Abstract:
:The etiology of schizophrenia is unclear, although family, twin, and linkage studies implicate genetic factors. Here, we identified adenomatous polyposis coli (APC), a tumor suppressor gene, as a risk factor for schizophrenia. We compared leukocytic gene expression patterns of six pairs of patients with schizophrenia and healthy controls by microarray. APC expression levels were significantly increased in all patients compared to healthy controls. To confirm the findings of microarray analysis, we measured expression levels of APC in the leukocytes from 30 relapse patients taking antipsychotic medication, 29 first-episode drug-naïve patients, and 30 healthy controls using real-time quantitative reverse transcription (RT)-polymerase chain reaction (PCR). APC expression levels were significantly increased in leukocytes of schizophrenics both taking and not taking antipsychotic medication and hence the increase of APC expression was not due to antipsychotic medication. APC is located at 5q21-22, which has been previously reported to be linked with schizophrenia. Further, we performed the transmission disequilibrium test (TDT) and TDT based on haplotypes to search for the association between schizophrenia and APC by examining 163 parent-offspring trios of Chinese descent. We analyzed three single-nucleotide polymorphisms (SNPs) (rs2229992, rs42427, rs465899) at the exon region of APC. TDT showed that the three SNPs are significantly associated with schizophrenia (TDT chi(2)=4.23, P<0.05; 4.15, P<0.05; 8.49 P<0.01, respectively; HHRRchi(2)=5.54, P<0.05; 4.40, P<0.05; 9.79, P<0.01, respectively). We found a significant association between the APC haplotypes from rs2229992-rs42427-rs465899 and schizophrenia (Global chi(2)=44.376,df=7, P<0.001). The C-A-T haplotype has a frequency of more than 57% and has a strong association with schizophrenia (chi(2)=15.04, P<0.001). These results indicate that the APC may be a candidate gene conferring susceptibility to schizophrenia and also may be associated with reduced vulnerability to cancer in schizophrenia.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Cui DH,Jiang KD,Jiang SD,Xu YF,Yao Hdoi
10.1038/sj.mp.4001653subject
Has Abstractpub_date
2005-07-01 00:00:00pages
669-77issue
7eissn
1359-4184issn
1476-5578pii
4001653journal_volume
10pub_type
临床试验,杂志文章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::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
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::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::Binge drinking is associated with disease and death, and developing tools to identify risky drinkers could mitigate its damage. Brain processes underlie risky drinking, so we examined whether neural and psychosocial markers could identify binge drinkers. Reward is the most widely studied neural process in addiction, b...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-0771-z
更新日期:2020-05-12 00:00:00
abstract::Whilst cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers for amyloid-β (Aβ) and tau pathologies are accurate for the diagnosis of Alzheimer's disease (AD), their broad implementation in clinical and trial settings are restricted by high cost and limited accessibility. Plasma phosphorylated-ta...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-00923-z
更新日期:2020-10-26 00:00:00
abstract::The aim of the study is to compare the prevalence of suicidal ideation and attempts in the United States in 1991-1992 and 2001-2002, and identify sociodemographic groups at increased risk for suicidal ideation and attempts. Data were drawn from the National Institute on Alcohol Abuse and Alcoholism 1991-1992 National ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2008.98
更新日期:2010-03-01 00:00:00
abstract::Cannabis is one of the most commonly and widely used psychoactive drugs. The rates of cannabis misuse have been increasing. Therefore, understanding the effects of cannabis use on the brain is important. Adolescent and adult rodents exposed to repeated administration of cannabinoids show persistent microstructural cha...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-00891-4
更新日期:2020-09-24 00:00:00
abstract::We searched Embase, PubMed, and CENTRAL from inception until 22 May 2020 to investigate which antipsychotics and/or mood stabilizers are better for patients with bipolar disorder in the maintenance phase. We performed two categorical network meta-analyses. The first included monotherapy studies and studies in which th...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-00946-6
更新日期:2020-11-11 00:00:00
abstract::The dopamine transporter (DAT) plays a central role in dopaminergic neurotransmission in the human brain. Genetic association studies have used a variable number of tandem repeat (VNTR) polymorphism in the 3'-flanking region of the dopamine transporter gene (DAT1) to implicate the DAT in the development of various neu...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000711
更新日期:2000-05-01 00:00:00
abstract::Circulating triglycerides (TGs) normally increase after a meal but are altered in pathophysiological conditions, such as obesity. Although TG metabolism in the brain remains poorly understood, several brain structures express enzymes that process TG-enriched particles, including mesolimbic structures. For this reason,...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2014.31
