Incidence, risk factors, and correlation with organ involvement of psychological disorders in patients with Sjögren’s syndrome

Abstract

BACKGROUND

Sjögren’s syndrome (SS) is a common systemic autoimmune disease that predominantly affects women, and typically manifests with lymphocytic infiltration of exocrine glands with wide-ranging extra glandular organ involvement. Depression and anxiety, two of the most common psychological disorders (PD) reported in patients with SS, remain undervalued on clinical practice. There are however limited, and conflicting data on the specific risk factors for PDs in SS which might be linked to severity of organ involvement, with respect to type distribution.

AIM

To evaluate the occurrence and risk factors of PDs in patients with SS and investigate their association with organ involvement.

METHODS

This retrospective study comprised a total of 286 patients with SS who met the diagnostic criteria for SS at the Department of Rheumatology and Immunology of our hospital between January 1, 2019 and December 1, 2024. Psychological status was assessed using the Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA), and patients were divided into the PD group (156 cases) and non-PD group (130 cases). Risk factors were analyzed with the help of logistic regression, while Pearson correlation analysis was applied to assess association with organ involvement.

RESULTS

Out of 286 SS patients, PDs were found in 156 patients (54.5%), including pure depression in 58 cases (20.3%), pure anxiety in 38 cases (13.3%) and depression-anxiety comorbidity, 60 cases (21.0%). PD group had higher HAMD scores (14.7 ± 6.2) and HAMA scores (12.3 ± 5.8) than without PD group respectively (all P < 0.001). Patients with PDs had more severe clinical manifestations, higher dry mouth visual analogue scale (VAS) scores (7.2 ± 1.8 vs 5.4 ± 2.1), dry eye VAS scores (6.9 ± 2.0 vs 5.1 ± 2.3) and joint pain incidence (78.27% vs 61.54%), inflammatory markers including erythrocyte sedimentation rate (42.3 ± 18.7 mm/hour vs 35.6 ± 16.17 mm/hour), C-reactive protein (8.93 ± 12.37 mg/L vs 5.68 ± 8.25 mg/L), anti-SSA/Ro52 antibody positivity rate (82.1% vs 69.2%), complement component 3 levels (85 ± 23 mg/L vs 94 ± 21 mg/L), more severe organ involvement with higher EULAR SS Disease Activity Index (ESSDAI) scores (12.4 ± 8.6 vs 7.8 ± 5.9), and significantly increased incidence of interstitial lung disease (18.5% vs 13.8%), peripheral neuropathy (16.8% vs 7.8%), and arthritis (56.4% vs 38.5%) (all P < 0.05). Multivariate analysis showed that female gender [odds ratio (OR) = 2.34], disease duration ≥ 5 years (OR = 1.89), ESSDAI ≥ 12 points (OR = 2.67), interstitial lung disease (OR = 2.15), and peripheral neuropathy (OR = 3.42) were independent risk factors. The severity of PDs was positively correlated with number of organs involved (r = 0.425), disease activity (r = 0.378), and disease duration (r = 0.589), and negatively correlated with quality of life (r = -0.656, all P < 0.001).

CONCLUSION

PDs are common in SS, predominantly as anxiety and depression. Female sex, long disease duration, high disease activity and involvement of particular organs remain key risk factors for PDs. The severity of organ involvement strongly correlates with the degrees of PDs, indicating that might be beneficial for psychologic health screening and total count administration in SS patients leading to better prognosis and quality of life.

Key Words: Sjögren’s syndrome; Mental disorders; Depression; Anxiety; Organ manifestations

Core Tip: Psychological disorders are Sjögren’s syndrome (SS), patient subjective stress inventory more than half of the studied population. Higher disease activity, longer disease duration and multi-organ involvement (especially interstitial lung disease and peripheral neuropathy) are closely tied with depression and anxiety. Quality of life correlates negatively, whereas psychological severity correlates positively with inflammatory markers. Independent risk factors included female sex and EULAR SS Disease Activity Index ≥ 12. These results demonstrate the two-way interaction between immune-mediated inflammation and mental health, indicating that regular psychological assessment alongside integrated multidisciplinary management of SS patients is warranted.

