Abstract
Schizophrenia is a severe mental disorder, with a highly complex and heterogenous clinical presentation. Our current perspectives posit that the pathogenic mechanisms of this illness lie in complex arrays of gene × environment interactions. Furthermore, several findings indicate that males have a higher susceptibility for schizophrenia, with earlier age of onset and overall poorer clinical prognosis. Based on these premises, several authors have recently begun exploring the possibility that the greater schizophrenia vulnerability in males may reflect specific gene × sex (G×S) interactions. Our knowledge on such G×S interactions in schizophrenia is still rudimentary; nevertheless, the bulk of preclinical evidence suggests that the molecular mechanisms for such interactions are likely contributed by the neurobiological effects of sex steroids on dopamine (DA) neurotransmission. Accordingly, several recent studies suggest a gender-specific association of certain DAergic genes with schizophrenia. These G×S interactions have been particularly documented for catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), the main enzymes catalyzing DA metabolism. In the present review, we will outline the current evidence on the interactions of DA-related genes and sex-related factors, and discuss the potential molecular substrates that may mediate their cooperative actions in schizophrenia pathogenesis.
Highlights
Schizophrenia is a chronic and severe neurodevelopmental disorder, characterized by a highly complex and heterogeneous set of perceptual, cognitive and emotional deficits (Breier, 1999; Rowley et al, 2001)
It is possible to theorize the existence of specific gene × sex (G×S) interactions that may contribute to schizophrenia pathogenesis
Gene-sex interactions in schizophrenia the concept that stimulation of D2 receptors in subcortical areas results in psychotic manifestations, other lines of evidence strongly suggest that negative and cognitive symptoms may be underpinned by the insufficient activation of D1-like receptors in the prefrontal cortex (PFC) (Goldman-Rakic and Selemon, 1997)
Summary
Reviewed by: Tertia Purves-Tyson, Neuroscience Research Australia, Australia Colm O’Tuathaigh, University College Cork, Ireland. Several findings indicate that males have a higher susceptibility for schizophrenia, with earlier age of onset and overall poorer clinical prognosis. Based on these premises, several authors have recently begun exploring the possibility that the greater schizophrenia vulnerability in males may reflect specific gene × sex (G×S) interactions. Several authors have recently begun exploring the possibility that the greater schizophrenia vulnerability in males may reflect specific gene × sex (G×S) interactions Our knowledge on such G×S interactions in schizophrenia is still rudimentary; the bulk of preclinical evidence suggests that the molecular mechanisms for such interactions are likely contributed by the neurobiological effects of sex steroids on dopamine (DA) neurotransmission.
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