Control Studies On Cognition, Sleep And Autonomic Nerve Function In Post-stroke Depression Patients

BACKGROUNDCerebral stroke is a disease which harms to human's health severity. Post-strokedepression(PSD) is a common complication of cerebral stroke, which incidence is25～60%. In 1924, the scholars had realized that the patients with cerebrovascularimpairment always companied behavioral and psychological disorders, thosedisorders could delay the neurofunctional recovery. Therefor, PSD not only results inphysical and mental suffering, but also increases family and social burden. Recentresearch shows that cognitive impairment is a common symptom of cerebral stroke,its incidence is 48.4～61%. Cerebral stroke can often cause nerve cells degeneration,softening and atrophia, in cerebral cortex and subcortex, accordingly result incognitive functional disturbance. PSD may be related with monoamineneurotransmitters. Cerebral stroke could induce some central nerve transmitters suchas 5-hydroxytryptamine(5-HT) and noradrenaline(NE) insufficiency of function.These nerve transmitters have important physiologic function and can regulateemotion activity, so stroke patients can lead to depression. Cognitive impairment canexacerbate depressive feeling of cerebral stroke patients, reversely, depression caninfluence cognitive function. Some studies have confirmed that depression oftencompanies sleep disorder and functional disorder of autonomic nerve. There aremutual influence among depressive emotion, cognitive impairment, sleep disorderand functional disorder of autonomic nerve of cerebral stroke, which decrease the patients' therapeutic efficacy and life quality.There are more studies on post-stroke depression in domestic and abroad, theresearches about its cognitive function and sleep become a hot spot gradually. Recentyears, cognitive function is paid more and more attention to, it can effect the patients'living, social intercourse and work ability, and can influence their long-term outcome.Event-related potentials(ERP) or cognitive potentials(CP) is a research focus inpsychiatry, neurology and psychology and so on at present, it provides an effectiveand non-invasive way to "spy on" the human's cognitive activity. ERP includes P300,N400, CNV and MMN et al, they reflect cognitive function from different profile.P300 is a late component of brain evoked potentials and a kind of endogenouspotential. It does not relay on the stimulant physical attribute, but correlates closely tothe stimulus-including information and the psychological state of the subjects such asattention, memory, intelligence and awareness level. N400 is related to languagecognitive function, it can demonstrate the treating process of the brain to the meaningof Chinese Character not only in time but in space. It has high time resolution onreflecting the cognitive process of words. CNV (Contingent negative variation) is akind of classical event-related potential correlated closely with the psychologicalactivities such as the expectation, action, preparation, orientation and attention toevent and so on. MMN(mismatch negative) is a new test technique on basis of P300.Compared with P300, the subjects have not to identify actively artifact stimulus in thetest of MMN, which can reflect the automatic recognition process of the subjects tothe standard stimulus and the deviation stimulus, therefore, whether the subjectsmatch or not is avoided. MMN shows significant preponderance in the clinical usage.P300 is a more classical and riper cognitive potential which is researched most. Atdomestic and abroad, patients of cerebral stroke were studied with ERP, the resultsshowed that the amplitude of P300 in patients with post-stroke depression decreasedobviously compared with that in stoke patients without depression, the latencyprolonged significantly, and the prolongation degree was correlation with depressionpost stoke. Correlation analysis discovered that the latency of P300 was negativecorrelation with the score of cognitive function evaluation. These studies confirmed that ERP had certain reference value to evaluate the cognitive function of cerebralstroke and post-stroke depression patients. Polysomnogram is a commonestelectrophysiology index to be used for assessing sleep state of cerebral stroke andpost-stroke depression patients. At home and abroad, patients with cerebral stroke andpost-stroke depression were observed by polysomnogram in order to understand theirsleep status. The results showed compared with healthy persons, cerebral strokepatients had abnormal sleep structural changes and low level slow-wave sleep andrapid eye movement sleep. Compared with stroke patients without depression, thesleep structure in patients with post-stroke depression had changed obviously, whichmanifested that the sleep latency