Investigation of Anxiety and Depression in Female Patients with Fibromyalgia on MR Images: A cross-sectional cohort study

Investigation of Anxiety and Depression in Female Patients with Fibromyalgia on MR Images: A cross-sectional cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Investigation of Anxiety and Depression in Female Patients with Fibromyalgia on MR Images: A cross-sectional cohort study Fatih ÇİÇEK, Ahmet PAYAS, Turgut SEBER, Fatma Gül Ülkü DEMİR, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5859495/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background High rates of depression and anxiety have been reported in patients with fibromiyalgia (FM). Therefore, the aim of our study was to determine the volume of the amygdala, medial frontal cortex, limbic system and hippocampus in participants with anxiety and depression and to compare the fibromyalgia and control groups by determining the afferent and efferent fibers of the amygdala, which play an important role in anxiety and depression, which will be the first in the literature. Methods Only female subjects, 30 with fibromyalgia and 30 controls, were included in this study. Visual analog scale was used for pain sensation, BECK depression inventory, Hospital anxiety and depression scale were used for anxiety and depression. From brain diffusion MR images, tractography of the targeted pathway was calculated in DSI Studio software and the volume of targeted structures was calculated in VolBrain software program. Results The total volume of the medial frontal cortex, amygdala, limbic cortex and hippocampus was found to be statistically significant higher in the control group than in the fibromyalgia group (p < 0.05). It was also found statistically significant (p < 0.05) that the total number of fibers on the right side of the amygdala was higher in the patient group (13710.60 ± 4926.09) than in the control group (13099.14 ± 3677.12), but the number of fibers on the left side was higher in the control group (4057.37 ± 1388.57) than in the patient group (3552.70 ± 1493.35). Conclusions It is observed that depression and anxiety in fibromyalgia patients affect both white matter and gray matter volume in the central nervous system. Therefore, we believe that treatments on the central nervous system may be more effective in the treatment of anxiety and depression disorders in patients with fibromyalgia. Anxiety Amygdala Depression Fibromyalgia Medial frontal cortex Figures Figure 1 Figure 2 Introduction Fibromyalgia (FM) is a rheumatic syndrome of unknown etiology characterized by chronic widespread body pain, fatigue, sleep disturbance, tender points and poor quality of life [ 1 – 3 ]. According to the American College of Rheumatology (ACR) criteria, it is defined as the presence of widespread pain lasting at least 3 months, as well as the presence of tenderness in at least 11 of the 18 points called tender points that cause pain with finger palpation. Fibromyalgia is the most common rheumatologic disease after osteoarthritis and mainly affects women between the ages of 40 and 55 [ 1 ]. The prevalence in the general population in highly industrialized countries varies between 1% and 4%. Fibromyalgia is consistently associated with other functional syndromes. The disease can occur alone or in association with other syndromes such as chronic headache, thyroid dysfunction, irritable colon syndrome, depression and anxiety [ 1 , 2 , 4 ]. The presence of chronic pain increases the risk of comorbid psychiatric disorders such as anxiety and depressive disorders [ 5 ]. This increases the frequency of anxious and depressive symptoms in the population. Studies show a close relationship between fibromyalgia and anxiety and depression [ 6 – 8 ], with one third of patients reporting this [ 6 ]. A study in the literature revealed a high prevalence of depression (89%) and anxiety (41%) in patients with FM [ 9 ]. In another study, it was reported that the prevalence of depression was 20%-80% and the prevalence of anxiety was 13%-63% [ 10 ]. Major depressive disorder, generalized anxiety disorder and social anxiety disorder are among the most common and most frequently comorbid psychiatric disorders in adults [ 11 ]. Estimates of depression and anxiety comorbidity range from 10% to over 50% [ 12 ]. Therefore, it has been suggested that depression and anxiety have a similar etiology and respond to the same treatment strategies [ 13 ]. A number of neuroimaging studies on depression and anxiety in humans have shown altered gray matter volumes in structures related to hypothalamic-pituitary-adrenal axis function, emotion perception and regulation, namely the hippocampus, amygdala, striatum, medial prefrontal cortex and anterior cingulate gyrus [ 14 – 20 ]. Many studies in the literature have reported a decrease in the volume of these structures [ 21 ], but the findings are not completely consistent [ 15 , 19 , 22 , 23 ]. Therefore, the aim of our study was to determine the volume of the amygdala, medial frontal cortex, limbic system and hippocampus in participants with anxiety and depression levels and to compare fibromyalgia and control groups by determining the afferent and efferent fibers of the amygdala, which play an important role in anxiety and depression, which will be the first in the literature. Methods This study is a single-center, randomized controlled, prospective and cross-sectional cohort study conducted in the Physical Therapy and Rehabilitation Department of Kayseri City Hospital in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from each patient and/or legal guardian while obtaining the images to be used in the study. In addition, approval for this study was obtained from Niğde Ömer Halisdemir University Non-Interventional Clinical Research Ethics Committee with protocol number 2025/3. Determination of Sample Size and Study Groups In order to determine the sample size of this study, it was calculated that at least 26 individuals with fibromyalgia and at least 26 individuals in the control group would be included in the study, with an effect size of 0.80, 90% power and 5% Type I error. This calculation was made with the G*power 3.1.9.6 program. In this context, a total of 62 individuals, 31 fibromyalgia patients and 31 control group individuals, belonging to individuals whose MR images were taken between November 2023 and December 2023, were included in this study. The inclusion and exclusion criteria for this study are shown in Table 1 (Table 1 ). Since the incidence of fibromyalgia is significantly higher in favor of the female gender and in order to create optimum homogenization, only female cases were included in both the patient and control groups, and the mean age of the individuals participating in the study was 45.29 (Age range: 18–85). Table 1. Inclusion and exclusion criteria for individuals participating in the study BECK Depression Inventory (BDI) The BDI is a widely used 21-item self-report inventory that measures the severity of depression in adolescents and adults. Individuals are asked to answer each question over a two-week time period. The BDI is widely used as an indicator of the severity of depression, but not as a diagnostic tool, and numerous studies provide evidence for its reliability and validity across different populations and cultural groups. It has also been used in numerous treatment outcome studies and in numerous studies with trauma-exposed individuals [ 24 ]. Hospital Anxiety and Depression Scale (HADS) In the hospital anxiety and depression scale, patients complete a 7-item questionnaire consisting of statements about general anxiety or 'depression'. In this questionnaire, 'depression' is assessed according to the following questions: “Are you as interested in things as you used to be? Do you laugh as easily as you used to? Do you feel cheerful? Do you feel optimistic about the future?”. The level of ‘anxiety’ was assessed by the following questions: “Do you feel tense and nervous? Do you worry a lot? Do you have panic attacks? Do you feel that something scary is about to happen?”