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Brain monoamine oxidase A activity predicts trait aggression.

ABSTRACT: The genetic deletion of monoamine oxidase A (MAO A), an enzyme that breaks down the monoamine neurotransmitters norepinephrine, serotonin, and dopamine, produces aggressive phenotypes across species. Therefore, a common polymorphism in the MAO A gene (MAOA, Mendelian Inheritance in Men database number 309850, referred to as high or low based on transcription in non-neuronal cells) has been investigated in a number of externalizing behavioral and clinical phenotypes. These studies provide evidence linking the low MAOA genotype and violent behavior but only through interaction with severe environmental stressors during childhood. Here, we hypothesized that in healthy adult males the gene product of MAO A in the brain, rather than the gene per se, would be associated with regulating the concentration of brain amines involved in trait aggression. Brain MAO A activity was measured in vivo in healthy nonsmoking men with positron emission tomography using a radioligand specific for MAO A (clorgyline labeled with carbon 11). Trait aggression was measured with the multidimensional personality questionnaire (MPQ). Here we report for the first time that brain MAO A correlates inversely with the MPQ trait measure of aggression (but not with other personality traits) such that the lower the MAO A activity in cortical and subcortical brain regions, the higher the self-reported aggression (in both MAOA genotype groups) contributing to more than one-third of the variability. Because trait aggression is a measure used to predict antisocial behavior, these results underscore the relevance of MAO A as a neurochemical substrate of aberrant aggression.

SUBMITTER: Alia-Klein N

PROVIDER: S-EPMC2430409 | biostudies-other | 2008 May

REPOSITORIES: biostudies-other

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Brain monoamine oxidase A activity predicts trait aggression.

Alia-Klein Nelly N Goldstein Rita Z RZ Kriplani Aarti A Logan Jean J Tomasi Dardo D Williams Benjamin B Telang Frank F Shumay Elena E Biegon Anat A Craig Ian W IW Henn Fritz F Wang Gene-Jack GJ Volkow Nora D ND Fowler Joanna S JS

The Journal of neuroscience : the official journal of the Society for Neuroscience 20080501 19

The genetic deletion of monoamine oxidase A (MAO A), an enzyme that breaks down the monoamine neurotransmitters norepinephrine, serotonin, and dopamine, produces aggressive phenotypes across species. Therefore, a common polymorphism in the MAO A gene (MAOA, Mendelian Inheritance in Men database number 309850, referred to as high or low based on transcription in non-neuronal cells) has been investigated in a number of externalizing behavioral and clinical phenotypes. These studies provide evidenc ...[more]

PMID: 18463263

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Project description:Early theorists (Freud and Darwin) speculated that extremely shy children, or those with anxious temperament, were likely to have anxiety problems as adults. More recent studies demonstrate that these children have heightened responses to potentially threatening situations reacting with intense defensive responses that are characterized by behavioral inhibition (BI) (inhibited motor behavior and decreased vocalizations) and physiological arousal. Confirming the earlier impressions, data now demonstrate that children with this disposition are at increased risk to develop anxiety, depression, and comorbid substance abuse. Additional key features of anxious temperament are that it appears at a young age, it is a stable characteristic of individuals, and even in non-threatening environments it is associated with increased psychic anxiety and somatic tension. To understand the neural underpinnings of anxious temperament, we performed imaging studies with 18-fluoro-deoxyglucose (FDG) high-resolution Positron Emission Tomography (PET) in young rhesus monkeys. Rhesus monkeys were used because they provide a well validated model of anxious temperament for studies that cannot be performed in human children. Imaging the same animal in stressful and secure contexts, we examined the relation between regional metabolic brain activity and a trait-like measure of anxious temperament that encompasses measures of BI and pituitary-adrenal reactivity. Regardless of context, results demonstrated a trait-like pattern of brain activity (amygdala, bed nucleus of stria terminalis, hippocampus, and periaqueductal gray) that is predictive of individual phenotypic differences. Importantly, individuals with extreme anxious temperament also displayed increased activity of this circuit when assessed in the security of their home environment. These findings suggest that increased activity of this circuit early in life mediates the childhood temperamental risk to develop anxiety and depression. In addition, the findings provide an explanation for why individuals with anxious temperament have difficulty relaxing in environments that others perceive as non-stressful.

Project description:BackgroundMonoamine oxidase A (MAOA) is a mitochondrial enzyme that is involved in prostate tumorigenesis and cancer metastasis. The predictive power of the preoperative clinical and pathological indicators for prostate cancer(PC) remains to be improved. To enrich evidence regarding the value of MAOA as a prognostic biomarker in clinical practice, this study explored the significance of MAOA expression as a prognostic marker for patients with PC after radical prostatectomy-pelvic lymph node dissection (RP-PLND).MethodsMAOA expression was analyzed in 50 benign prostate tissues and 115 low-intermediate risk and 163 high-risk PC tissues using tissue immunohistochemistry (IHC). Propensity score matching, survival analysis and COX regression analysis were conducted to investigate the correlation between high MAOA expression and progression free survival (PFS) in PC patients.ResultsMAOA expression was increased in PC patients, especially in those with high risk PC and pathological lymph node (pLN) metastasis. High MAOA expression was significantly associated with PSA recurrence for both low-intermediate risk PC patients (log-rank test: P = 0.02) and high risk PC patients (log-rank test: P = 0.03). Cox regression analysis revealed that high MAOA expression was an adverse prognostic factor for both low-intermediate risk PC patients (hazard ratio [HR] 2.74, 95% confidence interval [CI] 1.26-5.92; P = 0.011) and high risk PC patients (HR 1.73, 95% CI 1.11-2.71; P = 0.016). High MAOA expression was also significantly associated with PSA recurrence in high risk PC patients developed into castration-resistant prostate cancer (CRPC) and were receiving abiraterone therapy (log-rank: P = 0.01).ConclusionsMAOA expression correlates with the malignant progression of PC. High MAOA expression may be a poor prognostic marker for patients with PC after RP-PLND. More careful follow up or potential of adjuvant hormonal therapy may be addressed for patients with high MAOA expression.

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Brain monoamine oxidase A activity predicts trait aggression.

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Brain monoamine oxidase A activity predicts trait aggression.

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