Is psychological distress associated with carpal tunnel syndrome symptoms and nerve conduction study findings? A case–control study from Syria

Abstract Background Carpal tunnel syndrome (CTS) is a common entrapment neuropathy of the median nerve at the wrist which causes severe symptoms. However, psychological aspects can affect patients' perception of this pain and can cause similar pain in some instances. This study aims to determine the association between symptoms severity, functional status, and nerve conduction studies (NCS) of adult patients with CTS and their anger, anxiety, and depression status. Methods This case–control study was conducted in clinics in Damascus, Syria. Controls were frequency matched by gender and age from a general clinic. Interviews based on questionnaires were used that included the Boston Carpal Tunnel Questionnaire (BCTQ‐A), Hospital Anxiety and Depression Scale (HADS), Dimensions of Anger Reactions Scale‐5 (DAR‐5), and NCS. Results Overall, 242 patients (121 cases) were included in this study. Cases with CTS had significantly higher anxiety and depression when compared to controls, but not higher anger. Cases with higher anxiety, depression, and anger had significantly more CTS symptoms and less functional status. Anxiety was also higher in cases with normal NCS in the case group. When using regression, anxiety and depression remained significantly associated with having CTS. Conclusion Anxiety and depression are more prominent with CTS. Furthermore, having anxiety and depression were associated with more CTS symptoms in the hand. Having anger was also associated with more CTS symptoms among cases. These findings emphasize the importance of psychological aspects when having hand pain or CTS symptoms as these patients might have these symptoms despite having normal NCS.


INTRODUCTION
Carpal tunnel syndrome (CTS) is a common entrapment neuropathy of the median nerve at the wrist (Demino & Fowler, 2021). Much as the name implies, the median nerve is compressed when entering the carpal tunnel as it travels beneath the transverse carpal ligament (Bhatt et al., 2015). Though the underlying cause of the compression can be idiopathic, it can be attributable to a number of different factors such as malpositioning of the wrist, any condition that leads to an excess fluid within the body that leads to an increased volume in the tunnel, and masses that could occupy the volume of the tunnel (Genova et al., 2020).
The nerve damage from the compression produces sensory symptoms, such as numbness, tingling, and pain within the hand. As the disease progresses, soft tissue injury occurs, and disabling motor symptoms such as reduction of grip strength become apparent. This impairment may progress into thenar atrophy in advanced cases (Bhatt et al., 2015;Genova et al., 2020;McCallum et al., 2019).
These symptoms mostly aggravate at night and have a huge negative impact on the ability to work and perform daily activities leading to increased morbidity and inability to attend work (Demino & Fowler, 2021;Genova et al., 2020;McCallum et al., 2019). They can also affect patients' quality of life and cause a deteriorating in mental health (Jerosch-Herold et al., 2017;McCallum et al., 2019). Moreover, psychological distress itself can intensify symptom perception, or even produce subjective symptoms resembling CTS (McCallum et al., 2019;Papadopoulou et al., 2021). The prevalence of anxiety and depression in CTS patients is 28.7% and 37.6%, respectively, which is higher than the general population (Filho et al., 2020;McCallum et al., 2019). In addition, the prevalence of CTS is higher among women, usually after their sixth decade of age (Basiri & Katirji, 2015). It is speculated that decreased estrogen antinociceptive effect caused by the decreased estrogen concentrations is the reason behind the increased likeliness of anxiety and depression in women (Filho et al., 2020).
Since psychological distress affects CTS symptoms, diagnosis workup and treatment program, it is important to assess the presence of an association between them as it could affect patients' outcomes. The more symptomatic the patients are, the higher they scored in anxiety and depression scales even before having a confirmed CTS by electric studies (McCallum et al., 2019). There is still considerable controversy surrounding the association between psychological status and nerve conduction studies (NCS) (Papadopoulou et al., 2021). To our knowledge, there is a lack of studies discussing anger's effect on CTS symptoms and NCS. However, some studies included the association with anxiety and other psychological aspects. The aim of this study is to broaden current knowledge of the association between psychological status such as anger and anxiety and the severity of CTS symptoms along with NCS. This is the first study to include anger in CTS psychological factors' assessment.
It is noteworthy to mention that we undertook this study in Syria that has been in war for ten years. Therefore, by taking into account the effects of war environment on mental health, our study provides spe-cial insights on CTS in war time. As high prevalence of mental health disorders was found in Syria, particularly during war and COVID-19 (Levine et al., 1993), we speculated that they both might have indirectly led to an increase of CTS symptoms as well. This is a case-control study that aims to determine the association between symptoms severity, functional status, and NCS of adult patients with CTS and their anger, anxiety, and depression status. This is the first study to explore into CTS in Syria and its association with mental health during the war and COVID-19.

Study design
This case-control study was conducted at a neurophysiology outpatient clinic and general outpatient clinics at Al-Assad teaching hospital in Damascus, Syria. This study was conducted from December 2020 to June 2021. Interviews based on questionnaires were used to collect data after applying the inclusion and exclusion criteria for both, the cases or the controls. The interviewers were trained to facilitate data collection and explain any vague information in the questionnaires to overcome any educational or cultural barrier that might have prevented proper understanding.

