Relationship Between Alexithymia, Cognitive Function and the Pain and Emotional Symptoms in Adolescent Migraine Patients
Article information
Abstract
Objective
Exploring the relationship between alexithymia, cognitive function and the pain and emotional symptoms in adolescent patients with migraines.
Methods
The Toronto Alexithymia Scale (TAS)-20 was used to evaluate adolescent patients with migraines. A total score of TAS-20 ≤51 scores was defined as no alexithymia, and the patients were divided into alexithymia group and no alexithymia group. Both groups of patients were evaluated using a visual analog scale (VAS), Hamilton Anxiety Scale, Hamilton Depression Scale, and Chinese version of the Neuropsychological State Test (Repeatable Battery for the Assessment of Neuropsychological Status [RBANS]). Emotional symptoms, cognitive function, pain levels, serum levels of serotonin (5-HT), matrix metalloproteinase (MMP)-9, and lysophosphatidic acid were compared in the two groups. Structural equation modeling (SEM) was constructed.
Results
There were significant differences in the severity of emotional symptoms, pain, anxiety, and depression, as well as cognitive function between the two groups (p<0.05). There was a significant difference in serum 5-HT and MMP-9 levels between the two groups (p<0.05). Alexithymia was negatively correlated with immediate memory, speech function, delayed memory, and RBANS total score. Cognitive function may have a partial mediating role in pain, anxiety, and depression in the constructed SEM.
Conclusion
Alexithymia was shown to have a close relationship with cognitive function, and the pain, anxiety, and depression among adolescent patients with migraines. Alexithymia might affect the pain, anxiety, and depression in adolescent patients with migraines through partial mediation of cognitive function as shown in the constructed SEM.
INTRODUCTION
Migraines, a psychosomatic disorder, are common complaints among patients seeking evaluation and treatment in neurology departments. Moreover, migraines have a high morbidity rate in low- and middle-income countries. The prevalence of migraines is on the rise among adolescents [1]. Indeed, migraines occur most often in Chinese adolescents between 10 and 14 years of age [2] and follow an upward trajectory with advancing age [3]. Approximately 50% of migraine patients have alexithymia [1,4]. Adolescent patients with migraines typically have cognitive impairment in multiple cognitive domains, such as the speed of information processing, attention, executive function, memory, and language, which has a significant impact on mental status [5-7].
Alexithymia is an emotional expression disorder that is characterized by an identification and emotional description inability, as well as fantasy and externally oriented thinking deficiencies [8]. Psychological dysfunction or logical reasoning difficulty often occurs in patients with migraines, which may be related to alexithymia [9,10]. It has been reported that alexithymia has a complex relationship with migraines, depression, and anxiety [11], while another study showed that alexithymia occurs independent of psychiatric co-morbidities, such as anxiety and depression, although alexithymia exacerbated peri-cranial and cervical muscle tenderness in patients with migraines [12]. Moreover, a study showed that alexithymia indirectly correlated with cognitive function and age among older adults [13].
Previous reports also find that alexithymia is significantly correlated with anxiety and depression [11,14]. Migraine is not directly connected with alexithymia apparently, but the presence of alexithymia was significant in migraine patients because of the co-existence of depression and anxiety [11].
To summarize, alexithymia and cognitive function may be closely associated with migraines, which affects clinical prognosis and the quality of life in migraine patients. Indeed, alexithymia and cognitive function in adult patients with migraine have been the focus of many studies [5-14], while comprehensive studies involving alexithymia and cognitive function in adolescents with migraines are limited. Therefore, the aim of the current study was to determine the relationship between alexithymia, pain, emotional symptoms, and cognitive function in adolescents of migraines.
