title: The P300 event-related brain potential as a neurobiological endophenotype for substance use disorders: a meta-analytic investigation.
abstract: Endophenotypes are intermediate phenotypes on the putative causal pathway from genotype to phenotype and can aid in discovering the genetic etiology of a disorder. There are currently very few suitable endophenotypes available for substance use disorders (SUD). The amplitude of the P300 event-related brain potential is a possible candidate. The present study determined whether the P300 amplitude fulfils two fundamental criteria for an endophenotype: (1) an association with the disorder (disease marker), and (2) presence in unaffected biological relatives of those who have the disorder (vulnerability marker). For this purpose, two separate meta-analyses were performed. Meta-analysis 1 investigated the P300 amplitude in relation to SUD in 39 studies and Meta-analysis 2 investigated P300 amplitude in relation to a family history (FH+) of SUD in 35 studies. The findings indicate that a reduced P300 amplitude is significantly associated with SUD (d=0.51) and, though to a lesser extent, with a FH+ of SUD (d=0.28). As a disease maker, the association between reduced P300 amplitude and SUD is significantly larger for participants that were exclusively recruited from treatment facilities (d=0.67) than by other methods (i.e., community samples and family studies; d=0.45 and 0.32, respectively), and larger for abstinent SUD patients (d=0.71) than for current substance users (d=0.37). Furthermore, in contrast to FH+ males, a P300 amplitude reduction seems not to be present in FH+ females (d=-0.07). Taken together, these results suggest that P300 amplitude reduction can be both a useful disease and vulnerability marker and is a promising neurobiological endophenotype for SUD, though only in males. Implications and future directions are discussed.
authors.affiliation: Institute of Psychology, Erasmus University Rotterdam, The Netherlands. euser@fsw.eur.nl
authors.forename: Anja S
authors.initials: AS
authors.lastname: Euser
authors.forename: Lidia R
authors.initials: LR
authors.lastname: Arends
authors.forename: Brittany E
authors.initials: BE
authors.lastname: Evans
authors.forename: Kirstin
authors.initials: K
authors.lastname: Greaves-Lord
authors.forename: Anja C
authors.initials: AC
authors.lastname: Huizink
authors.forename: Ingmar H A
authors.initials: IH
authors.lastname: Franken
mesh_terms: D000293:Adolescent; D058068:Endophenotypes; D018913:Event-Related Potentials, P300 / Q000502:physiology*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D012737:Sex Factors; D019966:Substance-Related Disorders / Q000503:physiopathology*