The use and utility of EMG biofeedback with chronic schizophrenic patients

This study examined the efficacy of muscle relaxation training via electromyographic (EMG) biofeedback from the frontalis and forearm extensor muscles of schizophrenic inpatients. Thirty chronically hospitalized patients were randomly assigned to one of three conditions: EMG biofeedback from the forearm extensor and frontalis muscles, progressive relaxation, and a control group. Treatment consisted of one session of orientation and baseline, and six sessions of training. The results indicated that the schizophrenic patients receiving EMG training had significantly lower EMG recordings than the progressive relaxation group, which, in turn, was significantly lower than the control group. Analyses of covariance on the Tension-Anxiety scale from the Profile of Mood States revealed no significant effects, while finger-tapping rates were significantly improved only for the arm receiving feedback training in the EMG group. On the Nurses Observation Scale for Inpatient Evaluation the biofeedback group significantly improved on the Social Competence and Social Interest factors.We would like to express our appreciation for the contributions the following people made to this project: Drs. Barry Smith, Robert Steele, Agnes Hartfield, Jeffrey Barth, Althea Wagman, and the late Harold Weiner; Earl Downs and the participating staff at Springfield State Hospital Center; and Robert Kline and Michael Kelley, who performed the data analyses. This research was supported in part by a grant from the Computer Science Center at the University of Maryland.     

Targeted tandem affinity purification of PSD‐95 recovers core postsynaptic complexes and schizophrenia susceptibility proteins

The molecular complexity of mammalian proteomes demands new methods for mapping the organization of multiprotein complexes. Here, we combine mouse genetics and proteomics to characterize synapse protein complexes and interaction networks. New tandem affinity purification (TAP) tags were fused to the carboxyl terminus of PSD‐95 using gene targeting in mice. Homozygous mice showed no detectable abnormalities in PSD‐95 expression, subcellular localization or synaptic electrophysiological function. Analysis of multiprotein complexes purified under native conditions by mass spectrometry defined known and new interactors: 118 proteins comprising crucial functional components of synapses, including glutamate receptors, K⁺ channels, scaffolding and signaling proteins, were recovered. Network clustering of protein interactions generated five connected clusters, with two clusters containing all the major ionotropic glutamate receptors and one cluster with voltage‐dependent K⁺ channels. Annotation of clusters with human disease associations revealed that multiple disorders map to the network, with a significant correlation of schizophrenia within the glutamate receptor clusters. This targeted TAP tagging strategy is generally applicable to mammalian proteomics and systems biology approaches to disease.     

Performance deficit of alpha7 nicotinic receptor knockout mice in a delayed matching-to-place task suggests a mild impairment of working/episodic-like memory

Patients with schizophrenia exhibit deficits in a range of cognitive functions, particularly working and episodic memory, which are thought to be core features of the disorder. Memory dysfunction in schizophrenia is familial and thus a promising endophenotype for genetic studies. Both human and animal studies suggest a role for the neural nicotinic acid receptor family in cognition and specifically the alpha7-receptor subunit in schizophrenia and its endophenotypes. Consequently, we tested mice lacking the alpha7 subunit of the neural nicotinic receptor (B6.129S7-Chrna7(tm1Bay)/J) in the delayed matching-to-place (DMP) task of the Morris water maze, a measure of working/episodic memory akin to human episodic memory. We report that a minor impairment in alpha7 knockout mice was observed in the DMP task, with knockout mice taking longer to find the hidden platform than their wildtype controls. This suggests a role for the alpha7 subunit in working/episodic memory and a potential role for the alpha7 neural nicotinic receptor gene (CHRNA7) in schizophrenia and its endophenotypes.     

