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, including DRD4, DAT1, DRD2, and DRD5. In the present study, we genotyped a large multiplex sample of ADHD affected children and their parents for polymorphisms in genes previously reported to be associated with ADHD. Associations were tested by the transmission disequilibrium test (TDT). The sample is sufficient to detect genotype relative risks (GRRs) for putative risk alleles. The DRD4 gene 120-bp insertion/deletion promoter polymorphism displayed a significant bias in transmission of the insertion (chi(2)=7.58, P=0.006) as suggested by an analysis of a subset of these families. The seven repeat allele of the DRD4 48-bp repeat polymorphism (DRD4.7) was not significantly associated with ADHD in the large sample in contrast to our earlier findings in a smaller subset. We replicate an association of a dinucleotide repeat polymorphism near the DRD5 gene with ADHD by showing biased nontransmission of the 146-bp allele (P=0.02) and a trend toward excess transmission of the 148-bp allele (P=0.053). No evidence for an association was found for polymorphisms in DRD2 or DAT1 in this sample. The DRD5 146-bp (DRD5.146) allele and the DRD4 240-bp (DRD4.240) allele of the promoter polymorphism emerge as the two DNA variants showing a significant association in this large sample of predominantly multiplex families with ADHD, with estimated GRRs of 1.7 and 1.37, respectively.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Kustanovich V,Ishii J,Crawford L,Yang M,McGough JJ,McCracken JT,Smalley SL,Nelson SFdoi
10.1038/sj.mp.4001466subject
Has Abstractpub_date
2004-07-01 00:00:00pages
711-7issue
7eissn
1359-4184issn
1476-5578pii
4001466journal_volume
9pub_type
杂志文章abstract::The astrocytic cystine/glutamate antiporter system xc- represents an important source of extracellular glutamate in the central nervous system, with potential impact on excitatory neurotransmission. Yet, its function and importance in brain physiology remain incompletely understood. Employing slice electrophysiology a...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-0751-3
更新日期:2020-05-04 00:00:00
abstract::Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not ju...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0496-z
更新日期:2020-12-01 00:00:00
abstract::The G-protein coupled metabotropic glutamate receptors (GRMs/mGluRs) have been implicated in the aetiology of schizophrenia as they modulate the NMDA response and that of other neurotransmitters including dopamine and GABA.(1-3) Electrophysiological studies in GRM subtype 5 knockout mice reveal, in one study, a sensor...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000848
更新日期:2001-05-01 00:00:00
abstract::Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identifi...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0087-4
更新日期:2018-12-01 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::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::Stress and exposure to glucocorticoids (GC) during early life render individuals vulnerable to brain disorders by inducing structural and chemical alterations in specific neural substrates. Here we show that adult rats that had been exposed to in utero GCs (iuGC) display increased preference for opiates and ethanol, a...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2011.126
更新日期:2012-12-01 00:00:00
abstract::Exposure to severe stressors increases the risk for psychiatric disorders in vulnerable individuals, but can lead to positive outcomes for others. However, it remains unknown how severe stress affects neural functioning in humans and what factors mediate individual differences in the neural sequelae of stress. The amy...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2010.132
更新日期:2011-06-01 00:00:00
abstract::It is essential to elucidate brain-adipocyte interactions in order to tackle obesity and its comorbidities, as the precise control of brain-adipose tissue cross-talk is crucial for energy and glucose homeostasis. Recent studies show that in the peripheral adipose tissue, adenosine induces adipogenesis through peripher...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-00908-y
更新日期:2020-10-16 00:00:00
abstract::Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2013.2
更新日期:2014-03-01 00:00:00
abstract::Activation of the inflammatory response system has been related to the pathophysiology of schizophrenia by several recent studies. Schizophrenic patients have varied levels of proinflammatory cytokines, such as interleukin (IL)-1, -6, and tumor necrosis factor (TNF)alpha in their peripheral blood or cerebrospinal flui...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000483
更新日期:1999-03-01 00:00:00
abstract::The endogenous opioid system, which alleviates physical pain, is also known to regulate social distress and reward in animal models. To test this hypothesis in humans (n=18), we used an μ-opioid receptor (MOR) radiotracer to measure changes in MOR availability in vivo with positron emission tomography during social re...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2013.96
更新日期:2013-11-01 00:00:00
abstract::Nitric oxide (NO) is a widespread and multifunctional biological messenger molecule. It mediates vasodilation of blood vessels, host defence against infectious agents and tumors, and neurotransmission of the central and peripheral nervous systems. In the nervous system, NO is generated by three nitric oxide synthase (...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/sj.mp.4000272
更新日期:1997-07-01 00:00:00
