Davranışsal Bağımlılıkların Nörobiyolojisi
Özet
Davranışsal bağımlılıklar, olumsuz sonuçlara rağmen devam eden katılım, azalan öz kontrol ve yoğun aşerme ile karakterize kronik, tekrarlayan beyin hastalıklarıdır. ICD-11 ve DSM-5'te kumar oynama ve internette oyun oynama bozuklukları resmi olarak tanımlanmış olup, diğer davranışsal bağımlılıkların literatürdeki tartışmaları sürmektedir. Madde bağımlılıklarına benzer şekilde, bu durumlarda da mezokortikolimbik ödül sistemi merkezde yer alır; ventral tegmental alan, nükleus akumbens, striatum ve prefrontal korteks gibi yapılar kritik roller üstlenir. Dopamin, bu süreçlerde amaca yönelik ve madde dışı ödüllerin işlenmesine aracılık ederken; serotonin disregülasyonu ise dürtüsellik ve gecikmiş yanıt inhibisyonu ile ilişkilidir. Fonksiyonel MR çalışmaları, kumar bozukluğu olan bireylerde ventromedial prefrontal korteks (vmPFC) ve striatal bölgelerde aktivasyon değişiklikleri ile azalan yukarıdan aşağıya kontrol mekanizmalarını göstermektedir. Nörobiyolojik olarak süreç, anlık sonuçlara odaklanan reaktif "git" ağı ile engelleyici kontrol sağlayan yansıtıcı "dur" ağı arasındaki bir dengesizlik olarak kavramsallaştırılan ikili işlem modeliyle açıklanmaktadır. Genetik ikiz çalışmaları kumar bozukluğunda %50-60 oranında kalıtsallık öngörürken, ANKK1 gibi genlerdeki polimorfizmlerin striatal dopamin reseptör yoğunluğunu etkileyerek bağımlılık riskini artırdığı bildirilmiştir.
Behavioral addictions are chronic, recurrent brain diseases characterized by continued engagement despite negative consequences, diminished self-control, and intense craving. While gambling and internet gaming disorders are officially recognized in ICD-11 and DSM-5, discussions regarding other behavioral addictions continue in literature. Similar to substance addictions, the mesocorticolimbic reward system is central, with structures like the ventral tegmental area, nucleus accumbens, striatum, and prefrontal cortex playing critical roles. Dopamine mediates the processing of goal-directed and non-substance rewards, whereas serotonin dysregulation is associated with impulsivity and delayed response inhibition. Functional MRI studies reveal activation alterations in the ventromedial prefrontal cortex (vmPFC) and striatal regions in individuals with gambling disorder, indicating reduced top-down control mechanisms. Neurobiologically, the process is explained by the dual-process model, conceptualized as an imbalance between the reactive "go" network focusing on immediate outcomes and the reflective "stop" network providing inhibitory control. Genetic twin studies estimate heritability at 50-60% in gambling disorder, while polymorphisms in genes such as ANKK1 affect striatal dopamine receptor density, thereby increasing the risk of addiction.
Referanslar
Albayrak Ö., Wölfle S.M., Hebebrand J., Does food addiction exist? A phenomenological discussion based on the psychiatric classification of substance-related disorders and addiction, Obes. Facts 5 (2) (2012) 165–179
Beninger RJ, Miller R (1998) Dopamine D1-like receptors and reward-related incentive learning. Neurosci Biobehav Rev 22:335–345. 10.1016/S0149-7634(97)00019-5,
Cameron CM, Wightman RM, Carelli RM (2014) Dynamics of rapid dopamine release in the nucleus accumbens during goal-directed behaviors for cocaine versus natural rewards. Neuropharmacology 86:319–328.10.1016 /j.neuropharm. 2014.08.006
Marche K, Martel A-C, Apicella P (2017) Differences between dorsal and ventral striatum in the sensitivity of Tonically active neurons to rewarding events. Front Syst Neurosci 11:52. 10.3389/fnsys.2017.00052
Lipton DM, Gonzales BJ, Citri A (2019) Dorsal striatal circuits for habits, compulsions and addictions. Front Syst Neurosci 13:28. 10.3389/fnsys.2019.00028
Graveland GA, DiFiglia M (1985) The frequency and distribution of medium-sized neurons with indented nuclei in the primate and rodent neostriatum. Brain Res 327:307–311. 10.1016/0006-8993(85)91524-0
Oorschot DE (2013) The percentage of interneurons in the dorsal striatum of the rat, cat, monkey and human: a critique of the evidence. Basal Ganglia 3:19–24. 10.1016/j.baga.2012.11.001
Gittis AH, Kreitzer AC (2012) Striatal microcircuitry and movement disorders. Trends Neurosci 35:557–564. 10.1016/j.tins.2012.06.008
Weiss F. Neurobiology of craving, conditioned reward and relapse, Curr Opin Pharmacol. 2005 Feb;5(1):9-19.doi: 10.1016/ .coph.2004.11.001.
