"This task is based upon the new realization that in the mammalian brain there is complexity in the genomic networks that intimately interact with functional neural networks. Genes are under the regulatory control of epigenetic networks that may constitute a 'code' that shapes, and may even define, functional features of neural networks (Colvis et al., 2005). Failure at the genomic and epigenomic levels, through hereditary mechanisms or via exposure to environmental insults such as drugs of abuse, may impact the relationship between gene regulatory networks and widespread brain neural networks. "
[Show abstract][Hide abstract] ABSTRACT: Background:
Following the first association between the dopamine D2 receptor gene polymorphism and severe alcoholism, there has been an explosion of research reports in the psychiatric and behavioral addiction literature and neurogenetics. With this increased knowledge, the field has been rife with controversy. Moreover, with the advent of Whole Genome-Wide Studies (GWAS) and Whole Exome Sequencing (WES), along with Functional Genome Convergence, the multiple-candidate gene approach still has merit and is considered by many as the most prudent approach. However, it is the combination of these two approaches that will ultimately define real, genetic allelic relationships, in terms of both risk and etiology. Since 1996, our laboratory has coined the umbrella term Reward Deficiency Syndrome (RDS) to explain the common neurochemical and genetic mechanisms involved with both substance and non-substance, addictive behaviors.
This is a selective review of peer-reviewed papers primary listed in Pubmed and Medline.
A review of the available evidence indicates the importance of dopaminergic pathways and resting-state, functional connectivity of brain reward circuits.
Importantly, the proposal is that the real phenotype is RDS and impairments in the brain's reward cascade, either genetically or environmentally (epigenetically) induced, influence both substance and non-substance, addictive behaviors. Understanding shared common mechanisms will ultimately lead to better diagnosis, treatment and prevention of relapse. While, at this juncture, we cannot as yet state that we have "hatched the behavioral addiction egg", we are beginning to ask the correct questions and through an intense global effort will hopefully find a way of "redeeming joy" and permitting homo sapiens live a life, free of addiction and pain.
"Therefore, the use of bioinformatics tools becomes vital in order to analyze the enormity of data and identify patterns and phenotypes, as well as to decipher underlying interconnected physiological pathways . For example, high-throughput genomics provides an extraordinary view into the genetic architecture of animal and human behavior, the interconnectivity of complex traits  , and " network " models of animal phenotypes (as part of phenomics), which are crucial for exploring neuropsychiatric processes    . Nevertheless, further integration of heterogeneous data, especially gene and protein expression pathways, is critical because deciphering such networks and their interplay poses one of the greatest challenges in current systems biology . "
Behavioural brain research 02/2014; 276. DOI:10.1016/j.bbr.2014.01.038 · 3.03 Impact Factor
"Over the last decade, numerous studies have implicated epigenetic modifications in the regulation of learningdependent synaptic plasticity (Martinowich et al., 2003; Levenson et al., 2004, 2006; Colvis et al., 2005; Wood et al., 2006; Jiang et al., 2008; Lubin et al., 2008; Nelson et al., 2008; Gupta et al., 2010). Primarily, the focus has remained on histone acetylation and DNA methylation and there is now strong support that these epigenetic modifications are critical regulators of long-term memory formation in the mammalian brain. "
[Show abstract][Hide abstract] ABSTRACT: Abstract Histone lysine methylation is a well-established transcriptional mechanism for the regulation of gene expression changes in eukaryotic cells and is now believed to function in neurons of the central nervous system to mediate the process of memory formation and behavior. In mature neurons, methylation of histone proteins can serve to both activate and repress gene transcription. This is in stark contrast to other epigenetic modifications, including histone acetylation and DNA methylation, which have largely been associated with one transcriptional state in the brain. In this review, we discuss the evidence for histone methylation mechanisms in the coordination of complex cognitive processes such as long-term memory formation and storage. In addition, we address the current literature highlighting the role of histone methylation in intellectual disability, addiction, schizophrenia, autism, depression, and neurodegeneration. Further, we discuss histone methylation within the context of other epigenetic modifications and the potential advantages of exploring this newly identified mechanism of cognition, emphasizing the possibility that this molecular process may provide an alternative locus for intervention in long-term psychopathologies that cannot be clearly linked to genes or environment alone.
Reviews in the neurosciences 05/2013; 24(4):1-13. DOI:10.1515/revneuro-2013-0008 · 3.33 Impact Factor
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