Endophenotypes for Alcohol Use Disorder: An Update on the Field

Salvatore, Jessica E.; Gottesman, Irving I.; Dick, Danielle M.

doi:10.1007/s40429-015-0046-y

Cited by 50 publications

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References 161 publications

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“…In light of the current findings, future investigations of AUP focusing on neurochemical systems and networks involved in the neurobiology of sensation seeking may be especially compelling. However, enthusiasm over the endophenotype approach should also be tempered given that certain candidate endophenotypes may not be any "genetically simpler" than the psychiatric outcomes they are associated with (Salvatore et al, 2015). We await future genetically informed investigations that may shed light on other important neurobiological pathways and mechanisms underlying the risk for AUP that have yet to be uncovered.…”

Section: Discussionmentioning

confidence: 99%

Polygenic Risk, Personality Dimensions, and Adolescent Alcohol Use Problems: A Longitudinal Study

Savage

Kendler

et al. 2017

J. Stud. Alcohol Drugs

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ABSTRACT. Objective: Alcohol use problems are common during adolescence and can predict serious negative outcomes in adulthood, including substance dependence and psychopathology. The current study examines the notion that alcohol use problems are driven by polygenic influences and that genetic influences may indirectly affect alcohol use problems through multiple pathways of risk, including variations in personality. Method: We used a genome-wide approach to examine associations between genetic risk for alcohol use problems, personality dimensions, and adolescent alcohol use problems in two separate longitudinal population-based samples, the Finnish Twin Cohort (FinnTwin12) and the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were 1,035 young adults from FinnTwin12 and 3,160 adolescents from ALSPAC. Polygenic risk scores (PRS) were calculated for ALSPAC using genome-wide association results (on alcohol dependence symptoms as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) from FinnTwin12. A parallel multiple mediator model was tested to examine whether the association between PRS and alcohol use problems assessed at age 16 could be explained by variations in personality dimensions assessed at age 13, including sensation seeking and negative emotionality. Results: PRS were marginally predictive of age 16 alcohol use problems; this association was partially mediated by sensation seeking. Polygenic variation underlying risk for alcohol use problems may directly influence the effects of sensation seeking, which in turn influence the development of alcohol use problems in later adolescence. Conclusions: These findings contribute to the increasing evidence regarding the salience of sensation seeking during early adolescence as a potential constituent in the risk pathway underlying the development of alcohol use problems. (J. Stud. Alcohol Drugs, 78, 442-451, 2017)

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Section: Discussionmentioning

confidence: 99%

Polygenic Risk, Personality Dimensions, and Adolescent Alcohol Use Problems: A Longitudinal Study

Savage

Kendler

et al. 2017

J. Stud. Alcohol Drugs

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“…A long tradition of research has demonstrated reduction of the parietal target/ oddball P3 ERP in relation to various forms of SUDs, including alcohol, nicotine, and illicit drug use (Anokhin et al, 2000;Costa et al, 2000;Iacono, Carlson, Malone, & McGue, 2002;Patrick et al, 2006;Perlman, Markin, & Iacono, 2013;Porjesz et al, 1998; for a review, see Euser et al, 2012). Evidence from twin and family studies strongly supports the interpretation that P3 amplitude reduction (P3AR) indexes a substance use (Euser et al, 2012;Iacono & Malone, 2011;Porjesz et al, 2005;Salvatore et al, 2015).…”

Section: Introductionmentioning

confidence: 98%

Target‐related parietal P3 and medial frontal theta index the genetic risk for problematic substance use

