title: NEUROBIOLOGICAL BASES OF ALCOHOL ADDICTION.
abstract: Alcohol addiction is a heterogeneous psychiatric disorder according to both phenotype and etiology. Difference in phenotype characteristics manifests in the manner the addiction arises, history of the alcoholic and history of drinking, comorbid disorders, and the phenomenon of abstinence difficulties. Concerning the etiology of alcoholism, the disease itself is considered to be a consequence of an interactive influence of the environment and genetic factors. Numerous researches conducted in the last decades discovered many aspects of the biochemical, cell and molecular bases of alcohol addiction, leading to a conclusion that alcoholism is, like many other addictions, a brain disease. By recognizing alcoholism as a disease which basically implies changes of the neurobiological mechanisms, as well as a clear genetic basis, it was supposed that the disease, having its basis solely in the symptomatology, is essentially heterogeneous. By trying to solve the problem of a clinically heterogeneous nature of the disease during the last fifty years, various sub-classifications of such patients have been suggested. According to Cloninger, subtypes of alcoholism differ also according to changes in the brain neurotransmission systems, i.e. it is supposed that patients suffering from alcoholism type 1 have a more pronounced dopaminergic transmission deficit, while dopaminergic transmission is not disturbed significantly in patients diagnosed with alcoholism type 2, who, however, have a significant lack of serotonergic transmission. In such a way, Cloninger actually presented the basis of the so-called neurobiological alcoholism model. Since he has connected differences in neurotransmission with differences in personality characteristics, this model is also known as the psychobiological model of alcoholism. The characteristic of alcoholism type 1 is avoiding damage (Harm Avoidance, HA) decreased dopamine transmission and increased serotonin transmission, while the significant characteristic of alcoholism type 2 is seeking for excitement (Novelty Seeking, NS), unchanged dopamine transmission and decreased serotonin transmission. These neurochemical differences among alcoholism subtypes represent the basis for a different therapy approach. Intake of alcohol changes different gene expression in the human brain. The inheritance model of alcoholism is not fully explained, however, it is considered that the disease is connected to a larger gene number included in neurotransmission, cell mechanisms and general metabolic function, with a simultaneous influence of the environment. The contribution of genetic factors is stronger in certain types of alcoholism and thus we have been confronted in the last years of alcoholism research with studies researching the connections of some alcoholism subtypes with the polymorphism phenomenon in the genes coding the synaptic proteins included in the alcoholism etiology. The primary role of monoamine oxidase (MAO) in the brain is catalysis of deamination of the oxidative neurotransmitter amines, i.e. serotonin, adrenaline, noradrenaline and dopamine. Thus, this enzyme is the key factor for maintaining cytoplasmic concentration of various neurotransmitters and for regulation of the neurotransmitting synaptic activity. Taken this MAO function into consideration, MAO is the enzyme included in the etiology and pathogenesis of various neuropsychiatric and neurological disorders. The finding of the decreased platelet MAO activity in various psychiatric disorders has brought us to the assumption that this enzyme may be a constitutional/genetic indicator (trait marker) or an indicator of disease condition (state marker) in biologic psychiatry. There are only a few studies of alcohol addiction researching the connections of the MAO coding gene polymorphism and alcoholism; however, these studies are primarily related to the variable number of tandem repeats (VTNR) polymorphism in the regulatory gene region for MAO-A, considered to influence the transcription activity/functionality of the enzyme.
authors.forename: Ana
authors.initials: A
authors.lastname: Matošić
authors.forename: Srđan
authors.initials: S
authors.lastname: Marušić
authors.forename: Branka
authors.initials: B
authors.lastname: Vidrih
authors.forename: Ana
authors.initials: A
authors.lastname: Kovak-Mufić
authors.forename: Lipa
authors.initials: L
authors.lastname: Cicin-Šain
mesh_terms: D000077443:Acamprosate; D000427:Alcohol Deterrents / Q000627:therapeutic use; D000437:Alcoholism / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D004221:Disulfiram / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D018598:Minisatellite Repeats; D008995:Monoamine Oxidase / Q000235:genetics; D009271:Naltrexone / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use; D009478:Neuropeptide Y / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D017294:Ondansetron / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission; D013654:Taurine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000427:Alcohol Deterrents; D009292:Narcotic Antagonists; D009478:Neuropeptide Y; D013654:Taurine; D012701:Serotonin; D018698:Glutamic Acid; D017294:Ondansetron; D005680:gamma-Aminobutyric Acid; D009271:Naltrexone; D008995:Monoamine Oxidase; D000077443:Acamprosate; D004221:Disulfiram; D004298:Dopamine; D009638:Norepinephrine