Abstract：
:Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions in a fraction of cases. In addition, for both disorders, males are either more significantly or more severely affected than females, which may be explained in part by X-linked genetic factors. Therefore, we directly sequenced 111 X-linked synaptic genes in individuals with ASD (n = 142; 122 males and 20 females) or SCZ (n = 143; 95 males and 48 females). We identified >200 non-synonymous variants, with an excess of rare damaging variants, which suggest the presence of disease-causing mutations. Truncating mutations in genes encoding the calcium-related protein IL1RAPL1 (already described in Piton et al. Hum Mol Genet 2008) and the monoamine degradation enzyme monoamine oxidase B were found in ASD and SCZ, respectively. Moreover, several promising non-synonymous rare variants were identified in genes encoding proteins involved in regulation of neurite outgrowth and other various synaptic functions (MECP2, TM4SF2/TSPAN7, PPP1R3F, PSMD10, MCF2, SLITRK2, GPRASP2, and OPHN1).
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Piton A,Gauthier J,Hamdan FF,Lafrenière RG,Yang Y,Henrion E,Laurent S,Noreau A,Thibodeau P,Karemera L,Spiegelman D,Kuku F,Duguay J,Destroismaisons L,Jolivet P,Côté M,Lachapelle K,Diallo O,Raymond A,Marineau C,Chamdoi
10.1038/mp.2010.54subject
Has Abstractpub_date
2011-08-01 00:00:00pages
867-80issue
8eissn
1359-4184issn
1476-5578pii
mp201054journal_volume
16pub_type
杂志文章abstract：:We tested the hypothesis that, compared with subjects with no history of psychiatric illness (controls), changes in gene expression in the dorsolateral prefrontal cortex from two subgroups of subjects with schizophrenia, one with a marked deficit in muscarinic M1 receptors (muscarinic receptor-deficit schizophrenia (M...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.195
更新日期：2018-02-01 00:00:00
abstract：:The Raf kinases Raf-1 and B-Raf are upstream activators of the extracellular signal-regulated kinase (ERK)-signaling pathway and therefore participates in many physiological functions in brain, including neuronal survival and synaptic plasticity. Previously, we observed that activation of ERK-1/2, the downstream compo...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001744
更新日期：2006-01-01 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：:Exposure to traumatic events is common. While many individuals recover following trauma exposure, a substantial subset develop adverse posttraumatic neuropsychiatric sequelae (APNS) such as posttraumatic stress, major depression, and regional or widespread chronic musculoskeletal pain. APNS cause substantial burden to...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/s41380-019-0636-5
更新日期：2020-09-01 00:00:00
abstract：:Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2014.137
更新日期：2016-02-01 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：:Social deficits are common in many psychiatric disorders. However, due to inadequate tools for manipulating circuit activity in humans and unspecific paradigms for modeling social behaviors in rodents, our understanding of the molecular and circuit mechanisms mediating social behaviors remains relatively limited. Usin...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0422-4
更新日期：2019-04-16 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：:Many antidepressants stimulate adult hippocampal neurogenesis, but the mechanisms by which they increase neurogenesis and modulate behavior are incompletely understood. Here we show that hippocampal bone morphogenetic protein (BMP) signaling is modulated by antidepressant treatment, and that the changes in BMP signali...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.160
更新日期：2017-06-01 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：:Latency-reversing agents (LRAs), including histone deacetylase inhibitors (HDACi), are being investigated as a strategy to eliminate latency in HIV-infected patients on suppressive antiretroviral therapy. The effectiveness of LRAs in activating latent infection in HIV strains derived from the central nervous system (C...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.111
更新日期：2016-04-01 00:00:00
abstract：:A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy,...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.157
更新日期：2016-08-01 00:00:00
abstract：:Categorizing people with late-onset Alzheimer's disease into biologically coherent subgroups is important for personalized medicine. We evaluated data from five studies (total n = 4050, of whom 2431 had genome-wide single-nucleotide polymorphism (SNP) data). We assigned people to cognitively defined subgroups on the b...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-018-0298-8
更新日期：2020-11-01 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：:Normal development of cortical circuits, including experience-dependent cortical maturation and plasticity, requires precise temporal regulation of gene expression and molecular signaling. Such regulation, and the concomitant impact on plasticity and critical periods, is hypothesized to be disrupted in neurodevelopmen...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0635-6
更新日期：2020-01-03 00:00:00