shortened, the frequency of REM-NREM cycleincreased, REM latency shortened, the activity, intensity and density of REMincreased, sleep of S₁ stage increased and sleep of S₃ and S₄ stage decreased. Thestudies on autonomic nerve function in patients with cerebral stroke and post-strokedepression confirmed that cerebral stroke could change autonomic nerve function,especially the changes of heart autonomic nerve function could induce myocardialdamage and plasma treponin increasing. The cause is there exist capital centers ofaccommodation for cardiovascular sympathetic nerve and parasympathetic nerve atsome location in cerebral hemisphere(such as insular lobe, hypothalamus) and brainstem. The autonomic nerve in patients with stroke has different damage owing todifferent stroke region. The abnormal function of autonomic nerve with stroke takenin the right cerebral hemisphere and brain stem, especially in bulbus medullae alwayshints unfavourable prognosis.At present, the more studies about cognition, sleep and autonomic nerve ofpatients with post-stroke depression were independent studies, any reports oncorrelation research among the three were not found. There are lack of unified,objective and entirety studies about cognition, sleep and autonomic nerve in patientswith PSD. And the researches on cognitive function more concentrated on P300, thereexisted one-sidedness to some degree for evaluating the cognitive function. Therefor,to explore the cognition, sleep and autonomic nerve of the patients with post-strokedepression has important value to guide clinical treatment, prognosis and rehabilitation.AIMSThis study using many kind of cognitive potentials combined cognitivefunctional assessment(Wisconsin Card Sorting Test, WCST), polysomnogram andsympathetic nerve-skin reaction(SSR) conducts control research on post-strokedepression and post-stroke depression in different stage and different stroke location.The study is aimed to: 1. recognize cognition, sleep and autonomic nerve status ofpatients with PSD completely; 2. explore the characteristic of cognition, sleep andautonomic nerve after treatment with antidepressant; 3.provide objective referentialindexes to judge the clinical diagnosis, treatment and prognosis for PSD. So, ourstudy will bring out important guide value to diagnosis, treatment and prognosis forthe patients with PSD.MATERIALS AND METHODS1. Study subjects and methods1.1 Study subjects1.1.1 The participants were inpatients hospitalized in the department of neurologyin the second affiliated hospital of Xinxiang medical college from January, 2005 toDecember,2006. The PSD group and stroke without depression group were 68 and 65cases respectively. Cerebral stroke met the diagnostic criteria for cerebral hemorrhageand cerebral infarction edited at the 4th national academic conference oncerebrovascular disease hosted by Chinese Medical Association in 1995, anddepression met CCMD-3 for depressive episode.1.1.2 The depression group(60 cases) were the inpatients hospitalized indepartment of clinical psychology in the second affiliated hospital of Xinxiangmedical college from January,2005 to December,2006, met CCMD-3 for depressiveepisode.1.1.3 Normal control group were 60 cases healthy persons came from employeesin the hospital.and folks of patients. The controllers had no difference with theresearched subjects in age and culture degree (P＞0.05) .1.2. Methods 1.2.1Depressive emotion was evaluated with Hamilton DepressionScale(HAMD)-17 edition, which could reflect the changes of depressive moodefficiently.1.2.2 Cognitive function was assessed by WCST and ERP(including P300, N400,CNV and MMN).1.2.3 Using polysomnogram recorded the whole night sleep in order to evaluatedthe sleep state.1.2.4 Autonomic nerve function was tested with SSR, the status of autonomicnerve was reflected by the changes of sympathetic route.All the indexes above, the first evaluation was conducted at 1 week afterhospitalization, the second at 4 weeks after hospitalization.2. To explore the cognition, sleep and autonomic nerve function of the patientswith PSD, and compare with stoke without depression group, depression group andcontrol group, the results conducted correlation analysis.3. To explore the characteristic of cognition, sleep and autonomic nerve functionin different onset location(cortex and subcortex) and at different stage(acute stage andrecovery stage), and conduct correlation analysis among them.4. To explore the effect of antidepressant(prozac) on cognition, sleep, autonomicnerve function and depressive emotion.RESULTS1. The studies on cognition, sleep and autonomic nerve function of PSD patientsshowed:1.1 Compared with stroke without depression group, depression group and normalcontrol group, the PSD group had prolonged latency and degraded amplitude inERP(including