Cognitive dysfunctions in medicated and unmedicated patients with recent-onset schizophrenia

Schizophrenia is associated with impairments in many cognitive domains on which the influence of antipsychotics, whether conventional or atypical, remains unclear. We conducted a study of recent-onset schizophrenic patients (DSM IV) that included unmedicated (n=19), and medicated (n=19) patients matched for age and IQ. Both groups of patients had comparably low extra-pyramidal symptoms (EPS). Cognitive tasks included attentional tasks (alertness and divided attention tests), a working memory task (a verbal n-back test) and the Wisconsin Card Sorting Test (WCST). After adjustment for the Total PANSS score, we found no significant difference between the two groups of patients in any of the cognitive tasks. When compared to a group of healthy controls (n=20) matched for IQ level, unmedicated patients performed significantly worse in all cognitive tasks, with significantly longer reaction times for alertness, divided attention and working memory. These results confirm the presence of cognitive impairments in attentional and executive functions in recent-onset patients whether or not they are medicated. There was no evidence that either conventional or atypical antipsychotics had an influence on patients when EPS were excluded. Altogether, our results further support the idea that cognitive deficits in schizophrenia are enduring features per se and cannot be considered as secondary to psychiatric symptoms or to the adverse effects of medication. In addition our results suggest that antipsychotics do not have a major effect on these impairments.     

Non-linear complexity measures of heart rate variability in acute schizophrenia.

OBJECTIVE: Cardiovascular mortality is significantly increased in patients suffering from schizophrenia. The mechanisms currently discussed contain unhealthy lifestyle with obesity and smoking, increased incidence of diabetes, adverse pro-arrhythmic effects of antipsychotic medication and altered autonomic function. It is therefore likely that the adaptation of the heart rate to different requirements is faulty in schizophrenia. One way to detect adaptive capabilities and thus stability of regulation is to measure complexity of heart rate fluctuations, with more complex heart rate fluctuations indicating better adaptability of the underlying system. METHODS: We calculated novel non-linear measures for beat-to-beat interval complexity from short-term ECG recordings in 20 unmedicated patients suffering from acute schizophrenia and compared them to those obtained from matched controls. RESULTS: Data from all mathematical models applied, i.e. joint symbolic dynamics, compression entropy, fractal dimension and approximate entropy, revealed significantly reduced complexity of heart rate time series in acute schizophrenia. When using heart rate as a covariate, only fractal dimension remained significantly altered, thus appearing to be a relatively more important heart rate independent parameter. CONCLUSIONS: Complexity of heart rate modulation is significantly reduced in acute, untreated schizophrenia, thus indicating an increased risk for cardiovascular events in these patients. SIGNIFICANCE: These data might eventually add to the currently discussed monitoring of physical health in patients with schizophrenia, possibly providing a promising tool for cardio-arrhythmic risk stratification.     

Differential pattern of heart rate variability in patients with schizophrenia

The cardiac autonomic dysfunction has been reported in patients with schizophrenia. Heart rate variability (HRV) provides non-invasive indices of cardiac autonomic modulation. This study examined whether patients with schizophrenia may show a distinctive pattern of HRV compared to healthy controls. Nine measures of time, frequency and complexity domains were extracted from 5-min resting evaluation of HRV in 30 unmedicated patients with schizophrenia and 30 age- and gender-matched controls. In addition to inferential statistics, a hierarchical clustering (HC) was used to examine difference in the interrelationships among HRV measures between the two groups. Multivariate analysis of variance revealed a significant group effect. Significantly lower sample entropy (SampEn) and a trend towards a higher ratio of low- to high frequency (LF/HF) were observed in the schizophrenia group. In the results of HC using Ward's method, SampEn co-clustered with LF/HF ratio in patients with schizophrenia compared to the separation of LF/HF ratio in healthy controls. In concert with decreased parasympathetic activity, low complexity of heart rate dynamics may reduce adaptability of cardiovascular system to changes in internal or external environment, thus increasing the risk of cardiovascular events. Diverse HRV measures combined in a multivariate fashion appear to be useful in understanding the pattern of neurocardiac modulation in patients with schizophrenia.     