INTRODUCTION

Sjögren’s syndrome (SS) is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands resulting in dysfunction of lacrimal and salivary glands, manifesting clinically as dryness symptoms including dry mouth and dry eyes. The global prevalence of SS is approximately 0.1%-4.8% based on epidemiological surveys, and it is much more common in female patients than male, with a female-to-male ratio of approximately 9:1; age at onset mainly ranges from the fifth to seventh decades of life. SS is the second most common autoimmune rheumatic disease after rheumatoid arthritis (RA), and it destroys life quality of patients seriously and may be multi-systemic disorder so that causes numerous disease burden to patients[1-3]. SS has very heterogeneous clinical manifestations. However, besides the standard manifestations of oral and ocular dryness symptoms, it may also affect multiple organs including lungs, kidney, nervous system and hematological system. Extra glandular organ involvement occurs in 50%-60% of SS patients, with interstitial lung disease occurring in 9%-75%, peripheral neuropathy (quantified by clinical criteria) in 2%-60%, and tubulointerstitial nephritis (quantified by renal biopsy histopathology or renal functional tests) in 5%-27%. These instances of organ involvement reflect increased disease complexity, but they also have an important impact on patients’ prognosis and quality of survival. Recent years have seen more and more accurate knowledge of SS, researchers found that the degree of organ involvement in this disease is directly related to disease activity, and recommended assessment of its activity as a key index for clinical treatment guidance and prognosis judgment[4-6].

The chronicity, recurrence, and unpredictability of chronic diseases (CDs) impose substantial psychological stress on patients, resulting in a marked increase in the incidence of psychological disorders (PDs), including depression and anxiety. According to the World Health Organization, patients with CD have a prevalence of depression 2-3 times higher than that of the general population. Background for patients with rheumatic immune diseases, the incidence of PDs is even higher[7-9] due to chronic progressive disease nature, a diversity of symptoms and complexities in treatment. This has led to a growing number of studies focusing on the mental health condition in patients with SS. Internationally, the prevalence of depression in SS is reported from 11%-70%, which is more than seen in the general population, and anxiety from 20%-60%. This high incidence might be due to several reasons, such as pain from the disease itself, restricted social activity, fears of perceived prognosis & side effects of prolonged treatment. Besides, PDs may not only affect the quality of life of patients, but also aggravate SS disease progression through feedback circuit mechanism along with neuro-endocrine-immune networks, creating a vicious cycle[10-12]. Notably, the present literature on psychologic disorders in SS patients is primarily limited to prevalence and quality-of-life surveys, with far less data available on specific risk factors for specific psychologic disorder occurrence, correlation of organ involvement severity grades with psychological diagnoses in separate syndromes modules, and distribution characteristics across psychometric diagnosis types within individual study data. There are also discrepancies in existing research outcomes, probably due to reasons such as selection criteria of study population, use of diverse psychological assessment instruments and varied sample sizes. Moreover, nearly all studies are cross-sectional surveys without prospective longitudinal observation data that could elucidate the causative relation between PDs and disease progression[13]. Mental health problems in SS patients are frequently neglected or underestimated in clinical practice. Rheumatologists concern somatic complaints and laboratory data more in patients with rheumatic diseases, whereas the assessment and management of psychological status are relatively neglected. This scenario results in not only reduced overall treatment efficacy for patients but also in an additional waste of medical resources. Thus, it is very important to now how high-risk factors for PDs in SS patients are and establishing effective psychological health screening and assessment systems[14].

In light of the above background, we carried out a retrospective study design to perform an analysis with clinical data of a large cohort of SS patients with the objective of characterizing comprehensively both the incidence and type distribution of PDs in this population, thoroughly investigate risk factors for PD occurrence and concentrate on analyzing the correlation between severity-related variables regarding each organ involvement. The findings of this research will help clinicians set up the appropriate early recognition and intervene schemes for psychological health of SS patients, which in turn increases the total effectiveness of remedy and life fine of patients, as well as provide scientific support to achieve accurate precise, individualized treatment for SS.

