Colm M P O'Tuathaigh

..0mg/kg). These results indicate a differential contribution of NRG1 and DISC1 vis-à-vis COMT to the processing of thermal nociceptive stimuli and extend their phenotypic relationship to psychotic illness...

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..These data indicate a subtle role for NRG1 in modulating several schizophrenia-relevant processes including the effects of psychotomimetic N-methyl-D-aspartate receptor antagonists...

..These findings illuminate the interaction between genes and adverse environmental exposures over a particular stage of development in the expression of the psychosis phenotype...

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..These studies elaborate a pleiotropic role of neuregulin-1 in development, plasticity and function, including sexual dimorphism, by defining the elemental, temporal and sex-specific characteristics of the neuregulin-1 mutant ethogram...

..They indicate that NRG1 is involved in the regulation of reciprocal social interaction behaviour and thus suggest a putative role for NRG1 in a schizophrenia-related endophenotype...

..The breadth and depth of ongoing studies in mutants hold the prospect of addressing these shortcomings...

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..These findings illuminate how COMT deletion and adolescent cannabis use can interact to modulate the function of neurotransmitters systems implicated in schizophrenia...

..These data elaborate earlier findings of increased anxiety in female COMT KO mice and also clarify a role for COMT in modulating stress-related hormonal and immune parameters in a manner that depends on chronicity of the stressor...

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..We also consider methodological issues that are likely to influence phenotypic effects, as well as the limitations associated with existing molecular techniques...

..Finally, we identify current challenges associated with the use of genetic mutant models and highlight their potential value for exploring gene-gene and gene-environment interactions in relation to schizophrenia...

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..The brain and face emerge in embryologic intimacy, such that in neurodevelopmental disorders, brain dysmorphogenesis is accompanied by facial dysmorphogenesis...

..Bipolar disorder and schizophrenia might reflect similar insult(s) acting over slightly differing time-frames or slightly differing insult(s) acting over a similar time-frame...

..Emphasis is also placed on the importance of studying gene x environment and gene x gene interactions, as well as addressing methodological issues related to genetic modelling and phenotyping strategies...

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..Genetic background appears to modulate critically the magnitude but not the general nature of the D(1A)-null phenotype, which may involve compensatory processes independent of other D(1)-like or D(2)-like receptors...

..A role for D(3) receptors in inhibitory processes appeared topographically circumscribed and only when baseline levels of behaviour were low...

..However, whether polymorphisms in these genes contribute to the cause of essential hypertension in humans is still a matter of debate...

..Adversities operating over intrauterine life have been associated with risk of schizophrenia, but the biology of resultant developmental perturbation is poorly understood...

..Understanding the mechanistic bases of mitigation vs persistence of individual phenotypes in relation to neural adaptation consequent to cell loss may lead to novel therapeutic strategies for basal ganglia disorders...

..Events over early fetal life may be an important determinant of sexually dimorphic covariance of anterior facial shape and asymmetry with aspects of cognition that involve the anterior brain...

..Furthermore, there are poorly understood methodological factors that contribute to inconsistent phenotypic findings between laboratories...

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..As understanding of the pathobiology of schizophrenia increases, the challenge is to relate such measures to outcome at a functional level...

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..Heterozygous COMT deletion is associated with a distinctive phenotype. This differs from that which we have reported previously for heterozygous deletion of the schizophrenia risk gene neuregulin-1...

..Additionally, they indicate the involvement of phosphoinositide hydrolysis and D(5):D(2)-like interactions in regulating these processes...

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..It examines gene-gene and gene-environment interactions. Finally, it looks at future directions for research...

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..For example, the seizure and vacuous chewing responses appear to involve dopamine D1-like receptors that stimulate adenylyl cyclase, while intense grooming involves those which do not...

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..These studies identify novel functional roles for the D4 receptor that are distinct from those of closely related D2-like family members and involve interactions with their D1-like counterparts...

..D2 receptors exert topographically specific regulation of orofacial movements in a manner distinct from their D1A counterparts, while D3 receptors exert only minor regulation of such movements...

..Critically, the present data indicate that phenotypic effects of a given gene deletion using an agonist acting on the system disrupted cannot be generalized to a corresponding antagonist, and vice versa...

..These findings indicate that D(1), and to a lesser extent D(5), receptor coupling to DARPP-32, ERK1/2 and glutamatergic signalling is involved in mediating the convulsant effects of SKF 83822...

..Thus, interventions that shorten the duration of untreated psychosis (DUP) and arrest early deterioration may have long-term benefits...

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..This study examined concurrent associations and predictors at first indication of nonadherence to antipsychotic medication four years after a first episode of psychosis...

..9 points. CONCLUSIONS: This study extends the findings of short-term follow-up studies by confirming an association between duration of untreated psychosis and 'mid-term' outcome...

..The same haplotype is in excess in the Caucasian schizophrenia sample used by Chowdari et al. [2002: Hum Mol Genet 11: 1373-1380]. This study provides further support for the contribution of RGS4 to schizophrenia susceptibility...

..Four years later 18% had made a suicide attempt and 3% completed suicide. Suicide attempts prior to presentation were associated with a longer duration of untreated psychosis...

..No evidence was found to suggest an association between the DTNBP1 gene and schizophrenia in our sample. Possible reasons for these findings are discussed...

..These six genes are involved in diverse processes, such as maintenance of chromatin architecture, DNA-damage checkpoint and cell cycle regulation, which may contribute to the CIN and MIN phenotypes...

..In assuming that the well-recognised role of the D(1)-like family in regulating orofacial movements involves primarily D(1) receptors, a role for their D(5) counterparts may have been overlooked...