. The questionnaire analyzes the responses in the light of the results of this estimation of the severity of both anxiety and depression. Each item was answered by the patient on a four-point (0–3) response category, so possible scores range from 0 to 21 for anxiety and 0 to 21 for depression. It makes it possible to provide information for both subscales that a score between 0 and 7 can be considered within the normal range, a score of 11 or higher indicates the possible presence of a mood disorder ('being a case'), and a score between 8 and 10 only implies the presence of the relevant condition [ 25 ]. Radiological Evaluation Tractography Analysis Tractography of the targeted pathway from brain diffusion MR images was performed in the DSI Studio program downloaded from http://dsi-studio.labsolver.org/ . Before starting the tractography process, in the “Fiber tracking” tab; “Threshold” was set to 0.20, “Angular Threshold” was set to 70 degrees, “Smoothing” was set to 0.50, the shortest tract was set to 10 mm, the longest tract was set to 1000 mm, and “terminateif” was set to 100000 fibers. These parameters were adjusted again before starting tractography in each new image. In our study, afferent and efferent pathways of the amygdala were specifically analyzed. Total fiber counts of these pathways were calculated in the tractography process [ 26 ] (Fig. 1 ). Processing of images Medial Frontal Cortex, Amygdala, Limbic Cortex and Hippocampus Volume Calculation : To calculate the volume of the Medial Frontal Cortex, Amygdala, Limbic Cortex and Hippocampus from MR images of individuals with FM, T1 images in DICOM format were used to perform calculations on the cloud-based software “ https://volbrain.upv.es (volBrain: Automated MRI Brain Volumetry System)”. Before uploading the data to the site, the DICOM format T1 images of individuals with FM are converted to “niftii” format using the “dcm2niigui” conversion program. These files are then converted to “.zip” format using WinZip, a compression program. To use the Volbrain software, you must first register and log in to the site. After logging in to the Volbrain website, the “CERES1.0” tab is selected and the age and gender information of the individual is entered. After these procedures, it is uploaded to the specified area, converted to “.zip” format and sent to the server that creates the software. The images uploaded to the server give results in “pdf” format after the server performs some operations and calculates the volume within a certain time frame. The results are then retrieved and analyzed [ 27 ]. Statistical Analysis The Shapiro Wilk test was used to determine whether the variables were normally distributed and the measured parameters were found to be normally distributed. Numerical variables were summarized as Mean ± S.Deviation and Min-Max. Independent t-test was used for two group comparisons. Pearson correlation was used to examine the relationship between numerical variables. Statistical analyses were performed with IBM SPSS version 22 (SPSS, Inc., Chicago, IL, USA). p < 0.05 was accepted as the level of statistical significance. Results Table 2 shows the comparison of the measured parameters between fibromyalgia and control groups. According to Table 2 , there is no statistically significant difference between the two groups in terms of age and Body mass index (BMI) (kg/m2) (p = 0.280; p = 0.100). This situation supports that the individuals participating in this study were homogeneously distributed with gender. When Visual anologous scale (VAS), BECK depression ınventory, Hospital anxiety scale (HAAS) and Hospital depression scale (HDS) were compared between the two groups, it was found statistically significant that these scales were higher on average in the patient group than in the control group (p < 0.001) (Table 2 ). In this regard, the number of afferent and efferent fibers of the right-sided amygdala (TAmygdala(R)) was higher in the patient group (13710.60 ± 4926.09) than in the control group (13099.14 ± 3677.12), which was statistically significant (p = 0.044). However, it was found to be statistically significant that the number of afferent and efferent fibers of the left side amygdala (TAmygdala(L)) was higher in the control group than in the patient group (p = 0.027) (Table 2 ). In addition, when medial frontal cortex volume (MFC(V)), total Amygdala volume (Amygdala(V)), total Limbic cortex volume (LC(V)) and total Hippocampus volume (Hippocampus(V)) were compared between the two groups, it was found to be statistically significant that it was higher in the control group than in the patient group (p = 0.033; p = 0.041; p = 0.047; p = 0.019) (Table 2 ). As in the number of afferent and efferent fibers, the right side amygdala volume (Amygdala(V)(R)) was found to be statistically significantly higher in the patient group (1.02 ± 0.10) than in the control group (1.00 ± 0.10) (p = 0.036) (Table 2 ). However, when the left side amygdala volume (Amygdala(V)(L)) was compared between both groups, there was no statistically significant difference (p = 0.824) (Table 2 ). Table 2 Comparison of measured parameters between FM and control group Parameters Participants with FM (N = 30) Control Group (N = 30) p Mean ± SD Mean ± SD Age (Years) 46.80 ± 8.01 44.30 ± 9.67 0.280 BMI (kg/m 2 ) 28.23 ± 3.99 26.47 ± 4.13 0.100 VAS 7.26 ± 2.25 3.70 ± 2.87 < 0 . 001 BECK 18.06 ± 8.26 8.36 ± 6.27 < 0 . 001 HAS 11.10 ± 4.02 5.46 ± 3.30 < 0 . 001 HDS 7.93 ± 3.25 5.46 ± 3.30 < 0 . 001 TAmygdala (R) 13710.60 ± 4926.09 13099.14 ± 3677.12 0.044 TAmygdala (L) 3552.70 ± 1493.35 4057.37 ± 1388.57 0.027 MFC (V) 2.96 ± 0.47 3.15 ± 0.11 0.033 MFC (V) (R) 1.61 ± 0.44 1.53 ± 0.31 0.410 MFC (V) (L) 1.54 ± 0.50 1.43 ± 0.27 0.295 Amygdala (V) 1.98 ± 0.22 2.00 ± 0.19 0.041 Amygdala (V) (R) 1.02 ± 0.10 1.00 ± 0.10 0.036 Amygdala (V) (L) 0.98 ± 0.13 0.99 ± 0.10 0.824 LC (V) 38.24 ± 7.48 39.28 ± 4.16 0.047 LC (V) (R) 19.17 ± 1.86 19.47 ± 2.10 0.562 LC (V) (L) 20.04 ± 2.23 19.70 ± 2.30 0.564 Hippocampus (V) 5.67 ± 0.68 5.71 ± 0.74 0.019 Hippocampus (V) (R) 2.75 ± 0.32 2.74 ± 0.33 0.956 Hippocampus(V) (L) 2.98 ± 0.32 2.95 ± 0.41 0.779 BMI(kg/m2) : Body mass index; VAS : Visual analog scale; BECK : BECK Depression Inventory; HAS : Hospital anxiety scale; HDS : Hospital depression scale; TAmygdala (R) : Number of amygdala fibers on the right side; TAmygdala (L) : Number of amygdala fibers on the left side; MFC (V) : Medial frontal cortex volume (mm 3 ); MFC (V) (R) : Right side medial frontal cortex volume (mm 3 ); MFC (V) (L) : Left side medial frontal cortex volume (mm 3 ); Amygdala (V) : Total amygdala volume (mm 3 ); Amygdala (V) (R) : Right side amygdala volume (mm 3 ); Amygdala (V) (L) : Left side amygdala volume (mm 3 ); LC (V) : Total limbic cortex volume (mm 3 ); LC (V) (R) : Right side limbic cortex volume (mm 3 ); LC (V) (L) : Left side limbic cortex volume (mm 3 ); Hippocampus (V) : Total hippocampus volume (mm 3 ); Hippocampus (V) (R) : Right side hippocampus volume (mm 3 ); Hippocampus(V) (L) : Left side hippocampus volume (mm 3 ) In Table 3 , the correlation between the scales used in the study and the parameters measured in the FM group is analysed. Accordingly, when Table 3 is analysed, it is seen that there is a positive linear relationship between VAS, BECK, HAS and HDS and TAmygdala(R) (p = 0.046; p = 0.044; p = 0.026; p = 0.038) (Table 3 ). However, it was determined that there was no significant relationship between these scales and other measured parameters (p > 0.05) (Table 3 ). Table 3 Correlation results of the parameters measured with the scales used in the FM group Parameters TAmygdala (R) TAmygdala (L) MFC (V) Amygdala (V) Amygdala (V)(R) Amygdala (V)(L) LC (V) Hippocampus (V) HAS r 0.105 -0.162 -0.204 0.030 0.050 0.001 0.143 0.017 p 0.038 0.394 0.280 0.876 0.795 0.996 0.451 0.927 N 30 30 30 30 30 30 30 30 HDS r 0.406 * -0.074 -0.092 0.116 0.097 0.112 -0.360 -0.158 p 0.026 0.699 0.628 0.540 0.611 0.554 0.051 0.405 N 30 30 30 30 30 30 30 30 BECK r 0.370 * -0.328 -0.272 0.184 0.095 0.255 0.029 0.185 p 0.044 0.077 0.146 0.331 0.617 0.174 0.879 0.327 N 30 30 30 30 30 