Abstract:
:Pharmacological and genetic rodent models of schizophrenia play an important role in the drug discovery pipeline, but quantifying the molecular similarity of such models with the underlying human pathophysiology has proved difficult. We developed a novel systems biology methodology for the direct comparison of anterior prefrontal cortex tissue from four established glutamatergic rodent models and schizophrenia patients, enabling the evaluation of which model displays the greatest similarity to schizophrenia across different pathophysiological characteristics of the disease. Liquid chromatography coupled tandem mass spectrometry (LC-MSE) proteomic profiling was applied comparing healthy and "disease state" in human post-mortem samples and rodent brain tissue samples derived from models based on acute and chronic phencyclidine (PCP) treatment, ketamine treatment or NMDA receptor knockdown. Protein-protein interaction networks were constructed from significant abundance changes and enrichment analyses enabled the identification of five functional domains of the disease such as "development and differentiation", which were represented across all four rodent models and were thus subsequently used for cross-species comparison. Kernel-based machine learning techniques quantified that the chronic PCP model represented schizophrenia brain changes most closely for four of these functional domains. This is the first study aiming to quantify which rodent model recapitulates the neuropathological features of schizophrenia most closely, providing an indication of face validity as well as potential guidance in the refinement of construct and predictive validity. The methodology and findings presented here support recent efforts to overcome translational hurdles of preclinical psychiatric research by associating functional dimensions of behaviour with distinct biological processes.
journal_name
Schizophr Resjournal_title
Schizophrenia researchauthors
Cox DA,Gottschalk MG,Wesseling H,Ernst A,Cooper JD,Bahn Sdoi
10.1016/j.schres.2016.06.012subject
Has Abstractpub_date
2016-11-01 00:00:00pages
98-107issue
1-3eissn
0920-9964issn
1573-2509pii
S0920-9964(16)30279-1journal_volume
177pub_type
杂志文章abstract::This study determines that visuospatial working memory (VSWM) deficits are evident in adolescent-onset schizophrenia, while the spatial strategy and spatial span components of VSWM are spared. These findings imply that frontal-striatal-parietal neural networks are dysfunctional in adolescent-onset schizophrenia, while...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2006.04.025
更新日期:2006-10-01 00:00:00
abstract::Affective impairments were examined in patients with and without deficit syndrome schizophrenia. Two Emotional Stroop tasks designed to measure automatic processing of emotional information were administered to deficit (n=15) and non-deficit syndrome (n=26) schizophrenia patients classified according to the Schedule f...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2008.01.014
更新日期:2008-07-01 00:00:00
abstract:OBJECTIVE:Executive dysfunction is a common feature of schizophrenia and bipolar disorder (BP). While deficits in social cognitive abilities, including theory of mind (ToM), have been suggested to be specific to schizophrenia, available evidence suggests that there is also a significant overlap in social cognitive perf...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2016.06.007
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND:Heterogeneity in clinical outcomes may be caused by factors working at multiple levels, e.g., between groups, between subjects, or within subjects over time. A more nuanced assessment of differences in variation among schizophrenia patients and between patients and healthy comparison subjects can clarify eti...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2012.10.033
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Many patients recovering from a first psychotic episode will discontinue medication against medical advice, even before a 1-year treatment course is completed. Factors associated with treatment adherence in patients with chronic schizophrenia include beliefs about severity of illness and need for treatment, ...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2005.10.016
更新日期:2006-03-01 00:00:00
abstract::The frontal and temporal lobes have been implicated as pathogenic sites for schizophrenia, although there is a marked heterogeneity of brain function and structure between individual patients. It is currently unclear whether some patients with schizophrenia exhibit primarily frontal lobe dysfunction, while others exhi...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(00)00115-8
更新日期:2001-03-01 00:00:00
abstract::Using the fluorescent probe DPH (1,6-diphenyl-1,3,5-hexatriene), steady-state anisotropy (rs) values were determined in red blood cell (RBC) ghost membranes of schizophrenic patients before (n = 26) and after (n = 16) haloperidol withdrawal, and age- and sex-matched normal controls (n = 22). Patients on haloperidol we...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/0920-9964(94)90014-0
更新日期:1994-02-01 00:00:00
abstract::Serum prolactin (PRL) was correlated with clinical symptomatology in 17 drug-free patients suffering from non-affective psychoses. A clear-cut negative correlation was found between the Comprehensive Psychiatric Rating Scale (CPRS) items assessing hallucinations and serum PRL levels (r=-6.14, P=0.009). No correlation ...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(99)00195-4
更新日期:2000-09-01 00:00:00
abstract::Cognitive adaptation training (CAT) is a home-based, manualized treatment that utilizes environmental supports to improve target behaviors and functional outcomes in persons with schizophrenia. Although clinical trials have shown CAT to be effective across functional, clinical, and treatment adherence domains, when th...