Study population
Cases were at least 18 years old, able to give informed consent, and were diagnosed with CTS by a combination of clinical features, physical examination, and NCS findings. We excluded cases that had either a neuropathy other than CTS, such as ulnar neuropathy, or previous CTS surgery during the last year. Cases were frequency matched with a control group by gender and age (not more than ten years range). Controls were selected from the general outpatient clinics at Al-Assad University Hospital provided that they had no history of previous or current nerve entrapments and did not need neurology symptoms or referrals.
We excluded any case or control who had conditions causing chronic pain other than the pain from CTS in the case group.

Questionnaires
Questionnaires included demographics such as gender, age, educational level, work, marital status, number of children, along with handedness and shisha or cigarette smoking.
The evaluation of patients with suggestive CTS symptoms was made through taking a detailed history of their condition, performing a clinical examination, which includes Phalen and Tinel tests, and finally confirming the diagnosis by conducting NCS.
CTS symptoms severity was assessed by asking cases to complete the Arabic version of Boston Carpal Tunnel Questionnaire (BCTQ-A).
Boston Carpal Tunnel Questionnaire (BCTQ) is a self-report questionnaire that records symptom severity and functional status in CTS patients (Levine et al., 1993). It represents CTS severity in the last two weeks and consists of two scales; the first one is the symptom severity scale (SSS) that has 11 items that cover six domains include: pain, numbness, nocturnal symptoms, paraesthesia, weakness, and functional status. Its score ranges from 1 to 5, which is the most severe.
The second one is the functional status scale (FSS) that has 8 functional activities that are commonly affected by CTS (difficulty in writing, buttoning clothes, opening jars, holding a book, gripping a telephone handle, performing household chores, carrying grocery bags, bathing, and dressing). The scores also range from 1 to 5 that represent not being able to perform the activity at all (Alanazy et al., 2019). Since many patients were illiterate, we had to change the question asking about difficulties of writing or holding a book while reading to difficulties of using cutlery during their meals or holding their plate while eating, respectively.
The Hospital Anxiety and Depression Scale (HADS) was also used which is a brief, clinically meaningful scale that screens for the levels of anxiety and depression in clinics. The limitation of this version is that it does not have somatic symptoms of depression to reduce the effect of the current medical condition(s) on the scores. It consists of two subscales and scores can predict the psychosocial and physical outcomes.
HADS has 14 items as anxiety and depression have seven items each.
Each item is scored on a four-point scale ranging from 0 to 3 and the maximum score for each subscale is 21. Scores that range from 0 to 7 are considered normal while 8-10 are considered borderline, and 11-21 are considered as anxiety or depression cases (Terkawi et al., 2017;Zigmond & Snaith, 1983).
Dimensions of Anger Reactions Scale-5 (DAR-5) is used to assess problematic anger. It is a mini screening measure of anger reactions for the past four weeks. It assesses the frequency, intensity, and duration of anger, antagonism toward others, and social relations interference. Scores of each item range from 1 (None or almost none of the time) to 5 (All or almost all of the time). Total scores above 12 are considered problematic anger (Forbes et al., 2014;Kakaje et al., 2021).
NCS: Median distal motor latency (DML) and median sensory NCS (between the wrist and digit, between the wrist and palm) are of the best NCS tests to evaluate CTS according to a literature review of the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) (Basiri & Katirji, 2015). Of these tests, DML and distal sensory latency (DSL) are the most popular ones, so that we used them along with other tests such as sensory nerve conduction velocity (NCV) and amplitude in order to increase the sensitivity and specificity of our tests. The sensory conduction study was performed by placing an active electrode on the index at a distance of 13-14 cm from a stimulator in the middle of the wrist. We also stimulated the median nerve at the palm. The motor conduction study was done by placing an active electrode on the belly of the abductor pollicis brevis (APB) muscle. We stimulated the median nerve at the wrist at a distance of 4-6 cm from the active electrode.
Neurophysiological grading of CTS was done based on the study of Bland (2000)

Definitions
The classification of clinical symptoms such as numbness, tingling, or pain depended on the location where the patient experiences these symptoms. It comprised 4 categories: classic, probable, possible, and unlikely, which represent the following patterns of symptoms: two of three fingers (thumb, index, and long) without the involvement of the palm or hand dorsum, two of three fingers (thumb, index, and long) and the palm but no confinement to the ulnar side, one of three fingers (thumb, index, and long), and none of three fingers, respectively (Basiri & Katirji, 2015;Radwan et al., 2018

Ethics
The study was approved by the local ethics committee of Damascus University, faculty of medicine. In the case group, no statistically significant difference was found between left and right hand in terms of NCS except in sensory median nerve amplitude. It is noteworthy to mention that 31.4% of NCS in both hands showed normal results among cases. (Table 2) A statistically significant difference was found between cases and controls in terms of anxiety and depression. In contrast, the mean of the anger scale was not statistically different between the two groups.

