Povezanost polimorfizama gena za katehol-o-metil-transferazu i monoaminooksidazu tipa B i aktivnosti trombocitne monoaminooksidaze s agresivnim ponašanjem i psihopatološkim osobinama adolescenata u odgojnim domovima

Podobnik, Josip (2017) Povezanost polimorfizama gena za katehol-o-metil-transferazu i monoaminooksidazu tipa B i aktivnosti trombocitne monoaminooksidaze s agresivnim ponašanjem i psihopatološkim osobinama adolescenata u odgojnim domovima. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Introduction: Propensity for violence, aggressive and hostile behaviour, as well as psychopathic personality traits are often seen in adolescents in juvenile correctional facilities. Neurobiological basis of hostility and aggression can be associated with altered function of the dopaminergic system and its components: enzymes monoamine oxidase type B /MAO-B/ and catechol-O-methyl transferase /COMT/). Aim: The aim of the study was to determine the association between the distribution of the genotypes/alleles of the COMT Val108/158Met (rs4680) and MAOB A/G intron 13 (rs1799836) polymorphism, as well as changes in platelet MAO-B activity, and the severity of conduct disorder, according to the DSM-IV criteria, the presence or absence of the court imposed measure, major criminal offense (homicide attempt, serious damage to property) and antisocial behaviour features. Methods: The study included 182 male youth, divided into categories depending on the diagnosis of conduct disorder into those with partial, mild to moderate and severe form (based on DSM-IV), on the presence of the court imposed measure, on the homicide attempt, on the committing of serious damage to property and on the presence of agitation. Additionally all subjects were divided according to severity of symptoms assessed by the psychometric scales. Results: Subjects with conduct disorder, as well as those with severe form of conduct disorder, had significantly higher scores on the scales measuring depression, psychopathy, aggressive behaviour, and overt aggression than subjects with partial diagnosis or subjects with mild form of conduct disorder. Polymorphism rs4680 (Val108/158Met) of the COMT gene was significantly associated only with score of just one subscale from the domain of aggression OAS-M (Overt Aggression Scale –Modified) - `aggression against objects`. Subjects with symptoms of agitation, pronounced verbal attacks on others, and subjective irritability, had significantly increased platelet MAO-B activity compared to platelet MAO-B values in subjects without these symptoms. Platelet MAO-B activity was significantly decreased in subjects with the court imposed measure compared to participants without court imposed measure (`social cases`), while it did not differ between carriers of the A or G alleles of rs1799836 polymorphism of the MAOB gene. No significant associations were found between the polymorphism rs1799836 of the MAOB gene and phenotypic characteristics of conduct disorder. A lack of relationship between rs4680 polymorphism (Val108/158Met) of the COMT gene and conduct disorder, severity of this disorder, presence of court imposed measure, attempted murder, committing of severe material damage or presence of agitation, and particular characteristics of antisocial behaviour in adolescents with different degrees of symptoms intensity and signs of the conduct disorder was detected. Conclusion: A significant association between COMT Val108/158Met (rs4680) and attacks on objects from the aggression domain was detected, while platelet MAO-B activity was significantly increased in adolescents with present agitation, pronounced verbal attacks on the others and subjective irritability, and significantly decreased in subjects with court imposed measure compared to social cases. Polymorphism rs1799836 of the MAOB gene does not play a significant role in development of conduct disorder or intensity of delinquent behaviour, and is not related to presense or absence of court imposed measures, kind of criminal act, presence of agitation or antisocial features. These results might offer easily available biomarkers for aggression and associated psychopathological traits in youths accommodated in juvenile correctional facilities, with the purpose of improving therapeutic strategies.

Abstract in Croatian

Uvod: Sklonost nasilju, agresivno i nasilničko ponašanje, ali i psihopatske crte ličnosti često se javljaju u mladeži u odgojnim ustanovama. Neurobiološka podloga nasilništva i agresije veže se za poremećenu dopaminergičku neurotransmisiju, odnosno za određene komponente dopaminergičkog sustava (aktivnost enzima monoaminooksidaze tipa B /MAO-B/ i katehol-O-metiltransferaze /COMT/). Cilj: Cilj studije bio je istražiti povezanost raspodjele genotipova/alela COMT Val108/158Met (polimorfizam rs4680) i A/G 13. introna gena za MAO-B (polimorfizam rs1799836), kao i promjene aktivnosti trombocitne MAO-B, s težinom poremećaja ophođenja prema DSM-IV kriterijima, s postojanjem ili nepostojanjem sudski izrečene mjere, s postojanjem ili nepostojanjem teškog delikta (pokušaja ubojstva, teže materijalne štete), kao i s drugim disocijalnim obilježjima. Metode: Uključeno je 182 adolescenata muškog spola, podijeljenih prema dijagnozi poremećaja ophođenja na one s parcijalnim, blažim do srednjim i težim oblikom (prema DSM-IV), postojanju sudski izrečene mjere, pokušaju ubojstva, činjenju veće materijalne štete ili prisustvu agitacije. Dodatno su svi ispitanici podijeljeni prema težini simptoma određenih psihometrijskim ljestvicama. Rezultati: Ispitanici s poremećajem ophođenja, kao i oni s težim oblikom poremećaja ophođenja, imali su značajno veći broj bodova na skali depresivnosti, psihopatije, agresivnog ponašanja, i otvorene agresivnosti u odnosu na ispitanike s parcijalnom dijagnozom ili u odnosu na ispitanike s blažim oblikom poremećaja ophođenja. Polimorfizam rs4680 (Val108/158Met) gena COMT bio je značajno povezan samo sa značajkom iz domene agresije i to brojem bodova podljestvice napada na predmete. Ispitanici s prisutnom agitacijom, s naglašenim verbalnim napadima na druge i subjektivnom razdražljivosti, imali su značajno povišenu aktivnost trombocitne MAO-B prema vrijednostima MAO-B u trombocitima ispitanika koji nemaju izražene te simptome. Aktivnost trombocitne MAO-B bila je značajno snižena kod ispitanika sa sudski izrečenom mjerom prema socijalnim slučajevima, no, nije bila promijenjena u nosioca alela A ili G polimorfizma rs1799836 MAOB gena. Utvrđeno je da nema značajne povezanosti polimorfizma rs1799836 MAOB gena i fenotipskih značajki poremećaja ophođenja. Nije pronađena značajna povezanost između polimorfizma rs4680 (Val108/158Met) gena COMT i poremećaja ophođenja, stupnja tog poremećaja, postojanja sudski izrečene mjere, pokušaja ubojstva, činjenja veće materijalne štete ili prisustva agitacije, te određenih značajki disocijalnog ponašanja u ispitanika s različitim intezitetom simptoma i znakova poremećaja ophođenja. Zaključak: Pronađena je značajna povezanost polimorfizma rs4680 (Val108/158Met) gena COMT s napadima na predmete iz domene agresije, dok je aktivnost trombocitne MAO-B bila značajno povišena kod adolescenata s prisutnom agitacijom, s naglašenim verbalnim napadima na druge i subjektivnom razdražljivosti, a značajno snižena kod sudskih prema socijalnim slučajevima. Polimorfizam rs1799836 MAOB gena nema bitnu ulogu u nastanku poremećaja ophođenja, nije povezan s intezitetom delikventnog ponašanja, kao ni s tipom socijalno-odgojne mjere, vrstom kaznenog djela, postojanjem agitacije ili disocijalnih simptoma. Ti rezultati mogu ponuditi lako dostupne biomarkere agresivnosti i psihopatoloških karakteristika mladeži smještene u odgojnim ustanovama, u svrhu poboljšanja terapijskih strategija.

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