Prevalence and risk factors of depression among patients with perianal fistulizing Crohn’s disease

Abstract

BACKGROUND

Psychological distress, especially depression, associated with perianal fistulizing Crohn’s disease (PFCD) is widespread and refractory. However, there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD.

AIM

To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD.

METHODS

The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff. Depressive symptoms, life quality, and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9, Inflammatory Bowel Disease Patient Quality of Life Questionnaire (IBDQ), and Inflammatory Bowel Disease (IBD) Fatigue Patient Self-assessment Scale. The basic demographic information, overall disease features, perianal clinical information, and laboratory inflammation indicators were also gathered. Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD.

RESULTS

A total of 123 patients with PFCD were involved, and 56.91% were suffering from depression. According to multivariate logistic regression analysis, Perianal Disease Activity Index (PDAI) score [odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.50 to 0.95], IBDQ score (OR = 0.93, 95%CI: 0.88 to 0.97), modified Van Assche index (OR = 1.24, 95%CI: 1.01 to 1.53), and IBD Fatigue score (OR = 1.72, 95%CI: 1.23 to 2.42) were independent risk factors of depression-related prevalence among patients with PFCD (P < 0.05). Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index (β value = 0.166, 95%CI: 0.02 to 0.31) and decreasing IBDQ score (β value = -0.116, 95%CI: -0.14 to -0.09) were independently associated with the severity of depression (P < 0.05).

CONCLUSION

Depressive symptoms in PFCD patients have significantly high prevalence. PDAI score, modified Van Assche index, quality of life, and fatigue severity were the main independent risk factors.

Key Words: Crohn’s disease, Fistula, Depression, Inflammatory bowel diseases, Risk factors

Core Tip: Perianal fistulizing Crohn’s disease (PFCD) is the most prominent, invasive and common lesion among the phenotypes of Crohn’s disease (CD). Due to the unique disease experience of PFCD patients, they suffer from severe clinical and psychological consequences like depression. However, there is a lack of studies focusing on the risk factors of depression within specific disease types of CD. In this study, we analyzed the prevalence and risk factors of PFCD with depression, which could assist professionals in early identification and medical intervention in patients with PFCD.

INTRODUCTION

Crohn’s disease (CD), one of the main inflammatory bowel disease (IBD) types, is characterized by chronic nonspecific intestinal inflammation. The clinical features of CD, such as severe symptoms, complex complications, and chronic recurrent state without spontaneous healing, are significant enormous challenges to the physical and mental health of CD patients, who are more likely to be psychologically impaired. As reported by the newest systematic review, the composite morbidity of depressive symptoms in CD patients was around 25.3%[1], which is two to four times greater than the general population, with an approximate incidence rate of 6%[2].

China and other parts of Asia display a higher prevalence of perianal CD, which is one of the most challenging phenotypes of CD. More than half of the adult CD patients are accompanied with perianal lesions[3]. Of those, perianal fistulizing CD (PFCD) is the most prominent, invasive, and common lesion, with a prevalence of about 17% to 43% among all CD patients[4]. PFCD usually exhibits a complex clinical presentation that leads to persistent manifestations like continuous pus, pain, uncomfortable sitting posture, and fecal leakage. In addition, the severity of PFCD is associated with CD course and is the predictive factor of CD patients’ long-lasting poor prognoses[5]. These clinical features can further cause work disability, frequent admission, and psychological, sex, and social problems that significantly deteriorate a patient’s quality of life and lead to severe psychological impacts.

A study conducted by Mahadev et al[6] showed that 73% of PFCD patients were experiencing symptoms of depression. Remarkably, 13% of those had a strong tendency to suicide and were even willing to trade their lifespan (over 10%) for PFCD relief. To further investigate the prevalence of depression in CD patients, there was a cohort study[7] regarding perianal lesions as essential predictors of CD patients with depression. The prevalence of perianal lesions in CD patients with depression was almost two-fold greater than in patients without CD.

