Abstract：
:We conducted a 10 centimorgan (cM) linkage genome scan in a set of American extended pedigrees ascertained through probands with panic disorder. Several anxiety disorders segregate in these families. In this article, we describe results for simple phobia from 14 of these families (including 129 subjects of whom 57 are affected). A total of 422 markers were genotyped. Multipoint lod score analyses (fully parametric and simple parametric models) and nonparametric analyses were completed using ALLEGRO. We observed significant linkage of simple phobia to chromosome 14 markers. The highest lod score under a fully parametric model was 3.17, at marker D14S75, under a dominant model. Under a fully parametric recessive model, the maximum lod score, also at D14S75, was 2.86. Analysis under a simple parametric model resulted in lod scores of 3.70 (dominant model) or 3.30 (recessive model). The highest Zlr score observed was 3.93 (P = 4.1 x 10(-5)). The Zlr score was >1 for an extensive region, >77 cM. In all, 12 of the 14 families studied provided positive or zero lod scores at marker D14S75 (dominant model). The homologous genomic region has been implicated by studies mapping quantitative trait loci for a mouse model of fear. The linkage peak may be regarded as highly promising, owing to the breadth of the peak, the convergence of results under different models of inheritance and different analysis methods, and the support from an animal model. This is the first genome scan linkage study for simple phobia, a common disorder that causes high morbidity in the US population.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Gelernter J,Page GP,Bonvicini K,Woods SW,Pauls DL,Kruger Sdoi
10.1038/sj.mp.4001224subject
Has Abstractpub_date
2003-01-01 00:00:00pages
71-82issue
1eissn
1359-4184issn
1476-5578pii
4001224journal_volume
8pub_type
杂志文章abstract：:Studies using tissue obtained at autopsy suggest that changes in cholinergic neurons could be important in the pathology of schizophrenia.1-4 We have previously reported a decrease in [3H]pirenzepine binding5 and [3H]AF-DX 384 binding6 to caudate-putamen (CP) from subjects who had schizophrenia. Under the conditions c...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000684
更新日期：2000-03-01 00:00:00
abstract：:(+) 3,4-Methylenedioxymethamphetamine (MDMA) is a psychedelic drug of abuse that causes selective degeneration of serotonergic fibers of dorsal raphe neurons that project throughout the forebrain. Previous studies using pharmacological and behavioral approaches suggested that MDMA treatment leads to desensitization of...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000574
更新日期：1999-11-01 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：:A recent study found, in a large sample of Ashkenazi Jews, a highly significant association between schizophrenia and a particular haplotype of three polymorphic sites in the catechol-O-methyl transferase, COMT, gene: an IVS 1 SNP (dbSNP rs737865), the exon 4 functional SNP (Val158Met, dbSNP rs165688), and a downstrea...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001496
更新日期：2004-09-01 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：: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：: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-af...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：
更新日期：1996-09-01 00:00:00
abstract：:Circulating inflammatory mediators can signal neurons through a pathway in which cytokine activation of the cells of the blood-brain barrier causes the induction of the nuclear factor kappa B (NF-kappaB), leading to the transcription of target genes, such as the one encoding cyclooxygenase 2 (COX-2), the enzyme that i...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：
更新日期：1999-11-01 00:00:00
abstract：:The Wistar-Kyoto (WKY) rat strain demonstrates endogenous hormonal and behavioral abnormalities that emulate many of those found in symptom-presenting depressive patients. Evidence suggests that the WKY strain may harbor heterogeneity not found in other inbred strains, including greater behavioral and genetic variabil...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001345
更新日期：2003-11-01 00:00:00
abstract：:Several studies suggest that decreased expression of presynaptic proteins may be characteristic of schizophrenia. We examined one such protein, synapsin, in schizophrenia and bipolar disorder. Samples of hippocampal tissue from controls (n = 13), patients with schizophrenia (n = 16), or bipolar disorder (n = 6), and s...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001158
更新日期：2002-01-01 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：: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：:The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date i...
journal_title：Molecular psychiatry
pub_type： 杂志文章,meta分析
doi：10.1038/mp.2017.210
更新日期：2017-12-01 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：:Bipolar affective disorder is one of the most common mental illnesses with a population prevalence of approximately 1%. The disorder is genetically complex, with an increasing number of loci being implicated through genetic linkage studies. However, the specific genetic variations and molecules involved in bipolar sus...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001113
更新日期：2002-01-01 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 human 16p11.2 gene locus is a hot spot for copy number variations, which predispose carriers to a range of neuropsychiatric phenotypes. Microduplications of 16p11.2 are associated with autism spectrum disorder (ASD), intellectual disability (ID), and schizophrenia (SZ). Despite the debilitating nature of 16p11.2 d...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-020-0693-9
更新日期：2020-02-25 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：: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：:Suicide is a major public health concern and a leading cause of death in most societies. Suicidal behaviour is complex and heterogeneous, likely resulting from several causes. It associates with multiple factors, including psychopathology, personality traits, early-life adversity and stressful life events, among other...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/mp.2017.141
更新日期：2017-10-01 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 revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognit...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.182
更新日期：2017-02-01 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：: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：: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：:While localizing sensory and motor deficits is one of the cornerstones of clinical neurology, behavioral and cognitive deficits in psychiatry remain impervious to this approach. In psychiatry, major challenges include the relative subtlety by which neural circuits are perturbed, and the limited understanding of how ba...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/mp.2016.183
更新日期：2017-02-01 00:00:00
abstract：:An increase in corticotropin-releasing factor (CRF) is a putative factor in the pathophysiology of stress-related disorders. As CRF expression in the central nucleus of the amygdala (CeA) is important in adaptation to chronic stress, we hypothesized that unrestrained synthesis of CRF in CeA would mimic the consequence...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2008.91
更新日期：2009-01-01 00:00:00
abstract：:Neurotrophic factors, particularly brain-derived neurotrophic factor (BDNF) and other members of the neurotrophin family, are central mediators of the activity-dependent plasticity through which environmental experiences, such as sensory information are translated into the structure and function of neuronal networks. ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2017.61
更新日期：2017-08-01 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：:Depression is a common debilitating human disease whose etiology has defied decades of research. A critical bottleneck is the difficulty in modeling depressive episodes in animals. Here, we show that a transgenic mouse with chronic forebrain expression of a dominant negative mutant of Polg1, a mitochondrial DNA (mtDNA...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.156
更新日期：2016-01-01 00:00:00