Power Y, Goodyear B, Crockford D. Neural correlates of pathological gamblers preference for immediate rewards during the iowa gambling task: an fMRI study. J Gambl Stud. 2011:1–14.
Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010;35:217–38.
Weintraub D, Koester J, Potenza MN, et al. Impulse control disorders in parkinson disease: A cross-sectional study of 3090 patients. Arch Neurol. 2010;67:589–95.
Celik E, Ozkaya HM, Poyraz BC, Saglam T. Impulse control disorders in patients with prolactinoma receiving dopamine agonist therapy: a prospective study with 1 year follow-up. Endocrine. 2018 Dec;62(3):692-700. doi: 10.1007/s12020-018-1744-8. Epub 2018 Sep 11.
McElroy SL, Nelson E, Welge J, Kaehler L, Keck P. Olanzapine in the treatment of pathological gambling: a negative randomized placebo-controlled trial. Journal Clin Psychiatry. 2008;69:433–40.
Boileau I, Payer D, Chugani B, et al. In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [11C]-(+)-PHNO. Mol Psychiatry. 2014;19:1305–13.
Nordin C, Eklundh T. Altered CSF 5–HIAA disposition in pathological male gamblers. CNS Spectr. 1999;4:25–33
de Castro IP, Ibanez A, Saiz–Ruiz J, Fernandez–Piqueras J. Concurrent positive association between pathological gambling andfunctional DNA polymorphisms at the MAO-A and the 5-HT transporter genes. Mol Psychiatry. 2002;7:927–8.
Potenza MN, Walderhaug E, Henry S, et al. Serotonin 1B receptor imaging in pathological gambling. World J Biol Psychiatry. 2013;14:139–45.
Power Y, Goodyear B, Crockford D. Neural correlates of pathological gamblers preference for immediate rewards during the iowa gambling task: an fMRI study. J Gambl Stud. 2011:1–14.
Potenza MN, Steinberg MA, Skudlarski P, et al. Gambling urges in pathological gambling: a functional magnetic resonance imaging study. Arch Gen Psychiatry. 2003;60:828–36.
Power Y, Goodyear B, Crockford D. Neural correlates of pathological gamblers preference for immediate rewards during the iowa gambling task: an fMRI study. J Gambl Stud. 2011:1–14.
Balodis IM, Kober H, Worhunsky PD, Diminished frontostriatal activity during processing of monetary rewards and losses in pathological gambling. Biol Psychiatry. 2012;71:749–57
de Greck M, Enzi B, Prösch U, Northoff G. Decreased neuronal activity in reward circuitry of pathological gamblers during processing of personal relevant stimuli. Hum Brain Mapp. 2010;31:1802–12.
Reuter J, Raedler T, Rose M, Pathological gambling is linked to reduced activation of the mesolimbic reward system. Nat Neurosci. 2005;8:147–8.
Ko C-H, Liu G-C, Hsiao S, et al. Brain activities associated with gaming urge of online gaming addiction. J Psychiatr Res. 2009;43:739–47.
Weinstein AM. Computer and video game addiction—a comparison between game users and non-game users. Am J Drug Alcohol Abuse. 2010;36:268–76.
Joutsa J, Saunavaara J, Parkkola R, Extensive abnormality of brain white matter integrity in pathological gambling. Psychiatry Res. 2011;194:340–6.