Another investigation[8] demonstrated that perianal lesions were the main factor of both depression and anxiety. In addition, CD patients with depressive and anxiety disorder comorbidities had a triple occurrence rate of perianal lesions and surgical procedure rate in comparison with the CD patients without the above psychological disorders. Moreover, a notable relationship was noted between psychological diseases and CD[9]. The link possesses the possibility of CD exacerbations or other complications, therefore aggravating the healthcare-related economic burden. Thus, it is imperative to prioritize psychological issues in patients with PFCD and monitor the possible related risk factors.

Psychological disorders in IBD were shown to be independently associated with female sex, disease activity, and ostomy in previous research[10,11]. However, there is a scarcity of analogous studies focusing on specific disease types of IBD. In contrast to general CD patients, those with perianal lesions experience distinct and additional symptoms that substantially alter their disease experience. Furthermore, research on the factors of depression in this specific subset of PFCD patients is limited at present. In short, we conducted a cross-sectional study to screen the depressive symptoms of PFCD patients and examined the related clinical factors to determine the research deficiencies of IBD-related psychological issues.

MATERIALS AND METHODS

Subjects

Patients with PFCD who were admitted to the anorectal ward of the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine and diagnosed by perianal magnetic resonance imaging (MRI) during the period from September 2022 to September 2023 were included in this study consecutively. Prior to the enrollment, written informed consent was obtained from the subjects or their legal guardians. The study was approved by the Affiliated Hospital of Nanjing University of Chinese Medicine (Approval No. 2020NL-170-02).

Patients were considered for enrollment if they fit the following inclusion criteria: (1) Diagnosed by perianal MRI; (2) age between 16 years and 60 years; (3) minimum 6 years of education; and (4) basic reading and cell phone operation skills. Exclusion criteria were as follows: (1) Diagnosed with psychiatric disorders explicitly; (2) unable to understand the content in the questionnaire; (3) clinical data missing and not being able to be communicate; and (4) without any perianal MRI examination.

Data collection and extraction

In our study, data collection, including demographic and clinical information, was conducted by a questionnaire and professional IBD medical staff. All data were collected and organized within 1 wk of admission to the anorectal ward.

The following information was gathered through a uniform questionnaire: (1) Basic demographic information including age, sex, body height, weight, smoking history, marital and reproductive status, educational level, employment status, and income level; and (2) physiologic and psychological assessment by using the Patient Health Questionnaire-9 (PHQ-9), IBD Patient Quality of Life Questionnaire (IBDQ), and IBD Fatigue (IBD-F) Patient Self-assessment Scale. Specialized IBD medical staff registered the following variables: (1) Medical history and characteristics of CD involving the Montreal classification, CD course, gastrointestinal surgery history, ostomy history, CD Activity Index (CDAI) score and medication history; (2) laboratory inflammation indicators including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC); and (3) medical history and features of perianal disease covering PFCD course, perianal surgery history, Perianal Disease Activity Index (PDAI), Wexner Score, and modified Van Assche index. The modified Van Assche index was assessed by two or more radiologists specializing in the field of proctology to minimize errors in the analysis.

Measurements and instruments

PHQ-9: Our study utilized the PHQ-9 as a tool for evaluating the depressive symptoms of PFCD patients. The scale is a nine-item self-reported questionnaire and has emerged as the most dependable tool for detecting depression[12] because of its perfect sensitivity and specificity[13]. The scoring system of the PHQ-9 is as follows: Scores of 0-4 correspond to the absence of depression; scores of 5-9 correspond to mild depression; scores of 10-14 correspond to moderate depression; scores of 15-19 correspond to moderately severe depression; and scores of 20-27 correspond to severe depression.

IBDQ: We used the Chinese version of IBDQ to evaluate the quality of life among PFCD patients. This assessment encompasses not only gastrointestinal symptoms but also constitutional symptoms, social functioning, and emotional state. The total score of the IBDQ ranges from 32 to 224, with higher scores indicating a higher quality of life. The questionnaire demonstrated adequate validity and reliability[14].

IBD-F patient self-assessment scale: Czuber-Dochan et al[15] invented a self-assessment scale for IBD patients, which has good reliability and validity, and can be used as an initial screening tool for fatigue in IBD patients. The first part of the Chinese version of the IBD-F scale was used in this study to assess the level of fatigue in PFCD patients. The relevant scale in our study is as follows: No fatigue (0 points); mild to moderate fatigue (1-10 points); and severe fatigue (11-20 points).

