Abstract：
:Advances in genomics are opening new windows into the biology of schizophrenia. Though common variants individually have small effects on disease risk, GWAS provide a powerful opportunity to explore pathways and mechanisms contributing to pathophysiology. Here, we highlight an underappreciated biological theme emerging from GWAS: the role of glycosylation in schizophrenia. The strongest coding variant in schizophrenia GWAS is a missense mutation in the manganese transporter SLC39A8, which is associated with altered glycosylation patterns in humans. Furthermore, variants near several genes encoding glycosylation enzymes are unambiguously associated with schizophrenia: FUT9, MAN2A1, TMTC1, GALNT10, and B3GAT1. Here, we summarize the known biological functions, target substrates, and expression patterns of these enzymes as a primer for future studies. We also highlight a subset of schizophrenia-associated proteins critically modified by glycosylation including glutamate receptors, voltage-gated calcium channels, the dopamine D2 receptor, and complement glycoproteins. We hypothesize that common genetic variants alter brain glycosylation and play a fundamental role in the development of schizophrenia. Leveraging these findings will advance our mechanistic understanding of disease and may provide novel avenues for treatment development.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Mealer RG,Williams SE,Daly MJ,Scolnick EM,Cummings RD,Smoller JWdoi
10.1038/s41380-020-0753-1subject
Has Abstractpub_date
2020-12-01 00:00:00pages
3129-3139issue
12eissn
1359-4184issn
1476-5578pii
10.1038/s41380-020-0753-1journal_volume
25pub_type
杂志文章,评审abstract：:Anxiety and depression are devastating mental illnesses that are a significant public health concern. Selective serotonin-reuptake inhibitors are the first-line treatment strategy for these disorders, which despite being a significant advantage over older treatments, are hampered by a limited efficacy in a significant...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/mp.2011.162
更新日期：2012-04-01 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：:Abnormalities in the density of neuroreceptors that regulate norepinephrine and serotonin release have been repeatedly reported in brains of suicide victims with mood disorders. Recently, the modulation of the [(35)S]GTPgammaS binding to G-proteins has been introduced as a suitable measure of receptor activity in post...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001067
更新日期：2002-01-01 00:00:00
abstract：:Emerging evidence suggests that psychiatric disorders are associated with disturbances in structural brain networks. Little is known, however, about brain networks in those at high risk (HR) of bipolar disorder (BD), with such disturbances carrying substantial predictive and etiological value. Whole-brain tractography...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2016.216
更新日期：2018-02-01 00:00:00
abstract：:Cognitive impairment is common among individuals diagnosed with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). It has been suggested that some aspects of intelligence are preserved or even superior in people with ASD compared with controls, but consistent evidence is lacking. Few s...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.12
更新日期：2016-03-01 00:00:00
abstract：:Several lines of evidence implicate dopa decarboxylase (DDC) with schizophrenia. By analysis of two putative functional DDC variants in 173 schizophrenic patients and 204 controls we tested the hypotheses that DDC is involved in: (1) predisposition to schizophrenia; and (2) modulation of age at disease onset. No assoc...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000902
更新日期：2001-11-01 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：:Chronic methamphetamine use poses potentially devastating consequences for directly affected individuals and for society. Lower dopamine D2-type receptor availability has been observed in striata of methamphetamine users as compared with controls, but an analogous comparison of D1-type receptors has been conducted onl...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2017.172
更新日期：2018-05-01 00:00:00
abstract：:Traumatic life experiences are associated with alcohol use problems, an association that is likely to be moderated by genetic predisposition. To understand these interactions, we conducted a gene-by-environment genome-wide interaction study (GEWIS) of alcohol use problems in two independent samples, the Army STARRS (S...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2017.24
更新日期：2018-01-01 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
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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：: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：:The NEO-Five-Factor Inventory divides human personality traits into five dimensions: neuroticism, extraversion, openness, conscientiousness and agreeableness. In this study, we sought to identify regions harboring genes with large effects on the five NEO personality traits by performing genome-wide linkage analysis of...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2011.97
更新日期：2012-10-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2011.37
更新日期：2011-11-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2017.92
更新日期：2017-09-01 00:00:00
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 ...
