Abstract:
:The glutamate hypothesis of schizophrenia derived from evidence that phencyclidine, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, produces schizophrenia-like symptoms in healthy humans. Sensorimotor gating, measured by prepulse inhibition (PPI), is a fundamental form of information processing that is deficient in schizophrenia patients and rodents treated with NMDA antagonists. Hence, PPI is widely used to study the neurobiology of schizophrenia. As the use of PPI as a model of gating deficits in schizophrenia has become more widespread, it has become increasingly important to assess such deficits accurately. Here we identify a possible role of mGluR5 in PPI by using wild type (WT) and mGluR5 knockout (KO) mice of two different background strains, 129SvPasIco and C57BL/6. In both strains, PPI was disrupted dramatically in the mGluR5 KO mice throughout a range of interstimulus intervals and sensory modalities. The present findings further support the glutamate hypothesis of schizophrenia and identify a functional role for mGluR5 in sensorimotor gating.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Brody SA,Dulawa SC,Conquet F,Geyer MAdoi
10.1038/sj.mp.4001404subject
Has Abstractpub_date
2004-01-01 00:00:00pages
35-41issue
1eissn
1359-4184issn
1476-5578pii
4001404journal_volume
9pub_type
杂志文章abstract::We conducted a systematic review and meta-analysis of randomized controlled trials that compared second-generation antipsychotic (SGA) drugs with placebo in schizophrenic patients and which considered 13 different outcome measures. Thirty-eight randomized controlled trials with 7323 participants were included. All SGA...
journal_title:Molecular psychiatry
pub_type: 杂志文章,meta分析,评审
doi:10.1038/sj.mp.4002136
更新日期:2009-04-01 00:00:00
abstract::Microvascular pathology and ischemic lesions contribute substantially to neuronal dysfunction and loss that lead to Alzheimer disease (AD). To facilitate recovery, the brain stimulates neovascularization of damaged tissue via sprouting angiogenesis, a process regulated by endothelial cell (EC) sprouting and the EphB4/...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-0812-7
更新日期:2020-06-15 00:00:00
abstract::The development of the cerebral cortex is a tightly regulated process that relies on exquisitely coordinated actions of intrinsic and extrinsic cues. Here, we show that the communication between forebrain meninges and apical neural progenitor cells (aNPC) is essential to cortical development, and that the basal compar...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.236
更新日期:2018-03-01 00:00:00
abstract::Identifying genes for bipolar mood disorders through classic genetics has proven difficult. Here, we present a comprehensive convergent approach that translationally integrates brain gene expression data from a relevant pharmacogenomic mouse model (involving treatments with a stimulant--methamphetamine, and a mood sta...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001547
更新日期:2004-11-01 00:00:00
abstract::The urocortin (Ucn) family of neuropeptides is suggested to be involved in homeostatic coping mechanisms of the central stress response through the activation of corticotropin-releasing factor receptor type 2 (CRFR2). The neuropeptides, Ucn1 and Ucn2, serve as endogenous ligands for the CRFR2, which is highly expresse...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2009.115
更新日期:2010-04-01 00:00:00
abstract::An increase in corticotropin-releasing factor (CRF) is a putative factor in the pathophysiology of stress-related disorders. As CRF expression in the central nucleus of the amygdala (CeA) is important in adaptation to chronic stress, we hypothesized that unrestrained synthesis of CRF in CeA would mimic the consequence...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2008.91
更新日期:2009-01-01 00:00:00
abstract::Human neural progenitors from a variety of sources present new opportunities to model aspects of human neuropsychiatric disease in vitro. Such in vitro models provide the advantages of a human genetic background combined with rapid and easy manipulation, making them highly useful adjuncts to animal models. Here, we ex...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2011.60
更新日期:2012-02-01 00:00:00
abstract::To identify loci associated with Alzheimer disease, we conducted a three-stage analysis using existing genome-wide association studies (GWAS) and genotyping in a new sample. In Stage I, all suggestive single-nucleotide polymorphisms (at P<0.001) in a previously reported GWAS of seven independent studies (8082 Alzheime...