Modified van assche index: This study applied the perianal modified Van Assche index to objectively quantify the disease activity of fistulizing inflammation. In 2017, Samaan et al[16] amended the original Van Assche index[17], detailed the standardized score definition in each entry item, and improved the inter-rater reliability. The score was evaluated by two or more radiologists specializing in the field of proctology in our study. A higher total score indicated a more severe perianal inflammatory activity.

Statistical analysis

The statistical analyses were performed with SPSS 26.0 software (IBM Corp., Armonk, NY, United States). The measurement data were represented by mean ± standard deviation if they obeyed normal distribution, and the group data were compared using the independent sample t-test. In contrast, those not obeying normal distribution were analyzed by the Wilcoxon rank-sum test based on the description of the median ± interquartile range. Counting data were expressed as number of cases and percent, and Fisher’s exact probability method was applied for comparison between groups.

A logistic regression model was utilized to conduct a multivariate analysis. The outcomes were presented as odds ratios (ORs) and corresponding 95% confidence intervals (CI). Variables with P values < 0.10 in the univariate analysis were further analyzed in the multivariate analysis. The factors that showed statistical significance in the multivariate analysis were further subjected to Spearman rank correlation analysis to examine the relationship between the severity of depression and those variables. Furthermore, multiple linear regression analyses were conducted to ascertain the potential relationship between the demographic and clinical features of the cohort and the severity of depression.

The statistical methods of this study were reviewed by Jun-Qin Wang from the Department of Public Health, Nanjing University of Chinese Medicine.

RESULTS

General population information and clinical data

This research comprised a cohort of 123 PFCD patients eligible for enrollment. Of these patients, 85 (69.11%) were male and 38 (30.89%) were female. The age of the patients ranged from 16 years to 59 years, with a mean age of 28.55 ± 9.18 years. Almost one-third were married (36.59%), had a high school education or above (69.93%), and were employed (59.35%). An average CD duration of 4.26 ± 4.70 years and an average PFCD duration of 6.00 ± 23.00 months were shown. The majority of the lesions were located in the ileum (42.28%) among the study population, and 71.54% of the population used biologics. More detailed demographic data and clinical features are summarized in Table 1.

Table 1 Demographic and clinical characteristics of perianal fistulizing Crohn’s disease patients with and without depression, n (%).

Variable	Cohort, n = 123	Without depression, n = 53	With depression, n = 70	P value
Demographic characteristics
Female sex	38 (30.89)	12 (22.64)	26 (37.14)	0.115
Age in yr	28.55 ± 9.18	28.51 ± 9.17	28.59 ± 9.26	0.964
BMI in kg/m2	21.02 ± 3.85	21.56 ± 3.80	20.60 ± 3.86	0.175
Smoker	9 (7.32)	1 (1.89)	8 (11.43)	0.076
High school or above	86 (69.93)	41 (77.36)	45 (64.29)	0.164
Married	45 (36.59)	20 (37.74)	25 (35.71)	0.852
Procreated	38 (30.89)	15 (28.30)	23 (32.86)	0.694
Currently employed	73 (59.35)	32 (60.38)	41 (58.57)	0.855
Low-income population as ≤ 3.6 million yuan	61 (49.59)	27 (50.94)	34 (48.57)	0.856
Overall clinical characteristics
CD course in yr	4.26 ± 4.70	3.90 ± 4.10	4.53 ± 5.11	0.465
CD phenotypes
L1-Terminal ileum	52 (42.28)	25 (47.17)	27 (38.57)	0.362
L2-Colon	33 (26.83)	16 (30.19)	17 (24.29)	0.539
L3-Ileum and colon	38 (30.89)	12 (22.64)	26 (37.14)	0.115
B2-Stricturing	39 (31.71)	18 (33.96)	21 (30.00)	0.698
B3-Penetrating	3 (2.44)	2 (3.77)	1 (1.43)	0.577
CDAI score, median ± IQR	98.77 ± 119.39	46.67 ± 82.04	130.20 ± 99.21	0.000
History of gastrointestinal surgery	18 (14.63)	6 (11.32)	12 (17.14)	0.445
History of ostomy	8 (6.50)	5 (9.43)	3 (4.29)	0.289
Laboratory indicators, median ± IQR
ESR in mm/h	23.00 ± 29.00	14.00 ± 22.00	34.00 ± 39.00	0.000
CRP in mg/L	7.96 ± 17.80	5.72 ± 11.57	10.20 ± 25.47	0.004
FC in µg/g	732.80 ± 1128.30	374.20 ± 845.00	836.90 ± 1414.95	0.001
Current medication
Biologics therapy	88 (71.54)	35 (66.04)	53 (75.71)	0.313
Immunomodulator therapy	26 (21.14)	8 (15.09)	18 (25.71)	0.184
Corticosteroid therapy	15 (12.20)	5 (9.43)	10 (14.29)	0.580
Perianal clinical characteristics
PFCD course in month, median ± IQR	6.00 ± 23.00	5.00 ± 24.00	7.50 ± 28.00	0.146
History of perianal surgery of ≥ 2	57	24	33	0.857
PDAI score, median ± IQR	6.00 ± 5.00	4.50 ± 5.00	6.00 ± 5.00	0.001
Wexner score, median ± IQR	2.00 ± 7.00	1.00 ± 4.00	4.50 ± 7.00	0.001
Modified Van Assche index, median ± IQR	12.00 ± 8.00	8.00 ± 11.00	13.00 ± 5.00	0.000
Physiological and psychological characteristics
IBDQ score, median ± IQR	172 ± 50	194 ± 27	152 ± 37	0.000
IBD-F score, median ± IQR	6.00 ± 5.00	4.00 ± 5.00	8.00 ± 4.00	0.000

