"S chizophrenia is a complex neurological disorder where interactions between multiple genetic and environmental factors contribute to its etiology (Harrison et al., 2012; Kumarasinghe et al., 2012; Pelayo-Terán et al., 2012; Schultz et al., 2007; Sebat et al., 2009). Apart from direct influence of the genetic variants, several twin studies have shown that environmental factors such as low socioeconomic status, physical stress, and drug abuse can also modulate the functionality of the neurotransmitters and their receptors (Critchley et al., 2013; Evins et al., 2012; Fabi et al., 2013; Murray et al., 2013; Rabin et al., 2013; Van et al., 2088; Werner et al., 2007). In search of the genetic alterations, robust high-throughput technologies, including Genome Wide Association Studies (GWAS), have revealed numerous disease susceptibility loci. "
[Show abstract][Hide abstract] ABSTRACT: Schizophrenia, a complex neurological disorder, is comprised of interactions between multiple genetic and environmental factors wherein each of the factors individually exhibits a small effect. In this regard a network-based strategy is best suited to capture the combined effect of multiple genes with their definite pattern of interactions. Given that schizophrenia affects multiple regions of the brain, we postulated that instead of any single specific tissue, a mutual set of interactions occurs between different regions of brain in a well-defined pattern responsible for the disease phenotype. To validate, we constructed and compared tissue specific co-expression networks of schizophrenia candidate genes in twenty diverse brain tissues. As predicted, we observed a common interaction network of certain genes in all the studied brain tissues. We examined fundamental network topologies of the common network to sequester essential common candidates for schizophrenia. We also performed a gene set analysis to identify the essential biological pathways enriched by the common candidates in the network. Finally, the candidate drug targets were prioritized and scored against known available schizophrenic drugs by molecular docking studies. We distinctively identified protein kinases as the top candidates in the network that can serve as probable drug targets for the disease. Conclusively, we propose that a comprehensive study of the connectivity amongst the disease genes themselves may turn out to be more informative to understand schizophrenia disease etiology and the underlying complexity.
Omics A Journal of Integrative Biology 12/2014; 18(12):754 -766. DOI:10.1089/omi.2014.0082 · 2.36 Impact Factor
"Cognitive symptoms include deficits in attention and working memory that lead to an inability to organize one's life and to work effectively. Epidemiological studies suggest that cannabis use during adolescence confers an increased risk for developing psychotic symptoms later in life (D'Souza et al., 2009; Evins et al., 2012). However, epidemiological studies have a correlative nature and studies on human subjects are limited by the associated ethical concerns and experimental difficulties, which can be circumvented by animal models. "
[Show abstract][Hide abstract] ABSTRACT: Epidemiological studies suggest that Cannabis use during adolescence confers an increased risk for developing psychotic symptoms later in life. However, despite their interest, the epidemiological data are not conclusive, due to their heterogeneity, thus modeling the adolescent phase in animals is useful for investigating the impact of Cannabis use on deviations of adolescent brain development that might confer a vulnerability to later psychotic disorders. Although scant, preclinical data seem to support the presence of impaired social behaviors, cognitive and sensorimotor gating deficits as well as psychotic-like signs in adult rodents after adolescent cannabinoid exposure, clearly suggesting that this exposure may trigger a complex behavioral phenotype closely resembling a schizophrenia-like disorder. Similar treatments performed at adulthood were not able to produce such phenotype, thus pointing to a vulnerability of the adolescent brain towards cannabinoid exposure. The neurobiological substrate of the adolescent vulnerability are still largely unknown and experimental studies need to elucidate the cellular and molecular mechanism underlying these effects. However, the few data available seem to suggest that heavy adolescent exposure to cannabinoids is able to modify neuronal connectivity in specific brain areas long after the end of the treatment. This is likely due to disruption of maturational events within the endocannabinoid system during adolescence that in turn impact on the correct neuronal refinement peculiar of the adolescent brain, thus leading to altered adult brain functionality and behavior.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 07/2013; 52. DOI:10.1016/j.pnpbp.2013.07.020 · 3.69 Impact Factor
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