MAO A VNTR polymorphism and variation in human morphology: a VBM study

Cerasa, Antonio; Gioia, Maria Cecilia; Labate, Angelo; Lanza, P.; Magariello, A.; Muglia, M.; Quattrone, Aldo

doi:10.1097/wnr.0b013e3283060ab6

Cited by 25 publications

(21 citation statements)

References 20 publications

(38 reference statements)

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“…Different results might depend upon the different MRI volumetric approach employed by Meyer-Lindenberg et al (2006) (VBM), although in an our previous VBM study using an underpowered sample we did not detect significant association between MAO A and amygdala concentration (Cerasa et al, 2008b). Generally, VBM and volumetric studies often are not directly comparable.…”

Section: Discussionmentioning

confidence: 80%

“…Although there is consistent evidence that the MAO A polymorphism impacts limbic function, possible morphological changes underlying such a functional polymorphism remain to be clarified. In fact, there are few morphological studies that, using voxel-based morphometry (VBM), indirectly investigated the association of this genotype with amygdala volume, and these studies produced contrasting findings (Meyer-Lindenberg et al, 2006;Cerasa et al, 2008b). VBM is a morphological technique that performs a statistical mapping of differences in brain morphology voxel-byvoxel, which produces grey matter "density" or "concentration" measures, or volume differences between two groups, respectively; however, these are relative measures and not absolute volumes (Eckert et al, 2006;Makris et al, 2008).…”

Section: Introductionmentioning

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: 80%

Section: Introductionmentioning

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 spectrum of phenotypical features observed in MAO-A Neo mice is strikingly similar to the neuropsychological and morphological correlates of low-activity allelic MAO-A variants in humans, including structural abnormalities in the orbitofrontal cortex, social deficits, maladaptive threat perception, and lack of inherent aggressiveness (at least in the absence of concurring environmental factors) (Caspi et al, 2002;Cerasa et al, 2010;Cerasa et al, 2008;Kim-Cohen et al, 2006;Lee and Ham, 2008;MeyerLindenberg et al, 2006;Williams et al, 2009). These crossspecies analogies highlight the translational validity of MAO-A Neo mice as a dependable murine model to investigate the neurobiological bases of the subtle aberrances associated with low MAO-A activity, as well as their implication in the vulnerability to pathological aggression and related psychiatric disorders.…”

Section: Discussionmentioning

confidence: 88%

Social Deficits and Perseverative Behaviors, but not Overt Aggression, in MAO-A Hypomorphic Mice

Bortolato¹,

Chen²,

Godar³

et al. 2011

Neuropsychopharmacol

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Monoamine oxidase (MAO)-A is a key enzyme for the degradation of brain serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE). In humans and mice, total MAO-A deficiency results in high 5-HT and NE levels, as well as elevated reactive aggression. Here we report the generation of MAO-A(Neo) mice, a novel line of hypomorphic MAO-A mutants featuring the insertion of a floxed neomycin-resistance cassette in intron-12 of the Maoa gene. This construct resulted in a chimeric, non-functional variant of the Maoa-Neo transcript, with a truncated C-terminus, likely due to aberrant splicing; these deficits notwithstanding, small amounts of functional Maoa transcript were found in the brain of MAO-A(Neo) mice. In the prefrontal cortex and amygdala, MAO-A(Neo) mice showed low, yet detectable, MAO-A catalytic activity, as well as 5-HT levels equivalent to WT littermates; conversely, the hippocampus and midbrain of MAO-A(Neo) mice featured a neurochemical profile akin to MAO-A-knockout (KO) mice, with undetectable MAO-A activity and high 5-HT concentrations. MAO-A(Neo) mice showed significant increases in dendritic length in the pyramidal neurons of orbitofrontal cortex, but not basolateral amygdala, in comparison with WT littermates; by contrast, the orbitofrontal cortex of MAO-A KO mice showed significant reductions in basilar dendritic length, as well as a profound increase in apical dendritic length. MAO-A(Neo) mice showed a unique set of behavioral abnormalities, encompassing reduced open-field locomotion, perseverative responses, such as marble burying and water mist-induced grooming, and a lack of anxiety-like behaviors in the elevated plus-maze and light-dark box paradigms. Notably, whereas MAO-A(Neo) and KO mice showed significant reductions in social interaction, only the latter genotype showed increases in resident-intruder aggression. Taken together, our findings indicate that MAO A hypomorphism results in behavioral and morphological alterations distinct from those featured by MAO-A KO mice.

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“…In particular, several studies have shown that male individuals with the 3R haplotype exhibit morphological alterations of the orbitofrontal cortex (Meyer-Lindenberg et al , 2006; Cerasa et al , 2008, 2010), as well as functional abnormalities in several cortical and limbic regions, including prefrontal cortex, amygdala, and hippocampus (Meyer-Lindenberg et al , 2006; Passamonti et al , 2006). …”

Section: Phenotypical Outcomes Of Mao-a Deficitmentioning

confidence: 99%

Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence

Bortolato

Shih

2011

International Review of Neurobiology

110

109

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Monoamine oxidase (MAO) isoenzymes A and B are mitochondrial-bound proteins, catalyzing the oxidative deamination of monoamine neurotransmitters as well as xenobiotic amines. Although they derive from a common ancestral progenitor gene, are located at X-chromosome and display 70% structural identity, their substrate preference, regional distribution, and physiological role are divergent. In fact, while MAO-A has high affinity for serotonin and norepinephrine, MAO-B primarily serves the catabolism of 2-phenylethylamine (PEA) and contributes to the degradation of other trace amines and dopamine. Convergent lines of preclinical and clinical evidence indicate that variations in MAO enzymatic activity—due to either genetic or environmental factors—can exert a profound influence on behavioral regulation and play a role in the pathophysiology of a large spectrum of mental and neurodegenerative disorders, ranging from antisocial personality disorder to Parkinson’s disease. Over the past few years, numerous advances have been made in our understanding of the phenotypical variations associated with genetic polymorphisms and mutations of the genes encoding for both isoenzymes. In particular, novel findings on the phenotypes of MAO-deficient mice are highlighting novel potential implications of both isoenzymes in a broad spectrum of mental disorders, ranging from autism and anxiety to impulse-control disorders and ADHD. These studies will lay the foundation for future research on the neurobiological and neurochemical bases of these pathological conditions, as well as the role of gene × environment interactions in the vulnerability to several mental disorders.

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MAO A VNTR polymorphism and variation in human morphology: a VBM study

Cited by 25 publications

References 20 publications

MAO A VNTR polymorphism and amygdala volume in healthy subjects

MAO A VNTR polymorphism and amygdala volume in healthy subjects

Social Deficits and Perseverative Behaviors, but not Overt Aggression, in MAO-A Hypomorphic Mice

Behavioral outcomes of monoamine oxidase deficiency: preclinical and clinical evidence

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