Monoamine Oxidase A Binding in the Prefrontal and Anterior Cingulate Cortices During Acute Withdrawal From Heavy Cigarette Smoking

Bacher, Ingrid; Houle, Sylvain; Xu, Xin; Zawertailo, Laurie; Soliman, Alexandra; Wilson, Alan A.; Selby, Peter; George, Tony P.; Sacher, Julia; Miler, Laura; Kish, Stephen J.; Rusjan, Pablo; Meyer, Jeffrey H.

doi:10.1001/archgenpsychiatry.2011.82

Cited by 67 publications

(55 citation statements)

References 78 publications

(123 reference statements)

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“…Other inclusion criteria were good physical health and a HRSD of at least 14 on the 17-item HRSD. Exclusion criteria included co-morbid psychiatric or medical illness, current or past substance abuse, report of cigarette smoking within the past year (since recent heavy cigarette smoking may bias MAO-A V T (Bacher et al, 2011;Fowler et al, 1996)), positive urine toxicology drug screen, and herbal drug or medication use within the past 8 weeks with the exception of SSRIs for which the exclusion period was 2 weeks (37 participants had no SSRI use in the past month). Although SSRIs, through reducing extracellular clearance of serotonin, likely counter a downstream effect of greater serotonin metabolism from elevated MAO-A level, we previously demonstrated that SSRIs do not affect MAO-A V T in vivo (Meyer et al, 2009), a finding consistent with the pharmacological specificity of SSRIs.…”

Section: Participantsmentioning

confidence: 99%

Elevated Monoamine Oxidase A Binding During Major Depressive Episodes Is Associated with Greater Severity and Reversed Neurovegetative Symptoms

Chiuccariello

Houle

Miler

et al. 2013

Neuropsychopharmacol

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Inadequate treatment response occurs in approximately 40% of major depressive episodes (MDEs), and one approach to solve this is careful matching of treatment to the specific pathologies of MDE. One such biological abnormality is elevated monoamine oxidase A (MAO-A) levels, which occurs in the prefrontal and anterior cingulate cortex (PFC and ACC) during MDE; however, the subtypes for which this abnormality is most prominent are unknown. We hypothesized that MAO-A levels in the PFC and ACC are most elevated in MDE with greater severity and reversed neurovegetative symptoms (hypersomnia and either hyperphagia or weight gain). MAO-A V T (an index of MAO-A density) was measured using [ 11 C]harmine positron emission tomography (PET) in 42 subjects with MDEs secondary to major depressive disorder and 37 healthy controls. The effect of severity and reversed neurovegetative symptoms on MAO-A V T in the PFC and ACC was analyzed using a multivariate analysis of variance (MANOVA). Greater severity and reversed neurovegetative symptoms were associated with elevated MAO-A V T in the PFC and ACC (MANOVA, severity: F (2,38) ¼ 5.44, p ¼ 0.008; reversed neurovegetative symptoms: F (2,38) ¼ 5.13, p ¼ 0.01). Increased MAO-A level, when greater severity and reversed neurovegetative symptoms are present, may explain the association of these clinical features with a preferential response to MAO inhibitors, which is especially well-evidenced for reversed neurovegetative symptoms in MDE. As MAO-A creates oxidative stress, facilitates apoptosis, and metabolizes monoamines, therapeutics opposing these processes are predicted to best treat MDE with greater severity and reversed neurovegetative symptoms.