journal_title：Molecular psychiatry
pub_type： 临床试验,杂志文章
doi：10.1038/sj.mp.4001653
更新日期：2005-07-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2015.222
更新日期：2016-07-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2008.112
更新日期：2009-10-01 00:00:00
abstract：:Schizophrenia is a severe psychiatric disorder with a world-wide prevalence of 1%. The pathophysiology of the illness is not understood, but is thought to have a strong genetic component with some environmental influences on aetiology. To gain further insight into disease mechanism, we used microarray technology to de...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2009.18
更新日期：2009-12-01 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：:Although few studies dispute that there are gender differences in depression, the etiology is still unknown. In this review, we cover a number of proposed factors and the evidences for and against these factors that may account for gender differences in depression. These include the possible role of estrogens at puber...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：10.1038/mp.2009.94
更新日期：2010-01-01 00:00:00
abstract：:A polymorphism in the serotonin (5-HT) transporter gene regulatory region (5-HTTLPR) is associated with measures of 5-HT transporter (5-HTT) expression and 5-HT-mediated behaviors in humans. An analogous length variation of the 5-HTTLPR has been reported in rhesus monkeys (rh5-HTTLPR). A retrospective association stud...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4001157
更新日期：2002-01-01 00:00:00
abstract：:Dysthymia is characterized by long-lasting periods of lowered mood. Epidemiological studies in the USA and Europe have demonstrated that the prevalence of dysthymia is at least 3% of the general population. Its pervasive occurrence makes dysthymia a public health problem worldwide. One feature of this disorder is its ...
journal_title：Molecular psychiatry
pub_type： 杂志文章,评审
doi：
更新日期：1996-12-01 00:00:00
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journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-020-0701-0
更新日期：2020-03-04 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 goal of this study is to investigate the familial transmission of the spectrum of bipolar disorder in a nonclinical sample of probands with a broad range of manifestations of mood disorders. The sample included a total of 447 probands recruited from a clinically enriched community screening and their 2082 adult li...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/mp.2013.116
更新日期：2014-02-01 00:00:00
abstract：:Many human hereditary neurodegenerative diseases are caused by expanded CAG repeats, and anonymous CAG expansions have also been described in schizophrenia and bipolar disorder. We have isolated and sequenced a novel human cDNA encoding a neuronal, small conductance calcium-activated potassium channel (hSKCa3) that co...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/sj.mp.4000353
更新日期：1998-01-01 00:00:00
abstract：:Multiple lines of evidence point to glutamatergic signaling in the postsynaptic density (PSD) as a pathophysiologic mechanism in schizophrenia. Integral to PSD glutamatergic signaling is reciprocal interplay between GluN and mGluR5 signaling. We examined agonist-induced mGluR5 signaling in the postmortem dorsolateral ...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-018-0234-y
更新日期：2020-04-01 00:00:00
abstract：:The different serotonin (5-HT) receptors, including the serotonin transporter (5-HTT), are excellent candidate genes for suicide and suicidal behavior, and thus, they have been investigated in a large number of allelic association studies. The individual results of these studies have been inconsistent and definite con...
journal_title：Molecular psychiatry
pub_type： 杂志文章,meta分析,评审
doi：10.1038/sj.mp.4001336
更新日期：2003-07-01 00:00:00
abstract：:Current antidepressants act principally by blocking monoamine reuptake by high-affinity transporters in the brain. However, these antidepressants show important shortcomings such as slow action onset and limited efficacy in nearly a third of patients with major depression disorder. Here, we report the development of a...
journal_title：Molecular psychiatry
pub_type： 杂志文章
doi：10.1038/s41380-019-0548-4
更新日期：2020-06-01 00:00:00