MATERIALS AND METHODS

Study design and subjects

This study adopted a retrospective case-control study design and consecutively included patients diagnosed with SS in the outpatient and inpatient departments of the Department of Rheumatology and Immunology of our hospital from January 1, 2019 to December 1, 2024. Relevant cases were retrieved through the Hospital Information System (HIS) and electronic medical record system, and medical records were independently reviewed by two senior rheumatology and immunology physicians, with disputes resolved through discussion to reach consensus. Inclusion criteria included: Meeting the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for SS, age ≥ 18 years, disease duration ≥ 6 months, complete clinical data (including detailed medical history records, physical examinations, laboratory examinations, and imaging examination results), completion of standardized psychological status assessment scales, and patient informed consent to participate in the study. Exclusion criteria were: Comorbid other serious somatic diseases (such as malignant tumors, severe cardiovascular and cerebrovascular diseases, liver and kidney failure, etc.), previous history of mental illness or currently receiving psychiatric medication, pregnant or lactating women, cognitive dysfunction unable to complete psychological assessment scales, incomplete clinical data or lost to follow-up patients, and patients who died during the study period. Based on psychological status assessment results, 286 patients meeting inclusion criteria were divided into PD group [n = 156, Hamilton Depression Rating Scale (HAMD) score ≥ 8 points or Hamilton Anxiety Rating Scale (HAMA) score ≥ 7 points] and non-PD group (n = 130, HAMD score < 8 points and HAMA score < 7 points). Further subgroup analysis was performed based on PD types, including pure depression group (HAMD ≥ 8 points, HAMA < 7 points), pure anxiety group (HAMA ≥ 7 points, HAMD < 8 points), and depression-anxiety comorbidity group (HAMD ≥ 8 points and HAMA ≥ 7 points).

Observation indicators, primary and secondary endpoints

The observation indicators included demographic characteristics, socioeconomic status, lifestyle factors, disease-related variables, clinical symptoms, laboratory parameters, organ involvement, psychological assessment scores, and quality-of-life-related indicators. Demographic and socioeconomic variables included sex, age, body mass index, marital status, education level, employment status, household monthly income, and residence. Disease-related variables included disease duration, family history of autoimmune diseases, number of comorbidities, initial symptoms, time from symptom onset to diagnosis, and annual healthcare visits. Clinical and laboratory indicators included dry mouth and dry eye visual analogue scale (VAS) scores, joint pain, Raynaud’s phenomenon, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-SSA/Ro52 antibody status, complement component 3 (C3) level, and EULAR SS Disease Activity Index (ESSDAI) score. Organ involvement included arthritis or arthralgia, parotid gland swelling, hematological abnormalities, tubulointerstitial nephritis, interstitial lung disease, peripheral neuropathy, and cutaneous vasculitis. Psychological status was evaluated using the HAMD and HAMA.

The primary endpoint was the occurrence of PDs in patients with SS. Secondary endpoints included the distribution and severity of PD subtypes, risk factors for PDs, and correlations between PD severity and organ involvement, disease activity, inflammatory markers, disease duration, and healthcare utilization.

Psychological assessment protocol

Both the HAMD and HAMA scales were administered as part of standardized routine clinical care, not specifically for research purposes. All patients meeting inclusion criteria underwent structured psychological assessment by a dedicated clinical psychologist affiliated with the Department of Clinical Psychology of our hospital, following a uniform protocol that was in place throughout the entire enrollment period (January 1, 2019 to December 1, 2024). Assessments were conducted during inpatient admission or scheduled outpatient visits, under consistent conditions, and scores were recorded contemporaneously in the electronic medical record system alongside other clinical data. For this study, psychological assessment data were retrieved retrospectively from the electronic medical records by two independent investigators and verified against source documentation to ensure accuracy. Any discrepancies were resolved by consensus review. We acknowledge that retrospective extraction of scale scores, even from standardized routine clinical assessments, carries inherent risks of incomplete documentation or inter-rater variability in administration, and this is addressed in the limitations section below.

Statistical analysis

SPSS 26.0 software was used for statistical analysis. Continuous variables were expressed as mean ± SD, and t-tests were used for between-group comparisons; categorical variables were expressed as n (%), and χ² tests were used for between-group comparisons. Univariate and multivariate logistic regression analyses were used to analyze risk factors for PDs. To complement the primary binary classification analysis, PD severity was additionally analyzed as a continuous variable using linear regression, which preserved statistical power and enabled detection of dose-response relationships. Pearson or Spearman correlation analysis was used to evaluate the correlation between PDs and organ involvement. P < 0.05 was considered statistically significant.