P300, N400, CNV and MMN) (P＜0.05).1.2 The WCST total trials, persistent errors and random errors in PSD group weresignificantly increaser (P<0.05) than those in the other three groups, but thecorrects and sorting number were obviously decreasing (P＜0.05).1.3 In the study of polysomnogram, every index of polysomnogram in PSD group had significant difference compared with the control group. Compared with strokewithout depression group, total sleep time, sleep latency, deep sleep, awarenessfrequency, REM latency, REM time and density in PSD group had obvious difference(P＜0.05) . Compared with depression group, except REM sleep in PSD group hadconsistent changes with depression group, which showed that latency shorteded, theother indexes between the two groups had significanet difference (P＜0.05) . Theseresults illustrated PSD patients had poor quality sleep and had resemble biologicalmark with depression patients on REM latency.1.4 Compared with the other three groups, the latency of SSR in PSD groupprolonged, and the amplitude degrade (P＜0.05) .2. The studies on cognition, sleep and autonomic nerve function of PSD patientsin different stroke location and different stage found:2.1 Compared with PSD patients with subcortex damage, PSD patients withcortex damage had prolonged latency and lower amplitude in ERP(including P300,N400, CNV and MMN) (P＜0.05). The latency and amplitude of ERP in PSDpatients at acute stage were longer and lower than those at a recovery stagerespectively(P＜0.05).2.2 The WCST total trials, persistent errors and random errors in PSD groupwith cortex damage were significantly increaser than those in stroke withoutdepression group, and the corrects and sorting number were obviously decreasing(P＜0.05) . The WCST total trials, persistent errors and random errors in PSD groupat acute stage were significantly increaser than those at recovery stage, and thecorrects and sorting number were obviously decreasing (P＜0.05) .2.3 In the study of polysomnogram, compared with subcortex damage, all sleepindexes in PSD patients with cortex damage had significant difference(p＜0.05). Allthe sleep indexes in PSD patients at acute stage had significant difference withpatients at recovery stage(p＜0.05).2.4 Compared with PSD patients with subcortex damage, PSD patients with cortexdamage had prolonged latency and lower amplitude in SSR(P＜0.05). The latency and amplitude of SSR in PSD patients at acute stage were longer and lower than those atrecovery stage respectively(P＜0.05).3. The studies on cognition, sleep and autonomic nerve function of PSD patientsafter treatment with prozac:3.1 The latency and amplitude in every index of ERP in group treated withprozac obviously shortened and heightened respectively, there were significantdifference with pro-treatment group(P＜0.05).After treatment with prozac, PSDpatients was compared to routine treatment group , the latency of P300, N400, CNV(M₁), MMN and amplitude of N400, CNV (M₂), MMN obviously shortened andheightened respectively, there were significant difference between them(P＜0.05).3.2 After treatment with prozac, the PSD patients had better WCST total trials,persistent errors, random errors, corrects and classifies than pro-treatment with prozac.Their total trials, corrects and classifies had better than routine treatment group, therewas significant difference between them (P＜0.05).3.3 After treatment with prozac, the patients' polysomnogram indexes hadimproved better than pro-treatment patients(P＜0.05). Compared with routinetreatment group, the polysomnogram indexes of the patients trested with prozac hadsignificant difference except RD(P＜0.05).3.4 The latency and amplitude of SSR in group treated with prozac obviouslyshortened and heightened respectively, there were significant difference withpro-treatment with prozac and routine treatment group(P＜0.05).CONCLUSION1. The damage of cognition, sleep and autonomic nerve function in PSD group ismore serous than that in stroke without depression group and depression group. Thereexist cognition, sleep and autonomic nerve damage in both stroke without depressiongroup and depression group, there were not significant difference between them, butthey have significant difference with the control group.2. PSD patient with cortex stroke have more serous damage on cognition, sleepand autonomic nerve function than the PSD patients with subcortex stroke. PSD patient at acute stage have more serous damage on cognition, sleep and autonomicnerve function than the PSD patients with subcortex stroke at recovery stage.3. The cognition, sleep and autonomic nerve function in PSD patients is improvedobviously after treatment with proz.4.ERE polysomnogram and SSR can be used to assess cognition, sleep andautonomic nerve function in PSD patients and be used for clinic as laboratoryindexes.