BMI: Body mass index; CD: Crohn’s disease; CDAI: Crohn’s Disease Activity Index; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; FC: Fecal calprotectin; IBD-F: Inflammatory Bowel Disease Fatigue; IBDQ: Inflammatory Bowel Disease Patient Quality of Life Questionnaire; IQR: Interquartile range; PDAI: Perianal Disease Activity Index; PFCD: Perianal fistulizing Crohn’s disease.

Prevalence of depression among PFCD patients

As for the depression levels among 123 participants, 70 of them displayed depressive symptoms. To be specific, 53 patients exhibited mild depression (43.09%), 6 patients exhibited moderate depression (4.88%), 8 patients exhibited moderately severe depression (6.50%), and 3 patients exhibited severe depression (2.44%) (Table 2).

Table 2 Prevalence of depression among perianal fistulizing Crohn’s disease patients, n (%).

Clinical characteristic	No depression	Mild depression	Moderate depression	Moderately severe depression	Severe depression
PFCD	53 (43.09)	53 (43.09)	6 (4.88)	8 (6.50)	3 (2.44)

PFCD: Perianal fistulizing Crohn’s disease.

Analysis of influencing factors associated with depression in PFCD patients

Univariate analysis: The patients with PFCD were categorized into two groups: Those with depression and those without depression. The analysis of clinical data of both groups of patients showed that the use of ESR, CRP, FC, CDAI score, PDAI score, Wexner score, modified Van Assche index, IBDQ score, and IBD-F score between the depressive group and the non-depressive group had significant statistical differences (P < 0.05) (Table 1).

Multivariate logistic regression analysis: The possible factors (variables which adhered to P < 0.10 in Table 1) related to depressive symptoms were screened, and a multivariate logistic regression analysis was performed. The most obvious finding to emerge from this analysis was that the modified Van Assche index (OR = 1.24, 95%CI: 1.01 to 1.53), PDAI score (OR = 0.69, 95%CI: 0.50 to 0.95), IBDQ score (OR = 0.93, 95%CI: 0.88 to 0.97), and IBD-F score (OR = 1.72, 95%CI: 1.23 to 2.42) significantly influenced the prevalence of depression (P < 0.05) (Table 3 and Figure 1).

Figure 1 Factors associated with the presence of depression in patients with perianal fistulizing Crohn’s disease. PDAI: Perianal Disease Activity Index; IBDQ: Inflammatory Bowel Disease Patient Quality of Life Questionnaire; IBDF: Inflammatory Bowel Disease Fatigue; OR: Odds ratio; CI: Confidence interval.