RESULTS

Baseline characteristics

Group differences within the PD and non-PD group were also significant in several areas. Compared with the general respondents, PD patients were more likely to be female (92.3%, 84.6%), of older age (52.8, 48.6 years), and have longer disease duration (6.8 years, 4.9 years). They were more likely to be unemployed, have lower income and live in rural areas. Clinically, they had higher levels of comorbidities, were seen by healthcare more often and experienced longer time to diagnosis. sha highlighted that no group differences existed in BMI, education and marriage (Table 1).

Table 1 Comparison of baseline characteristics between two groups, n (%).

Variable	Psychological disorder group (n = 156)	Non-psychological disorder group (n = 130)	Statistical value	P value
Demographic characteristics
Female	144 (92.3)	110 (84.6)	χ² = 4.58	0.032
Age (years, mean ± SD)	52.8 ± 12.4	48.6 ± 11.7	t = 2.84	0.005
Disease duration (years, mean ± SD)	6.8 ± 4.2	4.9 ± 3.1	t = 4.32	< 0.001
BMI (kg/m2, mean ± SD)	22.6 ± 3.4	23.1 ± 3.2	t = 1.25	0.213
Socioeconomic status
Retired or unemployed	71 (45.5)	42 (32.3)	χ² = 5.59	0.018
Household monthly income < 5000 yuan	60 (38.5)	35 (26.9)	χ² = 5.11	0.024
Rural residence	64 (41.0)	37 (28.5)	χ² = 5.46	0.019
Education level ≤ junior high school	89 (57.1)	68 (52.3)	χ² = 0.68	0.410
Lifestyle factors
Smoking history	24 (15.4)	11 (8.5)	χ² = 4.13	0.042
Drinking history	20 (12.8)	13 (10.0)	χ² = 0.63	0.426
Disease-related factors
Family history of autoimmune diseases	36 (23.1)	18 (13.8)	χ² = 4.65	0.031
Number of comorbidities (n, mean ± SD)	2.3 ± 1.4	1.6 ± 1.1	t = 4.52	0.001
Oral and ocular dryness as initial symptoms	120 (76.9)	83 (63.8)	χ² = 6.98	0.008
Time from symptom onset to diagnosis (years, mean ± SD)	3.2 ± 2.8	2.1 ± 1.9	t = 3.78	0.003
Annual healthcare visits (times, mean ± SD)	8.6 ± 4.2	5.9 ± 3.1	t = 5.94	< 0.001
Marital status
Married	134 (85.9)	115 (88.5)	χ² = 0.47	0.495
Single/divorced/widowed	22 (14.1)	15 (11.5)

BMI: Body mass index.

Prevalence of PDs

Of 286 SS patients, 156 (54.5%) had PDs: Pure depression in 20.3%, pure anxiety in 13.3% and comorbidity between both in 21.0%. By severity, 31.1% were mild, 16.1% moderate and 7.3% severe (Figure 1). Prevalence was more common among females vs males (57.8% vs 35.7%, P = 0.028), patients aged ≥ 50 years (61.2% vs 46.8%, P = 0.015), and at disease duration ≥ 5 years (65.4% vs 42.1%, P < 0.001). This age group (40-60 years) consisted of 68.6% of all PDs (Table 2).

Figure 1 Comparison of clinical symptom severity between psychological disorder and non-psychological disorder groups in Sjögren’s syndrome patients. A: Dry mouth and dry eye visual analogue scale (VAS) scores; B: Incidence of joint pain and Raynaud’s phenomenon. Patients with psychological disorders (PD) demonstrated significantly more severe clinical symptoms compared to those without PDs, including higher VAS scores for dry mouth (7.2 ± 1.8 vs 5.4 ± 2.1) and dry eye symptoms (6.9 ± 2.0 vs 5.1 ± 2.3), as well as increased incidence of systemic manifestations such as joint pain (78.2% vs 61.5%) and Raynaud’s phenomenon (45.5% vs 30.8%). These findings indicate that PDs in Sjögren’s syndrome patients are associated with more severe subjective symptom burden and higher prevalence of systemic complications, suggesting a strong correlation between mental health status and disease-related symptom severity. ^aP < 0.05. VAS: Visual analogue scale.

Table 2 Incidence and related characteristics analysis of psychological disorders in patients with Sjögren’s syndrome, n (%).

