Devaraju, Abhijith

Kulkarni, Sacheta Sudhendra

Rao, Kishor Manohar

S, Shilpa Sam

English

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Manuscript 1038 Aggression and MAO-A gene Sacheta Sudhendra Kulkarni Shilpa Sam S Kishor Manohar Rao Abhijith Devaraju Follow this and additional works at: https://rescon.jssuni.edu.in/ijhas  Part of the Mental Disorders Commons, Molecular Genetics Commons, and the Psychiatric and Mental Health Commons LETTER TO THE EDITORAggression and MAO-A GeneSacheta S. Kulkarni, Sam S. Shilpa, Kishor M. Rao, Abhijith Devaraju*Department of Biochemistry, JSS Academy of Higher Education and Research, IndiaDepartment of Psychiatry, JSS Academy of Higher Education and Research, IndiaDear Sir,A ggression encompasses behavioural traitsthat can result in physical and psychologicaldamage to others. 30e40% of psychiatric patientswith Depression, Bipolar disorder, ADHD, Neuro-psychiatric and other degenerative disorders dostruggle with aggression [1,2]. India State-LevelDisease Burden Initiative Mental Disorders Collab-orators in their article published in 2020 report thatone out of seven people in India had a mental dis-order in 2017 itself [3]. Currently with increasedurbanisation, the numbers would be much more.Neural networks, neurotransmitters, hormones,and candidate genes have been associated withantisocial and aggressive behaviour in humans [4].Highly conserved brain areas, like amygdala, whichregulates neuronal pathways activating aggressive,or avoidant behavioural patterns, influence the linkbetween aggression and anxiety [1,5]. A PET studyon patients with ASPD showed reduced MAO-Alevels compared to controls in brain regionsinvolved in impulse control and aggression [6].Genetic factors attribute to around 40e50% risk ofaggressive behaviour. MAO-A gene, also called"warrior gene'' coding Monoamine Oxidase-Aenzyme involved in the deamination of neurotrans-mitters is one of the gene of interest. In the absence ofappropriate levels ofMAO-A,neurotransmittersmaynot be degraded appropriately and thereby accu-mulate in neurons which may lead on to acuteaggressive behaviours [1]. Knockout mice models forMAO-A gene, exhibited increased aggressivenesscompared to their controls [4]. Many variants inMAO-A gene have been identified which are associ-ated with aggression. These include the SNPs rs6323,rs909525, rs2064070 associated with outward-expressed anger in male suicidal patients, rs1465108leading to heightened aggression, rs6609257 alteringbrain activity in a network of frontal, parietal andoccipital cortex, rs2235186 linked to variations inanger control, aggression, and empathy [7], uVNTRin the promoter region with 3 and 3.5 repeatsresponsible for low activity & 4 and 5 repeatsresponsible for higher activity of the enzyme [8].Evolutionary aspects have to be studied as why na-ture has selectively preserved the low variant ofMAO-A despite it being responsible for aggressivebehaviour. The effect of MAO-A gene on personalityis age and sex dependent. As per a study, low variantof MAO-A results in happiness among women andaggression inmen [9]. Many confounding factors likeX-inactivation, hormonal differences due to gynae-cological conditions and mood swings have to beconsidered in women. In mice, prenatal suppressionofMAO-A leads to increased aggression inadulthoodwhich suggests a potential prenatal sensitizationmechanism [4]. Deficiency of Monoamine oxidase inearly developmental stages can lead to impairedbehavioural aspects manifesting in adulthood.Recently MAALIN, a novel lncRNA, has beenidentifiedwhich regulates the activity ofMAO-Agenein human brain [10]. Use of ARMS/RFLP-PCR, NGS,smMIPS and SGE to detect the common SNPs in tar-geted exons will ease the diagnosis [7]. Developmentof molecular techniques to identify individuals whoare genetically predestined to aggression can help inearly initiation of therapies. Meta-analysis examiningthe efficacy of different interventions for aggression inpatients with dementia showed that behaviouraltherapy and counselling, were more successful inreducing aggression in adults than pharmacologicaltherapy [4].Received 1 July 2022; revised 7 March 2023; accepted 11 March 2023.Available online 14 June 2023* Corresponding author.E-mail address: abhijithd@jssuni.edu.in (A. Devaraju).https://doi.org/10.55691/2278-344X.10382278-344X/© 2023 JSS Academy of Higher Education and Research. This is an open access article under the CC-BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/).Genetic susceptibility to aggression would be anon-modifiable risk factor and causal association ofaggression with MAO-A gene if found to exist wouldopen up a new arena of possibilities in future to beinvestigated and feasible options towards manage-ment and cure pertaining to genetic aspects can beexplored. Aggression being the most commonsymptom in psychiatric disorders definitely requiresa deep insight into its genetic pathophysiology.References[1] Pavlov KA, Chistiakov DA, Chekhonin VP. Genetic de-terminants of aggression and impulsivity in humans. J ApplGenet 2012;53(1):61e82.[2] Sharma M, Marimuthu P. Prevalence and psychosocial fac-tors of aggression among youth. [Internet] Indian J PsycholMed 2014 Jan;vol. 36(1):48 [cited 2022 Feb 7].[3] India State-Level Disease Burden Initiative Mental DisordersCollaborators. The burden of mental disorders across thestates of India: the Global Burden of Disease Study7;February 2020. p. P148e61 (2).[4] Mentis AFA, Dardiotis E, Katsouni E, Chrousos GP. Fromwarrior genes to translational solutions: novel insights intomonoamine oxidases (MAOs) and aggression. Transl Psy-chiat 2021;11(1).[5] Klasen M, Wolf D, Eisner PD, Eggermann T, Zerres K,Zepf FD, et al. Serotonergic contributions to human brainaggression networks. Front Neurosci 2019;13(FEB):1e11.[6] Kolla NJ, Matthews B, Wilson AA, Houle S, Michael Bagby R,Links P, et al. Lower Monoamine Oxidase-A Total Distri-bution Volume in Impulsive and Violent Male Offenderswith Antisocial Personality Disorder and High PsychopathicTraits: An [11C] Harmine Positron Emission TomographyStudy. [Internet] Neuropsychopharmacol 2015 Jun 17;40(11):2596e603 [cited 2023 Jan 19].[7] Kolla NJ, Bortolato M. The role of monoamine oxidase A inthe neurobiology of aggressive, antisocial, and violentbehavior: A tale of mice and men. [Internet] Prog Neurobiol2020;194:101875.[8] Sarwar S, Shabana Hasnain S. Association of variablenumber of tandem repeats (Vntr) and t941g polymorphismof monoamine oxidase (mao-a) gene with aggression inpakistani subjects. [Internet] Afr Health Sci 2021 Mar 1;21(1):180e8 [cited 2022 Jan 13].[9] Chen H, Pine DS, Ernst M, Gorodetsky E, Kasen S, Gordon K,et al. The MAOA gene predicts happiness in women. ProgNeuro-Psychopharmacol Biol Psychiat 2013;40(1):122e5.[10] Labonte B, Abdallah K, Maussion G, Yerko V, Yang J,Bittar T, et al. Regulation of impulsive and aggressive be-haviours by a novel lncRNA. [Internet] Mol Psychiatr 2020Jan 6;26(8):3751e64 [cited 2023 Jan 19].272 INTERNATIONAL JOURNAL OF HEALTH AND ALLIED SCIENCES 2023;11:271e272

Aggression and MAO-A gene

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Aggression and MAO-A gene

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