Abstract：
:The methionine-folate cycle-dependent one-carbon metabolism is implicated in the pathophysiology of schizophrenia. Since schizophrenia is a developmental disorder, we examined the effects that perturbation of the one-carbon metabolism during gestation has on mice progeny. Pregnant mice were administered methionine equivalent to double their daily intake during the last week of gestation. Their progeny (MET mice) exhibited schizophrenia-like social deficits, cognitive impairments and elevated stereotypy, decreased neurogenesis and synaptic plasticity, and abnormally reduced local excitatory synaptic connections in CA1 neurons. Neural transcript expression of only one gene, encoding the Npas4 transcription factor, was >twofold altered (downregulated) in MET mice; strikingly, similar Npas4 downregulation occurred in the prefrontal cortex of human patients with schizophrenia. Finally, therapeutic actions of typical (haloperidol) and atypical (clozapine) antipsychotics in MET mice mimicked effects in human schizophrenia patients. Our data support the validity of MET mice as a model for schizophrenia, and uncover methionine metabolism as a potential preventive and/or therapeutic target.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Alachkar A,Wang L,Yoshimura R,Hamzeh AR,Wang Z,Sanathara N,Lee SM,Xu X,Abbott GW,Civelli Odoi
10.1038/mp.2017.164subject
Has Abstractpub_date
2018-02-01 00:00:00pages
282-294issue
2eissn
1359-4184issn
1476-5578pii
mp2017164journal_volume
23pub_type
杂志文章abstract：:We and others have previously reported linkage to schizophrenia on chromosome 10q25-q26 but, to date, a susceptibility gene in the region has not been identified. We examined data from 3606 single-nucleotide polymorphisms (SNPs) mapping to 10q25-q26 that had been typed in a genome-wide association study (GWAS) of schi...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2008.108
更新日期：2009-01-01 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Molecular psychiatry
pub_type： 已发布勘误
doi：10.1038/s41380-020-00919-9
更新日期：2020-10-14 00:00:00
abstract：:Cannabis is one of the most commonly and widely used psychoactive drugs. The rates of cannabis misuse have been increasing. Therefore, understanding the effects of cannabis use on the brain is important. Adolescent and adult rodents exposed to repeated administration of cannabinoids show persistent microstructural cha...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-020-00891-4
更新日期：2020-09-24 00:00:00
abstract：:Whilst cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers for amyloid-β (Aβ) and tau pathologies are accurate for the diagnosis of Alzheimer's disease (AD), their broad implementation in clinical and trial settings are restricted by high cost and limited accessibility. Plasma phosphorylated-ta...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-020-00923-z
更新日期：2020-10-26 00:00:00
abstract：:Large numbers of single nucleotide polymorphisms (SNPs) are being identified by several laboratories for the purpose of developing dense genetic maps. Single-strand conformation polymorphism (SSCP) analysis has been widely used as a method for detecting novel sequence variations in PCR products. Differences in migrati...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000564
更新日期：1999-07-01 00:00:00
abstract：:DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0605-z
更新日期：2019-12-06 00:00:00
abstract：:In developing his mature concept of hebephrenic dementia praecox (DP) in his 4th (1893) through 6th textbook editions (1899), Kraepelin worked from the hebephrenic syndrome first described by Hecker (1871) and then carefully studied by his student Daraszkiewicz (1892). Working under Kraepelin's supervision, Daraszkiew...
journal_title：Molecular psychiatry
pub_type： 历史文章,杂志文章,评审
doi：10.1038/s41380-019-0411-7
更新日期：2020-01-01 00:00:00
abstract：:Environmental enrichment (EE) is known to have an anxiolytic effect in several animal models; however, the molecular mechanisms underlying these behavioral changes are not understood. In this study, we have shown that the anxiolytic effect of EE is associated with alterations in the corticotropin-releasing factor rece...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2009.151
更新日期：2010-09-01 00:00:00
abstract：:Research on avoidance conditioning began in the late 1930s as a way to use laboratory experiments to better understand uncontrollable fear and anxiety. Avoidance was initially conceived of as a two-factor learning process in which fear is first acquired through Pavlovian aversive conditioning (so-called fear condition...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/mp.2016.166
更新日期：2017-01-01 00:00:00
abstract：:Although therapeutic interventions in attention-deficit/hyperactivity disorder (ADHD) still focus on the dopaminergic system, recent studies indicate a serotonergic dysfunction in this disease as well. In that respect, several variants of the tryptophan hydroxylase gene (TPH2), which codes for the rate-limiting enzyme...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2008.39
更新日期：2009-11-01 00:00:00
abstract：:Accumulating research demonstrates the potential of intranasal delivery of psychopharmacological agents to treat a range of psychiatric disorders and symptoms. It is believed that intranasal administration offers both direct and indirect pathways to deliver psychopharmacological agents to the central nervous system. T...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/mp.2015.166
更新日期：2016-01-01 00:00:00
abstract：:Low dietary folate intake has been implicated as a risk factor for depression. However, observational epidemiological studies are plagued by problems of confounding, reverse causality and measurement error. A common polymorphism (C677T) in MTHFR is associated with methyltetrahydrofolate reductase (MTHFR) activity and ...
