Neuroscience and Biobehavioral Reviews 36 (2012) 572–603 Contents lists available at SciVerse ScienceDirect Neuroscience and Biobehavioral Reviews journa l h o me pa g e: www.elsevier.com/locate/neubiorev Review The P300 event-related brain potential as a neurobiological endophenotype for substance use disorders: A meta-analytic investigation Anja S. Euser a,b,∗ , Lidia R. Arends a,c , Brittany E. Evans b,d , Kirstin Greaves-Lord b , Anja C. Huizink d,e,f , Ingmar H.A. Franken a a Institute of Psychology, Erasmus University Rotterdam, The Netherlands b Department of Child and Adolescent Psychiatry, Erasmus Medical Center Rotterdam, The Netherlands c Department of Biostatistics, Erasmus Medical Center Rotterdam, The Netherlands d Research Institute of Child Development and Education, University of Amsterdam, Amsterdam, The Netherlands e Behavioral Science Institute, Radboud University, Nijmegen, The Netherlands f Research Institute for Addiction (IVO), Rotterdam, The Netherlands a r t i c l e i n f o Article history: Received 19 October 2010 Received in revised form 7 September 2011 Accepted 15 September 2011 Keywords: P300 Event-related potentials Endophenotype Substance use disorders Family history High-risk Oddball paradigm a b s t r a c t Endophenotypes are intermediate phenotypes on the putative causal pathway from genotype to pheno- type 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. © 2011 Elsevier Ltd. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 573 1.1. P300 amplitude: theoretical background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 573 1.2. P300 amplitude: heritability and genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 574 1.3. Main findings of P300 addiction research area . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 574 1.3.1. P300 amplitude as a disease marker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 574 1.3.2. P300 amplitude as a vulnerability marker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 575 1.4. Putative moderators: sample-, task- and study characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 576 1.5. Rationale of the present meta-analytic investigation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 577 2. Method . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 577 2.1. Literature search strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 577 2.2. Selection of studies for inclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 577 ∗ Corresponding author at: Institute of Psychology, Erasmus University Rotterdam, Woudestein T12-59, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Tel.: +31 10 4088827; fax: +31 10 4089009. E-mail address: euser@fsw.eur.nl (A.S. Euser). 0149-7634/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.neubiorev.2011.09.002