CMPH

Introduction

Psoriasis is a chronic immune-mediated inflammatory disease affecting approximately 2% of the global population [1,2]. Although it may occur at any age, psoriasis most commonly manifests during early adulthood (15-20 years) and later in life (55-60 years) [3]. Plaque psoriasis represents the predominant clinical phenotype, accounting for the majority of cases [3], while disease prevalence appears to be comparable between males and females [4].

Beyond its physical manifestations, psoriasis is associated with stress and substantial psychosocial burden. Visible skin lesions frequently lead to stigmatization, social exclusion, diminished self-esteem, and increased vulnerability to negative emotional states, including psychological distress [5]. These psychosocial challenges, combined with chronic physical symptoms, significantly impair the quality of life of psoriatic patients. Moreover, psoriasis has been linked to increased neurological and cognitive morbidity, including deficits in working memory and reduced cognitive performance [6-9]. Accumulating evidence further suggests that patients with psoriasis exhibit elevated rates of depressive symptoms and anxiety disorders [10,11]. These psychological comorbidities are thought to arise mainly from the dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and the hyperactivation of the inflammatory response, highlighting the close interplay between dermatological and psychological health.

Sleep disturbances constitute another prevalent and clinically relevant concern in psoriasis. Patients commonly report poor sleep quality, which has been strongly associated with depression, anxiety, fatigue, and impaired daily functioning [12]. Elevated perceived stress and disrupted sleep patterns are, in turn, linked to unhealthy lifestyle behaviors, such as smoking and excessive alcohol consumption [2,12]. These behaviors may exacerbate disease severity, diminish overall quality of life, and increase the risk of comorbid conditions, including cardiovascular disease [1317].

Psoriasis is widely recognized as a multifactorial disease, influenced by complex interactions between genetic predisposition and environmental factors. Among these, psychological stress plays a dual role, acting both as a trigger and a disease progressor, contributing to disease flares and exacerbations [18-20]. The impact of stress on psoriasis is thought to be mediated primarily through dysregulation of the HPA axis, a central system involved in stress regulation and immune modulation. Activation of the HPA axis leads to the sequential release of Corticotropin-Releasing Hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol, a glucocorticoid with potent anti-inflammatory properties.

Prior studies have demonstrated that patients with psoriasis often exhibit reduced cortisol levels, which may impair the physiological regulation of inflammatory responses and contribute to disease exacerbation [19,21]. Inadequate cortisol-mediated immunosuppression may predispose individuals to heightened inflammatory activity and increased disease severity. Concurrently, elevated levels of CRH have been observed in psoriatic patients, further supporting a direct link between psychological stress and inflammatory activation.

CRH plays a pivotal role in the transcriptional activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a key regulator of inflammatory signalling pathways. NF- κB activation initiates a cascade of pro-inflammatory processes that are central to psoriasis pathogenesis. In the skin, CRH stimulates mast cell activation, leading to the release of pro- inflammatory cytokines, including interleukins (IL-1, IL-6, IL-23) and tumor necrosis factor- alpha (TNF-α) [21-23]. These mediators promote neutrophil recruitment, increase vascular permeability, and amplify local inflammatory responses. The combination of elevated pro- inflammatory cytokine activity and diminished cortisol availability facilitates sustained inflammation and tissue damage in psoriatic lesions [18,19,24].

Given the central role of stress in both the psychological and immunological dimensions of psoriasis, stress management interventions have gained increasing attention as adjunctive therapeutic strategies. Mindfulness-based and cognitive– behavioral interventions have demonstrated beneficial effects on disease severity, psychological well-being, and physical functioning in patients with psoriasis [14,25,26]. Additionally, lifestyle modification programs targeting stress reduction and health-promoting behaviors have been shown to improve both psychological and physical outcomes in this population [27,28].

Given the multifactorial nature of psoriasis, we hypothesize that the implementation of a holistic stress management intervention may have beneficial effects for psoriatic patients.

The Pythagorean Self-Awareness Intervention (PSAI) represents a holistic stress management approach that integrates cognitive restructuring, self-reflection, and lifestyle modification [29]. Previous studies suggest that this technique may facilitate healthier behavioral patterns, enhance emotional regulation, and improve coping with daily stressors [30–34]. Its potential applicability to chronic stress-related conditions, such as psoriasis, warrants systematic investigation.

