Table 5.
Degree to which electrophysiological biomarkers satisfy threshold criteria for a putative endophenotype
| Measure | Evidence | Clinical Phenotype | Phenotypic Association | Observed in Unaffected Relatives |
Shared Genetic Liability |
Heritability |
|---|---|---|---|---|---|---|
| Spontaneous EEG activity (power) | ||||||
| Very low frequency | S | ADHD | Cooper 2014; Helps 2008; Tye 2012 | Tye 2012 | Tye 2012 | |
| Delta | S | Schizophrenia/Bipolar ↑ | Moran 2011; Narayanan 2014 | Narayanan 2014 | Malone 2014a; Smit 2005; Zietsch 2007 | |
| S | ADHD ↑ | Rudo-Hutt 2015 | ||||
| S | Binge drinking ↑ | Courtney 2010 | ||||
| S | Autism ↑ | Wang 2013 | ||||
| Theta | M | Schizophrenia/Bipolar ↑ | Hong 2012; Moran 2011; Narayanan 2014 | Hong 2012 | Tye 2014 | |
| S | Externalizing ↑ | Rudo-Hutt 2015 | ||||
| S | ADHD ↑ | Barry 2003a; Loo 2010; Rudo-Hutt 2015 | ||||
| S | Alcoholism ↑ | Rangaswamy 2003 | ||||
| S | Depression ↑ | Fingelkurts 2015 (frontal sites) | ||||
| S | Autism ↑ | Rommelse 2011; Wang 2013 | ||||
| Alpha | S | Schizophrenia/Bipolar ↑ | Narayanan 2014 | Narayanan 2014 | ||
| S+ | ASB/Aggression ↓ | Barry 2003a; Rudo-Hutt 2015 | Niv 2015 | |||
| S | Alcoholism ↓ | Ehlers 2007; Enoch 1999 | ||||
| S | Autism ↓ | Rommelse 2011; Wang 2013 | ||||
| S | Depression ↑ | Fingelkurts 2015 | ||||
| Beta | S | Schizophrenia/Bipolar ↑ | Kam 2013; Narayanan 2014 | Narayanan 2014 | ||
| S+ | Externalizing ↓ | Rudo-Hutt 2015 | Gilmore 2010 | |||
| S | ADHD ↓ | Barry 2003a; Loo 2010; Rudo-Hutt 2015 | ||||
| S | Alcoholism ↑ | Ehlers 2010; Rangaswamy 2002 | Rangaswamy 2004 | |||
| S | Binge drinking ↑ | Courtney 2010 | ||||
| S | Autism ↑ | Rommelse 2011; Wang 2013 | ||||
| S | Depression ↑ | Fingelkurts 2015 | ||||
| Gamma | S | Autism ↑ | Wang 2013 | Ehlers 2010 | ||
| S | Alcoholism ↑ | Ehlers 2010 | ||||
| Low-voltage alpha | S | Alcoholism-related, anxiety | Ehlers 2015; Enoch 1995 | Anokhin 1992; Vogel 1970 | ||
| Theta/beta ratio | B | ADHD | Arns 2013; Snyder 2006 | |||
| Frontal alpha asymmetry | S+ | Depression, anxiety | Allen 2015; Goldstein 2014; Thibodeau 2006 | Jacobs 2015 | Anokhin 2006; Smit 2007b | |
| S+ | Autism | Wang 2013 | Gabard-Durnam 2015 | |||
| S | Aggression | Harmon-Jones 2007; Keune 2012 | ||||
| Event-related EEG amplitude or power | ||||||
| Theta or delta power | M | Alcoholism | Chen 2009; Jones 2006; Jones 2004 | Kamarajan 2015; Kamarajan 2006; Rangaswamy 2007 | Gilmore 2010; Jones 2004; Zlojutro 2011 | |
| S+ | Externalizing | Bernat 2011; Gilmore 2010; Yoon 2013 | Gilmore 2010 | |||
| S | Schizophrenia | Ethridge 2012 | Ethridge 2012 | |||
| Beta or gamma power | M | Schizophrenia | Hall 2011b; Uhlhaas 2010 | Clementz 1998; Hall 2011b; Leicht 2011 | Hall 2011b | |
| S | Bipolar disorder | Kam 2013 | ||||
| S+ | Alcoholism | Padmanabhapillai 2006a | Padmanabhapillai 2006b | |||
| S+ | Autism | Uhlhaas 2006 | ||||
| S | Depression ↑ | Webb 2015 | ||||
| ITPC | S | Externalizing | Burwell 2014 | Hall 2011b; Malone 2016 | ||
| S+ | ADHD | McLoughlin 2014 | McLoughlin 2014 | |||
| S+ | Schizophrenia | Hall 2011b; Leicht 2015; Uhlhaas 2010 | Hall 2011b; Leicht 2011 | Hall 2011b | ||