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Section: Participantsmentioning

confidence: 99%

Elevated Monoamine Oxidase A Binding During Major Depressive Episodes Is Associated with Greater Severity and Reversed Neurovegetative Symptoms

Chiuccariello

Houle

Miler

et al. 2013

Neuropsychopharmacol

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“…This is because alcohol intake has two mechanisms that lead to elevated plasma levels of harman, a beta-carboline compound, which has moderate affinity for MAO-A and may influence available MAO-A binding in humans (9,10). To avoid temporary occupancy effects of harman, [ 11 C]-harmine PET scanning was timed when plasma harman levels were negligible.…”

Section: Discussionmentioning

confidence: 99%

“…Demographics are listed in Table 1. Some of the healthy participants (n = 14) participated in earlier studies (10,12). Participants were within the age range of 18 to 50 years and in good physical health.…”

Section: Study Participantsmentioning

confidence: 99%

“…Previous investigations of MAO-A activity in postmortem brain of AD were primarily negative, with no change reported in prefrontal cortex, and a decrease reported in the hypothalamus and caudate (7,8). Unfortunately, these studies were inconclusive because none of them addressed several recently discovered biases that influence MAO-A levels, such as cigarette smoking (9,10), exposure to current or past major depressive episodes (11)(12)(13), and impulsive-aggressive personality traits (14,15). The latter covary with MAO-A levels, likely because of a neurodevelopmental influence of inherited MAO-A levels (16).…”

mentioning

confidence: 99%

“…To investigate MAO-A levels in AD in humans and avoid confounding biases that influence MAO-A levels such as cigarette smoking and major depressive disorder, we chose an in vivo approach by applying [ 11 C]-harmine positron emission tomography (PET). [ 11 C]-harmine PET measures brain MAO-A V T , an index of MAO-A density, and [ 11 C]-harmine has properties of an excellent PET radiotracer for MAO-A, including high brain uptake, selective and reversible binding, and metabolites that are not brain penetrant (10). On the basis of the association between alcohol dependence and oxidative stress and the involvement of MAO-A in cellular responses to oxidative stress, we hypothesized that MAO-A level would be elevated in the prefrontal cortex during AD.…”

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confidence: 99%

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Greater Monoamine Oxidase A Binding in Alcohol Dependence

Matthews

Kish

et al. 2014

Biological Psychiatry

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Background-Alcohol dependence (AD) is a multiorgan disease in which excessive oxidative stress and apoptosis are implicated. Monoamine oxidase A (MAO-A) is an important enzyme on the outer mitochondrial membrane that participates in the cellular response to oxidative stress and mitochondrial toxicity. It is unknown whether MAO-A levels are abnormal in AD. We hypothesized that MAO-A V T , an index of MAO-A level, is elevated in the prefrontal cortex (PFC) during AD, because markers of greater oxidative stress and apoptosis are reported in the brain in AD and a microarray analysis reported greater MAO-A messenger RNA in the PFC of rodents exposed to alcohol vapor.

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Monoamine oxidase: radiotracer chemistry and human studies

Fowler

Logan

Shumay

et al. 2015

Labelled Comp Radiopharmac

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Monoamine oxidase (MAO) oxidizes amines from both endogenous and exogenous sources thereby regulating the concentration of neurotransmitter amines such as serotonin, norepinephrine, and dopamine as well as many xenobiotics. MAO inhibitor drugs are used in the treatment of Parkinson's disease and in depression stimulating the development of radiotracer tools to probe the role of MAO in normal human biology and in disease. Over the past 30 years since the first radiotracers were developed and the first positron emission tomography (PET) images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variables that have contributed to different MAO levels in brain and in peripheral organs. MAO radiotracers and PET have also been used to study the current and developing MAO inhibitor drugs including the selection of doses for clinical trials. In this article, we describe the following: (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological, and psychiatric disorders; and (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers that are currently used and possible new applications.

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Monoamine Oxidase A Binding in the Prefrontal and Anterior Cingulate Cortices During Acute Withdrawal From Heavy Cigarette Smoking

Cited by 67 publications

References 78 publications

Elevated Monoamine Oxidase A Binding During Major Depressive Episodes Is Associated with Greater Severity and Reversed Neurovegetative Symptoms

Elevated Monoamine Oxidase A Binding During Major Depressive Episodes Is Associated with Greater Severity and Reversed Neurovegetative Symptoms

Greater Monoamine Oxidase A Binding in Alcohol Dependence

Monoamine oxidase: radiotracer chemistry and human studies

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