Preliminary Study On The Mechanism Underlying The Interaction Of Intractable Vertigo And Anxiety Disorder

Objects1) To explore the anxiety-related behavioral changes of intratympanic gentamicin aministration induced vestibular impaired models.2) To explore the concentration alterations of monoamine neurotransmitters in MVN, LC and DRN following unilateral vestibular impairment.3) To investigate the correlation between psychological disorder and vestibular dysfunction in patients suffering from intractable peripheral vertigo.Methods1) Adult male SD rats were used in this research. Gentamicin was administrated transtympanically to the rats to establish the vestibular impaired animal model. Rotarod was use to test the vestibular function and the elevated plus maze and open field test were harnessed to evaluated the anxiety level.2) SD rats were sacrificed at3d and14d postoperatively respectively. Serial coronal sections (300v m) were cut in a cryostat kept at-10℃taking the decussation of seventh cranial nerve as an anatomical reference. Individual nuclei were dissected with micropunches (Uni-core Harris) by a means of a needle (500v m in diameter) using the atlas of Paxinos and Watson as a general guide (Paxinos and Watson,1986). Monoamines and their metabolites were assayed by High Performance Liquid Chromatography (HPLC).3) Prespective design of26patients with peripheral vestibular dysfunction and20controls recruited from the EENT hospital. Hospital Anxiety and Depression scale, Self-rating Anxiety scale, Self-rating Depression scale, Symptom Checklist-90were used in this study. Pre-and postoperative scores where compared.4) All the results were statistically analyzed using Stata8.0. One-way analysis of variance (ANOVA) or Kruskal-Wallis test followed by the Bonferroni method for multiple comparisons was performed in Part Ⅰ and Part Ⅱ. T-test or rank-sum test and paired-sample t test or rank-sum test were performed in Part Ⅲ. A level of P value<0.05was judged to be statistically significant. Results1) Rotarod test found that6days after GT administration (GT-6d), the average latency decreased significantly (P=0.009) compared with the control group and increased2weeks after the administration (GT-2w), but not significantly. Open field (OF) test showed that the travel distance of GT-3d group was apparantly lower than that of the control group (P<0.05), while no significant difference was noted between GT-2w group and the control group. Elevated plus maze (EPM) also proved that the entrance time of open arm was markedly lower in the GT-3d group than the control group (P=0.02) and no statistically significant difference was demonstrated between the GT-2w group and the control group. These results proved that vestibular function may be impaired by GT administration and might be compensated more or less with time. In accordance with these findings, EPM and OF also showed that the entrance time of open arm in the GT-3d group and the central zone time of GT-3d and GT-2w group were noticeably lower than that of the control group, demonstrating markedly increased anxiety level3days after GT administration and slightly decreased anxiety level2weeks after the administration with vestibular compensation, although still high above normal level.2) Within MVN, the concentration of NE and5-HIAA of GT-3d group increased significantly compared with the control group, and the concentration of DA and DOPAC increased markedly compared with the pseudosurgery group. The concentration of NE,5-HT and5-HIAA within LC of GT-3d group also increased compared with the control group and the concentration of DOPAC increased notably compared with the pseudosurgery group. The concentration of NE,5-HT,5-HIAA and DOPAC within DRN of GT-3d group also experienced a dramatic increase compared with the control group. The monoamine contrations of part of the neurotransmitters in the GT-2w group were lower than that of the GT-3d group, indicating the rapid activation and slow inactivation of MVN-LC and MVN-DRN pathways.3) The outcomes of Hospital Anxiety and Depression scale, Self-rating Anxiety scale, Self-rating Depression scale, Symptom Checklist-90are significantly greater in vertiginous group than that in normal controls (P<0.05). The preoperative scores of these4questionnaires are greater than the postoperative scores in vertiginous patients (P<0.05). No significant difference was noted between male and female participants in all the questionnaires used (P>0.05)Conclusion1) After transtympanic gentamicin administration, as is shown by the behavioral researche, anxiety level of animal models increased with the decline of vestibular function and then decreased with vestibular conpensation, demonstrating that vestibular impairment may lead to higher risk of anxiety.2) After transtympanic gentamicin administration, the concentrations of part or all of the monoamines and their metabolites increased dramatically in MVN, LC and DRN and decreased more or less with vestibular compensation, testifying that elevated anxiety levels might be attributed to increased monoamine concentrations within anxiety and vestibular related nuclei.3) Significant differences were noted between vertiginous patients and normal controls in psychiatric questionnaires, suggesting that psychological dysfunction may contribute to the vertigo attack.4) In addition to symptomatic treatment, cognitive behavior therapy and psychiatric drug therapy are needed to get a better prognosis for peripheral vertiginous patients combined with psychiatrical disorder such as anxiety and depression.