30 30 30 VAS r 0.007 -0.251 -0.237 -0.007 -0.055 0.031 -0.164 -0.188 p 0.046 0.181 0.207 0.972 0.773 0.870 0.387 0.319 N 30 30 30 30 30 30 30 30 BMI(kg/m2) : Body mass index; VAS : Visual analog scale; BECK : BECK Depression Inventory; HAS : Hospital anxiety scale; HDS : Hospital depression scale; TAmygdala (R) : Number of amygdala fibers on the right side; TAmygdala (L) : Number of amygdala fibers on the left side; MFC (V) : Medial frontal cortex volume (mm 3 ); MFC (V) (R) : Right side medial frontal cortex volume (mm 3 ); MFC (V) (L) : Left side medial frontal cortex volume (mm 3 ); Amygdala (V) : Total amygdala volume (mm 3 ); Amygdala (V) (R) : Right side amygdala volume (mm 3 ); Amygdala (V) (L) : Left side amygdala volume (mm 3 ); LC (V) : Total limbic cortex volume (mm 3 ); LC (V) (R) : Right side limbic cortex volume (mm 3 ); LC (V) (L) : Left side limbic cortex volume (mm 3 ); Hippocampus (V) : Total hippocampus volume (mm 3 ); Hippocampus (V) (R) : Right side hippocampus volume (mm 3 ); Hippocampus(V) (L) : Left side hippocampus volume (mm 3 ) Discussion In this study, the volume of the amygdala, medial frontal cortex, limbic system and hippocampus, which are the centres of these senses in the central nervous system, were evaluated between individuals with FM and healthy control group in order to examine the mechanism of symptoms related to depression and anxiety disorders in individuals with FM. In addition, afferent and efferent fiber counts of the amygdala, which has an important function directly in the perception and regulation of pain and mood disorders, were examined for the first time between FM and control groups in this study. In both groups, VAS was used for pain sensation and BECK, HAS and HDS scales were used to evaluate anxiety and depression sensations. The data obtained showed that individuals with FM had more pain, depression and anxiety moods (p < 0.001). Izuno et al. in a study with 34 FM (age 41.6 ± 7.4) and 25 control groups (age 39.5 ± 7.4) found a statistically significant difference when they compared both groups in terms of HAS and HDS (p < 0.001). They also analysed the white matter volume of the temporal lobe between both groups and found that the temporal lobe white matter volume of the FM group was higher than the control group (p = 0.021). When they examined the correlation between the bilateral grey matter volume of the amygdala due to depression and anxiety disorder in the FM group, it was found that the amygdala had a negative correlation with the grey matter volume (p < 0.05) [ 29 ]. In our study, when the HAS and HDS scales were compared between the FM and control groups, it was found statistically significant that the FM group had a worse emotional state (p < 0.001). In addition, in our study, it was found statistically significant that Amygdala (V), MFC (V), LC (V) and Hippocampus (V) volumes were higher in the control group than in the FM group (p < 0.05). This supports the study conducted by Izuno et al. In the literature, it has been stated that asymmetry occurs in the amygdala depending on the emotional state [ 30 – 32 ]. In this regard, it has been reported that the left amygdala hemisphere is dominant for processing positive emotions, while the right amygdala hemisphere is dominant for processing pain and negative emotions [ 28 , 31 ] (Fig. 2 ). In line with this information, it was found to be statistically significant that the number of afferent and efferent fibers of the right side amygdala was higher in the FM group compared to the left side (p < 0.05) (Table 2 ). In addition, as seen in Table 3 , there was a positive correlation between the VAS, BECK, HAS and HDS scales and the total number of afferent and efferent fibers of the right side amygdala (p < 0.05) (Table 3 ). In addition, it was found to be statistically significant that the volume of the right amygdala was higher in the FM group compared to the left side (p < 0.05) (Table 2 ). This supports the study of Izuno et al. and that the right amygdala is responsible for pain and negative mood disorders. Burgmer et al. found statistically significant (p < 0.05) that the volume of the prefrontal cortex was less in the FM group compared to the control group in their study conducted with 3T MRI on 14 FM and 14 healthy control groups [ 33 ]. In our study, it was determined that the medial frontal cortex volume was less in the FM group compared to the control group (p < 0.05) (Table 2 ). In a study conducted by McCrae et al. among 40 FM and 22 control groups, it was found to be statistically significant that the right and left hippocampus volumes were less in the FM group than in the healthy group (p < 0.05). However, it was reported that this was not associated with anxiety and depression [ 34 ]. Similarly, Murillo-Garcia et al. conducted a study with 47 FM and 43 healthy control groups and found that the FM group had less hippocampus volume than the control group [ 35 ]. In our study, when the two groups were compared in terms of total hippocampus volume, it was determined that the FM group had less hippocampus volume than the control group (p 0.05) (Table 3 ). Conclusion In this study, the relationship between anxiety and depression mood disorders occurring in individuals with FM and the central nervous system was investigated. In addition, afferent and efferent fiber numbers of the amygdala were examined by tractography method, which is the first in the literature related to this mood disorder. As a result, it is seen that depression and anxiety in FM patients affect both white matter and grey matter volume in the central nervous system. Therefore, we believe that treatments on the central nervous system may be more effective in the treatment of anxiety and depression disorders occurring in patients with FM. In addition, different centres and structures related to anxiety and depression should be examined by tractography method in order to investigate whether there is a relationship between these mood disorders. Declarations Ethics approval and consent to participate The study was granted approval by the Ethics Committee of Niğde Ömer Halisdemir University (Protocol number: 2025/3). Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no confict of interest. Authors' contributions All authors contributed to the study conception. FÇ, AP, TS, FGÜD carried out data collection and contributed to study design. Statistical analysis and data interpretation was performed by ATÇ, SSD. The frst draft of the manuscript was written by FÇ and İU. 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Phelps EA, LeDoux JE. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron. 2005;48(2):175–87. https://doi.org/10.1016/j.neuron.2005.09.025 . Burgmer M, Gaubitz M, Konrad C, Wrenger M, Hilgart S, Heuft G, et al. Decreased gray matter volumes in the cingulo-frontal cortex and the amygdala in patients with fibromyalgia. Psychosom Med. 2009;71(5). https://doi.org/10.1097/PSY.0b013e3181a32da0 . 566 – 73. McCrae CS, O’Shea AM, Boissoneault J, Vatthauer KE, Robinson ME, Staud R, et al. Fibromyalgia patients have reduced hippocampal volume compared with healthy controls. J pain Res. 2015;47–52. https://doi.org/10.2147/JPR.S71959 . Murillo-Garcia A, Leon-Llamas JL, Villafaina S, Gusi N. Fibromyalgia impact in the prefrontal cortex subfields: An assessment with MRI. Clin Neurol Neurosurg. 2022;219:107344. https://doi.org/10.1016/j.clineuro.2022.107344 . 