alpha-synuclein and Alcohol-Related-Disorders

A major focus of research in alcohol-related disorders is to identify the genes and pathways that modulate alcohol-seeking behavior. In light of this, animal models have been established to study various aspects of alcohol dependence. The selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines were developed from Wistar rats to model high and low voluntary alcohol consumption, respectively. Using inbred P and NP strains, a strong QTL (LOD-9.2) for alcohol consumption was identified on rat chromosome 4. To search for candidate genes that underlie this chromosomal region, complementary molecular-based strategies were implemented to identify genetic targets that likely contribute to the linkage signal. In an attempt to validate these genetic targets, corroborative studies have been utilized including pharmacological studies, knock-out/transgenic models as well as human association studies. Thus far, three candidate genes, neuropeptide Y (Npy), alpha-synuclein (Snca), and corticotrophin-releasing factor receptor 2 (Crhr2), have been identified that may account for the linkage signal. With the recent advancements in bioinformatics and molecular biology, QTL analysis combined with molecular-based strategies provides a systematic approach to identify candidate genes that contribute to various aspects of addictive behavior.

Topics: Alcohol Drinking; Alcohol-Related Disorders; Alcoholism; alpha-Synuclein; Animals; Chromosome Mapping; Humans; Models, Genetic; Neuropeptide Y; Quantitative Trait Loci; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone

Posttraumatic stress disorder (PTSD) often precedes comorbid substance use disorder and has been associated with aggression. Prior research has evidenced that alcohol use and other externalizing behaviors share genetic factors with PTSD; however, few studies have examined if specific genes are associated with externalizing behaviors in PTSD. The purpose of the current study was to investigate whether an α-synuclein gene polymorphism (SNCA rs356195) moderates the association of PTSD symptomatology with externalizing behaviors. We examined the separate and combined effects of PTSD symptomatology and SNCA rs356195 on alcohol- and aggression-related measures in nonclinical participants (N=138 European Americans; 15 diagnosed with probable PTSD). Probable PTSD status and SNCA were both associated with externalizing measures. SNCA also moderated the association of PTSD symptomatology with hazardous alcohol use, but not with aggression-related measures. Current findings suggest that variations in SNCA may increase the likelihood that PTSD symptomatology results in excessive alcohol use.

Topics: Adult; Aggression; Alcohol Drinking; Alcohol-Related Disorders; alpha-Synuclein; Analysis of Variance; Female; Humans; Male; Middle Aged; Polymorphism, Genetic; Psychiatric Status Rating Scales; Stress Disorders, Post-Traumatic; Surveys and Questionnaires; Young Adult

Topics: Adult; Alcohol-Related Disorders; alpha-Synuclein; Cross-Sectional Studies; Female; Humans; Impulsive Behavior; Male; Middle Aged; Young Adult