Epigenetics of major psychosis: progress, problems and perspectives
ABSTRACT Understanding the origins of normal and pathological behavior is one of the most exciting opportunities in contemporary biomedical research. There is increasing evidence that, in addition to DNA sequence and the environment, epigenetic modifications of DNA and histone proteins may contribute to complex phenotypes. Inherited and/or acquired epigenetic factors are partially stable and have regulatory roles in numerous genomic activities, thus making epigenetics a promising research path in etiological studies of psychiatric disease. In this article, we review recent epigenetic studies examining the brain and other tissues, including those from individuals with schizophrenia (SCZ) and bipolar disorder (BPD). We also highlight heuristic aspects of the epigenetic theory of psychiatric disease and discuss the future directions of psychiatric epigenetics.
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ABSTRACT: INTRODUCTION: Addiction is a substantial health issue with limited treatment options approved by the FDA and as such currently available. The advent of neuroimaging techniques that link neurochemical and neurogenetic mechanisms to the reward circuitry brain function provides a framework for potential genomic-based therapies. Areas Covered: Through candidate and genome-wide association studies approaches, many gene polymorphisms and clusters have been implicated in drug, food and behavioral dependence linked by the common rubric reward deficiency syndrome (RDS). The results of selective studies that include the role of epigenetics, noncoding micro RNAs in RDS behaviors especially drug abuse involving alcohol, opioids, cocaine, nicotine, pain and feeding are reviewed in this article. New targets for addiction treatment and relapse prevention, treatment alternatives such as gene therapy in animal models, and pharmacogenomics and nutrigenomics methods to manipulate transcription and gene expression are explored. Expert Opinion: The recognition of the clinical benefit of early genetic testing to determine addiction risk stratification and dopaminergic agonistic, rather than antagonistic therapies are potentially the genomic-based wave of the future. In addition, further development, especially in gene transfer work and viral vector identification, could make gene therapy for RDS a possibility in the future.Expert opinion on biological therapy 05/2015; DOI:10.1517/14712598.2015.1045871 · 3.65 Impact Factor
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ABSTRACT: Intracellular calcium (Ca(2+)) dyshomeostasis (ICDH) has been implicated in bipolar disorder (BD) pathophysiology. We previously showed that SNP rs956572 in the B-cell CLL/lymphoma 2 (Bcl-2) gene associates with elevated B lymphoblast (BLCL) intracellular Ca(2+) concentrations ([Ca(2+)]B) differentially in BD-I. Genome-wide association studies strongly support the association between BD and the SNP rs1006737, located within the L-type voltage-dependent Ca(2+) channel α1C subunit gene (CACNA1C). Here we investigated whether this CACNA1C variant also associates with ICDH and interacts with SNP rs956572 on [Ca(2+)]B in BD-I. CACNA1C SNP rs1006737 was genotyped in 150 BD-I, 65 BD-II, 30 major depressive disorder patients, and 70 healthy subjects with available BLCL [Ca(2+)]B and Bcl-2 SNP rs956572 genotype measures. SNP rs1006737 was significantly associated with BD-I. The [Ca(2+)]B was significantly higher in BD-I rs1006737 A compared with healthy A allele carriers and also in healthy GG compared with A allele carriers. There was no significant interaction between SNP rs1006737 and SNP rs956572 on [Ca(2+)]B. Our study further supports the association of SNP rs1006737 with BD-I and suggests that CACNA1C SNP rs1006737 and Bcl-2 SNP rs956572, or specific causal variants in LD with these proxies, act independently to increase risk and ICDH in BD-I.The World Journal of Biological Psychiatry 04/2015; DOI:10.3109/15622975.2015.1019360 · 4.23 Impact Factor
Article: A Century Of SchizophreniaJournal of Psychopharmacology 12/2012; 12:201-217. · 2.81 Impact Factor