journal_title:Molecular psychiatry
pub_type: 杂志文章,meta分析
doi:10.1038/mp.2013.86
更新日期:2014-06-01 00:00:00
abstract::Recent studies have shown an association between trinucleotide repeat expansions (TREs) and adult-onset schizophrenia (AOS). Childhood-onset schizophrenia (COS) is a severe variant of schizophrenia with onset of symptoms before age 12 years. We have used the repeat expansion detection (RED) method to investigate the o...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000405
更新日期:1998-07-01 00:00:00
abstract::Delivery of drugs into the brain is poor due to the blood brain barrier (BBB). This study describes the development of a novel liposome-based brain-targeting drug delivery system. The liposomes incorporate a diacylglycerol moiety coupled through a linker to a peptide of 5 amino acids selected from amyloid precursor pr...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-0742-4
更新日期:2020-05-05 00:00:00
abstract::To quantify aging- and disease-associated alterations in the integrative and interactive components of a pulsatile neuroendocrine axis, novel biomathematical strategies are required. Here, I illustrate as an investigative paradigm otherwise subtle aging-dependent disturbances of the gonadotropin-releasing-hormone (GnR...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/sj.mp.4000232
更新日期:1997-01-01 00:00:00
abstract::Identifying biomarkers in schizophrenia during the first episode without the confounding effects of treatment has been challenging. Leveraging these biomarkers to establish diagnosis and make individualized predictions of future treatment responses to antipsychotics would be of great value, but there has been limited ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0106-5
更新日期:2020-04-01 00:00:00
abstract::Attention-deficit hyperactivity disorder (ADHD) is one of the most common childhood behavioral disorders. Genetic factors contribute to the underlying liability to develop ADHD. Reports implicate variants of genes important for the synthesis, uptake, transport and receptor binding of dopamine in the etiology of ADHD, ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001466
更新日期:2004-07-01 00:00:00
abstract::Microdeletions of chromosomal region 2q23.1 that disrupt MBD5 (methyl-CpG-binding domain protein 5) contribute to a spectrum of neurodevelopmental phenotypes; however, the impact of this locus on human psychopathology has not been fully explored. To characterize the structural variation landscape of MBD5 disruptions a...
journal_title:Molecular psychiatry
pub_type: 杂志文章,多中心研究
doi:10.1038/mp.2013.42
更新日期:2014-03-01 00:00:00
abstract::Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by a number of environmental and cell-intrinsic factors to adapt to environmental changes. Accumulating evidence suggests that adult-born neurons may play distinct physiological roles in hippocampus-dependent functions, such as memory encod...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/s41380-018-0036-2
更新日期:2019-01-01 00:00:00
abstract::The evolution of human diets led to preferences toward polyunsaturated fatty acid (PUFA) content with 'Western' diets enriched in ω-6 PUFAs. Mounting evidence points to ω-6 PUFA excess limiting metabolic and cognitive processes that define longevity in humans. When chosen during pregnancy, ω-6 PUFA-enriched 'Western' ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0580-4
更新日期:2020-01-01 00:00:00
abstract::Induction of neuroprotective heat-shock proteins via pharmacological Hsp90 inhibitors is currently being investigated as a potential treatment for neurodegenerative diseases. Two major hurdles for therapeutic use of Hsp90 inhibitors are systemic toxicity and limited central nervous system permeability. We demonstrate ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2016.104
更新日期:2017-07-01 00:00:00
abstract::Psychotropic medications target glycogen synthase kinase 3β (GSK3β), but the functional integration with other factors relevant for drug efficacy is poorly understood. We discovered that the suggested psychiatric risk factor FK506 binding protein 51 (FKBP51) increases phosphorylation of GSK3β at serine 9 (pGSK3β(S9))....