Therefore, the objective of the present study was to explore the effects of PSAI on multiple stress- and disease-related outcomes in patients with psoriasis. Specifically, we assessed changes in perceived stress and stress-response indices (including HRV and hair cortisol levels), sleep quality, health-related behaviors, and emotional regulation. In addition, cognitive performance and body composition parameters [including body weight, Body Mass Index (BMI), Intermuscular Adipose Tissue (IMAT), Fat Mass (FM), and Fat-Free Mass (FFM)] were evaluated.

Materials and Methods

Participants

The study was conducted at the Specialized Psoriasis Unit of “Andreas Syggros” Hospital for Skin and Venereal Diseases in Athens, Greece. “Andreas Syggros” Hospital is the largest tertiary referral centre for dermatological and venereal diseases in Greece and serves as a reference centre for the greater Athens area and southern Greece.

All participants were informed in detail about the objectives and procedures of the study, and written informed consent was obtained prior to enrolment. The study protocol was approved by the Scientific and Ethics Committee of “Andreas Syggros” Hospital (Protocol No. 472/07-12- 2023) and was conducted in accordance with the principles of the Declaration of Helsinki.

Participants were recruited between January 2023 and March 2024. Inclusion criteria were: (a) a confirmed clinical diagnosis of psoriasis and (b) ability to communicate fluently in Greek. Exclusion criteria included: (a) current use of oral corticosteroids, (b) diagnosis of a psychiatric disorder, and (c) substance abuse.

Study design

Given the limited sample size, a one-group pre-test–post-test design with a double pre-test was employed to enhance methodological rigor [35]. Participants underwent two baseline assessments before the intervention and one assessment following completion of the intervention. All assessments included both questionnaire-based measures and objective physiological measurements.

The present study adopted a quasi-experimental single-group pre–post intervention design without a separate control group. To enhance internal validity and strengthen causal inference, two baseline assessments were conducted prior to the intervention. This repeated -baseline approach enabled verification of temporal stability in participants’ performance before the intervention, thereby reducing the likelihood that post-intervention changes reflected spontaneous variation, maturation, or regression to the mean. The absence of systematic change across the two preintervention measurements suggests that participants’ performance trajectories remained stable in the absence of the intervention. In contrast, the emergence of systematic change only following the intervention indicates a temporal discontinuity consistent with an intervention-related effect. By using each participant as their own control, the within- subjects repeated-measures framework minimized inter-individual variability and increased sensitivity to detecting intervention-specific effects. Collectively, these design and analytic features support the interpretation that the observed post-intervention changes were primarily attributable to the implemented intervention.

Statistical analysis

Statistical analyses were conducted by comparing (a) the two preintervention measurements and (b) the second pre-intervention measurement with the post-intervention assessment. Statistical analyses were performed using IBM SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics, including mean, standard deviation, median, and interquartile range, were calculated for demographic variables and quantitative measures. For comparisons between the groups, Shapiro-Wilk tests were performed for normality testing. Wilcoxon tests or t-tests for two independent samples were used to compare the measurements prior to and after the intervention. Given the exploratory nature of this pilot study, no correction for multiple comparisons was applied. Statistical significance was set at p<0.05.

Measures

Healthy Lifestyle and Personal Control Questionnaire (HLPCQ)

The Healthy Lifestyle and Personal Control Questionnaire (HLPCQ) is a self-report instrument assessing health-related lifestyle behaviors and perceived personal control. It includes items that focus on healthy eating habits, avoidance of harmful dietary choices, daily routines, engagement in organized physical exercise, and the promotion of social and mental well-being. While the questionnaire primarily evaluates lifestyle choices, some items also assess stress-related behaviours. The questionnaire consists of 26 items rated on a 4-point Likert scale (1 = never/rarely to 4 = always), with higher total scores indicating stronger engagement in health- promoting behaviors and greater personal control over one’s lifestyle choices [36].

Health Locus of Control Scale (HLC)

The Health Locus of Control (HLC) Scale was used to assess participants’ beliefs regarding control over their health. The 18item scale comprises three subscales: internal control (HLC-1), external control (HLC-2), and chance control (HLC-3). HLC1 subscale measures the extent to which an individual believes they are responsible for their own health and well-being. HLC2 subscale assesses the degree to which individuals attribute their health to external factors, such as other people or societal influences. HLC-3 subscale reflects beliefs that health outcomes are governed by chance or random factors beyond the individual’s control. Higher scores reflect stronger endorsement of each control orientation as a determinant of health [37]. The Greek version of the scale has demonstrated satisfactory psychometric properties and has been widely used in previous studies [38,39].

