Temporal variability of regional intrinsic neural activity in drug‐naïve patients with obsessive–compulsive disorder

Obsessive–compulsive disorder (OCD) displays alterations in regional brain activity represented by the amplitude of low‐frequency fluctuation (ALFF), but the time‐varying characteristics of this local neural activity remain to be clarified. We aimed to investigate the dynamic changes of intrinsic brain activity in a relatively large sample of drug‐naïve OCD patients using univariate and multivariate analyses. We applied a sliding‐window approach to calculate the dynamic ALFF (dALFF) and compared the difference between 73 OCD patients and age‐ and sex‐matched healthy controls (HCs). We also utilized multivariate pattern analysis to determine whether dALFF could differentiate OCD patients from HCs at the individual level. Compared with HCs, OCD patients exhibited increased dALFF mainly within regions of the cortical–striatal–thalamic–cortical (CSTC) circuit, including the bilateral dorsal anterior cingulate cortex, medial prefrontal cortex and striatum, and right dorsolateral prefrontal cortex (dlPFC). Decreased dALFF was identified in the bilateral inferior parietal lobule (IPL), posterior cingulate cortex, insula, fusiform gyrus, and cerebellum. Moreover, we found negative correlations between illness duration and dALFF values in the right IPL and between dALFF values in the left cerebellum and Hamilton Depression Scale scores. Furthermore, dALFF can distinguish OCD patients from HCs with the most discriminative regions located in the IPL, dlPFC, middle occipital gyrus, and cuneus. Taken together, in the current study, we demonstrated a characteristic pattern of higher variability of regional brain activity within the CSTC circuits and lower variability in regions outside the CSTC circuits in drug‐naïve OCD patients.     

Abnormal interhemispheric and intrahemispheric functional connectivity dynamics in drug‐naïve first‐episode schizophrenia patients with auditory verbal hallucinations

Numerous studies indicate altered static local and long‐range functional connectivity of multiple brain regions in schizophrenia patients with auditory verbal hallucinations (AVHs). However, the temporal dynamics of interhemispheric and intrahemispheric functional connectivity patterns remain unknown in schizophrenia patients with AVHs. We analyzed resting‐state functional magnetic resonance imaging data for drug‐naïve first‐episode schizophrenia patients, 50 with AVHs and 50 without AVH (NAVH), and 50 age‐ and sex‐matched healthy controls. Whole‐brain functional connectivity was decomposed into ipsilateral and contralateral parts, and sliding‐window analysis was used to calculate voxel‐wise interhemispheric and intrahemispheric dynamic functional connectivity density (dFCD). Finally, the correlation analysis was performed between abnormal dFCD variance and clinical measures in the AVH and NAVH groups. Compared with the NAVH group and healthy controls, the AVH group showed weaker interhemispheric dFCD variability in the left middle temporal gyrus (p < .01; p < .001), as well as stronger interhemispheric dFCD variability in the right thalamus (p < .001; p < .001) and right inferior temporal gyrus (p < .01; p < .001) and stronger intrahemispheric dFCD variability in the left inferior frontal gyrus (p < .001; p < .01). Moreover, abnormal contralateral dFCD variability of the left middle temporal gyrus correlated with the severity of AVHs in the AVH group (r = −.319, p = .024). The findings demonstrate that abnormal temporal variability of interhemispheric and intrahemispheric dFCD in schizophrenia patients with AVHs mainly focus on the temporal and frontal cortices and thalamus that are pivotal components of auditory and language pathways.     