Variable	Psychological disorder group (n = 156)	Non-psychological disorder group (n = 130)	Statistical value	P value
Distribution of psychological disorder types
Pure depression	58 (20.3)
Pure anxiety	38 (13.3)
Depression-anxiety comorbidity	60 (21.0)
Psychological assessment scale scores (mean ± SD)
HAMD score (points)	14.7 ± 6.2	3.2 ± 2.1	t = 22.15	< 0.001
HAMA score (points)	12.3 ± 5.8	2.8 ± 1.9	t = 19.84	< 0.001
Severity of psychological disorders
Mild	89 (31.1)
Moderate	46 (16.1)
Severe	21 (7.3)
Severity of depression
Mild depression	69 (58.5)
Moderate depression	35 (29.7)
Severe depression	14 (11.9)
Severity of anxiety
Mild anxiety	54 (55.1)
Moderate anxiety	32 (32.7)
Severe anxiety	12 (12.2)
Demographic characteristics
Female	144 (92.3)	110 (84.6)	χ² = 4.15	0.042
Age ≥ 50 years	107 (68.6)	64 (49.2)	χ² = 11.07	0.001
Age (years, mean ± SD)	52.8 ± 12.4	48.6 ± 11.7	t = 3.84	< 0.001
Disease characteristics
Disease duration ≥ 5 years	102 (65.4)	62 (47.7)	χ² = 9.18	0.002
Disease duration (years, mean ± SD)	6.8 ± 4.2	4.9 ± 3.1	t = 4.52	< 0.001

HAMD: Hamilton Depression Rating Scale; HAMA: Hamilton Anxiety Rating Scale.

Clinical symptom severity

PD patients experienced significantly more severe dryness symptoms (dry mouth VAS: 7.2 vs 5.4; dry eye VAS: 6.9 vs 5.1; both P < 0.001) and more frequent joint pain (78.2% vs 61.5%, P = 0.003) and Raynaud’s phenomenon (45.5% vs 30.8%, P = 0.012), which shows a higher overall symptom burden (Figure 1).

Laboratory parameters

In contrast, PD patients had more active inflammation and signs of immune dysregulation with increased ESR (42.3 mm/hour vs 35.6 mm/hour, P = 0.002), CRP (8.9 mg/L vs 5.7 mg/L, P = 0.017) and positivity for anti-SSA/Ro52 (82.1% vs 69.2%, P = 0.011), but lower complement C3 levels (85 mg/L vs 94 mg/L, P = 0.001, Figure 2).

Figure 2 Comparison of autoimmune and inflammatory markers between psychological disorder and non-psychological disorder groups in Sjögren’s syndrome patients. A: Anti-SSA/Ro52 antibody positivity rate and complement component 3 (C3) level; B: Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level. Patients with psychological disorders (PD) exhibited significantly more active autoimmune and inflammatory profiles, characterized by higher anti-SSA/Ro52 antibody positivity rates (82.1% vs 69.2%), lower complement C3 levels (85 ± 23 mg/L vs 94 ± 21 mg/L), and elevated inflammatory markers including ESR (42.3 ± 18.7 mm/hour vs 35.6 ± 16.2 mm/hour) and CRP (8.9 ± 12.4 mg/L vs 5.7 ± 8.3 mg/L). These laboratory findings suggest that PDs in Sjögren’s syndrome patients are associated with heightened systemic inflammation and more pronounced autoimmune activity, indicating a potential bidirectional relationship between immune dysfunction and mental health status. ^aP < 0.05. ESR: Erythrocyte sedimentation rate; CRP: C-reactive protein; C3: Complement component 3.

Organ involvement

The PD group had significantly higher ESSDAI scores (12.4 vs 7.8, P < 0.001). Increased involvement of other organ systems, including lungs (18.5% vs 13.8%), peripheral nerves (16.8% vs 7.8%), kidneys (18.6% vs 9.2%), and joints (56.4% vs 38.5%) in PD patients compared with non-PD patients was also noted (all P < 0.05; Table 3).

Table 3 Comparison of organ involvement rates between psychological disorder and non-psychological disorder groups.

Organ involvement	Psychological disorder group (n = 156) (%)	Non-psychological disorder group (n = 130) (%)	P value
Arthritis/arthralgia	56.4	38.5	0.003
Parotid gland swelling	42.3	26.9	0.009
Hematological abnormalities	31.4	18.5	0.008
Tubulointerstitial nephritis	18.6	9.2	0.015
Interstitial lung disease	18.5	13.8	0.002
Peripheral neuropathy	16.8	7.8	0.002
Cutaneous vasculitis	15.4	6.9	0.019

P < 0.05 for all comparisons between groups.