journal_title:Schizophrenia research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.schres.2014.03.026
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVE:While "dual diagnosis" involving both psychiatric and substance use disorders has long been a focus of schizophrenia research, recent studies have advocated for a shift of focus to multimorbidity, addressing comorbidity from both additional psychiatric disorders and substance use disorders. We hypothesized th...
journal_title:Schizophrenia research
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.schres.2018.04.035
更新日期:2018-11-01 00:00:00
abstract::The present study determined the minimal exposure time (i.e., critical stimulus duration (CSD) necessary for feature registration and recognition by normals and chronic schizophrenics. Our interest was whether the longer exposure times required by schizophrenics than by normals could be attributed to an inability of s...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/0920-9964(92)90049-b
更新日期:1992-07-01 00:00:00
abstract::Jumping to conclusions and bias against disconfirmatory evidence are two cognitive biases common in people with psychotic-like experiences and psychosis. However, many participants show comprehension problems doing traditional tasks; new paradigms with additional applied scenarios are thus needed. A large MTurk commun...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2019.12.016
更新日期:2020-02-01 00:00:00
abstract::The SELENBP1 gene previously was found to be up-regulated in microarray analysis of both peripheral blood cell and brain tissue samples from schizophrenia patients. Quantitative PCR analysis subsequently corroborated the altered expression of SELENBP1 in schizophrenia brain tissue samples from the Stanley Array Correc...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2009.06.011
更新日期:2009-09-01 00:00:00
abstract::There is some evidence that memory for temporal order is a process that may be impaired independently of other forms of memory. For example, patients with Korsakoff's syndrome have been shown to have poorer temporal-order memory than other amnesic patients, despite item memory being equivalent. Patients with schizophr...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(00)00014-1
更新日期:2000-12-15 00:00:00
abstract:BACKGROUND:Previous studies have shown that individuals with schizophrenia exhibit higher levels of unhelpful metacognitive beliefs than healthy controls, but no studies have explored metacognitive beliefs in early psychosis. AIMS:We examined i) differences in levels of unhelpful metacognitive beliefs between psychosi...
journal_title:Schizophrenia research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.schres.2015.10.026
更新日期:2015-12-01 00:00:00
abstract::We tested the hypothesis that the expression of schizophrenic psychopathology is dependent on the stage of adolescent development. The study had a retrospective design, using high-quality case-note material of cases of schizophrenia at first admission. Patients with onset of illness between the age of 11 and 21 years ...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/0920-9964(94)00020-9
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND:Severity of negative symptoms has been associated with poor functioning, cognitive deficits, and defeatist beliefs in schizophrenia patients. However, one area that remains understudied is persistent negative symptoms (PNS). Negative symptoms, including PNS, have been observed in those at clinical high-risk ...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2020.04.004
更新日期:2020-04-30 00:00:00
abstract::Because previous studies have shown deficits in olfactory identification for male patients with schizophrenia, either withdrawn from or receiving neuroleptic medication, the purpose of the current study was to determine if such deficits occurred in male patients who had never received neuroleptics. A sample of male (n...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/0920-9964(93)90022-b
更新日期:1993-01-01 00:00:00
abstract::The author previously proposed that schizophrenia has similar cytokine expression compared to melanoma, a neural crest cell tumor. One possible tumor model of schizophrenia includes anti-NMDA receptor encephalitis, a paraneoplastic syndrome. While examining the possible relationship of neural crest cell tumors to schi...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2016.08.012
更新日期:2016-10-01 00:00:00
abstract::Around 1 in 5 children under 13 years old experience sub-clinical psychotic experiences (PEs) like hallucinations and delusions. While PEs in childhood are a significant risk factor for adult psychotic disorders, the majority of those experiencing childhood PEs do not develop a psychotic disorder. Individual differenc...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2019.08.022
更新日期:2020-01-01 00:00:00
abstract::The aim of this paper is to provide a brief review of mitochondrial structure as it relates to function and then present abnormalities in mitochondria in postmortem schizophrenia with a focus on ultrastructure. Function, morphology, fusion, fission, motility, ΔΨmem, ATP production, mitochondrial derived vesicles, and ...
