Browsing by Author "Kanarik, Margus"

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ADHD co-morbidities: A review of implication of gene × environment effects with dopamine-related genes
(2022) Kanarik, Margus; Grimm, Oliver; Mota, Nina Roth; Reif, Andreas; Harro, Jaanus
ADHD is a major burden in adulthood, where co-morbid conditions such as depression, substance use disorder and obesity often dominate the clinical picture. ADHD has substantial shared heritability with other mental disorders, contributing to comorbidity. However, environmental risk factors exist but their interaction with genetic makeup, especially in relation to comorbid disorders, remains elusive. This review for the first time summarizes present knowledge on gene x environment (GxE) interactions regarding the dopamine system. Hitherto, mainly candidate (GxE) studies were performed, focusing on the genes DRD4, DAT1 and MAOA. Some evidence suggest that the DRD4 exon 3 variable number tandem repeat (VNTR) and MAOA uVNTR may mediate (GxE) interactions in ADHD generally, and comorbid conditions specifically. For other polymorphisms, evidence is contradictory and less convincing. Particularly lacking are longitudinal studies testing the interaction of well-defined environmental with polygenic risk scores reflecting the dopamine system in its entirety. Only such an approach would be less susceptible to false-positive findings and provide clues on how genes could interact with non-genetic factors to shape psychopathology over the life span.
Association of orexin/hypocretin receptor gene (HCRTR1) with reward sensitivity, and interaction with gender
(Elsevier, 2020) Pulver, Aleksander; Kiive, Evelyn; Harro, Jaanus; Kanarik, Margus
Orexins/hypocretins maintain wakefulness, increase appetite and participate in the coordination of stress response. We have recently provided evidence on the role of orexins in aggression, showing the association of the HCRTR1 genotype. (rs2271933 G > A; leading to amino acid substitution Ile408Val) with aggressiveness or breach of law in four independent cohorts. Aggressive behaviour can be reward driven and hence we have examined the association of HCRTR1 rs2271933 genotype with different aspects of reward sensitivity in the birth cohort representative Estonian Children Personality Behaviour and Health Study. HCRTR1 genotype was associated with reward sensitivity in a gender dependent manner. Male HCRTR1 A/A homozygotes had higher Openness to Rewards and the overall reward sensitivity score while, in contrast, female A/A homozygotes scored lower than G-allele carriers in Openness to Rewards. In the total sample, aggressiveness correlated positively with reward sensitivity, but this was on account of Insatiability by Reward. In contrast, the HCRTR1 A/A homozygotes had a positive association of aggressiveness and Openness to Rewards. Experience of stressful life events had a small but significant increasing effect on both aspects of reward sensitivity, and correlated in an anomalous way with reward sensitivity in the HCRTR1 A/A homozygotes. Conclusively, the higher aggressiveness of HCRTR1 A/A homozygotes appears based on a qualitative difference in sensitivity to rewards, in the form that suggests their lower ability to prevent responses to challenges being converted into overt aggression.
Eestikeelse Agressiivse provokatsiooni küsimustiku valideerimine ning provotseeritud agressiivsuse ja MAOA geeni metülatsioonitaseme seose uurimine ELIKTU vanemal kohordil
(2023) Epner, Karin-Margareth; Kanarik, Margus; Tartu Ülikool. Psühholoogia instituut; Tartu Ülikool. Sotsiaalteaduste valdkond
Inter-individual differences in vulnerability to depression: regional brain energy metabolism, serotonergic function and behaviour in animal models
(2011-10-24) Kanarik, Margus
Käesolev doktoriväitekiri keskendub depressiooni funktsionaalse neuroanatoomia ja depressiivse käitumise uurimisele, kasutades meeleoluhäirete loomkatsemudeleid. Depressiooni põhjustavad nii korduvad stressirikkad elusündmused kui ka individuaalne soodumus ja eelkõige nende kahe teguri koosmõju. Depressioonisoodumust saab mudeldada selekteerides rotte afektiivse käitumise testide alusel või mõjustades pikaajaliselt nende ajus depressiooni tõenäolisi neuraalseid alusmehhanisme. Käesolevas väitekirjas käsitletakse nelja depressioonisoodumuse mudelit - osaline serotonergiline närvikahjustus, puudulik emahool vastsündinueas, vähene püsi-sotsiaalsus ja püsiv magusaeelistus. Keskkonnast tuleneva stressi mudeldamiseks kasutati kroonilist muutlikku stressi, mille depressiooni-põhjustav mõju rajaneb mitmete mõõdukalt ebameeldivate stiimulite korduval esitamisel, ja kroonilist sotsiaalset stressi, mis rajaneb looma korduval alistamisel agressiivse liigikaaslase poolt. Ajupiirkondade pikaajalise närviaktiivsuse määramiseks hinnati mitokondriaalse elektronide transpordi-ahela talitlust tsütokroom c oksüdaasi aktiivsuse histokeemilise mõõtmise kaudu. Kõik depressioonisoodumuse ja kroonilise stressi mudelid eraldiseisvaina põhjustasid mõnedes ajupiirkondades muutuse närviaktiivsuses, kuid eri mudelite piirkondlikud aktivatsioonimustrid ei kattunud. Kui kroonilist stressi rakendati depressioonisoodumusega loomadele, ilmnesid mudelitevahelised kokkulangevused närviaktiivsuses eesmises taalamuses, hippokampuse CA3 alas ja mediaalses mandelkehas, s.o. piirkondades, mis on kesksel kohal organismi stressivastuse, õppimise ja hirmuga seotud käitumiste kontrollis. Kui tsütokroom c oksüdaasi aktiivsuse andmeid erinevatest katsetest koos analüüsiti, ilmnes, et depresioonisoodumusega rottidel oli närvitegevus aktiivsem retro-spleniaalses ajukoores ja retikulaarses taalamuses, krooniline stress aga taandas selle aktiivsuse kontroll-loomadega samale tasemele. Funktsionaalse ühenduvuse analüüs näitas, et depressioonisoodumus ja krooniline stress nõrgendasid ajupiirkondadevahelist seotust haistesibulate, tsentraalse mandelkeha, terminaaljuti sängituumade, prefrontaalkoore ja vöökääruga seotud ajuringetes. Käesolev töö tõi välja mitmeid ajupiirkondi, mida tasuks üksikasjalikumalt edasi uurida, nagu näiteks võrgustik, mis hõlmab eesmist taalamust, retrospleniaalset ajukoort, eesmist vöökääru, hippokampust ja retikulaarset taalamust.