| S | Autism | Rojas 2008 | Rojas 2008 | |||
| Connectivity | B | PTSD | Georgopoulos 2010; James 2015 | |||
| S | Depression | Fingelkurts 2007; Leuchter 2012; Pizzagalli 2003 | Smit 2010 | |||
| S | Schizophrenia | Ford 2002; Kam 2013; Micheloyannis 2006; Winterer 2003 | ||||
| S | Autism | Vissers 2012; Wass 2011 | ||||
| PFC broadband noise | S | Schizophrenia | Winterer 2004 | Winterer 2004 | ||
| P50 sensory gating | M | Schizophrenia | Adler 1982; Bramon 2004; de Wilde 2007; Freedman 1983; Patterson 2008; Siegel 1984 | de Wilde 2007; Thaker 2008 | M. Hall 2007 | Anokhin 2007b; Aukes 2008; Hall 2006; Young 1996 |
| S+ | Bipolar disorder | Schulze 2007; Thaker 2008 | Schulze 2007 | |||
| S | PTSD | Karl 2006; Neylan 1999 | ||||
| N1/P2 amplitude | S | Schizophrenia | Ethridge 2012; Salisbury 2010 | Sponheim 2006 | ||
| Oddball N2 amplitude | S | Alcoholism | Cristini 2003; Realmuto 1993 | Smit 2007a | ||
| Flanker/Nogo N2 amplitude | S+ | ADHD | Albrecht 2008; McLoughlin 2009 | Albrecht 2008; McLoughlin 2009 | Anokhin 2004 | |
| S | Alcoholism | Cristini 2003; Pandey 2012 | ||||
| P300 amplitude | S+ | Antisocial behavior | Gao 2009 | Viana-Wackermann 2007 | ||
| P | SUDs/Externalizing | Euser 2012; Iacono 2002; Iacono 2011 | Begleiter 1984; Iacono 2011; Polich 1994 | Gilmore 2010 | Malone 2014b; van Beijsterveldt 2002 | |
| P | Schizophrenia | Bramon 2004; Chen 2014; Jeon 2003; Qiu 2014 | Bramon 2005; Ethridge 2012 | M. Hall 2007 | ||
| S | ADHD | Barry 2003b; Szuromi 2011 | ||||
| M | Bipolar disorder | Hall 2009; Schulze 2008; Thaker 2008 | Hall 2009; Schulze 2008; Thaker 2008 | |||
| S | PTSD | Johnson 2013; Karl 2006; Kimble 2000; McFarlane 1993 | ||||
| P300 latency | P | Schizophrenia | Bramon 2004; Qiu 2014 | Bramon 2005 | M. Hall 2007 | Hall 2009; van Beijsterveldt 2002 |
| M | Bipolar disorder | Hall 2009; Lenox 2002; Muir 1991; Schulze 2008; Thaker 2008 | Hall 2009; Schulze 2008 | Hall 2009 | ||
| ERN amplitude | S+ | OCD, anxiety ↑ | Hajcak 2002; Olvet 2008; Moser 2016 (sex specific) | Olvet 2008 | Anokhin 2008 | |
| M | ADHD ↓ | Albrecht 2008; Geburek 2013 | Albrecht 2010; Albrecht 2008; McLoughlin 2009 | |||
| S | Externalizing ↓ | J. Hall 2007 | ||||
| S+ | SUDs ↓ | Franken 2007 | Euser 2013 | |||
| FRN amplitude | M | Depression | Moran 2016; Foti 2009 | Foti 2011; Kujawa 2015; Weinberg 2015 | ||
| Reward positivity | S | Depression | Proudfit 2015 | Proudfit 2015 | ||
| MMN amplitude | S | Schizophrenia | Erickson 2016; Haigh 2016; Shelley 1991; Takahashi 2013; Umbricht 2005 | Haigh 2016 (NS) | M. Hall 2007 | Hall 2009 |
| S | Psychosis | Ranlund 2015 | Ranlund 2015 | |||
| S | Alcoholism | Inconsistent findings | ||||
| M | Dyslexia (speech stimuli) | Kraus 1996; Schulte-Korne 2001 | Hommet 2009; Maurer 2009; Maurer 2003 | |||
| N400 amplitude | S | Alcoholism | Roopesh 2010 | Roopesh 2009 | ||
| N170/N250 amplitude | B | Schizophrenia | Feuerriegel 2015; McCleery 2015 | |||
| N170 latency | B | Autism | Dawson 2005a | |||
| Atypical lateralization | S | Autism | Dawson 2005a; Seery 2013 | Dawson 2005b | ||