journal_title:Schizophrenia research
pub_type: 杂志文章,评审
doi:10.1016/j.schres.2017.01.056
更新日期:2017-09-01 00:00:00
abstract:BACKGROUND:Genetic factors are important in the aetiology of psychotic disorders, but it is unclear how far they influence aspects of illness history within psychoses. AIMS:To investigate the extent, and type of familial aggregation for a range of illness history variables in psychosis. METHODS:Two-hundred-and-twenty...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2009.09.002
更新日期:2009-12-01 00:00:00
abstract::In order to test the hypothesis that a poor performance in the Wisconsin test (WCST) may be an indicator of liability to schizophrenia, we compared the WCST performances of patients with DSM III-R schizophrenia, normal controls, and patients with schizotypal personality disorder (SZT PD). While schizophrenic patients ...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/0920-9964(94)90007-8
更新日期:1994-12-01 00:00:00
abstract:INTRODUCTION:People with severe mental illness have greater risk of un-detected and inadequately treated medical disorders, adding up to the risk of premature death. This study investigated how chronic medical comorbidity evolved across the lifespan in schizophrenia and the associated impact on mortality. METHOD:A reg...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2018.10.020
更新日期:2019-04-01 00:00:00
abstract::Many neuropsychological studies have described deficits of memory and executive functions in patients with schizophrenia, and the severity of these deficits seems to be determinant in predicting the community outcome of these patients [Schizophr. Bull. 26 (2000) 119]. However, neuropsychological evaluation does not pr...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2003.07.005
更新日期:2004-08-01 00:00:00
abstract::Recent advances in our understanding of the genetic architecture of schizophrenia have shed light on the schizophrenia etiology. While common variation is one of the major genetic contributors, the majority of common variation reside in non-coding genome, posing a significant challenge in understanding the functional ...
journal_title:Schizophrenia research
pub_type: 杂志文章,评审
doi:10.1016/j.schres.2019.03.007
更新日期:2020-03-01 00:00:00
abstract::Arinami et al. (1994) reported an association between the Ser311/Cys311 variant of the DRD2 gene and schizophrenia in a Japanese population. We did not find statistically significant differences in the distribution of the allele frequencies between schizophrenics (103) and controls (97) in a case-control sample (chi 2...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/S0920-9964(97)00013-3
更新日期:1997-05-24 00:00:00
abstract::Our study aimed to investigate how recovery styles influence 12-month clinical outcome in first-episode psychosis patients. We hypothesised that patients who use an integrative recovery style would have better outcome than those who seal over. A total of 196 first-episode psychosis patients from the Early Psychosis In...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/s0920-9964(02)00428-0
更新日期:2003-07-01 00:00:00
abstract::Individuals with psychotic illnesses are known to have a reduced fertility. It is unclear whether this is due to biological or social factors. Most fertility studies have been conducted in chronic schizophrenia, where confounders like medication and hospitalisation make this difficult to elicit. A less severe reductio...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2014.04.007
更新日期:2014-07-01 00:00:00
abstract:BACKGROUND:The Heinrichs-Carpenter Quality of Life Scale (QLS) is the most extensively used real-world community functioning scale in schizophrenia research. However, the extensive time required to administer it and the inclusion of items that overlap conceptually with negative symptoms limit its use across studies. Th...
journal_title:Schizophrenia research
pub_type: 杂志文章
doi:10.1016/j.schres.2014.02.013
更新日期:2014-04-01 00:00:00