Rahman AS, Xu J, Potenza MN. Hippocampal and amygdalar volumetric differences in pathological gambling: a preliminary studyof the associations with the behavioral inhibition system. Neuropsychopharmacology. 2014;39:738–45.
Yip SW, Lacadie CM, Xu J, et al. Reduced genual corpus callosal white matter integrity in pathological gambling and its relationship to alcohol abuse or dependence. World J Biol Psychiatry. 2013;14:129–38.
Lin F, Zhou Y, Du Y, et al. Abnormal white matter integrity in adolescents with Internet addiction disorder: a tract-based spatial statistics study. PLoS One. 2012;7:e30253.
Miner MH, Raymond N, Mueller BA, Lloyd M. Preliminary investigation of the impulsive and neuroanatomical characteristics of compulsive sexual behavior. Psychiatry Res. 2009;174:146–51.
Paulus MP, Squeglia LM, Bagot K, et al Screen media activity and brain structure in youth: evidence for diverse structural correlation networks from the ABCD study. Neuroimage. 2019;185:140–153
Slutske WS, Zhu G, Meier MH, Martin NG. Genetic and environmental influences on disordered gambling in men and women. Arch Gen Psychiatry. 2010;67:624–30.
Lobo DS, Kennedy JL. Genetic aspects of pathological gambling: a complex disorder with shared genetic vulnerabilities. Addiction. 2009;104:1454–65.
Black DW, Monahan PO, Temkit MH, Shaw M. A family study of pathological gambling. Psychiatry Res. 2006;141:295–303.
White MJ, Morris CP, Lawford BR Behavioral phenotypes of impulsivity related to the ANKK1 gene are independent of an acute stressor. Behavioral and Brain Functions. 4, Article number: 54 (2008)
Han DH, Lee YS, Yang KC, Kim EY, Lyoo IK, Renshaw PF. Dopamine genes and reward dependence in adolescents with excessive internet video game play. J Addict Med. 2007;1:133–8.
Comings DE, Rosenthal RJ, Lesieur HR, et al. A study of the dopamine D2 receptor gene in pathological gambling. Pharmacogenetics. 1996;6:223–34
Lee YS, Han D, Yang KC, et al. Depression like characteristics of 5HTTLPR polymorphism and temperament in excessive internet users. J Affect Disord. 2008;109:165–9
Adisetiyo V., and Gray K.M.: Neuroimaging the neural correlates of increased risk for substance use disorders in attention-deficit/hyperactivity disorder—a systematic review. Am J Addict 2017; 26: pp. 99-111
Noël X., Van der Linden M., and Bechara A.: The neurocognitive mechanisms and loss of willpower. Psychiatry (Edgmont) 2006; 3: pp. 30-41
Noël X., Van der Linden M., and Bechara A.: The neurocognitive mechanisms and loss of willpower. Psychiatry (Edgmont) 2006; 3: pp. 30-41
Adisetiyo V., and Gray K.M.: Neuroimaging the neural correlates of increased risk for substance use disorders in attention-deficit/hyperactivity disorder—a systematic review. Am J Addict 2017; 26: pp. 99-1
Weinstein A, Lejoyeux M. New developments on the neurobiological and pharmaco-genetic mechanisms underlying Internet and videogame addiction. Am J Addict 2015;24(2):117–25.
Yip SW, Desai RA, Steinberg MA, et al. Health/functioning characteristics, gambling behaviors and gambling related motivations in adolescents stratified by gambling severity: Findings from a high school risk survey. Am J Addict. 2011; 20:495–508.
Wolkow ND., Wang GJ., Tomasi D., Unbalanced neuronal circuits in addiction. Curr Opin Neurobiol. 2013 Aug;23(4):639-48. doi: 10.1016/j.conb.2013.01.002. Epub 2013 Feb 21.
Worhunsky PD., Matuskey D., Gallezot JD., Regional and source-based patterns of [11C]-(+)-PHNO binding potential reveal concurrent alterations in dopamine D2 and D3 receptor availability in cocaine-use disorder. Neuroimage 2017; 148: pp. 343-351