Altered single‐subject gray matter structural networks in drug‐naïve attention deficit hyperactivity disorder children

Altered topological organization of brain structural covariance networks has been observed in attention deficit hyperactivity disorder (ADHD). However, results have been inconsistent, potentially related to confounding medication effects. In addition, since structural networks are traditionally constructed at the group level, variabilities in individual structural features remain to be well characterized. Structural brain imaging with MRI was performed on 84 drug‐naïve children with ADHD and 83 age‐matched healthy controls. Single‐subject gray matter (GM) networks were obtained based on areal similarities of GM, and network topological properties were analyzed using graph theory. Group differences in each topological metric were compared using nonparametric permutation testing. Compared with healthy subjects, GM networks in ADHD patients demonstrated significantly altered topological characteristics, including higher global and local efficiency and clustering coefficient, and shorter path length. In addition, ADHD patients exhibited abnormal centrality in corticostriatal circuitry including the superior frontal gyrus, orbitofrontal gyrus, medial superior frontal gyrus, precentral gyrus, middle temporal gyrus, and pallidum (all p < .05, false discovery rate [FDR] corrected). Altered global and nodal topological efficiencies were associated with the severity of hyperactivity symptoms and the performance on the Stroop and Wisconsin Card Sorting Test tests (all p < .05, FDR corrected). ADHD combined and inattention subtypes were differentiated by nodal attributes of amygdala (p < .05, FDR corrected). Alterations in GM network topologies were observed in drug‐naïve ADHD patients, in particular in frontostriatal loops and amygdala. These alterations may contribute to impaired cognitive functioning and impulsive behavior in ADHD.     

Eight‐week antidepressant treatment reduces functional connectivity in first‐episode drug‐naïve patients with major depressive disorder

Previous neuroimaging studies have revealed abnormal functional connectivity of brain networks in patients with major depressive disorder (MDD), but findings have been inconsistent. A recent big‐data study found abnormal intrinsic functional connectivity within the default mode network in patients with recurrent MDD but not in first‐episode drug‐naïve patients with MDD. This study also provided evidence for reduced default mode network functional connectivity in medicated MDD patients, raising the question of whether previously observed abnormalities may be attributable to antidepressant effects. The present study (ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03294525","term_id":"NCT03294525"}}NCT03294525) aimed to disentangle the effects of antidepressant treatment from the pathophysiology of MDD and test the medication normalization hypothesis. Forty‐one first‐episode drug‐naïve MDD patients were administrated antidepressant medication (escitalopram or duloxetine) for 8 weeks, with resting‐state functional connectivity compared between posttreatment and baseline. To assess the replicability of the big‐data finding, we also conducted a cross‐sectional comparison of resting‐state functional connectivity between the MDD patients and 92 matched healthy controls. Both Network‐Based Statistic analyses and large‐scale network analyses revealed intrinsic functional connectivity decreases in extensive brain networks after treatment, indicating considerable antidepressant effects. Neither Network‐Based Statistic analyses nor large‐scale network analyses detected significant functional connectivity differences between treatment‐naïve patients and healthy controls. In short, antidepressant effects are widespread across most brain networks and need to be accounted for when considering functional connectivity abnormalities in MDD.     

Calcium metabolism in schizophrenic patients on long-term neuroleptic therapy

The bone mineral content (BMC) in both forearms (highly related to total body calcium) was measured in a large group of schizophrenic patients receiving neuroleptic drugs. The mean BMC value was 86% of normal (p less than 0.001), and the decrease was independent of type of neuroleptic treatment. In contrast, the biochemical variables (serum calcium, magnesium, phosphate, and alkaline phosphatases) were virtually normal. This combination of osteopenia and normal biochemical variables suggests that schizophrenics have osteoporosis, be it due to the disease or the treatment given.     

利培酮与舒必利对首发精神分裂症患者血脂代谢的影响

目的：探讨利培酮和舒必利对首发精神分裂症患者血脂代谢的影响。方法：2006年2月至2009年2月期间我院门诊或住院的精神分裂症患者213例,测定利培酮或舒必利治疗8周前后的血胆固醇及三酰甘油浓度。结果：利培酮治疗后,血胆固醇（TC）及血三酰甘油（TG）明显升高（t=2.316,P〈0.05;t=2.438,P〈0.05）,且男性患者组升高较三酰甘油明显（t=2.118,P〈0.05;t=2.132,P〈0.05）;舒必利组治疗后血三酰甘油明显升高（t=2.355,P〈0.05）,且女性TG升高的程度显著大于男性患者（t=2.68,P〈0.01）。结论：利培酮治疗后血胆固醇及三酰甘油水平升高,男性更明显。舒必利治疗后血三酰甘油水平升高,女性更明显。利培酮对TC的影响大于舒必利。     