abstract：:Depression is a heritable disorder that is often precipitated by stress. Abnormalities of the stress-reactive hypothalamic-pituitary-adrenal (HPA) axis are also common in depressed patients. In animal models, the forced swim test (FST) is the most frequently used test of depressive-like behavior. We have used a propos...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001255
更新日期：2003-04-01 00:00:00
abstract：:The catechol-O-methyl transferase (COMT) gene is considered a leading schizophrenia candidate gene. Although its role in increasing schizophrenia susceptibility has been conflicting, recent studies suggest the valine allele may contribute to poor cognitive function in schizophrenia. V(158)M COMT genotype was obtained ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001616
更新日期：2005-03-01 00:00:00
abstract：:The serotonergic neurotransmitter system has been widely implicated in the pathophysiology of mood-related disorders such as anxiety and major depressive disorder (MDD). The onset of therapeutic efficacy of traditional antidepressants is delayed by several weeks. The 5-HT4 receptor has emerged as a new therapeutic tar...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2017.240
更新日期：2018-04-01 00:00:00
abstract：:Endogenous opioid and non-opioid mechanisms (for example, dopamine (DA), endocannabinoids (eCB)) have been implicated in the formation of placebo analgesic effects, with initial reports dating back three decades. Besides the perspective that placebo effects confound randomized clinical trials, the information so far a...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/mp.2014.164
更新日期：2015-04-01 00:00:00
abstract：:It is believed that genetic factors play a large role in the development of many cognitive and neurological processes; however, epidemiological evidence for the genetic basis of childhood neurodevelopment is very limited. Identification of the genetic polymorphisms associated with early-stage neurodevelopment will hel...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-018-0205-3
更新日期：2020-11-01 00:00:00
abstract：:The current study provides a novel in-depth assessment of the extent of antipsychotic drugs transport across the blood-brain barrier (BBB) into various brain regions, as well as across the blood-spinal cord barrier (BSCB) and the blood-cerebrospinal fluid barrier (BCSFB). This is combined with an estimation of cellula...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.229
更新日期：2016-11-01 00:00:00
abstract：:Medical treatment with various cytokines can provoke psychiatric symptoms. Conversely, psychiatric patients can display abnormalities in cytokine and neurotrophic factor expression. Such observations have pointed to the potential contribution of cytokines and growth factors to schizophrenic pathology and/or etiology. ...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/sj.mp.4000730
更新日期：2000-11-01 00:00:00
abstract：:Contactin genes CNTN5 and CNTN6 code for neuronal cell adhesion molecules that promote neurite outgrowth in sensory-motor neuronal pathways. Mutations of CNTN5 and CNTN6 have previously been reported in individuals with autism spectrum disorders (ASDs), but very little is known on their prevalence and clinical impact....
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.61
更新日期：2017-04-01 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：: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：:Inbreeding depression refers to lower fitness among offspring of genetic relatives. This reduced fitness is caused by the inheritance of two identical chromosomal segments (autozygosity) across the genome, which may expose the effects of (partially) recessive deleterious mutations. Even among outbred populations, auto...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.120
更新日期：2016-06-01 00:00:00
abstract：:Several reports have suggested the presence of anticipation in bipolar affective disorder (BPAD). In addition, independent studies using the RED (repeat expansion detection) have shown association between BPAD and longer CAG/CTG repeats. Therefore loci with large CAG/CTG repeats are plausible candidates in the inherit...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000898
更新日期：2001-09-01 00:00:00
abstract：:Previous studies have implicated DTNBP1 as a schizophrenia susceptibility gene and its encoded protein, dysbindin, as a potential regulator of synaptic vesicle physiology. In this study, we found that endogenous levels of the dysbindin protein in the mouse brain are developmentally regulated, with higher levels observ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2009.58
更新日期：2010-02-01 00:00:00
abstract：:Older patients with severe physical trauma are at high risk of developing neuropsychiatric syndromes with global impairment of cognition, attention, and consciousness. We employed a thoracic trauma (TxT) mouse model and thoroughly analyzed age-dependent spatial and temporal posttraumatic alterations in the central ner...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-020-0659-y
更新日期：2020-02-12 00:00:00
abstract：:Polyglutamine expansion (PGE) encoded by a CAG repeat underlies eight inherited neurodegenerative diseases, among which is Huntington's disease. CAG expansion has also been reported in schizophrenia, suggesting a role for PGE. To investigate the potential role of PGE as a candidate for schizophrenia, we searched for P...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000448
更新日期：1999-01-01 00:00:00
