Table 2.

Selected animal models of GxE in schizophrenia

Gene	Environmental Insult	Effects	Reference
Infection and Immunity Models
DISC1	Prenatal poly I:C	Synergistic increases in anxiety and depressive like behaviors	Abazyan, 2010
DISC1	Early postnatal poly I:C	Synergistic impairment of short term memory	Hikida, 2007 Ibi, 2010
DISC1	Prenatal poly I:C	Synergistic increase in IL6, impaired NOR and PPI	Lipina, 2013
Nurr1	Prenatal poly I:C	Synergistic impact on PPI, startle response, and latent inhibition	Vuillermot, 2011; Vuillermot, 2012
Nurr1	Toxopsalma gondii	Synergistic effect on locomotor activity in open field	Eells, 2015
Nrg1	Prenatal poly I:C	Several impacts: some additive, some with no combined effect	O’Leary, 2014
Tap1	Influenza virus	Synergistic effects on working memory, rearing activity and anxiety	Asp, 2009; 2010
Stress Models
Reelin	Maternal separation	Protective effect of mutation on social motivation	Laviola., 2009 Ognibene, 2007 Ognibene, 2008
Nurr1	Social isolation, restraint stress	Synergistic impairment of PPI	Eells, 2006
Sept5	Social isolation	Protective effect of mutation on anxiety like behaviors	Harper, 2012
Adycap1 (PACAP)	Social isolation vs. environmental enrichment	Synergistic elevation of aggression and impact on PPI Amelioration of deficit in fear conditioning by social enrichment	Ishihama, 2010 Takuma, 2014
DISC1	Social isolation	Synergistic increases in locomotion, immobility in FST, and PPI deficiencies	Niwa, 2013
Disc1	Chronic social defeat	Opposite effects of social defeat stress on mutant vs. WT in tests of anxiety, synergistic effect on PPI and social interaction	Haque, 2012
Gad67	Maternal stress	Synergistic effects on fetal cortisol and birth weight	Uchida, 2011, Uchida, 2014
SNAP25 (bdr)	Maternal stress	Synergistic effects on sociability and PPI	Oliver, 2009
Nrg1	Social stress	Additive effects on locomotion, memory, sociability, and synergistic effect on brain cytokine levels	Desbonnet, 2012
Nrg1	Stress in young (3–4 months) and adult (6–7 months) mice	Additive genotype-stress interaction in older mice Mutants did not display anxiety-like behavior while WT did	Chesworth, 2012
Nrg1	Restraint stress during adolescence (PND 36-49)	Synergistic disruption in PPI Decreased apical dendritic length and complexity in in the medial prefrontal cortex and hippocampus	Chohan, 2014a;b
Rat model of Nrg1	Chronic stress at PND37-44	Mutant and WT displayed less anxiety Only mutant females showed enhanced cued-fear extinction	Taylor, 2011; 2012; 2013
Drug Exposure Models
COMT	Cannabis	Additive decreases in size and density of dopaminergic cells	Behan, 2012
COMT	Cannabis	Additive increase in startle response, PPI deficit, and decreases in anxiety	O’Tuathaigh, 2012
Nrg1	Cannabis	Synergistic reduction of locomotor activity, increased anxiety, and impact on PPI	Boucher, 2007, 2013 Long, 2013
Nrg1	Cannabidiol (CBD)	Reduced hyperlocomotion and increased social interaction in Nrg1 improved PPI	Long, 2012
DISC1	Methamphetamine	Mutation blunted response to methamphetamine, synergistic attenuated response to conditioned place preference	Pogorelov, 2012
Toxin Exposure Models
Reelin	Prenatal Chlorpyrifos (CPF)	Protective impact of toxic exposure on USV and on stimulant response	Scattoni, 2009 Laviola, 2006 Mullen, 2013
DISC1	Prenatal lead	Synergistic increases in anxiety like behaviors and in response to MK-801 administration	Abazyan,2014

Abbreviation list:

GxE – gene-environment interaction

DSM-V - the Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders

GWAS - genome-wide-association studies

SNP - single nucleotide polymorphism

PGC - Psychiatric Genomics Consortium

MHC - the Major Histocompatibility Complex

CNV - copy number variations

DISC1 - Disrupted-In-Schizophrenia 1

LOD - logarithm of odds

MIA – maternal immune activation

HSV – herpes simplex virus

CMV – cytomegalovirus

HLA - the human leucocyte antigen

HERV - human endogenous retroviruses

FOXP2 - the Forkhead box protein P2 gene

MRI - magnetic resonance imaging

METH – Methamphetamine

ADHD – attention deficit hyperactivity disorder

TLR – toll-like receptor

DOX – doxycycline

GD – gestation day

mPFC - the medial prefrontal cortex

NURR1 - The nuclear receptor related 1