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5859495","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":405160388,"identity":"00498f71-8691-4ea5-9e61-30ac9a9aa316","order_by":0,"name":"Fatih ÇİÇEK","email":"","orcid":"","institution":"Niğde Ömer Halisdemir University: Nigde Omer Halisdemir Universitesi","correspondingAuthor":false,"prefix":"","firstName":"Fatih","middleName":"","lastName":"ÇİÇEK","suffix":""},{"id":405160389,"identity":"0a59f030-12e3-4314-9ff3-dd455e10e6a0","order_by":1,"name":"Ahmet PAYAS","email":"","orcid":"","institution":"Amasya University: Amasya Universitesi","correspondingAuthor":false,"prefix":"","firstName":"Ahmet","middleName":"","lastName":"PAYAS","suffix":""},{"id":405160391,"identity":"905fea64-fb4a-4310-86a6-98b3bda229ea","order_by":2,"name":"Turgut SEBER","email":"","orcid":"","institution":"Kayseri City Hospital: Kayseri Sehir Egitim ve Arastirma Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"Turgut","middleName":"","lastName":"SEBER","suffix":""},{"id":405160393,"identity":"2bd20abc-2280-43f3-8a58-bd9faac22037","order_by":3,"name":"Fatma Gül Ülkü DEMİR","email":"","orcid":"","institution":"Kayseri City Hospital: Kayseri Sehir Egitim ve Arastirma Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"Fatma","middleName":"Gül Ülkü","lastName":"DEMİR","suffix":""},{"id":405160394,"identity":"0f178f30-b6a7-4628-93f0-0d2a539aa980","order_by":4,"name":"Selman SOLGUN DAĞ","email":"","orcid":"","institution":"İnönü Üniversitesi Tıp Fakültesi: Inonu Universitesi Tip fakultesi","correspondingAuthor":false,"prefix":"","firstName":"Selman","middleName":"SOLGUN","lastName":"DAĞ","suffix":""},{"id":405160396,"identity":"0fde84a0-2e71-4c5f-bf70-d6b89289f6c3","order_by":5,"name":"İlyas UÇAR","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYBACNnY4k/kAkJCAsHnwaWFGMBNQtEjg1IPQwmOAEMWnhY+Zx/DjD4bD8vyzz3x8XFFjkdjPf4Dxwds2hjrzBlwO4zGW5mE4bDjjXO5mwzPHJBJnzkhgNpzbxiAhcwCnFgNpBobDCQxneLdJNjZIJG64wcAmzQvUgstlIFt+Ah2WIH+G5/lPkJb95w+w/yagxUwC6LAEgzM8bIxgWxgS2Jjxa2Ers+YxSDfceIbNWLLhmITxjBuJzZJzzklIzsChRb69efPNHxXW8nJnmB9+bKipk+3vP3zww5syG37cEcMBjA6kGHFsYGBsYMAXkwwM7A9QuPZ4lI6CUTAKRsEIBQCcw0xLSOmk0gAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-3646-5320","institution":"Erciyes Universitesi Tip Fakultesi","correspondingAuthor":true,"prefix":"","firstName":"İlyas","middleName":"","lastName":"UÇAR","suffix":""},{"id":405160398,"identity":"257031e1-fa71-4a8e-b064-cf4273f9749b","order_by":6,"name":"Ali Türker ÇİFTÇİ","email":"","orcid":"","institution":"Niğde Ömer Halisdemir University: Nigde Omer Halisdemir Universitesi","correspondingAuthor":false,"prefix":"","firstName":"Ali","middleName":"Türker","lastName":"ÇİFTÇİ","suffix":""}],"badges":[],"createdAt":"2025-01-19 12:52:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5859495/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5859495/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74587285,"identity":"a22401ea-f2c2-470e-b168-19ec6824e8b2","added_by":"auto","created_at":"2025-01-23 16:55:18","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":262986,"visible":true,"origin":"","legend":"\u003cp\u003eRevealing the afferent and efferent fiber numbers of the amygdala by tractography method\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5859495/v1/3d7007e0dd427683c278f8cd.jpg"},{"id":74586115,"identity":"2a940f1d-47ae-47bc-8995-39aece9a77fc","added_by":"auto","created_at":"2025-01-23 16:47:18","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":46367,"visible":true,"origin":"","legend":"\u003cp\u003eFunctional lateralisation of the Amygdala [28]\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5859495/v1/303bb5b61c2c22d8a08acff5.jpeg"},{"id":75966033,"identity":"411bcf22-4311-4701-981e-e38f80563cff","added_by":"auto","created_at":"2025-02-11 04:12:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1428868,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5859495/v1/c97ba00a-a4ed-4427-bbe0-85d970b2b765.pdf"}],"financialInterests":"","formattedTitle":"Investigation of Anxiety and Depression in Female Patients with Fibromyalgia on MR Images: A cross-sectional cohort study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFibromyalgia (FM) is a rheumatic syndrome of unknown etiology characterized by chronic widespread body pain, fatigue, sleep disturbance, tender points and poor quality of life [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. According to the American College of Rheumatology (ACR) criteria, it is defined as the presence of widespread pain lasting at least 3 months, as well as the presence of tenderness in at least 11 of the 18 points called tender points that cause pain with finger palpation. Fibromyalgia is the most common rheumatologic disease after osteoarthritis and mainly affects women between the ages of 40 and 55 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The prevalence in the general population in highly industrialized countries varies between 1% and 4%. Fibromyalgia is consistently associated with other functional syndromes. The disease can occur alone or in association with other syndromes such as chronic headache, thyroid dysfunction, irritable colon syndrome, depression and anxiety [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe presence of chronic pain increases the risk of comorbid psychiatric disorders such as anxiety and depressive disorders [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This increases the frequency of anxious and depressive symptoms in the population. Studies show a close relationship between fibromyalgia and anxiety and depression [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], with one third of patients reporting this [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. A study in the literature revealed a high prevalence of depression (89%) and anxiety (41%) in patients with FM [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In another study, it was reported that the prevalence of depression was 20%-80% and the prevalence of anxiety was 13%-63% [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Major depressive disorder, generalized anxiety disorder and social anxiety disorder are among the most common and most frequently comorbid psychiatric disorders in adults [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Estimates of depression and anxiety comorbidity range from 10% to over 50% [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Therefore, it has been suggested that depression and anxiety have a similar etiology and respond to the same treatment strategies [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. A number of neuroimaging studies on depression and anxiety in humans have shown altered gray matter volumes in structures related to hypothalamic-pituitary-adrenal axis function, emotion perception and regulation, namely the hippocampus, amygdala, striatum, medial prefrontal cortex and anterior cingulate gyrus [\u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18 CR19\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Many studies in the literature have reported a decrease in the volume of these structures [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], but the findings are not completely consistent [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Therefore, the aim of our study was to determine the volume of the amygdala, medial frontal cortex, limbic system and hippocampus in participants with anxiety and depression levels and to compare fibromyalgia and control groups by determining the afferent and efferent fibers of the amygdala, which play an important role in anxiety and depression, which will be the first in the literature.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This study is a single-center, randomized controlled, prospective and cross-sectional cohort study conducted in the Physical Therapy and Rehabilitation Department of Kayseri City Hospital in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from each patient and/or legal guardian while obtaining the images to be used in the study. In addition, approval for this study was obtained from Niğde \u0026Ouml;mer Halisdemir University Non-Interventional Clinical Research Ethics Committee with protocol number 2025/3.