更新日期:2014-10-01 00:00:00
abstract::A common polymorphism of the gene encoding acyl-coenzyme A: cholesterol acyltransferase 1 (SOAT1), which is involved in the regulation of beta-amyloid peptide generation, is associated with low brain amyloid load (P=0.03) and with low cerebrospinal fluid levels of cholesterol (P=0.005). This polymorphism of SOAT1 is a...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4001296
更新日期:2003-06-01 00:00:00
abstract::Schizophrenia (SCZ) is a highly heritable neuropsychiatric disorder of complex genetic etiology. Previous genome-wide surveys have revealed a greater burden of large, rare copy number variations (CNVs) in SCZ cases and identified multiple rare recurrent CNVs that increase risk of SCZ although with incomplete penetranc...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2014.40
更新日期:2014-07-01 00:00:00
abstract::Tonically active cholinergic interneurons (TANs) from the nucleus accumbens (NAc) are centrally involved in reward behavior. TANs express a vesicular glutamate transporter referred to as VGLUT3 and thus use both acetylcholine and glutamate as neurotransmitters. The respective roles of each transmitter in the regulatio...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2015.104
更新日期:2015-11-01 00:00:00
abstract::Cariprazine (CAR) is a strong inhibitor of the Dhcr7 enzyme, the last enzyme in the cholesterol biosynthesis pathway. We assessed the effects of CAR on maternally exposed Dhcr7+/- and wild-type mouse offspring, and tested the biochemical effects of CAR in human serum samples. Dhcr7+/- and wild-type time-pregnant mice ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-0801-x
更新日期:2020-11-01 00:00:00
abstract::Schizophrenia is a severe neurodevelopmental psychiatric affliction manifested behaviorally at late adolescence/early adulthood. Current treatments comprise antipsychotics which act solely symptomatic, are limited in their effectiveness and often associated with side-effects. We here report that application of non-inv...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0356-x
更新日期:2020-04-01 00:00:00
abstract::Genomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. From the Enhanci...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-020-01002-z
更新日期:2021-01-17 00:00:00
abstract::The dorsolateral prefrontal cortex (dlpfc) is strongly implicated in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BPD) and, within this region, abnormalities in glutamatergic neurotransmission and synaptic function have been described. Proteins associated with these functions are enriched in membrane ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2008.7
更新日期:2009-06-01 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::The evolution of human diets led to preferences toward polyunsaturated fatty acid (PUFA) content with 'Western' diets enriched in ω-6 PUFAs. Mounting evidence points to ω-6 PUFA excess limiting metabolic and cognitive processes that define longevity in humans. When chosen during pregnancy, ω-6 PUFA-enriched 'Western' ...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/s41380-019-0580-4
更新日期:2020-01-01 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::Converging advances in the fields of molecular biology, molecular genetics, cellular biology and embryology have given researchers the tools for the targeted delivery and stable germline transmission of foreign genes (transgenes) in the mouse. In the realm of neuropsychiatry, this so-named transgenic technology has be...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:
更新日期:1996-05-01 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::Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started wi...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2010.6
更新日期:2010-11-01 00:00:00
abstract::Epidemiological studies report strong association between mood disorders and tobacco addiction. This high comorbidity requires adequate treatment but the underlying mechanisms are unknown. We demonstrate that nicotine exposure, independent of drug withdrawal effects, increases stress sensitivity, a major risk factor i...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/mp.2017.145
更新日期:2018-07-01 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::Acetylcholinesterase (AChE), the enzyme involved in the hydrolysis of the neurotransmitter acetylcholine, has been implicated in non-cholinergic actions which may play a role in neurodegenerative diseases such as Alzheimer's disease. To study the potential cytotoxicity of brain AChE, the effects of affinity purified A...
journal_title:Molecular psychiatry
pub_type: 杂志文章
doi:10.1038/sj.mp.4000383
更新日期:1998-05-01 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::The search for susceptibility genes for bipolar disorder (BD) depends on appropriate definitions of the phenotype. In this paper, we review data on diagnosis and clinical features of BD that could be used in genetic studies to better characterize patients or to define homogeneous subgroups. Clinical symptoms, long-ter...
journal_title:Molecular psychiatry
pub_type: 杂志文章,评审
doi:10.1038/sj.mp.4001701
更新日期:2005-09-01 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