This study utilized data from the 2002-2013 Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC), provided by the National Health Insurance Service (NHIS) of Korea. South Korea operates a mandatory universal health insurance system that covers approximately 98% of the population, and enrollees are eligible for regular health screenings every 1 to 2 years based on their age, sex, and health risk factors [12]. The NHIS-NSC comprises approximately one million individuals who underwent health examinations in 2002, selected via a stratified random sampling method based on 1,476 strata defined by sex, age, and income level [13]. The dataset includes all healthcare utilization records, diagnostic codes, and health screening results assigned to the participants from January 2002 to December 2013.

The study was exempt from institutional review board (IRB) approval by the Sungshin Women’s University IRB (SSWUIRB-2025-034). Informed consent was waived as the NHIS data were anonymized and contained no personally identifiable information.

The CTS cohort was defined as individuals assigned the International Classification of Diseases, 10th Revision (ICD-10) diagnostic code G56.0 for CTS as a primary or secondary diagnosis at least twice during the observation period between January 2004 and December 2013 (Table 1). The index date for the CTS group was set as the date of the second recorded diagnosis. To include only newly diagnosed cases, a 2-year washout period (from 2002 to 2003) was applied, and individuals with a CTS diagnosis during this period were excluded.

To mitigate potential confounding by medical conditions associated with psychiatric disorders, individuals with preexisting neurological, infectious, congenital, or systemic conditions known to affect mental health were excluded. This included moderate-to-severe traumatic brain injury, stroke, brain tumors, congenital brain malformations, tuberculosis, human immunodeficiency virus (HIV), central nervous system infections, neurodevelopmental disorders, metabolic disorders, electrolyte imbalances, Alzheimer’s disease, dementia with Lewy bodies, and autoimmune encephalitis. Individuals with a history of congenital anomalies, previous exposure to general anesthesia for surgery, or a family history of malignancy were also excluded. However, individuals with common chronic conditions such as hypertension or diabetes were retained in the cohort because of their high population prevalence and relatively low direct psychiatric impact of these conditions.

Further exclusion criteria were as follows: 1) lack of a health screening record within two years before the index date, 2) age under 20 or over 79 years at the index date, and 3) diagnosis of any psychiatric outcome of interest within the 2 years preceding the index date.

Controls were selected from the eligible population not diagnosed with CTS during the observation period, after applying the same exclusion criteria as cases. Controls were selected in a 1:10 ratio from among individuals of the same age, sex, and year of health examination as cases with the closest propensity score to cases. The propensity score calculation included smoking status, alcohol consumption, body mass index (BMI), total cholesterol, systolic and diastolic blood pressure, fasting blood glucose (FBS), and income level. Single imputation using predictive mean matching was employed in cases of missing data. The index date for controls was assigned to be the same as that of the matched CTS cases. The selection process for the case and control groups is illustrated in Figure 1.

The primary outcomes of interest in this study were the new-onset diagnoses of four major psychiatric disorders: depressive disorders (F32, F33), anxiety disorders (F40, F41), somatoform disorders (F45), and sleep disorders (F51, G47). The occurrence of each outcome was defined as the assignment of the corresponding ICD-10 code at least once during the follow-up period (Table 1).

Variables included in the analysis were age, sex, smoking status, alcohol consumption, BMI, total cholesterol, systolic blood pressure, diastolic blood pressure, FBS, and income level. The values closest to the date of the health screening were used for each variable.

To compare baseline characteristics between the CTS and control groups, standardized differences (SDs) were calculated, with values <0.1 interpreted as indicating negligible differences. Incidence rates (IRs) per 1,000 person-years and incidence rate ratios (IRRs) were applied to compare the occurrence of psychiatric disorders between the CTS and control groups. Kaplan-Meier survival curves were constructed to illustrate the cumulative incidence of newly diagnosed psychiatric disorders, and the log-rank test was employed to assess differences between groups. The end of follow-up was defined as the earliest occurrence of a psychiatric diagnosis, death, or the end of the study period (December 31, 2013).

To evaluate the association between CTS and each psychiatric disorder, multivariable Cox proportional hazards regression models were employed to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). All statistical analyses were conducted using R software (version 4.4.1, R Foundation for Statistical Computing). Two-sided tests were conducted, and a p-value of <0.05 was considered statistically significant.

In this study, approximately 6,000 patients with CTS were propensity score-matched at a 1:10 ratio with controls for each of the following four psychiatric disorders: depression, anxiety, somatoform disorder, and sleep disorder. The results consistently demonstrated an elevated risk of all psychiatric outcomes among individuals with CTS. This increased risk persisted for up to 10 years following CTS diagnosis, suggesting a potential long-term psychological burden associated with the condition.

Neuropathic pain, a hallmark feature of CTS, may be a key contributor to the development of psychiatric disorders. Chronic pain can induce central sensitization, a process by which the central nervous system becomes hyperresponsive to nociceptive stimuli, thereby amplifying pain perception [5]. This heightened sensitivity may result in frustration, helplessness, and a perceived loss of control over one’s condition, which in turn may increase vulnerability to anxiety and depression [14]. Pain catastrophizing, a cognitive tendency to exaggerate the perceived threat of pain, is associated with elevated levels of anxiety and depression [15]. Furthermore, persistent pain may disrupt sleep architecture, leading to sleep disorders [16].