布南色林联合团体心理治疗慢性精神分裂症的疗效及对认知功能、社会功能和服药依从性的影响

摘要 目的：探讨布南色林联合团体心理治疗慢性精神分裂症（SZ）的疗效,分析其对认知功能、社会功能和服药依从性的影响。方法：选取124例慢性SZ患者随机分为对照组和观察组,对照组口服布南色林治疗,观察组在对照组基础上加以团体心理治疗,疗程均为2个月。治疗后,采用阳性与阴性症状量表（PANSS）和临床疗效总评量表-疾病严重程度（CGI-SI）评估两组患者治疗后的疗效,采用威斯康星卡片分类测验（WCST）评估两组患者治疗前后的认知功能,采用个人和社会功能量表（PSP）评估两组患者治疗前后的社会功能,评定两组患者治疗后的服药依从性。结果：治疗后,两组患者PANSS阳性症状、阴性症状、一般精神病理评分以及总评分均低于治疗前,且观察组低于对照组（P＜0.05）;两组患者CGI-SI评分均低于治疗前,且观察组低于对照组（P＜0.05）;两组患者WCST总应答数评分均高于治疗前,且观察组高于对照组（P＜0.05）;两组患者PSP总评分均高于治疗前,且观察组高于对照组（P＜0.05）;观察组服药依从性优于对照组（P＜0.05）。结论：布南色林联合团体心理治疗较单一布南色林治疗慢性SZ的治疗效果更好,能更好地提高患者的认知功能、社会功能以及服药依从性,值得临床借鉴推广。     

Sensorimotor gating and spatial learning in α7‐nicotinic receptor knockout mice

The role of acetylcholine and specific nicotinic receptors in sensorimotor gating and higher cognitive function has been controversial. Here, we used a commercially available mouse with a null mutation in the Chrna7^tm1Bay gene [α7‐nicotinic acetylcholine receptor (nAChR) knockout (KO) mouse] in order to assess the role of the α7‐nAChR in sensorimotor gating and spatial learning. We examined prepulse inhibition (PPI) of startle and nicotine‐induced enhancement of PPI. We also tested short‐ and long‐term habituation of the startle response as well as of locomotor behaviour in order to differentiate the role of this receptor in the habituation of evoked behaviour (startle) vs. motivated behaviour (locomotion). To address higher cognition, mice were also tested in a spatial learning task. Our results showed a mild but consistent PPI deficit in α7‐nAChR KO mice. Furthermore, they did not show nicotine‐induced enhancement of startle or PPI. Short‐ and long‐term habituation was normal in KO mice for both types of behaviours, evoked or motivated, and they also showed normal learning and memory in the Barnes maze. Thorough analysis of the behavioural data indicated a slightly higher degree of anxiety in α7‐nAChR KO mice; however, this could only be partially confirmed in an elevated plus maze test. In summary, our data suggest that α7‐nAChRs play a minor role in PPI, but seem to mediate nicotine‐induced PPI enhancement. We found no evidence to suggest that they are important for habituation or spatial learning .     

Neuropsychological effects of the CSMD1 genome‐wide associated schizophrenia risk variant rs10503253

The single‐nucleotide polymorphism (SNP) rs10503253, located within the CUB and Sushi multiple domains‐1 (CSMD1) gene on 8p23.2, was recently identified as genome‐wide significant for schizophrenia (SZ), but is of unknown function. We investigated the neurocognitive effects of this CSMD1 variant in vivo in patients and healthy participants using behavioral and imaging measures of brain structure and function. We compared carriers and non‐carriers of the risk ‘A’ allele on measures of neuropsychological performance typically impaired in SZ (general cognitive ability, episodic and working memory and attentional control) in independent samples of Irish patients (n = 387) and controls (n = 171) and German patients (205) and controls (n = 533). Across these groups, the risk ‘A’ allele at CSMD1 was associated with deleterious effects across a number of neurocognitive phenotypes. Specifically, the risk allele was associated with poorer performance on neuropsychological measures of general cognitive ability and memory function but not attentional control. These effects, while significant, were subtle, and varied between samples. Consistent with previous evidence suggesting that CSMD1 may be involved in brain mechanisms related to memory and learning, these data appear to reflect the deleterious effects of the identified ‘A’ risk allele on neurocognitive function, possibly as part of the mechanism by which CSMD1 is associated with SZ risk.     

DISC1 and the aggresome

Disrupted in Schizophrenia 1 (DISC1) is a key susceptibility gene for major psychiatric disorders. DISC1 plays a role in key neuronal processes such as neuronal proliferation, migration, integration and function via DISC1's roles at the centrosome and synapse, and in the regulation of intracellular signaling pathways. Recently, the idea of protein aggregation as a disease mechanism for DISC1 has been suggested. In our recent paper we explore these DISC1 protein aggregates in cell lines and neurons and find they are recruited to the aggresome and cause disruption of DISC1 function in intracellular transport.