Abstract：
:Episodic memory, a fundamental component of human cognition, is significantly impaired in autism. We believe we report the first evidence for this problem in the Fmr1-knockout (KO) mouse model of Fragile X syndrome and describe potentially treatable underlying causes. The hippocampus is critical for the formation and use of episodes, with semantic (cue identity) information relayed to the structure via the lateral perforant path (LPP). The unusual form of synaptic plasticity expressed by the LPP (lppLTP) was profoundly impaired in Fmr1-KOs relative to wild-type mice. Two factors contributed to this defect: (i) reduced GluN1 subunit levels in synaptic NMDA receptors and related currents, and (ii) impaired retrograde synaptic signaling by the endocannabinoid 2-arachidonoylglycerol (2-AG). Studies using a novel serial cue paradigm showed that episodic encoding is dependent on both the LPP and the endocannabinoid receptor CB1, and is strikingly impaired in Fmr1-KOs. Enhancing 2-AG signaling rescued both lppLTP and learning in the mutants. Thus, two consequences of the Fragile-X mutation converge on plasticity at one site in hippocampus to prevent encoding of a basic element of cognitive memory. Collectively, the results suggest a clinically plausible approach to treatment.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Wang W,Cox BM,Jia Y,Le AA,Cox CD,Jung KM,Hou B,Piomelli D,Gall CM,Lynch Gdoi
10.1038/mp.2017.221subject
Has Abstractpub_date
2018-08-01 00:00:00pages
1798-1806issue
8eissn
1359-4184issn
1476-5578pii
10.1038/mp.2017.221journal_volume
23pub_type
杂志文章abstract：:A polymorphism in the serotonin (5-HT) transporter gene regulatory region (5-HTTLPR) is associated with measures of 5-HT transporter (5-HTT) expression and 5-HT-mediated behaviors in humans. An analogous length variation of the 5-HTTLPR has been reported in rhesus monkeys (rh5-HTTLPR). A retrospective association stud...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001157
更新日期：2002-01-01 00:00:00
abstract：:Mental disorders cause more disability than any other class of medical illness in Americans between ages 15 and 44 years. The suicide rate is higher than the annual mortality from homicide, AIDS, and most forms of cancer. In contrast to nearly all communicable and most non-communicable diseases, there is little eviden...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/sj.mp.4001777
更新日期：2006-01-01 00:00:00
abstract：:Schizophrenia is a severe psychiatric disease with a strong genetic component. Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of schizophrenia and bipolar (BP) disorders. The present study has examined two polymorphisms in linkage disequilibrium in the BDNF gene, which have been vario...
journal_title：Molecular psychiatry
pub_type： 临床试验,杂志文章
doi：10.1038/sj.mp.4001575
更新日期：2005-02-01 00:00:00
abstract：:The literature on GWAS (genome-wide association studies) data suggests that very large sample sizes (for example, 50,000 cases and 50,000 controls) may be required to detect significant associations of genomic regions for complex disorders such as Alzheimer's disease (AD). Because of the challenges of obtaining such l...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2012.81
更新日期：2013-05-01 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：:Abnormalities in prefrontal gamma aminobutyric acid (GABA)ergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders, including schizophrenia, bipolar disorder, anxiety disorders and depression. Wh...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.222
更新日期：2016-07-01 00:00:00
abstract：:The long alleles (> or =6 repeats) of the dopamine D4 dopamine receptor exon III polymorphism have been linked in some, but not all, studies to Novelty Seeking (NS), one of four personality traits defined by Cloninger's tridimensional personality questionnarie (TPQ). In order to further examine the robustness of our o...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000333
更新日期：1997-10-01 00:00:00
abstract：:A correction 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/s41380-019-0529-7
更新日期：2020-08-01 00:00:00
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：:Transcranial direct current stimulation (tDCS) is a promising method for altering the function of neural systems, cognition, and behavior. Evidence is emerging that it can also influence psychiatric symptomatology, including major depression and schizophrenia. However, there are many open questions regarding how the m...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/s41380-019-0499-9
更新日期：2020-02-01 00:00:00
abstract：:Impulsivity, a multifaceted behavioral hallmark of attention-deficit/hyperactivity disorder (ADHD), strongly influences addiction vulnerability and other psychiatric disorders that incur enormous medical and societal burdens yet the neurobiological underpinnings linking impulsivity to disease remain poorly understood....