Perceived Stress Scale-14 (PSS-14)

The Perceived Stress Scale (PSS-14) [40] is a self-report tool consisting of 14 items designed to assess the degree to which individuals perceive situations in their lives as stressful. The items measure the frequency of feelings and thoughts related to stress over the past month. Responses are rated on a 5-point Likert scale (0 = never to 4 = very often). The scale includes seven positive and seven negative items. To calculate the total score, the ratings for the positive items are reversed, and the scores for all items are then summed. The total score can range from a minimum of 0 to a maximum of 56, with higher scores indicating higher levels of perceived stress during the past month. The scale has demonstrated good psychometric properties when used within the Greek population [41].

Pittsburgh Sleep Quality Index (PSQI)

Sleep quality was evaluated using the Greek version of the Pittsburgh Sleep Quality Index (PSQI). The PSQI comprises 19 self-reported questions that are grouped into seven components, such as subjective sleep quality, sleep latency, sleep duration, sleep efficiency (often referred to as usual sleep productivity), sleep disturbances, use of sleep medications, and daytime dysfunction. Each component is scored on a scale from 0 to 3, with higher scores indicating worse sleep quality. The overall PSQI score is calculated by summing the scores of all 7 components, with a possible total score ranging from 0 (indicating high sleep quality) to 21 (indicating poor sleep quality). A total score of ≥5 is indicative of poor sleep quality [42,43].

MedDiet Score

The MedDiet Score was developed to evaluate the degree of adherence to the Mediterranean dietary pattern. The overall score ranges from 0 to 56, with 0 indicating the lowest level of adherence and 56 representing the highest level of adherence to the Mediterranean diet.

Food consumption that closely aligns with Mediterranean dietary principles is rated higher, with scores ranging from 0 = never to 5 = highest consumption. Conversely, food consumption that deviates from the Mediterranean diet guidelines is assigned inverse scores, reflecting lower adherence [44].

State Shame and Guilt Scale (SSGS)

The State Shame and Guilt Scale (SSGS) is a 15-item self-report questionnaire assessing state levels of shame, guilt, and pride in response to specific situations. The scale also includes items related to pride. Participants rate their responses on a 5-point Likert scale, ranging from “I don’t feel that way at all” to “I feel very strongly that way” [45]. The scale has been validated in a Greek and has demonstrated good psychometric properties [46].

Brief International Cognitive Assessment for MS (BICAMS)

Cognitive function was assessed using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), which includes the Brief Visuospatial Memory Test–Revised (BVMT-R), the California Verbal Learning Test–II (CVLT-II), and the Symbol Digit Modalities Test (SDMT) [47]. These tests have been translated and validated for use in the Greek population [48].

Brief Visuospatial Memory Test Revised (BVMTR)

BVMTR is designed to assess visual memory through direct recall. During the task, the participant is first shown a series of abstract geometric shapes arranged in a 2x3 grid. The shapes are presented for a brief period, after which they are removed, and the participant is asked to reproduce the layout from memory, placing the correct shape in its original position. The participant is given three attempts, with a 10-second memorization period for each presentation. Each figure is scored based on two criteria: (a) whether the shape is correctly drawn, and (b) whether it is placed in the correct position. A maximum of 2 points can be awarded for each figure, yielding a maximum score of 12 points per attempt and a total possible score of 36 points across all three attempts California Verbal Learning Test-II (CVLT-II)

CVLT-II is a test that examines immediate word recall (verbal memory-immediate recall) with a duration of about 10 minutes. It includes a list of 16 words, falling into four conceptual groups, with four words each. The words are read aloud to the test taker five times with a gap of about one second between one word and the next. The test taker is then asked to recall as many words as possible from the list, in any order, and the process is repeated five times. The score is formed by the sum of the number of correct words in all attempts, with a maximum score of 80.

Symbol Digit Modalities Test (SDMT)

SDMT is a test that evaluates the speed of information processing. The test includes 9 different symbols corresponding to numbers from 1 to 9, and the participant is asked to mark under each number the symbol corresponding to 90 seconds. The total score is calculated from the sum of the correct answers.