Table 3 Multivariate logistic regression analysis of perianal fistulizing Crohn’s disease patients with depression.

Factor	β value	Wald value	P value	OR value	95%CI
Smoker	1.111	0.36	0.550	3.04	0.08 to 116.33
CDAI score	0.000	0.00	0.957	1.00	0.99 to 1.02
ESR in mm/h	0.029	2.20	0.138	1.03	0.99 to 1.07
CRP in mg/L	-0.030	1.28	0.258	0.97	0.92 to 1.02
FC in µg/g	0.001	3.17	0.075	1.00	1.00 to 1.00
PDAI score	-0.373	5.03	0.025	0.69	0.50 to 0.95
Wexner score	0.020	0.04	0.850	1.02	0.83 to 1.26
Modified Van Assche index	0.218	4.37	0.037	1.24	1.01 to 1.53
IBDQ score	-0.076	9.73	0.002	0.93	0.88 to 0.97
IBD-F score	0.545	10.02	0.002	1.72	1.23 to 2.42

CI: Confidence interval; CDAI: Crohn’s Disease Activity Index; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; FC: Fecal calprotectin; IBD-F: Inflammatory Bowel Disease Fatigue; IBDQ: Inflammatory Bowel Disease Patient Quality of Life Questionnaire; OR: Odds ratio; PDAI: Perianal Disease Activity Index.

Spearman rank correlation analysis: The PDAI score, IBDQ score, perineal modified Van Assche index, IBD-F score, and the severity of depression were analyzed using Spearman rank correlation analysis. The analysis showed the following conclusions: (1) A lower IBDQ score was associated with more severe depression (r = -0.711, P = 0.000); (2) a higher modified Van Assche score was associated with more severe depression (r = 0.466, P = 0.000); (3) a higher IBD-F score was associated with more severe depression (r = 0.593, P = 0.000); and (4) a higher PDAI score was associated with more severe depression (r = 0.333, P = 0.000). The relationship between depressive level and the above variables was presented using box plots (Figure 2).

Figure 2 Relationship between the severity of depression and variables. A: Inflammatory Bowel Disease Patient Quality of Life Questionnaire score; B: Modified Van Assche index; C: Inflammatory Bowel Disease Fatigue score; D: Perianal Disease Activity Index score. PFCD: Perianal fistulizing Crohn’s disease; PDAI: Perianal Disease Activity Index; IBDQ: Inflammatory Bowel Disease Patient Quality of Life Questionnaire; IBD-F: Inflammatory Bowel Disease Fatigue.

Multiple linear regression analysis: The increased modified Van Assche score (β value = 0.166, 95%CI: 0.02 to 0.31) and the decreased IBDQ score (β value = -0.116, 95%CI: -0.14 to -0.09) were independently associated with the severity of depression. These factors explained the variance of 65.0% (Table 4).

Table 4 Multiple linear regression analysis of perianal fistulizing Crohn’s disease patients with depression.

Factor	β value	t value	P value	95%CI	R2
Smoker	0.124	0.09	0.928	-2.58 to 2.83	0.650
CD activity index	0.006	0.96	0.341	-0.01 to 0.02
ESR in mm/h	0.005	0.25	0.804	-0.03 to 0.04
CRP in mg/L	-0.006	-0.32	0.746	-0.04 to 0.03
FC in µg/g	0.000	0.78	0.440	0.00 to 0.00
PDAI score	-0.134	-1.06	0.292	-0.39 to 0.12
Wexner score	-0.069	-0.88	0.380	-0.23 to 0.09
Modified Van Assche index	0.166	2.22	0.028	0.02 to 0.31
IBDQ score	-0.116	-8.58	0.000	-0.14 to -0.09
IBD-F score	0.169	1.61	0.109	-0.04 to 0.38

CI: Confidence interval; CD: Crohn’s disease; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate; FC: Fecal calprotectin; IBD-F: Inflammatory Bowel Disease Fatigue; IBDQ: Inflammatory Bowel Disease Patient Quality of Life Questionnaire; PDAI: Perianal Disease Activity Index.