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2017.80
更新日期：2018-05-01 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：:This study explores whether inflammatory biomarkers act as moderators of clinical response to omega-3 (n-3) fatty acids in subjects with major depressive disorder (MDD). One hundred fifty-five subjects with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) MDD, a baseline 17-item Hamilton Dep...
journal_title：Molecular psychiatry
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1038/mp.2015.22
更新日期：2016-01-01 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：:In our genome scan for schizophrenia genes in 265 Irish pedigrees, marker D5S818 in 5q22 produced the second best result of the first 223 markers tested (P = 0.002). We then tested an additional 13 markers and the evidence suggests the presence of a vulnerability locus for schizophrenia in region 5q22-31. This region ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000258
更新日期：1997-03-01 00:00:00
abstract：:Endocannabinoids and their attending cannabinoid type 1 (CB1) receptor have been implicated in animal models of post-traumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2013.61
更新日期：2013-09-01 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：: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：: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：:Although few studies dispute that there are gender differences in depression, the etiology is still unknown. In this review, we cover a number of proposed factors and the evidences for and against these factors that may account for gender differences in depression. These include the possible role of estrogens at puber...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/mp.2009.94
更新日期：2010-01-01 00:00:00
abstract：:High impulsive and aggressive traits associate with poor behavioural self-control. Despite their importance in predicting behavioural negative outcomes including suicide, the molecular mechanisms underlying the expression of impulsive and aggressive traits remain poorly understood. Here, we identified and characterize...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0637-4
更新日期：2020-01-06 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：:The 12/15-lipoxygenase (12/15LO) enzyme is widely distributed within the central nervous system. Previous work showed that this protein is upregulated in Alzheimer's disease (AD), and plays an active role in the development of brain amyloidosis in amyloid beta (Aβ)-precursor protein transgenic mice (Tg2576). In the pr...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2014.170
更新日期：2015-11-01 00:00:00
abstract：:Familial and twin studies have suggested that anorexia nervosa (AN) is a multifactorial disorder with a substantial genetic contribution. The hSKCa3 potassium channel gene, which contains polymorphic CAG repeats in the coding region and is involved in the regulation of neuronal activity, may be a candidate gene for AN...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000931
更新日期：2002-01-01 00:00:00
abstract：:The prefrontal cortex, a part of the limbic-thalamic-cortical network, participates in regulation of mood, cognition and behavior and has been implicated in the pathophysiology of major depressive disorder (MDD). Many neuropsychological studies demonstrate impairment of working memory in patients with MDD. However, th...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001894
更新日期：2007-02-01 00:00:00
abstract：:We assessed the ability of lithium to reduce neurodegeneration and to stimulate cell proliferation in a rat model of Huntington's disease in which quinolinic acid (QA) was unilaterally infused into the striatum. LiCl (0.5-3.0 mEq/kg) was injected subcutaneously 24 h before and 1 h after QA infusion. At 7 days after QA...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001463
更新日期：2004-04-01 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：: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：:Although disrupted in schizophrenia 1 (DISC1) has been implicated in many psychiatric disorders, including schizophrenia, bipolar disorder, schizoaffective disorder and major depression, its biological role in these disorders is unclear. To better understand this gene and its role in psychiatric disease, we conducted ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2011.37
更新日期：2011-11-01 00:00:00
abstract：:The different serotonin (5-HT) receptors, including the serotonin transporter (5-HTT), are excellent candidate genes for suicide and suicidal behavior, and thus, they have been investigated in a large number of allelic association studies. The individual results of these studies have been inconsistent and definite con...
journal_title：Molecular psychiatry
pub_type： 杂志文章,meta分析,评审
doi：10.1038/sj.mp.4001336
更新日期：2003-07-01 00:00:00