Time and frequency domain analyses of heart rate variability in patients with epilepsy

Heart rate variability (HRV) is a useful tool for the detection of sympathetic-parasympathetic balance of autonomic nervous system in patients at risk of sudden death (SD). SD is more common in patients with epilepsy and the exact mechanisms of SD are unknown. Autonomic nervous system involvement in patients with epilepsy has rarely been studied and has shown conflicting results. Our purpose was to determine if HRV showed any changes in patients with epilepsy in comparison with normal population. A short period analysis of HRV was performed for both the frequency and time domain in 43 epilepsy patients who had generalized tonic-clonic seizures (GTCS) and who were not taking any medications and also in 43 age and sex matched controls. In the time domain analysis, patients displayed higher SDNN (standard deviation of all R-R intervals), SDANN (standard deviation of mean NN intervals in 5 min recordings) and HRV triangular index than did healthy subjects (p < 0.0001). Patients tended to display higher pNN50 (number of R-R intervals differed by > 50 ms from adjacent interval divided by the total number of all R-R intervals) and RMSSD (root-mean-square of successive differences) values than did healthy subjects, but the differences were not statistically significant (p > 0.05). In the frequency domain analysis, the spectral measures of HRV showed a reduction of high frequency (HF) values (is a marker of parasympathetic activity) and an increase of low frequency (LF) values (is a measure of sympathetic activity); as a result, the ratio between low and high frequencies (LF/HF) was significantly increased (p < 0.0001, p < 0.0001 and p < 0.001, respectively). Our data suggests an increase in the sympathetic control of the heart rate in epilepsy patients who have GTCS. This increased sympathetic activity could play a key role in the development of ventricular tachyarrhythmias in patients with epilepsy and may be related to the higher incidence of sudden death in this disorder as compared to controls.     

Attentional markers of vulnerability to schizophrenia: performance of medicated and unmedicated patients and normals

Medicated and unmedicated schizophrenic patients (both n's = 14) were compared to a normal control sample (n = 15) on two attentional tasks hypothesized to be markers of vulnerability to schizophrenia. These tasks, the continuous performance test and the visual backward masking task, were found to be more deviant in schizophrenic patients than in normals. In addition, the group mean levels of performance did not differ consistently across medication status within the medicated patients. It was found, however, that the association between these tasks varied as a function of medication status, with unmedicated patients more similar to normals than to medicated patients. The implications of these results for the two tasks as markers are discussed, with special focus on those earlier studies that did not evaluate unmedicated patients.     

Neuropsychological performance in medicated and unmedicated patients with Tourette's disorder.

OBJECTIVE: To date, there have been no formal investigations of neuropsychological performance in patients with Tourette's disorder who are taking psychotropic medications. The authors conducted this study to provide such information. METHOD: They examined the neuropsychological performance of 96 patients 6-18 years old who met DSM-III-R criteria for Tourette's disorder; 51 of these patients were taking neuroleptic medications and 45 were not. The groups were well matched with regard to age, sex, education, and duration of symptoms. Each group was given a complete neuropsychological test battery as well as instruments rating symptoms of Tourette's disorder, obsessive-compulsive characteristics, and other behavioral disturbances. RESULTS: The patients taking medications did not differ from those not taking medications on any of the neuropsychological, intellectual, or educational measures. In addition, the groups did not differ with regard to level of Tourette's disorder symptoms. CONCLUSIONS: The results of this investigation suggest that patients with Tourette's disorder who do not experience intolerable side effects from neuroleptic medications are able to perform on educational, intellectual, and neuropsychological tests at a level comparable to that of unmedicated patients. These results have positive implications for patients with Tourette's disorder who respond to neuroleptic medications.     

Chaos and spectral analyses of heart rate variability during head-up tilting in essential hypertension.

To investigate nonlinear and linear components of heart rate variability (HRV) in essential hypertension (EHT), we analyzed HRV by chaos and spectral analyses in patients with EHT (n = 18) and normotensives (n = 10) during head-up tilting. We used the correlation dimension (CD) and Lyapunov exponents as the parameters of chaos. The CD, an index of complexity, was lower at rest in EHT group than in normotensives, and did not change in EHT group in response to head-up tilting, but decreased in normotensives. Head-up tilting did not change the Lyapunov exponents, an index of sensitive dependence on initial condition, a hallmark of chaos, in both groups. In the spectral analysis, the normalized high-frequency component (%HF) was decreased in EHT group at rest, and head-up tilting increased the low- to high-frequency ratio (L/H) and reduced the %HF in both groups. The CD and Lyapunov exponents at rest were correlated with the %HF and L/H. These results suggest that chaos analysis can assess the different aspect of HRV from spectral analysis and that nonlinear components of HRV may be associated with hypertension through an impaired dynamic regulation of HRV.     