MAOA gene methylation in association with alcohol use disorder : research project
(Tartu Ülikool, 2022) Mägimets, Marta; Kanarik, Margus; Tartu Ülikool. Psühholoogia instituut; Tartu Ülikool. Sotsiaalteaduste valdkond
Monoamiini oksüdaas A genotüüp ja metülatsioon modereerivad seost väärkohtlemise ning agressiivse ja impulsiivse käitumise vahel
(2022) Anja, Karolina; Harro, Jaanus; Kanarik, Margus; Tartu Ülikool. Psühholoogia instituut; Tartu Ülikool. Sotsiaalteaduste valdkond
Rottide uudiskäitumise neurokeemilised erinevused sugude vahel
(2023) Hanson, Marianne; Kanarik, Margus; Tartu Ülikool. Psühholoogia instituut; Tartu Ülikool. Sotsiaalteaduste valdkond
Search for brain regions involved in social behaviour and stress response: mapping of oxidative metabolism
(2007-05-24T11:44:56Z) Kanarik, Margus
Stressi seos trüptüfaani hüdroksülaasi 2 geeni metüleeritusega
(2022) Pastarus, Johan; Kanarik, Margus; Tartu Ülikool. Psühholoogia instituut; Tartu Ülikool. Sotsiaalteaduste valdkond
Täiskasvanuea agressiivse käitumise seosed teismeea hüperaktiivse ja agressiivse käitumise ja monoamiinide oksüdaasi A genotüübiga
(Tartu Ülikool, 2022) Ande, Piret; Sakala, Katre; Kanarik, Margus; Tartu Ülikool. Psühholoogia instituut; Tartu Ülikool. Sotsiaalteaduste valdkond
Variants of the aggression-related RBFOX1 gene in a population representative birth cohort study: aggressiveness, personality and alcohol use disorder
(2020) Vaht, Mariliis; Laas, Kariina; Fernàndez-Castillo, Noèlia; Kurrikoff, Triin; Kanarik, Margus; Faraone, Stephen V.; Tooding, Liina-Mai; Veidebaum, Toomas; Franke, Barbara; Reif, Andreas; Cormand, Bru; Harro, Jaanus
Background Recently RBFOX1, a gene encoding an RNA binding protein, has consistently been associated with aggressive and antisocial behaviour. Several loci in the gene have been nominally associated with aggression in genome-wide association studies; the risk alleles being more frequent in general population. We have hence examined the association of four RBFOX1 single nucleotide polymorphisms, previously found related to aggressive traits, with aggressiveness, personality, and alcohol use disorder in birth cohort representative samples. Methods We used both birth cohorts of the Estonian Children Personality Behaviour and Health Study (ECPBHS; original n=1,238). Aggressiveness was assessed using the Buss-Perry Aggression Questionnaire and the Lifetime History of Aggressiveness structured interview at age 25 (younger cohort) or 33 (older cohort). Big Five personality at age 25 was measured with self reports and the lifetime occurrence of alcohol use disorder assessed with the MINI interview. RBFOX1 polymorphisms rs809682, rs8062784, rs12921846 and rs6500744 were genotyped in all participants. Given the restricted size of the sample, correction for multiple comparisons was not applied. Results Aggressiveness was not significantly associated with RBFOX1 genotype. RBFOX1 rs8062784 was associated with neuroticism and rs809682 with extraversion. Two out of four analyzed RBFOX1 variants, rs8062784, and rs12921846, were associated with occurrence of alcohol use disorder. Conclusions In the birth cohort representative sample of the ECPBHS, no association of RBFOX1 with aggressiveness was found, but RBFOX1 variants affected basic personality traits and the prevalence of alcohol use disorder. Future studies on RBFOX1 should consider the moderating role of personality and alcohol use patterns in aggressiveness.