Correlation with disease activity

Significant correlations emerged between ESSDAI and both depression severity (HAMD) (r = 0.678; P < 0.001) as well as anxiety severity (HAMA) (r = 0.542; P < 0.001). Results: Overall, moderate positive correlations of PD severity with the number of organs involved (r = 0.625), disease duration (r = 0.589) and annual healthcare visits (r = 0.612), whilst quality of life was inversely correlated with r = -0.656. Although the CRP correlation was statistically significant (r = 0.234, P = 0.008), it only accounted for < 6% of variance as opposed to ESR which demonstrated a clinically meaningful association (r = 0.667). For future studies, more discrete cytokines (e.g., IL-6, IFN-α, TNF) should be examined as outlines the subsequent section (Table 4).

Table 4 Correlation between psychological disorder severity and clinical parameters in the psychological disorder group.

Variable (X)	Variable (Y)	Pearson r	P value
HAMD score	ESSDAI score	0.678	< 0.001
HAMA score	ESSDAI score	0.542	< 0.001
Number of organs involved	Psychological disorder severity	0.625	< 0.001
Disease duration (years)	Psychological disorder severity	0.589	< 0.001
ESR level (mm/h)	Psychological disorder severity	0.667	0.002
Annual healthcare visits	Psychological disorder severity	0.612	< 0.001

r: Pearson correlation coefficient. All analyses performed in the psychological disorder group (n = 156). HAMD: Hamilton Depression Rating Scale; HAMA: Hamilton Anxiety Rating Scale; ESSDAI: European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index.

Univariate logistic regression

The multifactorial aetiology of psychological morbidities amongst SS cohorts is supported by the associations between key risk factors for PDs and those with clinical evidence of high disease activity, female sex, duration ≥ 5 years, positive family history of autoimmune disease (all at least P < 0.05), unemployment (P < 0.001), rural residence (P = 0.002) and age ≥ 50 years old (P = 0.023; Figure 3).

Figure 3 Forest plot of univariate logistic regression analysis for risk factors of psychological disorders in Sjögren’s syndrome patients. Univariate logistic regression analysis identified seven significant risk factors for psychological disorders (PD) in Sjögren’s syndrome (SS) patients, including demographic characteristics (age ≥ 50 years, female gender), disease-related factors [disease duration ≥ 5 years, European League Against Rheumatism SS Disease Activity Index (ESSDAI) ≥ 12 points], and socioeconomic factors (retirement/unemployment, rural residence, family history of autoimmune diseases). Among these factors, ESSDAI ≥ 12 points demonstrated the strongest association with PDs [odds ratio (OR) = 3.21, 95% confidence interval: 1.98-5.20, P < 0.001], followed by female gender (OR = 2.45) and disease duration ≥ 5 years (OR = 2.14), suggesting that disease activity, demographic characteristics, and chronic disease progression are key determinants of psychological health in SS patients. ESSDAI: European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index; OR: Odds ratio; CI: Confidence interval.

DISCUSSION

SS is a complex chronic systemic autoimmune disease, and with multiple organ involvement as well as the variability of clinical manifestations and unpredictability of the whole course for patients, they typically suffer not only from physical pain but also severe psychological pressures. A new bio-psycho-social medical model is spreading around the world, in which there are no purely biomedical models. Psychological factors have been acknowledged to play an important role in the occurrence, development, and prognosis of CD nowadays. PDs are, in fact, not only comorbid symptoms of diseases but complicated neuro-endocrine-immune network mechanisms can influence the disease pathological processes which further create a vicious cycle that diseases harm and promote psychological problems[15-18].

Multiple mechanisms are responsible for the development of PDs in patients with CD. The first is the impact of physical symptoms, functional disability and social role alterations on patients' psychological conditions-direct effects. SS patients with persistent oral and ocular dryness symptoms adversely affect daily quality of life and may also develop difficulties in eating, speech disorders, vision problems etc. These symptoms are chronic and hard-to-cure, making the patients’ anxiety and depressive emotions easy to ignite. Second, uncertainty in disease is a strong driver of psychological stress. Patients remain in a chronic state of worry and fear concerning disease progression due to the unpredictable course of SS and unpredictable timing/degree of organ involvement, thus making this constant psychological stress-highly likely to induce psychiatric disorders[19-21].