Information processing deficits in acutely psychotic schizophrenia patients medicated and unmedicated at the time of admission

OBJECTIVE: In patients with schizophrenia, information processing deficits, such as those reported in studies that measured prepulse inhibition of the human startle response and habituation of startle magnitude, may be improved with atypical antipsychotic treatment. However, it remains unclear whether antipsychotic medication is directly responsible for the improvement or whether differences in prepulse inhibition reflect other factors, such as acuity status. The present study investigated the effects of antipsychotics on prepulse inhibition and startle habituation in acutely hospitalized patients with schizophrenia. METHOD: Forty-one acutely psychotic schizophrenia patients (21 who were unmedicated at the time of admission and 20 who had been receiving antipsychotic treatment) were tested within 72 hours of hospital admission. Thirteen healthy subjects were also studied for comparative purposes. Primary dependent measures were startle responsivity, reactivity, prepulse inhibition, and startle habituation. RESULTS: Schizophrenia patients, whether medicated or unmedicated at admission, showed prepulse inhibition deficits compared with healthy subjects and did not statistically differ from each other in startle magnitude, prepulse inhibition, or habituation. There was a higher number of startle "nonresponders" among those who had been receiving medication versus those unmedicated at the time of admission. CONCLUSIONS: The present findings suggest that antipsychotic effects on prepulse inhibition may not be evident at a time when schizophrenia patients are acutely symptomatic. These results suggest that the neurobiological substrate underlying prepulse inhibition deficits may be dysregulated during acute psychotic states while the patients are in early phases of medication treatment.     

Neuropsychological performance in medicated vs. unmedicated patients with obsessive-compulsive disorder

To date, there have been no formal investigations of neuropsychological performance in patients with obsessive-compulsive disorder (OCD) taking psychotropic medications. The purpose of this study was to determine whether medicated and unmedicated patients with OCD demonstrate differences in neuropsychological functioning. Fifty-two patients with a primary DSM-IV diagnosis of OCD participated in the study; 28 were taking serotonin reuptake inhibitors (SRIs), and 24 were treatment-na?ve (n=8) or had finished a washout period prior to their inclusion in other studies (n=16). The groups were well matched with regard to demographic and clinical variables, including symptom severity. Each group was administered a comprehensive neuropsychological battery to assess general intelligence, attention, verbal and non-verbal working memory, declarative and procedural learning, visuo-constructive skills, and executive functions. SRI-medicated did not differ from SRI-free patients on any neuropsychological measure. Benzodiazepines seemed to improve the patients' functioning on a semantic verbal fluency test. In addition, there were significant interactions between SRIs and benzodiazepines on the perseverative errors of the Wisconsin Card Sorting Test and on reaction times. SRI-medicated patients with OCD are able to perform on cognitive functioning tests at a comparable level with that of SRI-free patients, and these results have positive implications for OCD patients who respond to SRIs. The interactions between SRIs and benzodiazepines and their effect on cognition in OCD are likely to be complex and deserve further study.     

Impaired prepulse inhibition and prepulse-elicited reactivity but intact reflex circuit excitability in unmedicated schizophrenia patients: a comparison with healthy subjects and medicated schizophrenia patients