State–Trait Anger Expression Inventory (STAXI)

The State–Trait Anger Expression Inventory (STAXI) questionnaire examines how individuals respond or behave when they feel angry. The original inventory comprises 44 items [49], but in this study, the Greek version of the 24-item STAXI was used [50]. The items are rated on a four- point Likert-type scale (1 ¼ almost never to 4 ¼ almost always), three subscales: not expressing anger, expressing anger, and controlling anger. It has been standardized in Greek and has demonstrated good psychometric properties.

Biomedical indices

Body composition parameters, including body mass index (BMI), fat mass (FM), fat-free mass (FFM), and intermuscular adipose tissue (IMAT), were assessed using the BIA-ACC device (BIOTEKNA© Biomedical Technologies, Venice, Italy), which has already been validated in the Greek population, against the absorption of dual-energy X-rays (DXA). This device analyzes body composition using a multilevel bioelectric frequency impedance. It is a non-invasive diagnostic tool that quickly and accurately detects a wide range of the patient’s body structure.

Heart rate variability (HRV) data were collected using the NeXus-10 system in combination with BioTrace+ software (Mind Media, Herten, The Netherlands). The NeXus system integrates HRV-BF with psychophysiological research and offers ECG data in both time and frequency domains using self-adhesive electrodes. The researcher manually initiated NeXus measurements at the start of the PPG data collection to ensure simultaneous acquisition of both PPG and ECG data [51].

Hair cortisol concentration

Hair samples were collected from the posterior vertex of the scalp at two pre-intervention time points and once following the intervention. Cortisol concentrations were analyzed retrospectively by segmenting hair samples. The most proximal 1 cm segment represented cortisol secretion over the preceding month, while the second proximal 1 cm segment reflected cortisol secretion during the month prior to that [52]. Hair cortisol concentration was used as an indicator of long- term HPA axis activity.

Analyses were conducted at the Unit of Clinical and Translational Research in Endocrinology, First Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, and the Choremeio Research Laboratory in Athens, Greece.

Intervention

PSAI is based on the six core pillars of lifestyle medicine: healthy nutrition, regular physical activity, adequate and qualitative sleep, cultivation of healthy social relationships, stress management, and avoidance of harmful behaviors. The intervention protocol has been described in detail by Charalampopoulou et al. [30].

Results

Sociodemographic Characteristics of the Participants

The sociodemographic characteristics of the study sample are presented in Table 1. Patients who declined participation, were unable to participate, or did not meet the inclusion and exclusion criteria were excluded from the study. Consequently, a total of 21 patients comprised the final study cohort (N = 21).

Table 1: Socio-demographic characteristics of the sample (Ν=21).

Of these participants, 10 were male (47.6%), and 11 were female (52.4%). All patients were receiving treatment with biologic agents at the time of the study; details are presented in the flow-diagram of the study (Figure 1).

Figure 1: Flow Diagram.

Regarding sociodemographic characteristics, the majority of participants were married (57.1%), university graduates (42.4%), employed (81.0%), cohabitating with a partner or family members (85.7%), and had children (57.1%). Lifestyle-related behaviors such as alcohol consumption and smoking were also assessed. More than half of the participants reported current smoking (52.4%), whereas the majority did not report alcohol consumption (61.9%).

Comparison Between the Two Pre-test Measurements

The comparison between the two pre-intervention assessments is presented in Table 2 and includes both questionnaire-based measures and biological markers. No statistically significant differences were observed between the two Pre-test measurements across the majority of variables, indicating relative stability of baseline measurements over time.

Table 2: Comparison of the two pretest measurements (t0-t1).

An exception was observed for the Symbol Digit Modalities Test (SDMT), which showed a statistically significant difference between the two Pre-test measurements (p = 0.004). This finding indicates variability in processing speed performance across baseline assessments and was considered in subsequent analyses.

Comparison Between Pre-test and Post-test Measurements

To evaluate the effects of the intervention, the second Pre-test measurement was used as the baseline comparator for post-intervention outcomes. The results of these comparisons are summarized in Table 3.

Table 3: Comparison of the pretest with post-test measurements (t1-t2).

Overall, statistically significant changes were observed across the majority of assessed domains following the intervention. No significant changes were detected in selected subscales of the HLC, the SSGS, the STAXI, or in the biomedical indices of body weight and BMI.