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From Linkage Studies to Epigenetics: What We Know and What We Need to Know in the Neurobiology of Schizophrenia.

ABSTRACT: Schizophrenia is a complex psychiatric disorder characterized by the presence of positive, negative, and cognitive symptoms that lacks a unifying neuropathology. In the present paper, we will review the current understanding of molecular dysregulation in schizophrenia, including genetic and epigenetic studies. In relation to the latter, basic research suggests that normal cognition is regulated by epigenetic mechanisms and its dysfunction occurs upon epigenetic misregulation, providing new insights into missing heritability of complex psychiatric diseases, referring to the discrepancy between epidemiological heritability and the proportion of phenotypic variation explained by DNA sequence difference. In schizophrenia the absence of consistently replicated genetic effects together with evidence for lasting changes in gene expression after environmental exposures suggest a role of epigenetic mechanisms. In this review we will focus on epigenetic modifications as a key mechanism through which environmental factors interact with individual's genetic constitution to affect risk of psychotic conditions throughout life.

SUBMITTER: Cariaga-Martinez A

PROVIDER: S-EPMC4862989 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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From Linkage Studies to Epigenetics: What We Know and What We Need to Know in the Neurobiology of Schizophrenia.

Cariaga-Martinez Ariel A Saiz-Ruiz Jerónimo J Alelú-Paz Raúl R

Frontiers in neuroscience 20160511

Schizophrenia is a complex psychiatric disorder characterized by the presence of positive, negative, and cognitive symptoms that lacks a unifying neuropathology. In the present paper, we will review the current understanding of molecular dysregulation in schizophrenia, including genetic and epigenetic studies. In relation to the latter, basic research suggests that normal cognition is regulated by epigenetic mechanisms and its dysfunction occurs upon epigenetic misregulation, providing new insig ...[more]

PMID: 27242407

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Project description:BACKGROUND: Alzheimer's disease (AD) pathophysiology is mostly (>95%) not inherited in a Mendelian fashion. Such sporadic AD (sAD) forms do not exhibit familial aggregation and are characterized by complex genetic inheritance. Growing evidence indicates that multiple genes contribute to sAD-characteristic endophenotypes, molecular mechanisms, signaling pathways and biomarker signatures either individually or through complex gene-gene interactions, lifestyle and the environment. DISCUSSION: Under the hypothesis that low-prevalence variants showing moderate-to-high effect size may be associated with risk for sAD, two independent research groups have demonstrated that a rare variant (rs75932628, encoding a substitution of arginine by histidine at residue 47 (R47H), in the TREM2 gene, which encodes the triggering receptor expressed on myeloid cells 2) is significantly associated with an increased susceptibility to sAD. Another study has provided intriguing evidence that a low-frequency variant (rs63750847) in the APP gene is associated with a reduced risk of developing AD and a lower likelihood of age-related cognitive decline in elderly subjects without AD. SUMMARY: Recent years have witnessed tremendous development in genetics technology that has allowed full individualized genome-wide or genomic screening embracing all of the risk and protective variants for sAD, both across populations and within individuals. Hopefully, the integration of neurogenetics with systems biology and high-throughput genotyping will further pave the way to decipher all of the related causes, mechanisms, and biomarkers across the spectrum of distinct AD forms. After an almost lost apprentice decade in AD therapy development, the epoch of individualized asymptomatic screening and progress in primary and secondary prevention of sAD is probably at its dawn. Even though we are more at the beginning than at the end of sAD genetics, there is some reason for optimism given the recent identification of novel risk or protective variants (such as rare TREM2 and APP mutations) showing strong statistical associations with sAD.

Dataset Information

From Linkage Studies to Epigenetics: What We Know and What We Need to Know in the Neurobiology of Schizophrenia.

Publications

From Linkage Studies to Epigenetics: What We Know and What We Need to Know in the Neurobiology of Schizophrenia.

Similar Datasets

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