PDs occur due to a lot of socioeconomic factors. The chronic process of these diseases makes the climb fewer, and the climb gradually consumes physical strength, reducing work capacity, increasing medical expenses and economic burden; These real problems in turn aggravate patients’ psychological pressure. Especially for patients in rural areas, because of the relative lack of medical resources and restricted ways to obtain professional knowledge, a limited understanding of diseases may bring greater psychological pressure. At the same time, lack of social support systems is another key risk factor. Patients have been reported to feel vulnerable and powerless because of a lack of understanding from family members and society[22,23] making them more susceptible to developing PDs when confronted with disease challenges[24].

Gender differences in mental health issues associated with autoimmune diseases

In addition to sex differences in incidence rates of SS being markedly higher among female patients than male, PDs exhibit obviously different incidences between sexes. This variation could be associated with women’s atypical physiological response to stress, changes in hormone levels, the social roles they occupy, and ways of coping with stress. CD more affects the appearance and social function, which results in higher levels of psychological pressure for women; who are also often responsible for more family responsibilities. Moreover, women could be more sensitive to pain and discomfort[25-27], which also raises the likelihood of PD incidence.

Age is an intricate element influencing the prevalence of PDs. More complex psychological challenges are often faced by middle-aged and elderly patients. They have to deal not only with the effects of the disease itself, but also the multiple pressures associated with changing occupation, age-related decline in physical capacity and a transition between social roles. The retirement or unemployment status is not just an economic income path and means, more so, loss of social value and loss of self-identity. The psychological impact may be more detrimental to mental health than the disease itself[28-30].

Disease activity is intertwined with PDs in a bidirectional fashion. High disease activity accuses directly to the physical feeling and quality of life of the patient, as well as through inflammatory mediator actions it may indirectly conquer brain function with emotional regulation disturbances. Inflammatory mediators including interleukins and tumor necrosis factors may inhibit neurotransmitter synthesis and metabolism, modify the function of the hypothalamic-pituitary-adrenal axis, which lead to a higher risk of developing depression and anxiety. Simultaneously, neuroendocrine pathways could lead to the influence of psychological stress states on immune system function by exaggerating disease inflammatory responses and creating vicious cycles[31].

Surprisingly organ involvement can also adopt extremes ranging diversity/diversity but severity/number of the organ involved will affect from mental health. Patients with symptomatic multiorgan diseases face increased psychological burdens posed by more complex symptom management, more frequent medical interventions, and less clear disease prognoses. Awareness of disease severity and anxiety about the future have a strong impact on psychological status, especially with diseases involving critical organs such as the lungs, kidneys, and nervous system. Involvement of specific organs like peripheral neuropathy can have direct impacts on patients’ motor and sensory function, potentially impacting quality of life but also questioning the limitations that patients are putting on themselves as well as concerns about what lies ahead[32].

For example, the impact of family history illustrates the factor of genetic vulnerability in mental health. Patients with family histories of autoimmune disease face increased risk of disease, but perhaps also increased psychological pressure due to previous knowledge of the family members' experience with their own diseases. Patients might develop a perception of genetic burden, causing them to be overly concerned with disease development and impairing their psychological adaptation abilities[33].

Psychological stress is also caused by CD management process itself. Medical follow-ups, complicated drug therapy protocols and frequent monitoring examinations interfere patients' regular life flow and add more psychological burden to their situation. Over a long time, patients may form the psychology of helplessness and dependence, which can not only deteriorate mental health but also reduce quality of life due to continuous medical reliance[34,35].

CONCLUSION

According to the study results, PDs occurred in 54.5% of SS patients, which was significantly higher than that in the general population. According to the multivariate analysis, female sex, longer duration of disease, hyperactive condition and particular organ involvement were independent risk factors for PDs. Such findings corroborate the impression that PD occurrence is an interplay of multiple factors. Correlation analyses demonstrated significant correlations between the severity of psychological illnesses with both disease severity, number of organs affected and inflammatory activity leading to an assumption that psychological intervention must be a major part of holistic treatment approach to SS. These findings offer important assistance to clinical practice and indicate that psychological health screening in high-risk patients, as well as the establishment of multidisciplinary collaborative comprehensive management models in medical personnel are crucial elements to improve patients’ overall prognosis as a result of their quality of life.