METHODS
Patients of study
Two hundred fifty-four adolescent patients diagnosed with migraines at the hospital between October 2019 and October 2023 were screened upon approval by the Ethics Committee. The inclusion criteria were as follows: 1) all patients were diagnosed with migraines by neurologists according to the Chinese Migraine Prevention and Treatment Guidelines [3], 2) all patients had clear consciousness, and clear cognitive ability to communicate and answer questions normally, 3) this study was conducted based on patient agreement, voluntary participation, and signed informed consent form by the parents, and 4) <18 years of age. Demographic data including sex and age were collected. The information on migraine among these patients was collected. These data included age of onset, location of pain, nature, frequency, duration, presence or absence of aura, concomitant symptoms, inducing and mitigating factors, medication history, family history, etc. The patients were diagnosed of migraine were included.
The exclusion criteria were as follow: 1) patients with other primary and secondary headaches, 2) patients who were diagnosed with a severe psychiatric disorder such as schizophrenia, mental retardation and other serious mental diseases; the patients were scored with related psychology scales at the time of pre-enrollment and the history collection of diseases, 3) patients with a combination of diseases, including severe somatic and nervous systemic diseases, and 4) patients with incomplete data or incomplete scores.
This study was approved by the Institutional Ethical Review Board of Shijiazhuang People’s Hospital (Sciences-Ethical-Review No. [2022]-066). Written informed consent was obtained from the adolescents and their parents.
Group evaluation index
According to the Toronto Alexithymia Scale (TAS) in Chinese version [15], a patient is considered to have alexithymia at a total TAS-20 score ≥52. Alexithymia is not diagnosed at a total TAS-20 score ≤51. The included patients were evaluated by TAS-20 by two professional unified-trained psychological evaluators, then were divided into alexithymia and no alexithymia groups based on the TAS-20 results. Then, the patients were evaluated using visual analog scale (VAS), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Scale by two professional unified-trained psychological evaluators.
TAS-20
To assess the degree of alexithymia, 3 dimensions and 20 items were included (difficulty identifying feelings, difficulty describing feelings, and externally-oriented thinking). Higher scores indicate more severe alexithymia [15]. TAS was completed within 30 minutes for the evaluation of each patient. The Cronbach alpha of TAS-20 is 0.82.
VAS
To assess the severity of headache on a score of 0–10, a higher score indicates a higher level of pain [16]. VAS was completed within 1 minute for the evaluation of each patient instantaneously.
HAMA
To assess the severity of anxiety, 14 items are scored 0–4; a higher score indicates a higher level of anxiety [17]. HAMA was completed within 15 minutes for the evaluation of each patient. A total score of HAMA ≤7 was classified as no anxiety symptoms, a total score of 8–20 was classified as mild to moderate anxiety symptoms, and a total score of ≥21 was classified as severe anxiety symptoms.
HAMD
To assess the degree of depression, 17 items are scored 0–4; a higher score indicates a higher level of depression [18]. HAMD was completed within 15 minutes for the evaluation of each patient. HAMD score ≤7 is classified as no depressive symptoms, score 8–23 is classified as mild to moderate depressive symptoms, and score ≥24 is classified as severe depressive symptoms.
RBANS scale
To assess cognitive function, a total of 12 items and 5 factors were included (immediate memory, visual breadth, speech function, attention function, and delayed memory) [18]. The higher score indicates better cognitive function. RBANS was completed within 30 minutes for the evaluation of each patient.
Laboratory testing
Five mL of fasting venous blood was drawn from the patients and centrifuged at 3,000 r/minutes. The serum was isolated within 30 minutes. Then, the serum levels of 5-hydroxytryptamine (5-HT), matrix metalloproteinase (MMP)-9, and lysophosphatidic acid (LPA) were determined with an enzyme linked immunosorbent assay (Nanjing Jiancheng Bioengineering Institute) according to the kit instruction.
Quality control
All the steps, including the design and implementation of the project, questionnaire collection, and data analysis, were under the professional guidance of expert members of the Institutional Ethical Review Board and strict quality control. All investigators underwent professional training and consistency assessment. The test results were input into a computer and managed, examined, and analyzed by the same study member of the author group. An additional support personnel was responsible for the review and verification of the data.
