Interaction between a functional MAOA locus and childhood sexual abuse predicts alcoholism and antisocial personality disorder in adult women

Ducci, Francesca; Ma, Enlong; Hodgkinson, Colin A.; Xu, Ke; Catena, Mario; Robin, Robert W.; Goldman, David

doi:10.1038/sj.mp.4002034

Cited by 202 publications

(175 citation statements)

References 57 publications

(89 reference statements)

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“…Human studies have shown the relevance of genetic and environmental interaction for the development of violent behavior, i.e., it has been reported a high concentration of criminality within families (for review, Farrington et al, 2001), and an increased susceptibility of developing violent and antisocial behavior in the adulthood of children of violent parents growing up in stressful environments (for review, Koenen, 2005). Similar gene x environment interaction was shown in female subjects (Ducci et al, 2008).…”

Section: Discussionsupporting

confidence: 54%

Long-term programming of enhanced aggression by peripuberty stress in female rats

Cordero

Ansermet

Sandi

2013

Psychoneuroendocrinology

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Summary Human literature has linked adverse early life experiences with an increased risk to develop violent behaviors in both boys and girls. We have previously shown that male rats submitted to stress during the peripuberty period display as adults abnormal aggressive behavior against both male intruders and female partners. In the present study, we examined whether the same stress protocol would affect the development of aggressive behaviors in female rats. We evaluated the behavior of these peripuberty stressed female rats when confronted, at adulthood, with either female or male intruders, and during their cohabitation with male partners. Given that estrus cycle influences mood and aggressive behaviors, female aggressive behavior was assessed at different estrus cycle phases: estrus and diestrus, and during pregnancy and lactancy. Additionally, we evaluated postpartum plasma levels of vasopressin, oxytocin and corticosterone, hormones associated with aggression and the regulation of social behavior. Compared to control females, females submitted to stressful events during puberty exhibited higher and more sustained rates of aggression during adulthood independently on the estrus cycle or the sex of the intruder, and they had higher levels of plasma vasopressin. Significant correlations between plasma levels of vasopressin and corticosterone and aggressive behavior were also found. Strikingly, our results showed opposite intragroup correlations suggesting a different role of these hormones on aggression depending on life experiences. We provide here an animal model, devoid of cultural influences strongly supporting a role for biological factors in the development of aggressive behaviors following exposure to stressful events at puberty in females. #

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Section: Discussionsupporting

confidence: 54%

Long-term programming of enhanced aggression by peripuberty stress in female rats

Cordero

Ansermet

Sandi

2013

Psychoneuroendocrinology

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“…It seems that an allele with 3 repeats and a lower transcription activity represents the risk allele for vulnerability to alcoholism, primarily with regard to the antisocial form and antisocial behavior type when under alcohol intoxication in general and in connection of the genotype and the phenotype has been modulated with psychosocial conditions; a significantly stronger connection was recorded in the individuals that had been abused sexually or in childhood 95,96 . Some studies also took the type of alcoholism in consideration, but difference between these types was either not shown at all or only a higher presence of 3-repeat allele was recorded in type 2 alcoholism 97,98 .…”

Section: Polymorphic Gene Variant For Mao-b and Alcohol Addictionmentioning

confidence: 94%

“…Our preliminary studies performed in a small number of individuals did not show differences in the MAO-B genotype between the patients suffering from alcoholism and control population 100 . A study in a small number of female patients addicted to alcohol revealed that, as opposed to MAO-A, the MAO-B haplotype was connected to alcoholism independently of the antisocial behavior 95 .…”

Section: Polymorphic Gene Variant For Mao-b and Alcohol Addictionmentioning

confidence: 99%

Neurobiological Bases of Alcohol Addiction

Matošić¹,

Marušić²,

Vidrih³

et al. 2016

ACC

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SUMMARY -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 a...

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“…Heterozigot olanlarda orta düzeyde bir risk tespit edilmiştir. Asıl önemli olan, cinsel istismara maruz kalmayan kadınlarda MAOA-uVNTR genotipinin alkol bağımlılığı veya antisosyal davranış ile ilişkisinin bulunmamasıdır (48).…”

Section: Dopaminerjik Sistemunclassified