Identifying a whole‐brain connectome‐based model in drug‐naïve Parkinson's disease for predicting motor impairment

Identifying a whole‐brain connectome‐based predictive model in drug‐naïve patients with Parkinson''s disease and verifying its predictions on drug‐managed patients would be useful in determining the intrinsic functional underpinnings of motor impairment and establishing general brain–behavior associations. In this study, we constructed a predictive model from the resting‐state functional data of 47 drug‐naïve patients by using a connectome‐based approach. This model was subsequently validated in 115 drug‐managed patients. The severity of motor impairment was assessed by calculating Unified Parkinson''s Disease Rating Scale Part III scores. The predictive performance of model was evaluated using the correlation coefficient (r _true) between predicted and observed scores. As a result, a connectome‐based model for predicting individual motor impairment in drug‐naïve patients was identified with significant performance (r _true = .845, p < .001, p _permu = .002). Two patterns of connection were identified according to correlations between connection strength and the severity of motor impairment. The negative motor‐impairment‐related network contained more within‐network connections in the motor, visual‐related, and default mode networks, whereas the positive motor‐impairment‐related network was constructed mostly with between‐network connections coupling the motor‐visual, motor‐limbic, and motor‐basal ganglia networks. Finally, this predictive model constructed around drug‐naïve patients was confirmed with significant predictive efficacy on drug‐managed patients (r = .209, p = .025), suggesting a generalizability in Parkinson''s disease patients under long‐term drug influence. In conclusion, this study identified a whole‐brain connectome‐based model that could predict the severity of motor impairment in Parkinson''s patients and furthers our understanding of the functional underpinnings of the disease.     

Aberrant dynamic structure–function relationship of rich‐club organization in treatment‐naïve newly diagnosed juvenile myoclonic epilepsy

Neuroimaging studies have shown that juvenile myoclonic epilepsy (JME) is characterized by impaired brain networks. However, few studies have investigated the potential disruptions in rich‐club organization—a core feature of the brain networks. Moreover, it is unclear how structure–function relationships dynamically change over time in JME. Here, we quantify the anatomical rich‐club organization and dynamic structural and functional connectivity (SC–FC) coupling in 47 treatment‐naïve newly diagnosed patients with JME and 40 matched healthy controls. Dynamic functional network efficiency and its association with SC–FC coupling were also calculated to examine the supporting of structure–function relationship to brain information transfer. The results showed that the anatomical rich‐club organization was disrupted in the patient group, along with decreased connectivity strength among rich‐club hub nodes. Furthermore, reduced SC–FC coupling in rich‐club organization of the patients was found in two functionally independent dynamic states, that is the functional segregation state (State 1) and the strong somatomotor‐cognitive control interaction state (State 5); and the latter was significantly associated with disease severity. In addition, the relationships between SC–FC coupling of hub nodes connections and functional network efficiency in State 1 were found to be absent in patients. The aberrant dynamic SC–FC coupling of rich‐club organization suggests a selective influence of densely interconnected network core in patients with JME at the early phase of the disease, offering new insights and potential biomarkers into the underlying neurodevelopmental basis of behavioral and cognitive impairments observed in JME.     

Regional glucose metabolism in schizophrenic patients before and during neuroleptic treatment

Wiesel, Frits-Axel: Regional glucose metabolism in schizophrenic patients before and during neuroleptic treatment. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 871–881.

1. 1. Determination of regional glucose metabolism has been considered to be a tool to elucidate the mechanisms of action of neuroleptics.

2. 2. D₂-dopamine antagonists seem to increase glucose consumption in dopamine innervated areas.

3. 3. Studies in humans do not give results in complete accordance with animal findings.

4. 4. In patients neuroleptic compounds and dopamin agonists probably increase and decrease striatal metabolism respectively.

5. 5. Changes in metabolism, especially in the right hemisphere may be coupled with improvement of the patients.

6. 6. Future research must be based on protocols specially designed for the study of drug effects.