DISCUSSION

Our cross-sectional study revealed a significant prevalence of depressive symptoms among PFCD patients in which 56.91% of them were in distress. It is noteworthy that even 13.82% of them exhibited moderate to severe levels of depression. Risk factors of depression in CD patients were shown to be linked with the activity of perianal lesions, quality of life, and fatigue. To the best of our knowledge, this study was one of the few studies about the prevalence of depression among PFCD patients and the related factors. Furthermore, our analysis encompassed various variables that might be directly associated with depression, including the course of perianal lesions, frequency of perianal surgeries, the modified Van Assche score, quality of life, and fatigue. Notably, unique characteristics of the perianal condition were examined infrequently in prior studies.

The prevalence of depressive symptoms was markedly greater in patients with PFCD compared to those with typical CD and IBD. Two meta-analyses[1,11] determined that the occurrence rate of depressive symptoms in IBD patients was around 25.2% and 21.6%, respectively. Likewise, the occurrence rate of depression in CD patients varied from 17.5% in a survey based on a primary care database in the United Kingdom to 41.7% in a different study that examined a population-based group[18,19]. The existing findings on the prevalence of depression in IBD were still multiform. It might be attributed to factors such as sample size, geographical and age disparities within the study population, and the selection of the depressive rating scale.

The findings of our study exhibited a notable increase compared to the prior studies. This distinction may be due to the fact that our investigation specifically focused on PFCD. Patients with PFCD exhibit diverse disease manifestations compared to those without perianal fistulas. They suffer from challenging therapeutic dilemmas and alterations of body image and living habits, exacerbating life quality and psychological consequences due to persistent defecation, suppuration, pain, infection, and impairments in the sphincter and perineal tissues. In addition, this discrepancy could be linked to the different applications of psychological assessment instruments. When comparing with the structured diagnostic interviews (gold standard clinical diagnosis) of depression, there was a possibility of overestimating symptoms referred to the PHQ-9 self-reported scale. Nevertheless, our study revealed a significant prevalence of depressive symptoms in CD patients, particularly in a specific subset of patients with PFCD, where mental health issues play a crucial role.

Previous literature had reported a higher occurrence rate of depression among patients in active CD state compared to those in remission state[20], and the overall increased disease activity was independently associated with the development of depression[21,22]. However, we did not find any correlation between the prevalence of depression and disease activity indicators (CDAI score and inflammatory factors like FC, ESR, and CRP). This might be ascribed to the patient population in this study, which was mainly diagnosed with PFCD with low overall disease activity. This study also disclosed that two indicators of perianal disease activity, the PDAI score and the modified Van Assche score, were the main factors associated with depression in PFCD. In particular, the modified Van Assche score, an objective MRI indicator, showed statistically significant results in multivariate logistic and multiple linear regression analysis, making the results more reliable.

A case-control study including more than 1300 patients revealed that perianal disease was a significant risk factor for anxiety and depression in patients with IBD[7]. Another investigation also documented that history of perianal disease was the major risk factor for anxiety and depression in CD patients[8]. Not surprisingly, all of the studies mentioned above involved perianal disease history as their experimental criteria without quantifying the perianal disease activity. Our present study utilized two quantitative indicators for evaluating perianal fistulizing activity and the modified Van Assche score, which expressed the existence of a correlation between perianal activity and depression. Higher perianal inflammatory activity is associated with more complex fistulas, more secretions, swelling, and pain and is accompanied by an uncomfortable sitting posture, unpleasant odor, low self-esteem, and feelings of embarrassment, thus increasing the risk of depression. In order to detect depressive disorder in PFCD patients, physicians should go beyond laboratory parameters in clinical practice since inflammatory markers that react to disease activity do not correlate with depression. Perianal MRI is particularly important.

CD patients with perianal comorbidities such as perianal abscesses and fistulas have a lower quality of life than the general population[23]. The delayed healing and intractable nature of PFCD means that patients often experience uncomfortable symptoms and the impacts of repeated surgeries, disrupting their daily life, relationships, social participation, and psychological well-being, which may lead to a lower quality of life. In this study, we found that the life quality of PFCD patients with depressive symptoms was lower than that of those without depressive symptoms. This is similar to the findings of García-Alanís et al[24].