Structural equation modeling
Structural equation modeling (SEM) was adopted to examine the adaptability of the model and analyze the intermediary effect of the quality and quantity through the path between the latent variables. The main information that SEM statistics can give us is the size of the effect, which can be divided into direct, indirect, and total effects. For the standardized path coefficient, its absolute value is less than 0.10 is a small effect, its absolute value is about 0.30 is a medium effect, and its absolute value is more than 0.50 is a large effect (Figure 1).
The intermediary effect model of the cognitive function in alexithymia, pain, anxiety, and depressive symptoms. Through multiple model adjustments, cognitive function is regarded as the intermediary factor between alexithymia, pain, anxiety and depression, which further aggravates the influence of alexithymia on pain, anxiety and depression in adolescent migraine patients. Cognitive function partially mediates alexithymia, depressive symptoms, anxiety symptoms, and pain symptoms. **all the mediating pathways of cognitive function were significant, suggesting the existence of mediating effects.
Statistical methods
Statistical analysis, calculation, and description of relevant data was performed using SPSS 24.0 statistical software (IBM Corp.). Measurement data are expressed as mean differences±standard deviation. For the inter-group comparison, a t-test was used. A χ2 test was used to evaluate the inter-group measurement data. Pearson correlation analysis was used to determine the correlation between variables. SEM was adopted to examine the adaptability of the model and analyze the intermediary effect of the quality and quantity through the path between the latent variables. There was statistical significance at a p<0.05.
RESULTS
A total of 118 patients were included in the alexithymia group with 52 males and 66 females, 9–17 years of age. The mean age was 15.23±1.90 years. A total of 136 patients were included in the no alexithymia group with 54 males and 82 females 10–18 years of age. The mean age was 15.66±2.00 years. No significant difference was detected in the age and sex between the groups (p>0.05).
Comparison of alexithymia, pain, and emotional symptoms between the groups
The results of the comparisons between alexithymia, pain, and emotional symptoms are shown in Table 1. The alexithymia, pain, depressive, and anxious symptom scores in the no alexithymia group were significantly lower than the alexithymia group (p<0.001).
Comparisons of alexithymia, pain, and emotional symptoms between the groups
Comparison of cognitive function between the groups
Based on the comparison of the groups, the immediate memory, visual breadth, speech function, and delayed memory on RBANS scales were significantly lower in the alexithymia and no alexithymia groups (p<0.05) (Table 2).
Comparison of cognitive function between the groups
Comparison of 5-HT, MMP-9, and LPA levels between groups
The significant difference was found on the level of 5-HT and MMP-9 between the groups (p<0.05) (Table 3). No statistical difference was found on LPA between the groups (p=0.121).
Comparison of the 5-HT, MMP-9, and LPA levels between groups
Correlation analysis of pain, emotional symptoms, and cognitive function among adolescent migraine patients in the alexithymia group
The correlation analysis showed that alexithymia was negatively correlated with immediate memory, speech function, delayed memory, and the total RBANS score. The pain was negatively correlated with immediate memory, speech function, attention, delayed memory, and the total RBANS score. Anxiety and depression were negatively correlated with different dimensions of RBANS and the total test scores (Table 4).
Correlation analysis of pain, emotional symptoms, and cognitive function
Intermediary effect analysis of cognitive function in adolescent migraine patients
Based on the results of correlation analysis, a SEM was built based on alexithymia as the independent variable, cognitive function as the intermediary variable, and pain, anxiety, and depression as dependent variables. After continuous adjustment, the Goodness of Fit Index, Comparative Fit Index, and Non-Normal Fit Index were >0.9 and the Root Mean Square Error of Approximation was <0.1, the results of the fit index were acceptable, indicating that the model had proper fit results (Table 5). For the SEM, Figure 1 shows that all intermediary pathways of cognitive function were significant, indicating the intermediary effect. The cognitive function may have had a partial mediating role between the alexithymia and the pain, anxiety, and depressive symptoms in the participants in the SEM, and the indirect effect is moderate. The predictive effect of alexithymia on the consequence variables (pain, anxiety, and depressive symptoms) in the SEM was shown in Table 6.