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eDetermination of Sample Size and Study Groups\u003c/h2\u003e \u003cp\u003eIn order to determine the sample size of this study, it was calculated that at least 26 individuals with fibromyalgia and at least 26 individuals in the control group would be included in the study, with an effect size of 0.80, 90% power and 5% Type I error. This calculation was made with the G*power 3.1.9.6 program. In this context, a total of 62 individuals, 31 fibromyalgia patients and 31 control group individuals, belonging to individuals whose MR images were taken between November 2023 and December 2023, were included in this study. The inclusion and exclusion criteria for this study are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Since the incidence of fibromyalgia is significantly higher in favor of the female gender and in order to create optimum homogenization, only female cases were included in both the patient and control groups, and the mean age of the individuals participating in the study was 45.29 (Age range: 18\u0026ndash;85).\u003c/p\u003e \u003cp\u003eTable 1. Inclusion and exclusion criteria for individuals participating in the study\u003c/p\u003e\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/127393_c7e80a1c9bb65875/127393_custom_files/img1737649155.png\"\u003e\u003cbr\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eBECK Depression Inventory (BDI)\u003c/h3\u003e\n\u003cp\u003eThe BDI is a widely used 21-item self-report inventory that measures the severity of depression in adolescents and adults. Individuals are asked to answer each question over a two-week time period. The BDI is widely used as an indicator of the severity of depression, but not as a diagnostic tool, and numerous studies provide evidence for its reliability and validity across different populations and cultural groups. It has also been used in numerous treatment outcome studies and in numerous studies with trauma-exposed individuals [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eHospital Anxiety and Depression Scale (HADS)\u003c/h3\u003e\n\u003cp\u003eIn the hospital anxiety and depression scale, patients complete a 7-item questionnaire consisting of statements about general anxiety or 'depression'. In this questionnaire, 'depression' is assessed according to the following questions: \u0026ldquo;Are you as interested in things as you used to be? Do you laugh as easily as you used to? Do you feel cheerful? Do you feel optimistic about the future?\u0026rdquo;. The level of \u0026lsquo;anxiety\u0026rsquo; was assessed by the following questions: \u0026ldquo;Do you feel tense and nervous? Do you worry a lot? Do you have panic attacks? Do you feel that something scary is about to happen?\u0026rdquo;. The questionnaire analyzes the responses in the light of the results of this estimation of the severity of both anxiety and depression. Each item was answered by the patient on a four-point (0\u0026ndash;3) response category, so possible scores range from 0 to 21 for anxiety and 0 to 21 for depression. It makes it possible to provide information for both subscales that a score between 0 and 7 can be considered within the normal range, a score of 11 or higher indicates the possible presence of a mood disorder ('being a case'), and a score between 8 and 10 only implies the presence of the relevant condition [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eRadiological Evaluation\u003c/h3\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eTractography Analysis\u003c/h2\u003e \u003cp\u003eTractography of the targeted pathway from brain diffusion MR images was performed in the DSI Studio program downloaded from \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://dsi-studio.labsolver.org/\u003c/span\u003e\u003cspan address=\"http://dsi-studio.labsolver.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Before starting the tractography process, in the \u0026ldquo;Fiber tracking\u0026rdquo; tab; \u0026ldquo;Threshold\u0026rdquo; was set to 0.20, \u0026ldquo;Angular Threshold\u0026rdquo; was set to 70 degrees, \u0026ldquo;Smoothing\u0026rdquo; was set to 0.50, the shortest tract was set to 10 mm, the longest tract was set to 1000 mm, and \u0026ldquo;terminateif\u0026rdquo; was set to 100000 fibers. These parameters were adjusted again before starting tractography in each new image. In our study, afferent and efferent pathways of the amygdala were specifically analyzed. Total fiber counts of these pathways were calculated in the tractography process [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eProcessing of images\u003c/h2\u003e \u003cp\u003e \u003cb\u003eMedial Frontal Cortex, Amygdala, Limbic Cortex and Hippocampus Volume Calculation\u003c/b\u003e: To calculate the volume of the Medial Frontal Cortex, Amygdala, Limbic Cortex and Hippocampus from MR images of individuals with FM, T1 images in DICOM format were used to perform calculations on the cloud-based software \u0026ldquo; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://volbrain.upv.es\u003c/span\u003e\u003cspan address=\"https://volbrain.upv.es\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (volBrain: Automated MRI Brain Volumetry System)\u0026rdquo;. Before uploading the data to the site, the DICOM format T1 images of individuals with FM are converted to \u0026ldquo;niftii\u0026rdquo; format using the \u0026ldquo;dcm2niigui\u0026rdquo; conversion program. These files are then converted to \u0026ldquo;.zip\u0026rdquo; format using WinZip, a compression program. To use the Volbrain software, you must first register and log in to the site. After logging in to the Volbrain website, the \u0026ldquo;CERES1.0\u0026rdquo; tab is selected and the age and gender information of the individual is entered. After these procedures, it is uploaded to the specified area, converted to \u0026ldquo;.zip\u0026rdquo; format and sent to the server that creates the software. The images uploaded to the server give results in \u0026ldquo;pdf\u0026rdquo; format after the server performs some operations and calculates the volume within a certain time frame. The results are then retrieved and analyzed [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eThe Shapiro Wilk test was used to determine whether the variables were normally distributed and the measured parameters were found to be normally distributed. Numerical variables were summarized as Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;S.Deviation and Min-Max. Independent t-test was used for two group comparisons. Pearson correlation was used to examine the relationship between numerical variables. Statistical analyses were performed with IBM SPSS version 22 (SPSS, Inc., Chicago, IL, USA). p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was accepted as the level of statistical significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the comparison of the measured parameters between fibromyalgia and control groups. According to Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, there is no statistically significant difference between the two groups in terms of age and Body mass index (BMI) (kg/m2) (p\u0026thinsp;=\u0026thinsp;0.280; p\u0026thinsp;=\u0026thinsp;0.100). This situation supports that the individuals participating in this study were homogeneously distributed with gender. When Visual anologous scale (VAS), BECK depression ınventory, Hospital anxiety scale (HAAS) and Hospital depression scale (HDS) were compared between the two groups, it was found statistically significant that these scales were higher on average in the patient group than in the control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In this regard, the number of afferent and efferent fibers of the right-sided amygdala (TAmygdala(R)) was higher in the patient group (13710.60\u0026thinsp;\u0026plusmn;\u0026thinsp;4926.09) than in the control group (13099.14\u0026thinsp;\u0026plusmn;\u0026thinsp;3677.12), which was statistically significant (p\u0026thinsp;=\u0026thinsp;0.044). However, it was found to be statistically significant that the number of afferent and efferent fibers of the left side amygdala (TAmygdala(L)) was higher in the control group than in the patient group (p\u0026thinsp;=\u0026thinsp;0.027) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In addition, when medial frontal cortex volume (MFC(V)), total Amygdala volume (Amygdala(V)), total Limbic cortex volume (LC(V)) and total Hippocampus volume (Hippocampus(V)) were compared between the two groups, it was found to be statistically significant that it was higher in the control group than in the patient group (p\u0026thinsp;=\u0026thinsp;0.033; p\u0026thinsp;=\u0026thinsp;0.041; p\u0026thinsp;=\u0026thinsp;0.047; p\u0026thinsp;=\u0026thinsp;0.019) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). As in the number of afferent and efferent fibers, the right side amygdala volume (Amygdala(V)(R)) was found to be statistically significantly higher in the patient group (1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10) than in the control group (1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10) (p\u0026thinsp;=\u0026thinsp;0.036) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). However, when the left side amygdala volume (Amygdala(V)(L)) was compared between both groups, there was no statistically significant difference (p\u0026thinsp;=\u0026thinsp;0.824) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of measured parameters between FM and control group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eParticipants with FM (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Group (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (Years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e46.80\u0026thinsp;\u0026plusmn;\u0026thinsp;8.