BDI.

Table 1

Sociodemographic and clinical data of psoriasis patients (with and without depression) and healthy controls. Median value: 25–75%

Parameter	Psoriasis patients			Control groupN = 98
	Whole groupn = 110	BDI ≥ 12n = 65	BDI < 12n = 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 depression significant at #p < 0.001. Mann-Whitney U test.

Results of correlations between subscales of TEMPS-A in psoriasis patients are displayed in Table 2. Highest positive 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-α coefficient show high internal consistency of the five subscales measuring five domains of affective temperament (Table 3). These results indicate the usefulness of TEMPS-A autoquestionnaire in the evaluation of affective temperament in psoriasis.

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-α

Temperament	Cronbach-α
Depressive	0.79
Cyclothymic	0.80
Hyperthymic	0.55
Irritable	0.79
Anxious	0.83

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 hyperthymic temperament. Psoriasis patients with depression (BDI ≥ 12) showed higher levels of depressive and anxious temperaments compared to patients without depression. They also scored somewhat lower on the hyperthymic scale, however the difference was not statistically significant.

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 groupn = 98
	Whole groupn = 110	BDI ≥ 12n = 65	BDI < 12n = 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 depression significant at #p < 0.001. U Mann-Whitney test.

The results of correlations between duration of illness, 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 applied to all correlations. Severity of psoriasis was positively 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 parameters 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 depression were noted. Such correlation was not found in patients without depression.

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 controlsn = 98
	Whole groupn = 110		BDI ≥ 12n = 65		BDI < 12n = 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 presents the correlations between five affective 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 psoriasis patients, the intensity of depressive and anxious temperaments correlated with the intensity of depressive 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.

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
	IL-6	0.20	0.11	–0.27	0.20	0.13

Correlation statistically significant at p<0.001, Bonferroni correction for multiple correlations.

Discussion

The results of the present study revealed a considerable prevalence of depressive symptoms in psoriasis patients. More than 50% of subjects from this group present moderate to severe depression. This clearly indicates that psoriasis and depression may co-occur, and considerable worsening of symptoms of depression in some patients indicates the need for better recognition and desirability of implementation of antidepressant treatment in these patients. These results are concordant with those obtained by other researchers who have observed a greater incidence of depression in dermatological disorders 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 severity 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 disease 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 psoriasis is significantly increased in patients with moderate or severe depression, which may indicate common etiological mechanisms in these two disorders [20].

As indicated by other authors, severity of depression is associated with worse quality of life in dermatological 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 suicidal 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 define 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 temperaments in patients with psoriasis as compared to the control group. The investigated healthy subjects have obtained results similar to those observed in the population 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 duration 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 “challenge 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 conditions [32].

An increasing number of reports support the immune hypothesis of depression, which emphasizes the importance 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 immune 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 necrosis factor-α (TNF-α) are present within the thalamus and hippocampus, and IL-1, IL-6 and TNF-α are continuously 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 cytokine rates are observed in the acute phase of the disease 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 differences in cytokine levels.

We found a significant correlation between the severity of psoriasis in the PASI scale and the level of depressive symptoms measured with the BDI. The level of IL-6 was positively correlated with BDI and PASI scores, however, for the BDI score, it failed to hold significance after the correction for multiple correlations. This observation 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-α, IFN-γ, but found no correlation with IL-6 [44]. These differences may result from the presence, in patients 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 affective 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 temperament traits may constitute a predisposition to both diseases.