RESULTS
Both groups have DAR-5 scores greater than 12. In comparison with cases, the percentages of normal anxiety and depression scores, as well as mild ones, were higher in controls (74.4% for anxiety and 83.4% for depression). Based on the HADS score for anxiety and depression, severe scores were higher in cases in comparison with controls. Psychological factors and their association with CTS are summarized in (Table 3).
The patients with normal NCS had the highest mean of anxiety among other NCS groups. When doing the one-way ANOVA test, the difference between groups was only statistically significant in the left hand. However, that difference was only significant between the normal and moderate groups after running the post hoc test (Table 4).
There is a significant negative correlation between anxiety and both left-and right-hand NCS, whereas the correlation was insignificant for the depression scale (Table 5).
When using forward linear regression to regress anxiety score on case-control groups, education and working status, case control was  significant with p < .001 and R 2 of 6.2% and work with p = .004 and R 2 of 9.4%. When using the same methods to regress depression score, case-control was significant with p < .001 and R 2 of 7.8%, work with p = .004 and R 2 of 10.9%, and education with p = .022 and R 2 of 12.9%.

TA B L E 5 Correlations between psychological factors and EDX findings
However, when using the same method to regress anger, only work was significant with p = .025 and R 2 of 1.7%.

DISCUSSION
This study found a strong association between CTS symptoms severity along with functional status and anxiety, depression, and anger. In regard to anger, this study surprisingly revealed that both cases and controls have problematic anger, and no significant difference between them was found. Furthermore, there was no correlation between anger and NCS. However, regarding anxiety and depression, controls have more normal and milder anxiety and depression when compared to cases of CTS who had more severe anxiety and depression. Anxiety was correlated with milder NCS as it had an inverse correlation with This study confirms previous findings (Beleckas et al., 2018;Filho et al., 2020Moghadam-Ahmadi et al., 2017  (2020) and Beleckas et al. (2018); this may be explained by the war environment of Syria, where the study took place.
Our study is consistent with previous research (Sun et al., 2019) regarding the strong association between CTS symptoms severity along with functional status and anxiety and depression. However, these results differ slightly from an earlier study reported by Shin et al. (2018) who states that only CTS symptoms severity is associated with depression and anxiety. Shin et al. (2018) Although it is believed that having more severe symptoms is associated with a greater underlying pathophysiology, this is mostly not true with pain (Nunez et al., 2010) since many studies demonstrate that psychological distress act synergistically on pathophysiology at a personal level, and there is a positive correlation between this distress and CTS, as well (Mansfield et al., 2018). Since association does not mean causation, the limitation of our study is that it does not investigate whether CTS causes psychological distress or vice versa is true.
There was an inverse association between anxiety and EDX findings for both right and left hands in terms of general grading. This correlation demonstrates the association between the high grade of anxiety and the low grade of EDX.
The inverse association between anxiety and DML indicates that anxiety is more associated with normal to mild electrodiagnostic CTS grades than moderate to severe grades.  (Khan et al., 2017;Papadopoulou et al., 2021).
The specific correlation between anxiety and the left hand may shed the light on the psychometric origin of these symptoms. While CTS is known to be most prominent in the dominant hand, this phenomenon may be explained by the idea that symptoms in the left hand may be due to the anxiety itself rather than median nerve injury.
Psychological support should be offered for CTS patients with mild NCS in case positive anxiety and depression were found (Khan et al., 2017).
Research on anger's relationship with CTS lags far behind studying that of anxiety and depression with CTS. To the best of our knowledge, there are no studies in the literature that explore the association of self-reported anger with symptom severity and functional status in patients with CTS. Our study reveals that both case and control groups have problematic anger, which may be attributable to the traumatic war environment in Syria (Kakaje et al., 2021). There were significant positive correlations between anger and both symptom severity and functional status in our study. In general, the association between pain and anger was highly reported in previous studies. Anger exacerbates pain intensity in both, chronic and acute conditions (Estlander et al., 2008;Greenwood et al., 2003), and vice versa was true as a systematic review stated that patients experiencing chronic pain reported higher degrees of anger in comparison to controls (Sommer et al., 2019). This study provides new insight into anger as its association with CTS is never studied before.
Our study did not come with any limitations. The questionnaires of assessing psychological status cannot substitute clinical diagnosis by medical professionals. Having other factors such as work and education could also affect the results. Finally, a larger sample size could also help determine the differences between the groups, which was not feasible in our study.
In conclusion, this is the first study in Syria about CTS and its association with mental health. There was a strong association between psychological aspects of anger, anxiety, and depression and symptoms severity and functional status of CTS patients. Having CTS symptoms with normal NCS was associated with higher anxiety and depression score. These findings may suggest that being in the war with major distress such as COVID-19 might indirectly increase CTS symptoms. These findings emphasize the importance of psychological aspects when having hand pain or CTS symptoms. Further studies are needed to evaluate the association between anger and CTS symptoms.

FUNDING INFORMATION
We received no funding in any form.

CONFLICT OF INTEREST
The authors declare no conflict of interest.