journal_title：Molecular psychiatry
pub_type： 杂志文章,meta分析,评审
doi：10.1038/sj.mp.4001790
更新日期：2006-04-01 00:00:00
abstract：:Several epidemiological studies confirmed that Anxiety Disorders as a group are the most prevalent psychiatric conditions in the United States. The importance of these conditions is underlined by the fact that they cause significant disability, poor quality of life, alcohol and drug abuse. Anxiety disorders are treata...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/sj.mp.4001852
更新日期：2006-09-01 00:00:00
abstract：:Early-life disruption of the parent-child relationship, for example, in the form of abuse, neglect or loss, dramatically increases risk for psychiatric, as well as certain medical, disorders in adulthood. The neuropeptide oxytocin (OT) plays a seminal role in mediating social affiliation, attachment, social support, m...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2008.112
更新日期：2009-10-01 00:00:00
abstract：:The lack of strong association between brain beta-amyloid deposition and cognitive impairment has been a challenge for the Alzheimer's disease (AD) field. Although beta-amyloid is necessary for the pathologic diagnosis of AD, it is not sufficient to make the pathologic diagnosis or cause dementia. We sought to identif...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.35
更新日期：2017-02-01 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：: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：:Volume reduction and shape abnormality of the hippocampus have been associated with mood disorders. However, the hippocampus is not a uniform structure and consists of several subfields, such as the cornu ammonis (CA) subfields CA1-4, the dentate gyrus (DG) including a granule cell layer (GCL) and a molecular layer (M...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.262
更新日期：2017-09-01 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：:Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations betwee...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-020-00976-0
更新日期：2021-01-07 00:00:00
abstract：:Biological characterization of genetic variants identified in genome-wide association studies (GWAS) remains a substantial challenge. Here we used human-induced pluripotent stem cells (iPSC) and their neural derivatives to characterize common variants on chromosome 3p22 that have been associated by GWAS with major men...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-018-0207-1
更新日期：2019-04-01 00:00:00
abstract：:Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental syndrome characterized by hyperactivity, inattention and increased impulsivity. To detect micro-deletions and micro-duplications that may have a role in the pathogenesis of ADHD, we carried out a genome-wide screen for cop...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2010.29
更新日期：2011-05-01 00:00:00
abstract：:Significant evidence for linkage between bipolar affective disorder and markers on chromosome 4p16 has been reported in Scottish families. Linkage analyses using 16 DNA markers covering more than 50 cM from chromosome 4pter-4p12, including candidate genes encoding the dopamine D5 receptor and an adrenergic receptor (2...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000420
更新日期：1998-09-01 00:00:00
abstract：:Psychiatric diseases have a strong heritable component known to not be restricted to DNA sequence-based genetic inheritance alone but to also involve epigenetic factors in germ cells. Initial evidence suggested that sperm RNA is causally linked to the transmission of symptoms induced by traumatic experiences. Here, we...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-018-0271-6
更新日期：2020-09-01 00:00:00
abstract：:Although schizophrenia is considered a brain disorder, the role of brain organization for symptomatic improvement remains inadequately defined. We investigated the relationship between baseline brain morphology, resting-state network connectivity and clinical response after 24-weeks of antipsychotic treatment in patie...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-018-0269-0
更新日期：2020-04-01 00:00:00
abstract：:Chronic stress contributes to the development of psychiatric disorders including anxiety and depression. Several inflammatory-related effects of stress are associated with increased interleukin-1 (IL-1) signaling within the central nervous system and are mediated by IL-1 receptor 1 (IL-1R1) on several distinct cell ty...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-020-0788-3
更新日期：2020-05-22 00:00:00
abstract：:Autistic individuals experience significantly elevated rates of childhood trauma, self-harm and suicidal behaviour and ideation (SSBI). Is this purely the result of negative environmental experiences, or does this interact with genetic predisposition? In this study we investigated if a genetic predisposition for autis...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0550-x
更新日期：2019-10-29 00:00:00
abstract：:Higher scores on the personality trait of neuroticism, the tendency to experience negative emotions, are associated with worse mental and physical health. Studies examining links between neuroticism and health typically operationalize neuroticism by summing the items from a neuroticism scale. However, neuroticism is m...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0387-3
更新日期：2020-11-01 00:00:00
abstract：:Epidemiological studies report strong association between mood disorders and tobacco addiction. This high comorbidity requires adequate treatment but the underlying mechanisms are unknown. We demonstrate that nicotine exposure, independent of drug withdrawal effects, increases stress sensitivity, a major risk factor i...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2017.145
更新日期：2018-07-01 00:00:00
abstract：:With the advent of technologies that allow simultaneous genotyping of thousands of single-nucleotide polymorphisms (SNPs) across the genome, the genetic contributions to complex diseases can be explored at an unprecedented detail. This study is among the first to apply the genome-wide association study (GWAS) approach...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2008.141
更新日期：2010-07-01 00:00:00