abstract::Corticotropin-releasing hormone (CRH) is both a main regulator of the hypothalamic-pituitary-adrenocortical axis and the autonomic nervous system. CRH receptor type 1 (CRHR1)-deficient mice demonstrate alterations in behavior, impaired stress responses with adrenocortical insufficiency and aberrant neuroendocrine deve...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001143
更新日期:2002-01-01 00:00:00
abstract::Polymorphism in the human dopamine D4 receptor gene (DRD4) exon III has been associated in some but not all studies of the human personality trait of Novelty Seeking. We searched for polymorphisms in the 5' region of DRD4 and identified six polymorphisms as follows: -1217G Ins/Del, -809G/A, -616C/G, -603T Ins/Del, -60...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000563
更新日期:2000-01-01 00:00:00
abstract::Previous work has demonstrated associations between lower cognitive ability and childhood and adult non-psychotic psychopathology. As both cognitive ability (CA) and child psychopathology (CP) are influenced by genetic factors, one explanation for the association is that they are the pleiotropic manifestations of the ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000971
更新日期:2002-01-01 00:00:00
abstract::Perturbation of Disrupted-In-Schizophrenia-1 (DISC1) and D-serine/NMDA receptor hypofunction have both been implicated in the pathophysiology of schizophrenia and other psychiatric disorders. In the present study, we demonstrate that these two pathways intersect with behavioral consequences. DISC1 binds to and stabili...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2012.97
更新日期:2013-05-01 00:00:00
abstract::Contemporary models of psychosis suggest that a continuum of severity of psychotic symptoms exists, with subthreshold psychotic experiences (PEs) potentially reflecting some genetic and environmental risk factors shared with clinical psychosis. Thus, identifying abnormalities in brain activity that manifest across thi...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-00983-1
更新日期:2021-01-18 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
abstract::We posit in this article that hierarchical temporal processing deficit is the underlying basis of reality distortion and psychoses. Schizophrenia is a prototypical reality distortion disorder in which the patient manifests with auditory hallucinations, delusions, disorganized speech and thinking, cognitive impairment,...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2010.63
更新日期:2011-02-01 00:00:00
abstract::Disruption of persistent, stress-associated memories is relevant for treating posttraumatic stress disorder (PTSD) and related syndromes, which develop in a subset of individuals following a traumatic event. We previously developed a stress-enhanced fear learning (SEFL) paradigm in inbred mice that produces PTSD-like ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0432-2
更新日期:2020-05-01 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::Epidermal growth factor (EGF) comprises a structurally related family of proteins containing heparin-binding EGF-like growth factor (HB-EGF) and transforming growth factor alpha (TGFalpha) that regulates the development of dopaminergic neurons as well as monoamine metabolism. We assessed the contribution of EGF to sch...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001081
更新日期:2002-01-01 00:00:00
abstract::We previously reported that expression level of LIM (ENH, PDLIM5) was significantly and commonly increased in the brains of patients with bipolar disorder, schizophrenia, and major depression. Expression of LIM was decreased in the lymphoblastoid cells derived from patients with bipolar disorders and schizophrenia. LI...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001719
更新日期:2005-11-01 00:00:00
abstract::There is evidence that obesity-related disorders are increased among people with depression. Variation in the FTO (fat mass and obesity associated) gene has been shown to contribute to common forms of human obesity. This study aimed to investigate the genetic influence of polymorphisms in FTO in relation to body mass ...
journal_title:Molecular psychiatry
pub_type: 杂志文章,meta分析
doi:10.1038/mp.2011.45
更新日期:2012-06-01 00:00:00
abstract::A recent report showed significant associations between several SNPs in a previously unknown EST cluster with schizophrenia. (1). The cluster was identified as the human dystrobrevin binding protein 1 gene (DTNBP1) by sequence database comparisons and homology with mouse DTNBP1. (2). However, the linkage disequilibriu...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001263
更新日期:2003-05-01 00:00:00
abstract::Two recent association studies have implicated the neuregulin-1 gene (NRG1) at chromosome 8p21-22 as a susceptibility gene for schizophrenia. Stefansson et al identified three 'at-risk' haplotypes (HapA, B and C) which spanned the NRG1 locus and shared a common core haplotype. Subsequently, they demonstrated evidence ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001412
更新日期:2004-02-01 00:00:00
abstract::Lipids are essential to brain functions, yet they remain largely unexplored. Here we investigated the lipidome composition of prefrontal cortex gray matter in 396 cognitively healthy individuals with ages spanning 100 years, as well as 67 adult individuals diagnosed with autism (ASD), schizophrenia (SZ), and Down synd...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0200-8
更新日期:2020-11-01 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::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