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2015.38
更新日期:2016-02-01 00:00:00
abstract::A genetic predisposition to the development of neuroleptic malignant syndrome (NMS) has been suggested by clinical studies. Although the molecular basis of NMS is unclear, a dopaminergic blockade mechanism has been considered the main cause. We therefore investigated the association between NMS and three functional po...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001422
更新日期:2004-03-01 00:00:00
abstract::5-HT(2C) receptor (5HT(2C)R, serotonin-2C) RNA undergoes editing to produce several receptor variants, some with pharmacological differences. This investigation comprised two parts: the characterisation of 5-HT(2C)R RNA editing in a larger human control sample than previously examined, and a comparative study in subje...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000920
更新日期:2001-07-01 00:00:00
abstract::Psychotic symptoms occur in ~40% of subjects with Alzheimer's disease (AD) and are associated with more rapid cognitive decline and increased functional deficits. They show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. We undertook a combined analysi...
journal_title:Molecular psychiatry
pub_type: 杂志文章,meta分析,多中心研究
doi:10.1038/mp.2011.125
更新日期:2012-12-01 00:00:00
abstract::Schizophrenia is a severe neurodevelopmental psychiatric affliction manifested behaviorally at late adolescence/early adulthood. Current treatments comprise antipsychotics which act solely symptomatic, are limited in their effectiveness and often associated with side-effects. We here report that application of non-inv...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0356-x
更新日期:2020-04-01 00:00:00
abstract::With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.92
更新日期:2017-09-01 00:00:00
abstract::Neuregulin and the neuregulin receptor ERBB4 have been genetically and functionally implicated in schizophrenia. In this study, we used the yeast two-hybrid system to identify proteins that interact with ERBB4, to identify genes and pathways that might contribute to schizophrenia susceptibility. We identified the MAGI...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001991
更新日期:2008-02-01 00:00:00
abstract::Leptin is a hormone with pleiotropic functions affecting several tissues. Because leptin has a crucial role in the adaptation of an organism to semi-starvation, anorexia nervosa (AN) serves as a model disorder to elucidate the functional implications of hypoleptinaemia; vice versa, several symptoms in patients with th...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/sj.mp.4001909
更新日期:2007-01-01 00:00:00
abstract::Various neuropathological findings have been reported in bipolar disorder (BD). However, it is unclear which findings are well established. To address this gap, we carried out a systematic review of the literature. We searched over 5000 publications, identifying 103 data papers, of which 81 were eligible for inclusion...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0213-3
更新日期:2020-08-01 00:00:00
abstract::The Wistar-Kyoto (WKY) rat strain demonstrates endogenous hormonal and behavioral abnormalities that emulate many of those found in symptom-presenting depressive patients. Evidence suggests that the WKY strain may harbor heterogeneity not found in other inbred strains, including greater behavioral and genetic variabil...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001345
更新日期:2003-11-01 00:00:00
abstract::We searched Embase, PubMed, and CENTRAL from inception until 22 May 2020 to investigate which antipsychotics and/or mood stabilizers are better for patients with bipolar disorder in the maintenance phase. We performed two categorical network meta-analyses. The first included monotherapy studies and studies in which th...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-00946-6
更新日期:2020-11-11 00:00:00
abstract::The human serotonin transporter gene (5-HTT) demonstrates two polymorphisms with possible functional impact: a 44-bp insertion/deletion polymorphism of the promoter region and a 17-bp variable number of tandem repeat polymorphism (VNTR) in intron 2 (STin2). Such genetic polymorphisms in the serotoninergic system may i...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000821
更新日期:2001-03-01 00:00:00
abstract::A recent study using a 'partial' rodent model of schizophrenia has employed amygdalar activation to induce reported changes in the expression of hippocampal genes associated with metabolic and signaling pathways in response to amygdalar activation. The amygdalo-hippocampal pathway plays a central role in the regulatio...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001769
更新日期:2006-02-01 00:00:00