2019

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Theoretical and empirical work suggests that problematic substance use (PSU) is associated with individual differences in prefrontal cortex activity. While research has strongly linked parietal P3 amplitude reduction (P3AR) to genetic risk for problematic substance use, few studies have tested whether prefrontal EEG measures are sensitive to this genetic liability. In addition to P3, oddball target detection tasks elicit medial frontal theta power, reflecting attentional allocation, and parietal delta, indexing decision making or stimulus-response link updating. Midfrontal theta and parietal delta may index neurocognitive processes relevant to PSU beyond P3AR.The present investigation examined the etiological relationship between PSU and P3, frontal theta, and parietal delta in a large twin sample (N = 754). EEG was recorded during a visual oddball task. Greater PSU was associated with reduced target P3 amplitude and midfrontal theta/parietal delta power, and increased mean reaction time and reaction time variability (RTV; indexing attentional fluctuations). P3, theta, and RTV, but not delta or mean RT, explained unique variance in PSU (R 2 = 0.04). Twin biometric modeling indicated a genetic relationship between PSU and P3, theta, and RTV. Theta accounted for distinct genetic variance in PSU beyond P3 and RTV. Together, 23% of the total additive genetic variance in PSU was explained by the three endophenotypes. Results replicate P3AR as an endophenotype and provide support for additional behavioral (RTV) and neurophysiological (midfrontal theta) endophenotypes of PSU. Reduced theta and greater RTV may reflect variations in a prefrontal attentional network that confers genetic risk for substance use problems.

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“…Many thoughtful endophenotype articles populate the literature (for recent examples, see Anokhin, 2014; Beauchaine, 2009; Burton et al, 2015; Campanella, Pogarell, & Boutros, 2014; Euser et al, 2012; Faraone, Bonvicini, & Scassellati, 2014; Ferrarelli, 2013; Glahn et al, 2014; Goldstein & Klein, 2014; W. G. Iacono & Malone, 2011; Lenzenweger, 2013; Loo, Lenartowicz, & Makeig, 2015; Manoach & Agam, 2013; Miller & Rockstroh, 2013; Moses-Kolko, Horner, Phillips, Hipwell, & Swain, 2014; Owens, Bachman, Glahn, & Bearden, 2016; Pearlson, 2015; Rosen, Spellman, & Gordon, 2015; Rubenstein, Wiggins, & Lee, 2015; Salvatore, Gottesman, & Dick, 2015; Swerdlow, Gur, & Braff, 2015), and many of these share a conviction that endophenotypes are valuable for identifying genetic liability . However, despite their introduction to psychiatry by Gottesman and Shields (I.…”

Section: 0 Introductionmentioning

confidence: 99%

Endophenotype best practices

Iacono

Malone

Vrieze

2017

International Journal of Psychophysiology

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This review examines the current state of electrophysiological endophenotype research and recommends best practices that are based on knowledge gleaned from the last decade of molecular genetic research with complex traits. Endophenotype research is being oversold for its potential to help discover psychopathology relevant genes using the types of small samples feasible for electrophysiological research. This is largely because the genetic architecture of endophenotypes appears to be very much like that of behavioral traits and disorders: they are complex, influenced by many variants (e.g., tens of thousands) within many genes, each contributing a very small effect. Out of over 40 electrophysiological endophenotypes covered by our review, only resting heart, a measure that has received scant advocacy as an endophenotype, emerges as an electrophysiological variable with verified associations with molecular genetic variants. To move the field forward, investigations designed to discover novel variants associated with endophenotypes will need extremely large samples best obtained by forming consortia and sharing data obtained from genome wide arrays. In addition, endophenotype research can benefit from successful molecular genetic studies of psychopathology by examining the degree to which these verified psychopathology-relevant variants are also associated with an endophenotype, and by using knowledge about the functional significance of these variants to generate new endophenotypes. Even without molecular genetic associations, endophenotypes still have value in studying the development of disorders in unaffected individuals at high genetic risk, constructing animal models, and gaining insight into neural mechanisms that are relevant to clinical disorder.

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Endophenotypes for Alcohol Use Disorder: An Update on the Field

Cited by 50 publications

References 161 publications

Polygenic Risk, Personality Dimensions, and Adolescent Alcohol Use Problems: A Longitudinal Study

Polygenic Risk, Personality Dimensions, and Adolescent Alcohol Use Problems: A Longitudinal Study

Target‐related parietal P3 and medial frontal theta index the genetic risk for problematic substance use

Endophenotype best practices

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