Limits...
A common genetic network underlies substance use disorders and disruptive or externalizing disorders.

Arcos-Burgos M, Vélez JI, Solomon BD, Muenke M - Hum. Genet. (2012)

Bottom Line: Here we summarize evidence obtained by our group during the last two decades, and contrasted it with a review of related data from the available literature to show that behavioral syndromes involving attention deficit/hyperactivity disorder (ADHD), externalizing disorders, and substance-use disorder (SUD) share similar signs and symptoms (i.e., have a biological basis as common syndromes), physiopathological and psychopathological mechanisms, and genetic factors.Furthermore, we will show that the same genetic variants harbored in different genes are associated with different syndromes and that non-linear interactions between genetic variants (epistasis) best explain phenotype severity, long-term outcome, and response to treatment.We found that networks related to pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse are overrepresented.

View Article: PubMed Central - PubMed

Affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3717, USA. arcosburgosm@mail.nih.gov

ABSTRACT
Here we summarize evidence obtained by our group during the last two decades, and contrasted it with a review of related data from the available literature to show that behavioral syndromes involving attention deficit/hyperactivity disorder (ADHD), externalizing disorders, and substance-use disorder (SUD) share similar signs and symptoms (i.e., have a biological basis as common syndromes), physiopathological and psychopathological mechanisms, and genetic factors. Furthermore, we will show that the same genetic variants harbored in different genes are associated with different syndromes and that non-linear interactions between genetic variants (epistasis) best explain phenotype severity, long-term outcome, and response to treatment. These data have been depicted in our studies by extended pedigrees, where ADHD, externalizing symptoms, and SUD segregate and co-segregate. Finally, we applied here a new formal network analysis using the set of significantly replicated genes that have been shown to be either associated and/or linked to ADHD, disruptive behaviors, and SUD in order to detect significantly enriched gene categories for protein and genetic interactions, pathways, co-expression, co-localization, and protein domain similarity. We found that networks related to pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse are overrepresented. In summary, we provide compiled evidence of complex networks of genotypes underlying a wide phenotype that involves SUD and externalizing disorders.

Show MeSH

Related in: MedlinePlus

Physiopathological and psychopathological mechanisms, and genetic factors shared by attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), oppositional defiant disorder (ODD) and substance-use disorder (SUD)
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3351604&req=5

Fig1: Physiopathological and psychopathological mechanisms, and genetic factors shared by attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), oppositional defiant disorder (ODD) and substance-use disorder (SUD)

Mentions: Evidence derived from several studies by our group suggests that common mental disorders of childhood and adolescence form a similar picture to that of the AIDs. The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) includes in its classification attention deficit/hyperactivity disorder (ADHD), disruptive behavior disorders including conduct disorder (CD) and oppositional defiant disorder (ODD), as well as substance-use disorder (SUD). In the following sections, we will present data that support our model proposing that these constructs, grouped under the label “externalizing disorders”, can be considered to be related syndromes, and that they share common physiopathological and psychopathological mechanisms, with evidence for common underlying genetic factors (Fig. 1) (Acosta et al. 2004; Arcos-Burgos et al. 2004a, 2010; Elia et al. 2009; Jain et al. 2011; Martinez et al. 2011; Pineda et al. 2011; Ribases et al. 2011).Fig. 1


A common genetic network underlies substance use disorders and disruptive or externalizing disorders.

Arcos-Burgos M, Vélez JI, Solomon BD, Muenke M - Hum. Genet. (2012)

Physiopathological and psychopathological mechanisms, and genetic factors shared by attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), oppositional defiant disorder (ODD) and substance-use disorder (SUD)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351604&req=5

Fig1: Physiopathological and psychopathological mechanisms, and genetic factors shared by attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), oppositional defiant disorder (ODD) and substance-use disorder (SUD)
Mentions: Evidence derived from several studies by our group suggests that common mental disorders of childhood and adolescence form a similar picture to that of the AIDs. The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) includes in its classification attention deficit/hyperactivity disorder (ADHD), disruptive behavior disorders including conduct disorder (CD) and oppositional defiant disorder (ODD), as well as substance-use disorder (SUD). In the following sections, we will present data that support our model proposing that these constructs, grouped under the label “externalizing disorders”, can be considered to be related syndromes, and that they share common physiopathological and psychopathological mechanisms, with evidence for common underlying genetic factors (Fig. 1) (Acosta et al. 2004; Arcos-Burgos et al. 2004a, 2010; Elia et al. 2009; Jain et al. 2011; Martinez et al. 2011; Pineda et al. 2011; Ribases et al. 2011).Fig. 1

Bottom Line: Here we summarize evidence obtained by our group during the last two decades, and contrasted it with a review of related data from the available literature to show that behavioral syndromes involving attention deficit/hyperactivity disorder (ADHD), externalizing disorders, and substance-use disorder (SUD) share similar signs and symptoms (i.e., have a biological basis as common syndromes), physiopathological and psychopathological mechanisms, and genetic factors.Furthermore, we will show that the same genetic variants harbored in different genes are associated with different syndromes and that non-linear interactions between genetic variants (epistasis) best explain phenotype severity, long-term outcome, and response to treatment.We found that networks related to pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse are overrepresented.

View Article: PubMed Central - PubMed

Affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3717, USA. arcosburgosm@mail.nih.gov

ABSTRACT
Here we summarize evidence obtained by our group during the last two decades, and contrasted it with a review of related data from the available literature to show that behavioral syndromes involving attention deficit/hyperactivity disorder (ADHD), externalizing disorders, and substance-use disorder (SUD) share similar signs and symptoms (i.e., have a biological basis as common syndromes), physiopathological and psychopathological mechanisms, and genetic factors. Furthermore, we will show that the same genetic variants harbored in different genes are associated with different syndromes and that non-linear interactions between genetic variants (epistasis) best explain phenotype severity, long-term outcome, and response to treatment. These data have been depicted in our studies by extended pedigrees, where ADHD, externalizing symptoms, and SUD segregate and co-segregate. Finally, we applied here a new formal network analysis using the set of significantly replicated genes that have been shown to be either associated and/or linked to ADHD, disruptive behaviors, and SUD in order to detect significantly enriched gene categories for protein and genetic interactions, pathways, co-expression, co-localization, and protein domain similarity. We found that networks related to pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse are overrepresented. In summary, we provide compiled evidence of complex networks of genotypes underlying a wide phenotype that involves SUD and externalizing disorders.

Show MeSH
Related in: MedlinePlus