Deficient sensorimotor gating as indexed by prepulse inhibition (PPI) of the startle response has been reported repeatedly in patients suffering from schizophrenia. According to the widely accepted "protective hypothesis," PPI reflects the protection of ongoing information processing against interference by other stimuli. Alternatively, it has been proposed that PPI might be regulated by startle reflex circuit excitability. In the present study, we evaluated these 2 conceptually divergent approaches underlying the regulation of PPI. To this end, we assessed sensorimotor gating as indexed by PPI, the reactivity to the prepulse-alone stimulus indexed as prepulse-elicited reactivity (PPER), and acoustic blink reflex excitability in terms of paired pulse suppression (PPS) within a single recording session in 13 unmedicated and 24 medicated (11 first break) schizophrenia patients in comparison to 43 healthy control subjects. The results showed that PPI was significantly reduced in unmedicated, but not in medicated schizophrenia patients. Furthermore, unmedicated patients could be distinguished from the medicated patients and control subjects in terms of PPER. In contrast to PPI, PPS did not differ between patients and control subjects. These findings are in line with the "protective hypothesis" of PPI and indicate that reduced sensorimotor gating in schizophrenia patients might be based on a reduced perception and/or processing of the prepulse stimulus. The extent to which PPER may or may not be causally associated with sensorimotor gating in schizophrenia has to be further investigated in human and animal studies.     

Neurocognitive function in unmedicated manic and medicated euthymic pediatric bipolar patients

OBJECTIVE: A systematic evaluation of neuropsychological functioning in individuals with pediatric bipolar disorder is necessary to clarify the types of cognitive deficits that are associated with acutely ill and euthymic phases of the disorder and the effects of medication on these deficits. METHOD: Unmedicated (N=28) and medicated (N=28) pediatric bipolar patients and healthy individuals (N=28) (mean age=11.74 years, SD=2.99) completed cognitive testing. Groups were matched on age, sex, race, parental socioeconomic status, general intelligence, and single-word reading ability. A computerized neurocognitive battery and standardized neuropsychological tests were administered to assess attention, executive function, working memory, verbal memory, visual memory, visuospatial perception, and motor skills. RESULTS: Subjects with pediatric bipolar disorder, regardless of medication and illness status, showed impairments in the domains of attention, executive functioning, working memory, and verbal learning compared to healthy individuals. Also, bipolar subjects with comorbid attention deficit hyperactivity disorder (ADHD) performed worse on tasks assessing attention and executive function than patients with bipolar disorder alone. CONCLUSIONS: The absence of differences in the deficits of neurocognitive profiles between acutely ill unmedicated patients and euthymic medicated patients suggests that these impairments are trait-like characteristics of pediatric bipolar disorder. The cognitive deficits found in individuals with pediatric bipolar disorder suggest significant involvement of frontal lobe systems supporting working memory and mesial temporal lobe systems supporting verbal memory, regardless of ADHD comorbidity.     

Distinguishing depression and negative symptoms in unmedicated patients with schizophrenia

Depression can occur in schizophrenia but can be difficult to distinguish from negative symptoms of the illness. To evaluate whether concurrent use of the Hamilton Rating Scale for Depression (HRSD) and the Brief Psychiatric Rating Scale (BPRS) could successfully separate depression and negative symptoms, we examined ratings on 69 unmedicated schizophrenic inpatients. A classical BPRS depression subscale score correlated highly (rho = 0.80) with the HRSD total score. The classical BPRS "negative symptom" subscale score was unrelated to both the BPRS and HRSD depression summary measures. Among individual HRSD items, negative symptoms correlated only with work/activities and retardation. The findings suggest that negative and depressive symptoms may be assessed independently.     

脑中风患者心率变异的初步分析

目的：探讨中风后植物神经的变化规律及其变化机制。方法：采用反映植物神经功能折心率变异指标，对其时域指标进行分析、应用方差分析及ｔ检验，比较了健康对照组与中风组的心率变异情况。结果：（１）中风组ＳＤＮＮ及ＨＲＶＩ均明显低于健康对照组。（２）中风组随病程的处长，其心率变异逐渐增高，到半年后基本恢复到对照组的水平。     

Autonomic control of heart period in duodenal ulcer patients insights from spectral analysis of heart rate variability