Immediate effects of risperidone on cerebral activity in healthy subjects: a comparison with subjects with first-episode schizophrenia

OBJECTIVE: To test the hypothesis that administration of risperidone to healthy subjects produces reductions in metabolism in the frontal cortex similar to those produced by administration of risperidone to patients experiencing a first episode of schizophrenia. METHODS: Positron emission tomography was used to measure the changes in regional metabolism produced by a single 2-mg dose of risperidone and by placebo, administered under randomized, double-blind conditions, in 9 healthy subjects. Conjunction analysis was used to identify those cerebral sites where changes in metabolism in the healthy subjects coincided with similar changes in metabolism observed in patients with schizophrenia. RESULTS: Compared with placebo, risperidone produced reductions in metabolism in the left lateral frontal cortex and right medial frontal cortex in healthy subjects. Conjunction analysis revealed that these changes occurred at locations similar to the loci of change produced by risperidone in patients with schizophrenia. CONCLUSION: Because the reduction in metabolism in the medial frontal cortex produced by risperidone is associated with alleviation of positive symptoms in patients with schizophrenia, the observation of a reduction in metabolism at a similar site in healthy subjects supports the hypothesis that the antipsychotic effect of risperidone arises, at least in part, from a physiologic effect that occurs in both patients with schizophrenia and healthy subjects.     

氯氮平和利培酮对首发精神分裂症患者糖代谢影响的研究

目的　探讨氯氮平和利培酮对首发精神分裂症患者糖代谢的影响。方法　 6 8例首发精神分裂症患者随机分为两组 ,分别给予氯氮平治疗 ( 34例 ,氯氮平组 )和利培酮治疗 ( 34例 ,利培酮组 )。两组患者治疗前和治疗后第 4周末做糖耐量试验 ,测定空腹胰岛素、C肽、甘油三酯、胆固醇、瘦素 ,并测量身高、体重 ,计算体重指数 [BMI,体重 (kg) /身高 (m2 ) ]。共观察 4周。结果　治疗第 4周末 ,氯氮平组餐后 1h、2h的血糖值 [分别为 ( 8 6± 1 8)mmol/L和 ( 6 7± 1 1)mmol/L]比治疗前 [分别为( 7 4± 2 2 )mmol/L和 ( 5 8± 1 4 )mmol/L]明显升高 (P <0 0 5 ,P <0 0 1) ,而利培酮组无明显变化。治疗后氯氮平组 ( 2 0 % ,7例 )患者糖耐量减低的发生率高于利培酮组 ( 3% ,1例 ) ,差异有显著性 ( χ2 =3 972 ,P <0 0 5 )。结论　氯氮平对首发精神分裂症患者餐后血糖值的影响大于利培酮     

生殖激素水平对女性精神分裂症患者利培酮所致月经延迟的影响

目的 探讨服用利培酮精神分裂症患者出现月经延迟的危险因素及可能机制.方法 采用前瞻性巢式病例-对照研究设计,将未接受抗精神病药治疗、符合中国精神疾病分类与诊断标准第3版精神分裂症诊断标准、常规服用利培酮治疗8周后出现月经延迟>4周的31例患者(研究组)和月经仍然规律的32例患者(对照组),于治疗前1 d和治疗第8周末检...     

利培酮对精神分裂症患者肝功能的影响

目的：了解利培酮对精神分裂症患者肝功能的影响。方法：对183例单一服用利培酮的住院患者在治疗前及治疗后作肝功能检测：结果：服用利培酮后肝功能异常者50例(27．32％)，男性患者高于女性患者。结论：利培酮可损害肝功能，但多较轻微且易于恢复。     

Effect of adjuvant reserpine treatment on catecholamine metabolism in schizophrenic patients under long-term neuroleptic treatment

Summary The clinical and biochemical effects of adjuvant reserpine treatment were investigated in 12 chronic schizophrenic patients on long-term neuroleptic medication. The global severity of the symptoms using the Brief Psychiatric Rating Scale did not change significantly in the whole group, however, a moderate decrease in positive symptoms (factors though disturbance, activation and hostile-suspiciousness) was observed for 5 patients. Cerebrospinal fluid (CSF) noradrenaline levels showed a consistent decrease, but other biochemical parameters (CSF dopamine metabolites, platelet MAO and serum dopamine--hydroxylase activities) did not change significantly. The changes of clinical symptoms and biochemical parameters did not show any correlation.This work was supported by the State Office for Technical Development.     