| B | Depression | Trinkl 2015 | ||||
| ANS and electromyographic measures | ||||||
| Acoustic startle | S | PTSD/anxiety | Pole 2007 | Anokhin 2003; Hasenkamp 2010; Vaidyanathan 2014b | ||
| S | Schizophrenia | Braff 1992; Light 2012; Quednow 2008 | ||||
| Startle modulation | S | Psychopathy | Benning 2005; Patrick 1993 | Weak h2 (Anokhin 2007a; Vaidyanathan 2014c) | ||
| S+ | Anxiety/fearfulness | Cuthbert 2003; Grillon 1993; Grillon 2003; Vaidyanathan 2009 | Grillon 1997 | |||
| S | Borderline personality | Hazlett 2007 | ||||
| S | Bipolar disorder | Giakoumaki 2010 | Giakoumaki 2010 | |||
| Prepulse inhibition | M | Schizophrenia | Braff 1978; Braff 2010; Swerdlow 2014; Turetsky 2007 | Cadenhead 2000; Kumari 2005 | Anokhin 2003; Greenwood 2015 | |
| M | Bipolar disorder | Thaker 2008 | Thaker 2008 | |||
| Resting HR | M | ASB/psychopathy ↓ | Lorber 2004; Ortiz 2004 | Mednick 1972, cited in Venables 1987 | Baker 2009 | Wang 2015 |
| S | PTSD ↑ | Pole 2007 | ||||
| ED activity/reactivity | S | Externalizing ↓ | Isen 2013; Isen 2012 | Herpertz 2007 | Hettema 2003; Tuvblad 2012; Vaidyanathan 2014a | |
| S+ | PTSD/anxiety ↑ | Pole 2007 | Balle 2013 | |||
| S | Schizophrenia ↑ | Iacono 1999 | Iacono 1999 | |||
| RSA patterns | S | Depression | Yaroslavsky 2014 | Yaroslavsky 2014 | ||
| B | ADHD | Beauchaine 2015 | ||||
| B | Antisocial behavior | Beauchaine 2015 | ||||
| EDA modulation | B | SUDs | Taylor 2009 | |||
| Eye tracking | ||||||
| Antisaccade error rate | M | Schizophrenia | Clementz 1998; Fukushima 1988; Turetsky 2007 | Calkins 2008; Levy 2004 | Greenwood 2007; Vaidyanathan 2014b | |
| S | Psychosis | Reilly 2014 | Reilly 2014 | |||
| S | OCD | Lennertz 2012 | Lennertz 2012 | |||
| Smooth pursuit tracking | M | Schizophrenia | Calkins 2000; Hong 2008; Levy 1993; O'Driscoll 2008; Thaker 2008 | Calkins 2008; Hong 2008; Ross 2002; Thaker 2008 | Blekher 1997; Katsanis 2000 | |
Note: References are provided in the Supplementary Material. Columns represent the threshold criteria for an endophenotype (see Section I, Table 1). Citations include seminal papers establishing associations between biomarker and clinical phenotype, as well as meta-analytic and narrative reviews (in bold face and italics, respectively) of the literature concerning a biomarker and evidence that it is a candidate endophenotype. First author and publication year are listed for each citation. The strength of the empirical evidence supporting a measure as a putative endophenotype was coded as follows: P = persuasive, M = moderate, S = suggestive (S+ = strongly suggestive), B = biomarker only, evidence does not support measure as a putative endophenotype. NS indicates a nonsignificant effect (e.g., in a meta-analysis).
Abbreviations: ADHD, attention deficit-hyperactivity disorder; ASB, antisocial behavior; PTSD, posttraumatic stress disorder; OCD, obsessive-compulsive disorder; SUDs, substance use disorders; ITPC, inter-trial phase consistency; FRN, feedback-related negativity; MMN, mismatch negativity; HR, heart rate; ED, electrodermal; EDA, electrodermal activity; RSA, respiratory sinus arhythmia