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e44.30\u0026thinsp;\u0026plusmn;\u0026thinsp;9.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.280\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI (kg/m\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e28.23\u0026thinsp;\u0026plusmn;\u0026thinsp;3.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e26.47\u0026thinsp;\u0026plusmn;\u0026thinsp;4.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVAS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e7.26\u0026thinsp;\u0026plusmn;\u0026thinsp;2.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.70\u0026thinsp;\u0026plusmn;\u0026thinsp;2.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0\u003c/b\u003e.\u003cb\u003e001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBECK\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e18.06\u0026thinsp;\u0026plusmn;\u0026thinsp;8.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.36\u0026thinsp;\u0026plusmn;\u0026thinsp;6.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0\u003c/b\u003e.\u003cb\u003e001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHAS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e11.10\u0026thinsp;\u0026plusmn;\u0026thinsp;4.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e5.46\u0026thinsp;\u0026plusmn;\u0026thinsp;3.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0\u003c/b\u003e.\u003cb\u003e001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHDS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e7.93\u0026thinsp;\u0026plusmn;\u0026thinsp;3.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e5.46\u0026thinsp;\u0026plusmn;\u0026thinsp;3.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0\u003c/b\u003e.\u003cb\u003e001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTAmygdala (R)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e13710.60\u0026thinsp;\u0026plusmn;\u0026thinsp;4926.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e13099.14\u0026thinsp;\u0026plusmn;\u0026thinsp;3677.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.044\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTAmygdala (L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3552.70\u0026thinsp;\u0026plusmn;\u0026thinsp;1493.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4057.37\u0026thinsp;\u0026plusmn;\u0026thinsp;1388.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.027\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMFC (V)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.033\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMFC (V) (R)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.53\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.410\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMFC (V) (L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.295\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAmygdala (V)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.041\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAmygdala (V) (R)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.036\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAmygdala (V) (L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.824\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLC (V)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e38.24\u0026thinsp;\u0026plusmn;\u0026thinsp;7.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e39.28\u0026thinsp;\u0026plusmn;\u0026thinsp;4.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.047\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLC (V) (R)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e19.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e19.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.562\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLC (V) (L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e20.04\u0026thinsp;\u0026plusmn;\u0026thinsp;2.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e19.70\u0026thinsp;\u0026plusmn;\u0026thinsp;2.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.564\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHippocampus (V)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e5.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.019\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHippocampus (V) (R)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.956\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHippocampus(V) (L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.779\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003eBMI(kg/m2)\u003c/b\u003e: Body mass index; \u003cb\u003eVAS\u003c/b\u003e: Visual analog scale; \u003cb\u003eBECK\u003c/b\u003e: BECK Depression Inventory; \u003cb\u003eHAS\u003c/b\u003e: Hospital anxiety scale; \u003cb\u003eHDS\u003c/b\u003e: Hospital depression scale; \u003cb\u003eTAmygdala (R)\u003c/b\u003e: Number of amygdala fibers on the right side; \u003cb\u003eTAmygdala (L)\u003c/b\u003e: Number of amygdala fibers on the left side; \u003cb\u003eMFC (V)\u003c/b\u003e: Medial frontal cortex volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eMFC (V) (R)\u003c/b\u003e: Right side medial frontal cortex volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eMFC (V) (L)\u003c/b\u003e: Left side medial frontal cortex volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eAmygdala (V)\u003c/b\u003e: Total amygdala volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eAmygdala (V) (R)\u003c/b\u003e: Right side amygdala volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eAmygdala (V) (L)\u003c/b\u003e: Left side amygdala volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eLC (V)\u003c/b\u003e: Total limbic cortex volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eLC (V) (R)\u003c/b\u003e: Right side limbic cortex volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eLC (V) (L)\u003c/b\u003e: Left side limbic cortex volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eHippocampus (V)\u003c/b\u003e: Total hippocampus volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eHippocampus (V) (R)\u003c/b\u003e: Right side hippocampus volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eHippocampus(V) (L)\u003c/b\u003e: Left side hippocampus volume (mm\u003csup\u003e3\u003c/sup\u003e)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, the correlation between the scales used in the study and the parameters measured in the FM group is analysed. Accordingly, when Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e is analysed, it is seen that there is a positive linear relationship between VAS, BECK, HAS and HDS and TAmygdala(R) (p\u0026thinsp;=\u0026thinsp;0.046; p\u0026thinsp;=\u0026thinsp;0.044; p\u0026thinsp;=\u0026thinsp;0.026; p\u0026thinsp;=\u0026thinsp;0.038) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). However, it was determined that there was no significant relationship