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

Fowler, Joanna S.; Alia‐Klein, Nelly; Kriplani, A.; Logan, Jean; Williams, Benjamin; Zhu, Wei; Craig, Ian W.; Telang, Frank; Goldstein, Rita Z.; Volkow, Nora D.; Vaska, P.; Wang, Gene‐Jack

doi:10.1016/j.biopsych.2006.08.038

Cited by 106 publications

(92 citation statements)

References 25 publications

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“…140 A polymorphism located 1.2 kb upstream of the MAOA coding sequences (variable number tandem repeat; VNTR) was reported to affect the transcription of the MAOA promoter: alleles with 3.5 or 4 copies of the repeat sequence are transcribed 210 times more efficiently than those with 3 or 5 copies of the repeat, suggesting an optimal length for the regulatory region. 141 In contrast, a recent study reported that the genotype is not associated with MAOA activity, as measured by imaging techniques; 142 however, we suggest that this is not sufficient to rule out a role of the MAOA variations in psychiatric disorders. It can be hypothesized that a disrupted variation of a single enzyme is counteracted by the modulation of the signalling cascades that are associated with its activity.…”

Section: Monoamine Oxidase Acontrasting

confidence: 92%

Pharmacogenetics of antidepressant response

Porcelli

Drago

Fabbri

et al. 2011

J Psychiatry Neurosci

156

103

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87Personalized medicine -the adaptation of therapies based on an individual's genetic and molecular profile -is one of the most promising aspects of modern medicine. The identification of the relation between genotype and drug response, including both the therapeutic effect and side effect profile, is expected to deeply affect medical practice. In this paper, we review the current knowledge about the genes related to antidepressant treatment response and provide methodologic proposals for future studies. We have mainly focused on genes associated with pharmacodynamics, for which a list of promising genes has been identified despite some inconsistency across studies. We have also synthesized the main results for pharmacokinetic genes, although so far they seem less relevant than those for pharmaco dynamic genes. We discuss possible reasons for these inconsistent findings and propose new study designs.

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Section: Monoamine Oxidase Acontrasting

confidence: 92%

Pharmacogenetics of antidepressant response

Porcelli

Drago

Fabbri

et al. 2011

J Psychiatry Neurosci

156

103

View full text Add to dashboard Cite

show abstract

“…One recent study positron emission tomography study of brain MAOA activity in relation to MAOA-LPR genotype suggests that genotype does not have a direct effect on transcriptional activity (Fowler et al, 2006). This finding may possibly be explained by the fact that the study did not take hormonal and/or environmental factors into account.…”

Section: Discussionmentioning

confidence: 98%

A Non-Additive Interaction of a Functional MAO-A VNTR and Testosterone Predicts Antisocial Behavior

Sjöberg

Ducci²,

Barr³

et al. 2007

Neuropsychopharmacol

122

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A functional VNTR polymorphism in the promoter of the monoamine oxidase A gene (MAOA-LPR) has previously been shown to be an important predictor of antisocial behavior in men. Testosterone analogues are known to interact with the MAOA promoter in vitro to influence gene transcription as well as in vivo to influence CSF levels of the MAO metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in human males. We examined the possible joint effects of testosterone (measured in CSF) and MAOA-LPR genotype on antisocial personality disorder and scores on the Brown-Goodwin Aggression scale in 95 unrelated male criminal alcoholics and 45 controls. The results confirm that MAOA genotype and CSF testosterone interact to predict antisocial behaviors. The MAOA/testosterone interaction also predicted low levels of CSF MHPG, which tentatively suggests the possibility that the interaction may be mediated by a direct effect on gene transcription. If replicated these findings offer plausible explanations for previous inconsistencies in studies of the relationship between testosterone and male human aggression, as well as for how MAOA genotype may influence aggressive behavior in human males.

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“…However, an important question remains concerning the point in time at which MAOA expression is thought to influence negative emotions and behavior. It is noteworthy that the relationship between MAOA genotype and in vivo MAOA activity remains unresolved (Fowler et al, 2007), and low MAOA levels in the brain may be a better predictor of trait aggressiveness than genotype (Alia-Klein, Goldstein, et al, 2008). Thus, the association of genotype and aggressive reactivity to provocation may not be because of MAOA functioning at the time of provocation.…”

Section: Discussionmentioning

confidence: 99%

A Functional Polymorphism of the MAOA Gene Is Associated with Neural Responses to Induced Anger Control

Denson

Dobson‐Stone

Ronay³

et al. 2014

Journal of Cognitive Neuroscience

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Abstract■ Aggressiveness is highly heritable. Recent experimental work has linked individual differences in a functional polymorphism of the monoamine oxidase-A gene (MAOA) to anger-driven aggression. Other work has implicated the dorsal ACC (dACC) in cognitive-emotional control and the amygdala in emotional arousal. The present imaging genetics study investigated dACC and amygdala reactivity to induced anger control as a function of MAOA genotype. A research assistant asked 38 healthy male undergraduates to control their anger in response to an insult by a rude experimenter. Men with the low-expression allele showed increased dACC and amygdala activation after the insult, but men with the high-expression allele did not. Both dACC and amygdala activation independently mediated the relationship between MAOA genotype and self-reported anger control. Moreover, following the insult, men with the high-functioning allele showed functional decoupling between the amygdala and dACC, but men with the low-functioning allele did not. These results suggest that heightened dACC and amygdala activation and their connectivity are neuroaffective mechanisms underlying anger control in participants with the low-functioning allele of the MAOA gene. ■

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

Cited by 106 publications

References 25 publications

Pharmacogenetics of antidepressant response

Pharmacogenetics of antidepressant response

A Non-Additive Interaction of a Functional MAO-A VNTR and Testosterone Predicts Antisocial Behavior

A Functional Polymorphism of the MAOA Gene Is Associated with Neural Responses to Induced Anger Control

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