Monoamine Oxidase-A Genetic Variations Influence Brain Activity Associated with Inhibitory Control: New Insight into the Neural Correlates of Impulsivity

Passamonti, Luca; Fera, Francesco Saverio; Magariello, A.; Cerasa, Antonio; Gioia, Maria Cecilia; Muglia, M.; Nicoletti, Giuseppe; Gallo, Olivier; Provinciali, Leandro; Quattrone, Aldo

doi:10.1016/j.biopsych.2005.07.027

Cited by 143 publications

(108 citation statements)

References 45 publications

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“…Generally, this genotype has a profound impact on both neuroanatomy and functional activity of two specific brain regions, critically involved in emotional processing and aggressive behaviour: the orbitofrontal cortex (Meyer-Lindenberg et al, 2006;Passamonti et al, 2006;Passamonti et al, 2008;Buckholtz et al, 2008;Cerasa et al, 2008a,b) and the cingulate cortex (Meyer-Lindenberg et al, 2006;Passamonti et al, 2008). By contrast, this combined neuroanatomical/functional impact of the MAO A VNTR polymorphism is not evident in the amygdala.…”

Section: Discussionmentioning

confidence: 99%

“…Genotyping for the MAO A VNTR polymorphism was performed as described previously (Furlong et al, 1999;Passamonti et al, 2006;Passamonti et al, 2008;Cerasa et al, 2008a,b;Cerasa et al, 2010). Briefly, the VNTR promoter MAO A polymorphism was amplified from genomic DNA using primers designed by the Web Primer site (http://www.seq.yeastgenome.org/ cgi-bin/web-primer) that flanked the polymorphic region located approximately 1200 bp upstream from the translation start site (Furlong et al, 1999) (GeneBank accession number AJ004833).…”

Section: Genotypingmentioning

confidence: 99%

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MAO A VNTR polymorphism and amygdala volume in healthy subjects

Cerasa

Quattrone

Gioia

et al. 2011

Psychiatry Research: Neuroimaging

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The X-linked Monoamine Oxidase A (MAO A) gene presents a well known functional polymorphism consisting of a variable number of tandem repeats (VNTR) (long and short variants) previously associated with altered neural function of the amygdala. Using automatic subcortical segmentation (Freesurfer), we investigated whether amygdala volume could be influenced by this genotype. We studied 109 healthy subjects (age range 18-80 years; 59 male and 50 female), 74 carrying the MAO A High-activity allele and 35 the MAO A Low-activity allele. No significant effect of the MAO A polymorphism or interaction effect between polymorphism × gender was found on amygdalar volume. Thus, our findings suggest that the reported impact of the MAO A polymorphism on amygdala function is not coupled with consistent volumetric changes in healthy subjects. Future studies are needed to investigate whether the association between volume of the amygdala and the MAO A VNTR polymorphism is influenced by social/psychological variables, such as impulsivity, trauma history and cigarette smoking behaviour, not taken into account in this work.

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Section: Discussionmentioning

confidence: 99%

Section: Genotypingmentioning

confidence: 99%

MAO A VNTR polymorphism and amygdala volume in healthy subjects

Cerasa

Quattrone

Gioia

et al. 2011

Psychiatry Research: Neuroimaging

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“…The prevalence of the high and low MAO A genotypes in the male population has stimulated many studies on the association of MAO A genotype with impulsivity, inhibitory control, and aggression (Huang et al 2004;Manuck et al 2000;Passamonti et al 2006). Of particular interest are a number of studies showing that MAO A genotype influences vulnerability to environmental stress both in humans (Caspi et al 2002) and animals (Newman et al 2005) and that this biological process can be initiated early in life (Kim-Cohen et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Evidence That Brain MAO A Activity Does Not Correspond to MAO A Genotype in Healthy Male Subjects

Fowler

Alia‐Klein

Kriplani

et al. 2007

Biological Psychiatry

106

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“…To date, three studies have found evidence for an impact of the MAOA u-VNTR on brain function during tasks that index inhibitory control. Fan et al 22,23 found decreased dorsal cingulate activation during conflict resolution in MAOA-L subjects, and Passamonti et al 24 showed diminished ventrolateral prefrontal engagement during response inhibition in these individuals. A recent investigation of the effect of this genetic variant on brain structure and function in a large sample of healthy volunteers found a pronounced impact on amygdala and perigenual cingulate cortex, as well as gender-dimorphic (males only) effects on limbic circuitry for emotional arousal, memory and cognitive control, including orbitofrontal cortex and dorsal anterior cingulate.…”

Section: Introductionmentioning

confidence: 99%

“…However, clinical associations of the MAOA u-VNTR with personality traits and cerbrospinal fluid monoamine metabolite levels are mixed, with heterogeneity in the personality measures used and inconsistent directionality of effects making interpretation difficult. [19][20][21][22][23][24][25][26][27][28][29][30] A more consistent picture has emerged showing the relevance of MAOA genetic variation to a complex behavior, impulsive violence. In a large longitudinal study of at-risk children, Caspi et al 31 found evidence for a gene-environment interaction, whereby childhood abuse predicted later life antisocial behavior in men hemizygous for the MAOA-L allele.…”

Section: Introductionmentioning

confidence: 99%

Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality

Buckholtz¹,

Callicott²,

Kolachana³

et al. 2007

Mol Psychiatry

198

170

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Little is known about neural mechanisms underlying human personality and temperament, despite their considerable importance as highly heritable risk mediators for somatic and psychiatric disorders. To identify these circuits, we used a combined genetic and imaging approach focused on Monoamine Oxidase A (MAOA), encoding a key enzyme for monoamine metabolism previously associated with temperament and antisocial behavior. Male carriers of a low-expressing genetic variant exhibited dysregulated amygdala activation and increased functional coupling with ventromedial prefrontal cortex (vmPFC). Stronger coupling predicted increased harm avoidance and decreased reward dependence scores, suggesting that this circuitry mediates a part of the association of MAOA with these traits. We utilized path analysis to parse the effective connectivity within this system, and provide evidence that vmPFC regulates amygdala indirectly by influencing rostral cingulate cortex function. Our data implicate a neural circuit for variation in human personality under genetic control, provide an anatomically consistent mechanism for vmPFC-amygdala interactions underlying this variation, and suggest a role for vmPFC as a superordinate regulatory area for emotional arousal and social behavior.

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Monoamine Oxidase-A Genetic Variations Influence Brain Activity Associated with Inhibitory Control: New Insight into the Neural Correlates of Impulsivity

Cited by 143 publications

References 45 publications

MAO A VNTR polymorphism and amygdala volume in healthy subjects

MAO A VNTR polymorphism and amygdala volume in healthy subjects

Evidence That Brain MAO A Activity Does Not Correspond to MAO A Genotype in Healthy Male Subjects

Genetic variation in MAOA modulates ventromedial prefrontal circuitry mediating individual differences in human personality

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