Clinical And Basic Research On The Relationship Between Affective Disorders And Meniere’s Disease

Objective: The aim was to assess the incidence of co-morbid affective disorders in patients with Meniere’s disease(MD).To analyse the relationship between peripheral blood levels of inflammatory factors and them.To investigate the structural and functional damage in the cochlea of rats with anxiety and depression-like behaviour in relation to inflammation and apoptosis.Methods: The anxiety self-rating scale and depression self-rating scale were used to assess the presence of affective disorders in 30 patients with MD and 20 normal subjects,and then the MD patients were divided into the group with and without affective disorders.The levels of Interleukin-1β(IL-1β)and Tumor necrosis factor-α(TNF-α)in the peripheral blood of control and MD patients were measured by Enzyme linked immunosorbent assay(ELISA).40 rats were randomly divided into 4 groups of 10 rats each,including control and model groups(2 week,3 week and 4 week groups respectively).The Chronic unpredictable mild stress(CUMS)model was used and the ABR response thresholds of both ears were tested again at the end of the modeling and behavioural assessment was done.The cochlea was dissected and stained with hematoxylin-eosin to observe its morphology.Immunohistochemistry was used to observe the expression of Cysteinyl aspartate-specific protease-3(Caspase-3)in the cochlear spiral ganglion.Western blot was performed to investigate the expression of Glucocorticoid receptors(GR),p38 mitogen-activated protein kinase(p38MAPK),and phospho-p38 mitogen-activated protein kinase(p-p38MAPK)in cochlear tissues.The results were statistically analyzed by SPSS 24.0 software.Results:1.Clinical findings:(i)11(37%)of MD patients with affective disorders and 19(63%)without affective disorders,with control group scores in the normal range.(ii)ELISA results: IL-1β was significantly higher in the group with affective disorder compared to the control group(P<0.05),but no significant increase in the group without affective disorder(P>0.05),and the difference between the group without affective disorder and the control group was not statistically significant(P>0.05);TNF-α was significantly higher in the group with affective disorder compared to the group without affective disorder and the control group(P<0.05,P<0.01),but no statistically significant difference was found in the group without affective disorder compared to the control group(P>0.05).2.Animal experiments results:(i)Behavioural results: Open field experiment: compared to the pre-modelling period,the distance traveled in the 2week,3week and 4week groups decreased significantly(P<0.01,P<0.001,P<0.001),the upright times decreased significantly(P<0.01,P<0.001,P<0.001)and the central area distance was not significantly different only in the 2week group(P>0.05),while in the other two groups the distance traveled,upright times and central area distance decreased significantly(P<0.05,P<0.001).There was no statistically significant difference in distance traveled,upright times and central area distance in the control group after modelling(P>0.05);Sucrose preference test: compared to the pre-modelling period,there was no significant change in pure water consumption in the 2week,3week and 4week groups after modelling(P>0.05),and sugar water consumption in all groups decreased significantly(P<0.01,P<0.001,P<0.001)and sucrose preference significantly decreased(P<0.01,P<0.001,P<0.001),in the control group after modelling(P>0.05);(ii)ABR threshold: compared to the control group,only the 4week group was elevated by 5 d B(P<0.001),with insignificant changes in the remaining two groups(P>0.05);(iii)Hematoxylin-eosin staining: no endolymphatic hydrops was observed in the control group,with hydrops rate of 0%,and 50%,25% and36% in the 2week,3week and 4week groups,respectively;(iv)Immunohistochemistry: Caspase-3 expression in spiral ganglia was elevated in the 4week group compared to the control group(P<0.05),with no significant difference in the remaining two groups(P>0.05);(V)Western blot: compared with the control group,p-p38/p38 MAPK expression was significantly increased in the 2week and 3week groups(P<0.01,P<0.01),but not significantly changed in the 4week group(P>0.05);GR expression was increased in the 2week and 3week groups(P<0.001,P<0.01),but decreased in the 4week group(P>0.05).Conclusions:1.Affective disorders are an important factor in the development of certain MD patients;increased TNF-α may be a causative factor in the MD combined with affective disorders population.2.CUMS modeling for 2,3 and 4 weeks resulted in anxiety-depressionlike behavior in rats.3.Anxiety and depression state can make some rats develop endolymphatic hydrops and auditory function impairment.4.The raised hearing threshold in rats with anxiety-depression-like behavior may be a combination of Caspase-3 mediated apoptotic pathway and p38 MAPK mediated inflammatory pathway;p38MAPK regulated inflammatory pathway and decreased GR are possible mechanisms of endolymphatic hydrops.