Abstract:
:The actions of CRF in the brain and in the periphery are mediated through multiple binding sites. There are three receptors, CRF1, CRF2 alpha and CRF2 beta, which encode 411, 415 and 431 amino acid proteins and transduce signals via the stimulation of intracellular cAMP production. The recent identification of high-affinity non-peptide CRF receptor antagonists should allow for rapid progress in drug development of CRF receptor antagonists. In addition to the receptors, the actions of CRF in brain and in the periphery can also be modulated by a binding protein of 322 amino acids. Ligands of CRF-BP, such as CRF (6-33) can elevate brain levels of 'free' CRF and improve learning and memory without stress-like side effects of CRF receptor agonists. Urocortin, a mammalian CRF-related peptide with close sequence homology to fish urotensin, interacts with CRF1, CRF2 receptors and with CRF-BP. These data indicate that CRF receptor antagonists may be useful for the treatment of the disease states where CRF is elevated such as anxiety and depression, anorexia nervosa and stroke and that ligand inhibitors of CRF-BP may be used to elevate brain levels of 'free' urocortin and other CRF-related peptides.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Behan DP,Grigoriadis DE,Lovenberg T,Chalmers D,Heinrichs S,Liaw C,De Souza EBsubject
Has Abstractpub_date
1996-09-01 00:00:00pages
265-77issue
4eissn
1359-4184issn
1476-5578journal_volume
1pub_type
杂志文章,评审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::Posttranscriptional regulation of gene expression plays an important role in the maturation, transport, stability and translation of coding and noncoding RNAs. RNA-binding protein (RBP) is a key factor of the regulation. Regulator of calcineurin 1 (RCAN1) is a multifunctional protein involved in neurodegeneration, mit...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0487-0
更新日期:2019-08-27 00:00:00
abstract::The s allele variant of the serotonin transporter gene (5-HTT) has recently been observed to moderate the relationship of stress to depression and anxiety. To date no study has considered interactive effects of 5-HTT genotype, stress and hypothalamic-pituitary-adrenal (HPA) function on cognition in healthy, older adul...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001978
更新日期:2007-06-01 00:00:00
abstract::Depression often accompanies the perimenopausal transition and it often precedes overt symptomology in common neurodegenerative diseases (NDDs, such as Alzheimer's, Parkinson's, Huntington, amyotrophic lateral sclerosis). Serotonin dysfunction is frequently found in the different etiologies of depression. We have show...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2014.178
更新日期:2015-12-01 00:00:00
abstract::Use of substances such as cannabis, alcohol, and tobacco, has been associated with increased risk of suicide attempt in several observational studies. However, establishing whether these associations are causal is challenging when using observational designs. To evaluate the potential causal contributions of cannabis ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-0785-6
更新日期:2020-06-08 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::Schizophrenia is a highly heritable disorder for which anatomical brain alterations have been repeatedly reported in clinical samples. Unaffected at-risk groups have also been studied in an attempt to identify brain changes that do not reflect reverse causation or treatment effects. However, no robust associations hav...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0355-y
更新日期:2020-04-01 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::Between 1997 and 2002, 48 data sets from the hippocampus were produced on samples from the Stanley Neuropathology Consortium. From these data sets, 224 total measures were available from the various subdivisions of the hippocampus. An integrative analysis of these measures was performed using a multivariate, nonparame...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001471
更新日期:2004-06-01 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::Benzodiazepines facilitate the inhibitory actions of GABA by binding to γ-aminobutyric acid type A receptors (GABAARs), GABA-gated chloride/bicarbonate channels, which are the key mediators of transmission at inhibitory synapses in the brain. This activity underpins potent anxiolytic, anticonvulsant and hypnotic effec...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-018-0100-y
更新日期:2018-09-01 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::The effect of endogenous dopamine (DA) on neostriatal DA D(1) and D(2) receptor binding potentials (D(1)RBP and D(2)RBP, respectively) in vivo was evaluated with positron emission tomography (PET) and the radiotracers [(11)C]SCH23390 and [(11)C]raclopride, respectively, by comparing the D(1)RBP and D(2)RBP before and ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001062
更新日期:2002-01-01 00:00:00
abstract::Psychopathy is strongly associated with serious criminal behaviour (for example, rape and murder) and recidivism. However, the biological basis of psychopathy remains poorly understood. Earlier studies suggested that dysfunction of the amygdala and/or orbitofrontal cortex (OFC) may underpin psychopathy. Nobody, howeve...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2009.40
更新日期:2009-10-01 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::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
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journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2016.82
更新日期:2017-02-01 00:00:00
abstract::Amyloid-β peptide (Aβ) accumulation in the brain is a hallmark of Alzheimer's Disease. An important mechanism of Aβ clearance in the brain is uptake and degradation by microglia. Presenilin 1 (PS1) is the catalytic subunit of γ-secretase, an enzyme complex responsible for the maturation of multiple substrates, such as...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-0856-8
更新日期:2020-08-13 00:00:00
abstract::Several lines of evidence have suggested altered functions of the brain-derived neurotrophic factor (BDNF) in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD). In the search for polymorphisms in the 5'-flanking and 5'-noncoding regions of the BDNF gene, we found a novel nucleotide subs...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000792
更新日期:2001-01-01 00:00:00
abstract::Genetic variation underlying hypothalamic pituitary adrenal (HPA) axis overactivity in healthy controls (HCs) and patients with severe forms of major depression has not been well explored, but could explain risk for cortisol dysregulation. In total, 95 participants were studied: 40 patients with psychotic major depres...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2013.129
更新日期:2014-02-01 00:00:00
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journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000744
更新日期:2000-07-01 00:00:00
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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
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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::Variance in IQ is associated with a wide range of health outcomes, and 1% of the population are affected by intellectual disability. Despite a century of research, the fundamental neural underpinnings of intelligence remain unclear. We integrate results from genome-wide association studies (GWAS) of intelligence with ...
journal_title:Molecular psychiatry
pub_type: 杂志文章,meta分析
doi:10.1038/s41380-018-0040-6
更新日期:2019-02-01 00:00:00
abstract::The GRIA1 locus, encoding the GluA1 (also known as GluRA or GluR1) AMPA glutamate receptor subunit, shows genome-wide association to schizophrenia. As well as extending the evidence that glutamatergic abnormalities have a key role in the disorder, this finding draws attention to the behavioural phenotype of Gria1 knoc...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/mp.2014.91
更新日期:2014-10-01 00:00:00
abstract::Serum antibodies against amyloid-β peptide (Aβ) in humans with or without diagnosis of Alzheimer's disease (AD) indicate the possibility of immune responses against brain antigens. In an unbiased screening for antibodies directed against brain proteins, we found in AD patients high serum levels of antibodies against t...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2012.70
更新日期:2013-03-01 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::After psychological trauma, recurrent intrusive visual memories may be distressing and disruptive. Preventive interventions post trauma are lacking. Here we test a behavioural intervention after real-life trauma derived from cognitive neuroscience. We hypothesized that intrusive memories would be significantly reduced...
journal_title:Molecular psychiatry
pub_type: 杂志文章,随机对照试验
doi:10.1038/mp.2017.23
更新日期:2018-03-01 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::The prefrontal cortex (PFC), seat of the highest-order cognitive functions, constitutes a conglomerate of highly specialized brain areas and has been implicated to have a role in the onset and installation of various neurodevelopmental disorders. The development of a properly functioning PFC is directed by transcripti...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/mp.2014.147
更新日期:2015-07-01 00:00:00