Beyond the fundamental pathogenetic importance of Helicobacter Pylori a possible additional role of vagal innervation in favouring or modulating the clinical history of duodenal ulcer (DU) has been suggested by old studies employing invasive methodologies. Aim of this study was to assess whether vagal prevalence in autonomic modulation was present in healed DU patients (n=20) as compared to controls,(n=50), using a validated non-invasive methodology, based on spectral analysis of cardiovascular variability. This approach provides markers of the sympathetic and vagal modulations of the SA node, respectively by way of the normalized low frequency (LF(RR)) and high frequency (HF(RR)) components of RR interval variability; LF/HF ratio furnishes a marker of sympatho-vagal balance. In addition, sham feeding (SF) provided a means to assess, in DU patients, neurally mediated acid secretion, as the SF acid output (SAO) to basal acid output (BAO) ratio (SAO/BAO). Results showed that LF(RR) was smaller in DU patients than in controls (40.3+/-3.9 vs. 52.3+/-2.3 normalized units, nu; P<0.05). On the contrary, HF(RR) was greater (52.1+/-3.7 vs. 35.7+/-2.3 nu; P<0.05). Conversely the LF component of SAP variability, a marker of sympathetic vasomotor modulations, and the index alpha, a measure of baroreflex control of the SA node, as well as respiratory patterns, were similar in the two groups. SAO/BAO ratio was significantly correlated with markers of autonomic control of the SA node (r = -0.67, P<0.0083 with HF(RR)). In conclusion results suggest an enhanced vagal modulation of heart period in DU patients at rest, that appears linked to indices of neurally mediated gastric acid secretion response.     

偏头痛患者的自主神经功能及其定量测定

用心率变异频谱分析定量测定６５例偏头痛患者和５０例健康人仰卧位和站立位自主神经系统功能。结果发现，偏头痛患者站立位中频段积分较对照组显著降低（Ｐ〈０．００１），表明其交感神经功能低下，且随着疼痛程度的增加及病程的延长，其交感神经功能低下的程度迹越重，本文还初步探讨了其机理及临床应用意义。     

Facial expression recognition in people with medicated and unmedicated Parkinson's disease

Recognition of facial expressions of emotion was investigated in people with medicated and unmedicated Parkinson's disease (PD) and matched controls (unmedicated PD, n=16; medicated PD, n=20; controls, n=40). Participants in the medicated group showed some visual impairment (impaired contrast sensitivity) and performed less well on perception of unfamiliar face identity, but did not show significant deficits in the perception of sex, gaze direction, or familiar identity from the face. For both Parkinson's disease groups, there was evidence of impaired recognition of facial expressions in comparison to controls. These deficits were more consistently noted in the unmedicated group, who were also found to perform worse than the medicated group at recognising disgust from prototypical facial expressions, and at recognising anger and disgust in computer-manipulated images. Although both Parkinson's disease groups showed impairments of facial expression recognition, the consistently worse recognition of disgust in the unmedicated group is consistent with the hypothesis from previous studies that brain regions modulated by dopaminergic neurons are involved in the recognition of disgust.     

Observer variations in short period spectral analysis of heart rate variability

25% of the corresponding mean LF/HF ratio. The smallest interobserver variations were found for the 'fixed frequency' method. The data showed that it is advantageous to select the 3-min ECG periods but not to select the frequency regions. Selection of the latter led to an increase in interobserver variation. The results of this study give a realistic impression of the intrasubject and interobserver variation to be expected when measuring the LF/HF ratio. This variation is considerable.     

齐拉西酮对首发男性精神分裂症患者心率及变异性的影响

目的 研究齐拉西酮对首发精神分裂症男性患者的心率及变异性影响,为临床安全用药提供参考.方法 将2011年1月～2012年10月收治的首发精神分裂症男性患者61例纳入研究,给予齐拉西酮治疗;健康体检者63例作为对照组,比较治疗前两组心率及变异性的指标差异以及齐拉西酮治疗8周前后心率变异性的指标差异,了解齐拉西酮对精神分裂症男性患者的心率变异性影响.结果 在基线时,研究组和对照组相比,HR及HRV所有指标(SDNN、SDNNi、PNN50、SDANN)的差异均有统计学意义(P＜0.01);研究组治疗8周前后比较,除SDNNi外,其余指标的差异均有统计学意义(P＜0.01);研究组治疗8周后,与对照组比较,除PNN50外,其余指标的差异均有统计学意义(P＜0.01).结论 精神分裂症患者存在心率变异性下降,交感神经张力增加,迷走神经张力降低,有可能增加心源性猝死的几率,齐拉西酮的治疗可能加重其影响;故对于使用齐拉西酮治疗的精神分裂症男性患者需要加强观察以及实行心率变异性的监测,以加强医疗安全.