The fit index of the intermediary effect model of cognitive function in adolescent migraine patients
Prediction effect of alexithymia on the consequence variables
DISCUSSION
In this study adolescents with migraines and alexithymia had more severe symptoms of pain, anxiety, and depression, poorer cognitive function, and more abnormal 5-HT and MMP-9 levels than adolescents with migraines but without alexithymia. The correlative analysis results suggested that alexithymia, pain, anxiety, and depression had a significant negative correlation with cognitive function. The intermediary effect analysis showed that cognitive function may have a partial mediating role in alexithymia, depression symptoms, anxiety, and pain in the constructed SEM.
Alexithymia is a type of negative emotional experience that widely occurs in psychosomatic diseases, leaving a large negative impact on psychosomatic health and the daily life adaptations of individuals [8-10]. Previous findings have suggested that patients with migraines have cognitive function disorders [5-7], possibly combined with alexithymia [19] and anxious and depressive symptoms [20]. A review of the literature revealed that the degree of alexithymia in children and adolescents with migraines was higher than the control group [21]. Based on the study by Pakalnis et al. [22], emotional symptoms commonly exist in adolescent migraine patients. In this study the level of pain, anxiety, and depression in adolescent migraine patients was shown to be significantly higher in alexithymia group than the no alexithymia group, which is in agreement with past findings [9,10,21,22]. Adolescents’ migraine patient in the alexithymia group had difficulties in identification and expression of self-emotion and -feeling, which caused a battery of emotional problems, including depression and anxiety [5-7,9,10]. The patients with alexithymia had deficits in emotional cognitive processing and regulation [23], which also facilitated the transformation of negative emotional responses and symptoms into somatic symptoms, further deteriorating the negative experience of patient pain and decreasing pain tolerance. The current study identifies a 28% reduction in serum serotonin levels in alexithymic migraine adolescents, suggesting serotonergic dysregulation’s role in migraine pathophysiology. The reduction in serum serotonin could exacerbate both nociceptive signaling and affective responses via the trigeminovascular and limbic-pain pathways [24]. Therefore, the patients may have experienced more feelings of pain.
Cognitive function disorder has become an increasing concern as a critical issue in migraineurs. It has been shown that migraines lead to a decrease in cognitive function, as revealed in a number of fields, including execution function, visual breadth, attention, and language [5-7]. All of these factors are attributed to cognitive function symptoms as the second leading cause of migraines [25]. The immediate memory, visual breadth, speech function, delayed memory, and total scores of testing on RBANS were significantly lower in the alexithymia group than the no alexithymia group. These results indicate that more severe damage may occur on cognitive function in the alexithymia group of migraine adolescent patients, including attention, memory, speech, reaction, and execution. The possible reason for this finding might be the inaccurate description and expression of self-emotion in individuals with alexithymia. The adolescents with alexithymia have less control on self-thinking and are more vulnerable to interference from the outside world that may occur during the process of thinking, which may lead to a decrease of self-expression and communication with others [26]. This finding also has an impact on cognitive function, including memory, understanding, and judgment [26]. Therefore, an effective response and management on negative emotion is difficult.
Previous studies concluded that degenerative changes in neurologic function accelerate in individuals with long-term, high level alexithymia [27], which causes cognitive degeneration, such as memory degeneration. There is no correlation between the changes in cognitive function and the level of 5-HT and MMP-9 [28,29]. In this study, we found that the level of 5-HT was significantly lower in the alexithymia group than in no alexithymia group. As an inhibitory neurotransmitter, 5-HT widely presents within the cerebral cortex and neural synapses. The decrease in plasma 5-HT level suggests that 5-HT is not only involved in the reaction process of the cognitive function impairment, but also easily induces the negative emotion, including anxiety and depression [30]. The level of plasma MMP-9 was significantly higher in the alexithymia group than the no alexithymia group, indicating the elevated MMP-9 may cause a decrease in cognitive ability through the modulation extracellular matrix degradation and vascular permeability [31]. These findings further support impairment of cognitive function in adolescent migraine patients with alexithymia may be related to more anxiety and depressive emotions in patients.
