The Associations Among Tension-type Headache, Fibromyalgia And Major Depressive Disorder

Background: Tension-type headache (TTH), fibromyalgiais (FM) and major depressive disorder (MDD) are common diseases in out-patient clinic of neurology. Epidemiological data show that the two kinds of chronic painful disease (TTH and FM) are comorbidity, and both are highly concomitant with MDD. All the three kinds of diseases have chronic process with somatic symptoms (e.g., pain) but no objective findings. The pain symptom in these patients usually cannot be satisfactorily resolved by simple application analgesic drug, resulting in that patients frequently go and back among hospitals. Currently, the clinicians diagnose these patients semeiologically with no diagnostic detection. With regard to the studies of pathogenesis on the three kinds of disease, the attention is mainly paid for a single disease or comorbidity (e.g. TTH comorbid MDD or FM comorbid MDD), but not for three diseases assocciatedly within one study. Therefore, it is interesting to study the pathogenesis correlations among the three diseases in order to search for the objectively diagnostic detection and guide to treat for these diseases.Objective: To explore the association among TTH, FM and MDD and their blood marks.Methods: A total of 115 subjects participated in this study—30 healthy volunteers served as controls and 29 patients with TTH, 26 patients with FM and 30 patients with MDD recruited from our clinic. Patients fulfilled the criteria, including International Classification of Headache Disorders 2 for TTH, the American College of Rheumatology criteria for FM and American Diagnostic and Statistical Manual of Mental Disorders-IV for MDD. The venous blood was collected from the antecubital vein at least 2 ml in every examinee at 9～10 AM, and the plasma was stored at–80°C. The enzyme-linked immuno sorbent assay was used to detect the plasma conenetration of corticotropin releasing hormone (CRH), thyrotropin releasing hormone (TRH), gonadotropin releasing hormone (GnRH), interleukin-1β(IL-1β)and tumor necrosis factor (TNF-a). The pain intensity was appraised by Visual Analogue Scale. The skull membrane tenderness in the patients with TTH was evaluated by palpating in five pericranial muscles (temporalis, masseter, suboccipital, posterior cervical, middle trapezius) bilaterally using thumbs. The tenderness in the fibromyalgia patients was acquired by a thumb pressure of 4 kilograms according to the criteria of American College of Rheumatology. The general cognitive function was evaluated by Montreal Cognitive Assessment Scale (MoCA). The spatial (working and reference) memory and object (working and reference) memory were detected by Nine-Box Maze task. Statistical analysis was done with the help of SPSS 17.0 version for Windows.Results:1. The background data, including gender, age and education degree, matched among groups (Ps﹥0.05).2. Promote hormone releasing hormones Compared to the controls, the levels of CRH, TRH and GnRH significantly increased in all groups of the patients (Ps < 0.05) with the highest levels of TRH and GnRH in the TTH patients, and highest CRH level in the FM patients. Refered to the controls, the area under the ROC curve was 1 for TRH and GnRH and 0.685 for CRH in the TTH patients. In the FM patients, the ROC area was 1 for CRH and 0.684 and 0.854 for TRH and GnRH. In the MDD patients, the areas were respectively 0.864, 0.964 and 0.953 for CRH, TRH and GnRH.3. Proinflammatory factors The concentrations of TNF-a and IL-1βwere significantly higher in all patients than that in the controls with the highest concentration in the MDD. The ROC areas were 1 for TNF-a and IL-1βin all patients, relative to the controls.4. Cognitive functions The score of MoCA significantly lowered in all the patients compared to the controls (Ps<0.01). The errors of reference memory (object and spatial) and working memory (object and spatial) were significantly more in all patients than those in the controls (Ps<0.01).5. Multivariate linear regression analysis①For the intensity of depression and/or pain, the results showed that only the depressive degree in the TTH patients positively mild correlated with age (β= 0.132, P = 0.041).②For the cognitive functions combined with all patients, MoCA values significantly correlated with educated years (β= 0.364,P = 0.001) and HAMD scores (β= 0.246,P =0.040); the errors of spatial working memory respectively correlated with educated years (β= ? 0.598,P = 0.001), HAMD scores (β= 0.246,P = 0.003) and the levels of TNF-a (β= ? 0.309,P = 0.007) and IL-1β(β= 0.350,P = 0.007) with different directions (Ps﹥0.05).Conclusions: TTH, FM and MDD appears belong to homology diseases with similar direction of changes in the promote hormone releasing hormones, inflammatory factors andl cognitive functions. The promote hormone releasing hormones and inflammatory factor may be valuable for diagnosis of these diseases, i.e., CRH for FM, TRH and GnRH for TTHand MDD, and TNF-a and IL-1βfor TTH, FM and MDD. The plasma level of TNF-a and IL-1βmight affect spatial working memory in these patients.