In the multivariate regression analysis, a reduction in quality of life was significantly associated with the presence and severity of depression. A lower IBDQ score was associated with a more severe depression. Geiss et al[21] reported a strong correlation between life quality and PHQ-9 score among IBD patients. The IBDQ score used in this research incorporated the impact of the disease on psychological functioning and, to some extent, overlapped with patients’ psychoemotional evaluations, which may partly explain the stronger correlation between life quality and depression. Poor quality of life will aggravate psychological distress, such as anxiety and depression, in patients with IBD[25]. A lower quality of life is manifested in anxiety about the loss of bowel control, worry about systemic symptoms, fear of socialization, stress from not being able to work and study normally, and a lack of confidence in body image, which will contribute to an increasing risk of depression.

Fatigue coexists with psychosomatic problems such as depression and anxiety in chronic conditions[26,27], including IBD[28]. Our findings suggested that fatigue was significantly associated with the presence of depression in PFCD, which might have the same behavioral, emotional, and cognitive characteristics. The main symptom of fatigue is a lack of energy or persistent tiredness that is disproportionate to physical exertion, limiting daily activities, and not being able to be relieved by rest[29]. CD patients have a higher prevalence of fatigue[30]. They describe fatigue as one of the most bothersome symptoms[31] and may even be more debilitating and depressing than CD symptoms. This trouble severely affects patient quality of life and reduces labor productivity. Jonefjäll et al[32] found that fatigue could have a negative psychological impact on IBD patients, exacerbating clinical symptoms and promoting disease progression. Another study also showed that concurrent depression was the most substantial risk factor of IBD with fatigue[33]. These findings complement our results and suggest that there may be complex interactions and interdependencies between depression and fatigue.

Age, smoking history, education level, marital status, annual income, and related medication were not associated with depression in PFCD according to our research. Being female had been reported as a predictor of depression in patients with IBD in several papers[34,35], and previous abdominal surgeries and ostomy had also been reported to be associated with depression in perianal CD patients[6]. Our findings, however, did not show any significant association between depression and sex or abdominal surgery treatment. This might be related to the small sample size and heterogeneity of participants in our study.

We included, for the first time, three parameters regarding the characteristics of perianal disease, namely the PFCD course, the number of perianal surgeries and the Wexner score, which can reflect the chronic course and severity of anal fistula in patients. However, we were puzzled when the three perianal parameters did not significantly intensify depression as we had hypothesized they would, and the longer intervals between fistula recurrences and surgeries might overestimate the duration of PFCD and the number of perianal surgeries. In addition, the overall Wexner score was low, and anal incontinence was not that critical in our study population.

Our analyses had some limitations. First, the sample size of our study was relatively small. Further extensive sample size studies are necessary to screen for the prevalence of depression in PFCD patients more accurately and to identify risk further factors for depression. Second, the IBDQ was used in this study to assess the overall quality of life of CD patients, but it did not allow for a comprehensive assessment of the impact of fistula. The Crohn’s Anal Fistula Quality of Life scale[36] is a brand-new measurement tool for complex PFCD. In the future, we can use it to evaluate the quality of life of PFCD patients, and the results may be more meaningful. Furthermore, none of the patients enrolled in this study underwent antidepressant psychotherapy although they were exhibiting diverse levels of depressive symptoms. This condition could potentially stem from the limited awareness of depression associated with PFCD among medical professionals and patients. Moving forward, we are committed to broadening our research scope and conducting comparative analyses on the alterations in prior and post antidepressant therapy, thereby enhancing the specificity of our study. Finally, there may be an interconnection between depression, quality of life, and fatigue, necessitating further studies to test causal and more complex models of depression related to PFCD.

CONCLUSION

In conclusion, our study suggested that patients with PFCD had a higher prevalence of depression, and the related risk factors of depression included the PDAI score, the modified Van Assche score, quality of life, and fatigue. The above suggestion may help physicians to emphasize, accurately identify, and encourage high-risk groups for psychological disorders, thus alleviating patients’ symptoms and improving quality of life and prognosis.

ACKNOWLEDGEMENTS

The authors would like to thank the members of the Department of Radiology and the Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine for their technical support. The authors also thank Jun-Qin Wang for her biostatistics assistance.