利培酮治疗老年期精神分裂症对照研究

目的:比较利培酮和奋乃静治疗老年期首发精神分裂症的疗效和安全性. 方法:将96例老年期首发精神分裂症住院患者,随机分为利培酮组和奋乃静组,分别给予利培酮和奋乃静治疗.疗程8周.以简明精神病评定量表(BPRS)评定疗效,用副反应量表(TESS)评定不良反应. 结果:利培酮与奋乃静临床疗效差异无显著性.利培酮的不良反应主要为失眠,恶心、呕吐.奋乃静锥体外系反应较重. 结论:利培酮治疗老年期首发精神分裂症疗效较好,安全性高,有利于长期巩固维持治疗.     

Quantitative tractography reveals changes in the corticospinal tract in drug-naïve children with attention-deficit/hyperactivity disorder

BackgroundThe specific role of the corticospinal tract with respect to inattention and impulsive symptoms in children with attentiondeficit/hyperactivity disorder (ADHD) has been explored in the past. However, to our knowledge, no study has identified the exact regions of the corticospinal tract that are affected in ADHD. We aimed to determine comprehensive alterations in the white matter microstructure of the corticospinal tract and underlying neuropsychological substrates in ADHD.MethodsWe recruited 38 drug-naïve children with ADHD and 34 typically developing controls. We employed a tract-based quantitative approach to measure diffusion parameters along the trajectory of the corticospinal tract, and we further correlated alterations with attention and response inhibition measures.ResultsCompared with controls, children with ADHD demonstrated significantly lower fractional anisotropy and higher radial diffusivity at the level of cerebral peduncle, and higher fractional anisotropy at the level of the posterior limb of the internal capsule in the right corticospinal tract only. As well, increased fractional anisotropy in the posterior limb of the internal capsule was negatively correlated with continuous performance test attention quotients and positively correlated with reaction time on the Stroop Colour–Word Test; increased radial diffusivity in the right peduncle region was positively correlated with omissions in the Stroop test.LimitationsThe sample size was relatively small. Moreover, we did not consider the different subtypes of ADHD and lacked sufficient power to analyze subgroup differences. Higher-order diffusion modelling is needed in future white matter studies.ConclusionWe demonstrated specific changes in the right corticospinal tract in children with ADHD. Correlations with measures of attention and response inhibition underscored the functional importance of corticospinal tract disturbance in ADHD.     

Effects of risperidone on event-related potentials in schizophrenic patients

In order to examine the effects of risperidone on cognitive impairment in schizophrenia, event-related potentials (ERPs) were recorded before and after switching from conventional neuroleptics to risperidone in schizophrenic patients. ERPs were recorded during two auditory discrimination tasks (an oddball task and a distraction task) in 10 medicated schizophrenic patients during conventional neuroleptic and risperidone treatments. The amplitudes and latencies of N 100 and P300 component were measured in ERPs for target stimuli in the oddball task and in ERPs for target and novel stimuli in the distraction task. Although N 100 amplitude and latency and P 300 amplitude did not change significantly after switching the drug compared to that during conventional neuroleptic treatment, P 300 latency for target stimuli shortened significantly during risperidone treatment in both tasks, accompanied by the shortening of the reaction time in the distraction task. The P 300 latency change did not correlate with the change of the severity of psychopathology. These findings suggest that risperidone may speed the information processing in schizophrenic patients, contributing to the improvement of cognitive functions.     

Positron emission tomography in schizophrenic patients with and without neuroleptic medication

Positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose was performed in nine chronic schizophrenic patients both when medication-free and when medicated with neuroleptics. Total brain cortex, temporal cortex, and basal ganglia glucose use was significantly increased with medication; however, there was no change in anterior/posterior metabolic gradients.