Depressive disorder showed the greatest increase in risk among all psychiatric outcomes following CTS diagnosis, with patients exhibiting an approximately 1.6-fold higher risk compared to controls. A large-scale retrospective cohort study using data from general practices in Germany similarly reported an elevated risk of depression within five years after a new diagnosis of CTS, with an aHR of 1.29 (95% CI, 1.25-1.33) [14]. This finding aligns with a prior cross-sectional study, which reported that approximately 40% of CTS patients experience depressive symptoms [8,15].

In patients with CTS, depressive symptoms are commonly characterized by diminished motivation, a sense of helplessness in managing symptoms, and a pessimistic outlook on recovery. These symptoms are closely associated with pain intensity, increased functional impairment, and higher overall symptom burden [7,17]. Furthermore, baseline depressive symptoms have been associated with less favorable postoperative outcomes, underscoring the clinical relevance of incorporating psychological assessment and management into the overall treatment strategy for CTS [18].

Anxiety disorders exhibited the second-highest aHR following CTS diagnosis, at 1.41 (95% CI, 1.31-1.52). A comprehensive retrospective study using general practice data from Germany similarly reported a significantly higher 5-year incidence of anxiety among CTS patients (3.9%) compared to controls (3.6%; p<0.001), with an aHR of 1.14 (95% CI, 1.08-1.21) after adjusting for comorbidities [14]. A case-control study conducted in Syria also demonstrated significantly higher anxiety scores among CTS patients compared to matched controls [7]. Notably, higher anxiety levels were associated with increased symptom perception, and a few patients reported significant anxiety despite normal findings on nerve conduction studies. These findings suggest that anxiety may exacerbate the perception of pain and sensory disturbances in patients with CTS.

Somatoform disorders are characterized by physical symptoms that are medically unexplained or disproportionate to clinical findings, and are often considered to be driven by psychological distress [19]. In the present study, patients with CTS exhibited a 1.4-fold increased risk of developing somatoform disorders compared to matched controls. Although research on the prevalence of somatoform disorders following CTS remains scarce, a 1994 study comparing psychiatric comorbidity in patients with CTS and chronic low-back pain reported a 14% prevalence of somatoform symptoms among CTS patients [20]. These findings suggest that chronic pain conditions such as CTS may trigger or exacerbate somatization tendencies in susceptible individuals and highlight the potential role of psychological interventions in improving treatment outcomes. In this study, CTS was not associated with an increased risk of somatoform disorders in males, consistent with previous findings that these disorders are more prevalent in females because of biological and sociocultural factors [21-24].

CTS was associated with a 1.36-fold increased risk of sleep disorders, likely due to nocturnal symptoms such as pain and numbness [16]. Previous studies have consistently reported that the majority of patients with CTS experience poor sleep quality and reduced sleep duration, underscoring sleep disturbance as a key clinical characteristic of the condition [9]. Furthermore, increased symptom severity has significantly correlated with shorter sleep duration and poorer sleep quality. Notably, impaired sleep quality may exacerbate symptoms of depression and anxiety, contributing to a self-reinforcing cycle of psychological distress [25-27]. These findings suggest that early recognition and management of sleep disturbances in patients with CTS may be critical for mitigating mental health decline and improving overall clinical outcomes.

In this study, a significantly increased risk of all examined psychiatric disorders was observed among younger individuals, and among male patients for all disorders except somatoform disorder. These findings suggest that the psychological impact of CTS is not limited to traditionally high-risk groups such as older adults or females, but may extend across demographic groups regardless of age or sex.

In working-age adults, CTS-related functional impairment may undermine occupational identity and exacerbate psychological burden, particularly among primary income earners. Previous studies have linked CTS with unemployment, diminished work performance, and elevated rates of depression and anxiety, with males potentially at greater risk because of internalization of distress [5,28,29]. These findings suggest that CTS may serve as both a physical and mental health risk, underscoring the need for age- and sex-specific psychiatric screening and intervention.

This study has several limitations. First, the analysis did not account for the severity of CTS or the specific treatments received. Second, both CTS and psychiatric diagnoses were based on administrative claims data, which may be subject to misclassification or diagnostic coding errors. Third, potential confounding factors such as family history of psychiatric disorders were not available and, therefore, could not be considered. Nevertheless, the study has notable strengths. It utilized a large, nationwide, population-based cohort, thereby enhancing statistical power and generalizability. Additionally, rigorous propensity score matching and adjustment for multiple confounders enhanced the validity of the observed association between CTS and subsequent psychiatric disorders.

In conclusion, this study utilized a nationwide population-based cohort in South Korea to demonstrate that patients with CTS experience elevated risk of developing depressive disorders, anxiety disorders, somatoform disorders, and sleep disorders over 10 years following diagnosis. The risk was particularly pronounced among individuals aged under 60 years across all psychiatric outcomes, and among males for all outcomes except somatoform disorder.