between these scales and other measured parameters (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation results of the parameters measured with the scales used in the FM group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTAmygdala\u003c/p\u003e \u003cp\u003e(R)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTAmygdala\u003c/p\u003e \u003cp\u003e(L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMFC\u003c/p\u003e \u003cp\u003e(V)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAmygdala\u003c/p\u003e \u003cp\u003e(V)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAmygdala\u003c/p\u003e \u003cp\u003e(V)(R)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAmygdala\u003c/p\u003e \u003cp\u003e(V)(L)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eLC\u003c/p\u003e \u003cp\u003e(V)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eHippocampus\u003c/p\u003e \u003cp\u003e(V)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eHAS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.204\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.050\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.143\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.038\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.394\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.876\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.795\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.996\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.451\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.927\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eHDS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.406\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.074\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.092\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.112\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.360\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-0.158\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.026\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.699\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.628\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.540\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.611\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.554\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.405\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eBECK\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.370\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.328\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.272\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.095\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.255\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.185\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.044\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.077\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.146\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.331\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.617\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.879\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.327\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eVAS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.251\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.237\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.055\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-0.164\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-0.188\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.046\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.181\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.207\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.972\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.773\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.870\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.387\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0.319\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"10\"\u003e\u003cb\u003eBMI(kg/m2)\u003c/b\u003e: Body mass index; \u003cb\u003eVAS\u003c/b\u003e: Visual analog scale; \u003cb\u003eBECK\u003c/b\u003e: BECK Depression Inventory; \u003cb\u003eHAS\u003c/b\u003e: Hospital anxiety scale; \u003cb\u003eHDS\u003c/b\u003e: Hospital depression scale; \u003cb\u003eTAmygdala (R)\u003c/b\u003e: Number of amygdala fibers on the right side; \u003cb\u003eTAmygdala (L)\u003c/b\u003e: Number of amygdala fibers on the left side; \u003cb\u003eMFC (V)\u003c/b\u003e: Medial frontal cortex volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eMFC (V) (R)\u003c/b\u003e: Right side medial frontal cortex volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eMFC (V) (L)\u003c/b\u003e: Left side medial frontal cortex volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eAmygdala (V)\u003c/b\u003e: Total amygdala volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eAmygdala (V) (R)\u003c/b\u003e: Right side amygdala volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eAmygdala (V) (L)\u003c/b\u003e: Left side amygdala volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eLC (V)\u003c/b\u003e: Total limbic cortex volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eLC (V) (R)\u003c/b\u003e: Right side limbic cortex volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eLC (V) (L)\u003c/b\u003e: Left side limbic cortex volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eHippocampus (V)\u003c/b\u003e: Total hippocampus volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eHippocampus (V) (R)\u003c/b\u003e: Right side hippocampus volume (mm\u003csup\u003e3\u003c/sup\u003e); \u003cb\u003eHippocampus(V) (L)\u003c/b\u003e: Left side hippocampus volume (mm\u003csup\u003e3\u003c/sup\u003e)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, the volume of the amygdala, medial frontal cortex, limbic system and hippocampus, which are the centres of these senses in the central nervous system, were evaluated between individuals with FM and healthy control group in order to examine the mechanism of symptoms related to depression and anxiety disorders in individuals with FM. In addition, afferent and efferent fiber counts of the amygdala, which has an important function directly in the perception and regulation of pain and mood disorders, were examined for the first time between FM and control groups in this study. In both groups, VAS was used for pain sensation and BECK, HAS and HDS scales were used to evaluate anxiety and depression sensations. The data obtained showed that individuals with FM had more pain, depression and anxiety moods (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eIzuno et al. in a study with 34 FM (age 41.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4) and 25 control groups (age 39.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4) found a statistically significant difference when they compared both groups in terms of HAS and HDS (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). They also analysed the white matter volume of the temporal lobe between both groups and found that the temporal lobe white matter volume of the FM group was higher than the control group (p\u0026thinsp;=\u0026thinsp;0.021). When they examined the correlation between the bilateral grey matter volume of the amygdala due to depression and anxiety disorder in the FM group, it was found that the amygdala had a negative correlation with the grey matter volume (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In our study, when the HAS and HDS scales were compared between the FM and control groups, it was found statistically significant that the FM group had a worse emotional state (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In addition, in our study, it was found statistically significant that Amygdala (V), MFC (V), LC (V) and Hippocampus (V) volumes were higher in the control group than in the FM group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). This supports the study conducted by Izuno et al.