Sympathetic Skin Response And R-R Interval Variation In The Assessment Of The Clinical Recovery Of Bipolar Disorder

BackgroundBipolar disorder is characterized as a class of mood disorders with both manic or hypomanic episode and depressive episode. Most patients suffered recurrent episodes, most of which can be alleviated, and some may have residual symptoms or become chronic. Angst et al.(1980) showed that24%of bipolar patients have residual symptoms during the intervals between episodes in a longitudinal follow-up study. These residual symptoms include cognitive symptoms, mood symptoms, social, behavioral and neurovegetative symptoms, etc. Studies have shown that the high recurrence rate of bipolar disorder is relevant to those residual symptoms.Clinical recovery is the goal of treatment, and also is the most important factor to reduce the recurrence rate. At present, the assessment of the clinical recovery with bipolar disorder mainly refers to the rating of scales, such as the Hamilton depression scale (HAMD) score≤7, Hamilton Anxiety Scale (HAMA) score≤7, Bech-Rafaelsen Mania Rating Scale (BRMS) score≤5, etc. However, it has been found that even if clinical recovery is achieved by the scale grading, the patient may still have residual symptoms, or even core symptoms. As a result, the specificity of scales in the assessment of clinical recovery remains unclear. Guides point out that, when the patient is clinically recovered, he still needs1-2years of maintenance therapy, which is based on the evidence from evidence-based medicine. Therefore, how to identify the sensitivity and specificity of the scales in the assessment of clinical recovery should be made clear, so as to guide the maintenance therapy. This can make great significance in reducing the rate of recurrence.The residual symptoms present as many clinical manifestations of autonomic nervous system dysfunction in patients with BD, such as sleep disturbances, sweating, loss of appetite, sexual dysfunction, cardiac and gastrointestinal anomalies. The autonomic nervous system dysfunction is related to the dysfunction of5-HT and NE. Current drug therapy is mainly associated with neurotransmitters, and can improve autonomic nervous system dysfunction of patients with BD. So, accurate evaluation of autonomic nerve function can be used as a means of assessing the clinical recovery of BD.Sympathetic skin response (SSR) and R-R interval variation rate (RRIV) are used for the non-invasive assessment of the sympathetic and parasympathetic nervous system. Relevant studies have approved SSR as a sensitive and easy-take assessment of the effectiveness of antidepressant treatment. But it has not yet been applied to the observation of therapeutic effect of patients with BD.We assumed that after the progress of treatment and the full remission of the clinical symptoms of patients with BD, the value of SSR and RRIV will return normal.ObjectWe intend to study the relationship of changes of the value of SSR and RRIV and the severity of bipolar disorder.MethodsAs a retrospective study, we chose the patients who met the inclusion criteria of bipolar disorder. Correlation analysis was carried out between the changes of SSR and RRIV before treatment and after1year±1month of treatment and scores of scales, such as HAMD, HAMA and BRMS. Besides, the sensitivity and specificity of HAMD, HAMA and BRMS which were used as the assessment of clinical recovery were calculated.1. Participants26outpatients (men:n=14, women:n=12) were diagnosed as bipolar disorder by psychiatric doctor using the (International classification of diseases, ICD-10) criteria. Of these cases, there were1case of hypomania,18cases in depressive phase of bipolar disorder,5cases of remission bipolar disorder and2cases in mixed phase of bipolar disorder. 2. StatisticsThere were2participants whose lower limb SSR could not be recorded before treatment, but could be recorded after treatment. So the statistics was based on the remaining24participants, excluding the2patients above.Single-sample t test was used to compare the value of SSR and RRIV before and after treatment with normal reference value; paired samples t test was used to compare the value of SSR, RRIV, HAMD, HAMA and BRMS before and after treatment. Besides, Pearson correlation analysis and linear regression analysis were used to analyze the correlation between changes of SSR, RRIV and scales of HAMD, HAMA and BRMS. The same analyses were done after treatment. Take the SSR, RRIV, SSR&RRIV as the evaluation standard of recovery respectively, we analyzed the sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index of the scales of HAMD, HAMA and BRMS in assessing the recovery of BD. ROC curve analyses were also done.Results(1) Before treatment, the latency of the upper limb SSR was significantly longer than the normal reference value. R%was significantly higher, D%-R%and D%:R%were significantly lower than the reference values (P<0.05). After treatment, the amplitude of the lower limb SSR were higher than the normal reference (P<0.05).(2) R%and the sore of the scales (HAMD, HAMA and BRMS) were significantly decreased after treatment, comparing with those before treatment (P<0.05).(3) There were no correlation between the difference values of the parameters of SSR and RRIV before and after treatment and those of the scales (HAMD, HAMA and BRMS). The latency of lower limb SSR after treatment showed a positive linear correlation with HAMA (F=4.449,P=0.047). The related coefficient is0.41.(4) Taking the scales as the assessment of the recovery of BD, the participants could be divided into two groups:recovery group (including17patients) and unrecovered group (including7patients). The normality tests were done and parameters of both groups were shown as a normal distribution, In the recovery group, the amplitude of the upper limb SSR presented a positive linear correlation with BRMS (F=5.644, P=0.031). The correlation coefficient is0.523. R%presented a positive linear correlation with BRMS (F=9.383,P=0.008). The correlation coefficient is0.62. In the unrecovered group, D%-R%had a linear negative correlation withî™'AMA(F=7.401, P=0.042), with correlation coefficient-0.773. D%presented a linear negative correlation with BRMS (F=20.586, P=0.006), and the correlation coefficient is-0.897. R%also presented a linear negative correlation with BRMS(F=11.168P=0.021), with the correlation coefficient-0.831.(5) Taking the scales (HAMD<7, HAMA≤7and BRMS≤5) as the assessment of the recovery of BD, there were17patients achieved clinical recovery after treatment. Taking the normal reference value of SSR, RRIV, SSR&RRIV as the golden standard of the recovery of BD respectively, the sensitivity of scales is73.7%-80%, the specificity of them is33.3%-44.4%, the accuracy is54.2%～66.7%, and Youden index is8.3%-24.4%. The area under the ROC curve is0.542～0.622.Conclusions(1) The SSR latency of the upper limbs is significantly prolonged; R%is significantly increased and the D%-R%and D%:R%values are significantly decreased in untreated patients with bipolar disorder.(2) The sensitivity of scales which are considered as the assessment of clinical recovery for bipolar disorder is relatively high but the specificity is low.(3) The SSR latency of the lower limbs and R%can be seen as an indicator of the recovery of bipolar disorder in the clinical assessment. Besides, R%can also be seen as an indicator in the evaluation of the therapeutic effect.