In this study, the structural equation was established on the basis of relevant studies and the intermediary effect was analyzed. The SEM results showed that alexithymia may have some impacts on the levels of pain, anxiety, and depression in adolescent migraine patients through the partial role of mediation on cognitive function. The patients with severe migraine focus on external outcomes rather than descriptions [10]. Aaron et al. [32] reported that alexithymia is associated with a high level of pain intensity, physical interference, depression, and anxiety. Somatization and catastrophization of pain might be the mediating factors between alexithymia and headache [32]. But this research indicated the possible mediation effect of cognitive function in the SEM between alexithymia and pain, and mental status for adolescent migraine patients.
According to our investigation, adolescent migraine patients had restricted emotional expression behavior owing to the effect of alexithymia, which may cause interference on the physiologic level and nervous system given long-term accumulation of anxiety and depression in the body. A series of psychosomatic problems, such as cognitive function impairment, anxiety, depression, and pain will occur. Self-cognition and evaluation ability may decrease combined with catastrophic cognitive behavioral patterns when cognitive function is impaired in adolescent migraine patients. This finding may result in an increased possibility of negative emotional experience, including anxious and depressive emotion, thus reducing tolerance to pain, generating a large negative impact on patient acceptance on the level of disease and quality of life. Therefore, the attentions should be paid on alleviation of pain symptoms and psychological problems in adolescent migraine patients, as well as alexithymia and cognitive function.
There were three limitations in this study: First, this was a single-center study with a small sample size that may bring potential sample bias, as higher mean Multiple Intelligences Developmental Assessment Scales scores suggest an overrepresentation of severe cases. This limitation may limit the generalizability of this study. Second, this was a cross-sectional study, the data mainly relied on patient retrospective self-reports, and the longitudinal neuroimaging data was lacking. This may lead to the bias in the results. Third, this study focused on an analysis of the correlation with no intervention in adolescent migraine patients. Corollary studies on the intervention and analysis of the intervention methods are warranted in the future to effectively improve patient clinical symptoms. In the future, the researchers should expand the sample size and adopt multi-center, longitudinal studies to improve the generalization of the findings.
In conclusion, alexithymia in adolescent migraine patients correlates with their perception of pain symptoms, the risks of anxiety and depression, and possible damages to cognitive function. In the SEM constructed in this study, the cognitive function acts as a mediating factor between alexithymia and the pain, anxiety, and depression in the adolescent migraine patients. Based on the results, we suggest utilizing TAS-20 scores ≥61 to identify at-risk patients might improve both cognitive and emotional patient outcomes. Additionally, incorporating cognitive-behavioral therapy with metacognitive training could enhance management strategies for migraineurs with alexithymia. Reviewing treatment options like Selective Serotonin Reuptake Inhibitors or serotonin precursors may offer therapeutic benefits by addressing both pain modulation and emotional dysregulation.
Notes
Availability of Data and Material
The original contributions presented in the study are included in the article/ supplementary material, further inquiries can be directed to the corresponding author/s.
Conflicts of Interest
The authors have no potential conflicts of interest to disclose.
Author Contributions
Conceptualization: Ming Liu, Hui Wang. Data curation: Yanmin Wu, Hui Wang. Formal Analysis: Ci Ge, Shuang Tian. Funding acquisition: Ming Liu. Supervision: Ming Liu. Visualization: Yanmin Wu, Shuang Tian. Writing—original draft: Ming Liu, Ci Ge, Hui Wang. Writing—review & editing: Ming Liu, Yanmin Wu, Shuang Tian.
Funding Statement
The study was supported by Shijiazhuang Science and Technology Research and Development Self-funded Project (No. 221200743).
Acknowledgments
None