\u003c/p\u003e \u003cp\u003eIn the literature, it has been stated that asymmetry occurs in the amygdala depending on the emotional state [\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In this regard, it has been reported that the left amygdala hemisphere is dominant for processing positive emotions, while the right amygdala hemisphere is dominant for processing pain and negative emotions [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In line with this information, it was found to be statistically significant that the number of afferent and efferent fibers of the right side amygdala was higher in the FM group compared to the left side (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). In addition, as seen in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, there was a positive correlation between the VAS, BECK, HAS and HDS scales and the total number of afferent and efferent fibers of the right side amygdala (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In addition, it was found to be statistically significant that the volume of the right amygdala was higher in the FM group compared to the left side (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This supports the study of Izuno et al. and that the right amygdala is responsible for pain and negative mood disorders.\u003c/p\u003e \u003cp\u003eBurgmer et al. found statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) that the volume of the prefrontal cortex was less in the FM group compared to the control group in their study conducted with 3T MRI on 14 FM and 14 healthy control groups [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In our study, it was determined that the medial frontal cortex volume was less in the FM group compared to the control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn a study conducted by McCrae et al. among 40 FM and 22 control groups, it was found to be statistically significant that the right and left hippocampus volumes were less in the FM group than in the healthy group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, it was reported that this was not associated with anxiety and depression [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Similarly, Murillo-Garcia et al. conducted a study with 47 FM and 43 healthy control groups and found that the FM group had less hippocampus volume than the control group [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. In our study, when the two groups were compared in terms of total hippocampus volume, it was determined that the FM group had less hippocampus volume than the control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). However, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows that there was no significant correlation between VAS, BECK, HAS and HDS scales and hippocampus volume (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this study, the relationship between anxiety and depression mood disorders occurring in individuals with FM and the central nervous system was investigated. In addition, afferent and efferent fiber numbers of the amygdala were examined by tractography method, which is the first in the literature related to this mood disorder. As a result, it is seen that depression and anxiety in FM patients affect both white matter and grey matter volume in the central nervous system. Therefore, we believe that treatments on the central nervous system may be more effective in the treatment of anxiety and depression disorders occurring in patients with FM. In addition, different centres and structures related to anxiety and depression should be examined by tractography method in order to investigate whether there is a relationship between these mood disorders.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was granted approval by the Ethics Committee of Niğde \u0026Ouml;mer Halisdemir University (Protocol number: 2025/3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no confict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception. F\u0026Ccedil;, AP, TS, FG\u0026Uuml;D carried out data collection and contributed to study design. Statistical analysis and data interpretation was performed by AT\u0026Ccedil;, SSD. The frst draft of the manuscript was written by F\u0026Ccedil; and İU. All authors provided input and comments on the manuscript. All authors read and approved the fnal manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by Erciyes University Scientific Research Project (BAP) unit with the number \u0026ldquo;TDK-2023-13366\u0026rdquo;.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSantos EBD, Quintans Junior LJ, Fraga BP, Macieira JC, Bonjardim LR. An evaluation of anxiety and depression symptoms in fibromyalgia. 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Fibromyalgia impact in the prefrontal cortex subfields: An assessment with MRI. Clin Neurol Neurosurg. 2022;219:107344. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.clineuro.2022.107344\u003c/span\u003e\u003cspan address=\"10.1016/j.clineuro.2022.107344\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Anxiety, Amygdala, Depression, Fibromyalgia, Medial frontal cortex","lastPublishedDoi":"10.21203/rs.3.rs-5859495/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5859495/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eHigh rates of depression and anxiety have been reported in patients with fibromiyalgia (FM). Therefore, the aim of our study was to determine the volume of the amygdala, medial frontal cortex, limbic system and hippocampus in participants with anxiety and depression and to compare the fibromyalgia and control groups by determining the afferent and efferent fibers of the amygdala, which play an important role in anxiety and depression, which will be the first in the literature.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eOnly female subjects, 30 with fibromyalgia and 30 controls, were included in this study. Visual analog scale was used for pain sensation, BECK depression inventory, Hospital anxiety and depression scale were used for anxiety and depression. From brain diffusion MR images, tractography of the targeted pathway was calculated in DSI Studio software and the volume of targeted structures was calculated in VolBrain software program.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe total volume of the medial frontal cortex, amygdala, limbic cortex and hippocampus was found to be statistically significant higher in the control group than in the fibromyalgia group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). It was also found statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) that the total number of fibers on the right side of the amygdala was higher in the patient group (13710.60\u0026thinsp;\u0026plusmn;\u0026thinsp;4926.09) than in the control group (13099.14\u0026thinsp;\u0026plusmn;\u0026thinsp;3677.12), but the number of fibers on the left side was higher in the control group (4057.37\u0026thinsp;\u0026plusmn;\u0026thinsp;1388.57) than in the patient group (3552.70\u0026thinsp;\u0026plusmn;\u0026thinsp;1493.35).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIt is observed that depression and anxiety in fibromyalgia patients affect both white matter and gray matter volume in the central nervous system. Therefore, we believe that treatments on the central nervous system may be more effective in the treatment of anxiety and depression disorders in patients with fibromyalgia.\u003c/p\u003e","manuscriptTitle":"Investigation of Anxiety and Depression in Female Patients with Fibromyalgia on MR Images: A cross-sectional cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-23 16:47:13","doi":"10.21203/rs.3.rs-5859495/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f7de4503-27a8-4e4f-9c6a-eecb6583218a","owner":[],"postedDate":"January 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-14T04:38:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-23 16:47:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5859495","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5859495","identity":"rs-5859495","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}