Table 1.

Environmental models of autism and schizophrenia

Environmental factors	Animal models	Behavioral alterations	Cerebellar pathology	Strengths	Caveats	Refs
Borna virus	Neonatal brain infection in rats	Hyper-reactivity Elevated anxiety Deficient learning Abnormal social behaviors	Hypoplasia Gradual loss of PC	Comprehensive face validity Neurotropic virus	No human infection Intracerebral inoculation Widespread effects	Pletnikov et al., 2002; 2003; Dietz, 2004; Lancaster, 2007
Valproic acid (VPA)	Prenatal exposure in rodents	Impaired PPI Eye blink conditioning Stereotypy and hyperactivity Decreased social behaviors	Reduction of PC Decreased cerebellar volume	Relevance to human conditions Abnormalities start during development	Responsible for limited numbers of cases Widespread effects on the brain and whole body	Ingram et al., 2000; Schneider, 2006, 2008; Dufour-Rainfray et al., 2009; Markram, 2007, 2008 ; Stanton et al., 2007; Mychasiuk, 2012; Yochum et al., 2008
Influenza virus	Prenatal and early postnatal exposure in mice	Altered anxiety Deficit in Morris water maze	Not reported	Relation to human	Specificity of flu in mice vs. humans Confounding effects of sickness and stress	Fatemi et al., 2008a,b, 2009; Beraki et al., 2005
Immune activation	Prenatal exposure to poly IC or LPS	Elevated anxiety Decreased social behaviors Deficits in learning and memory	A localized deficit in PC in lobule VII of the cerebellum Heterotopic PC Delayed migration of granule cells in lobules VI and VII	Relevance to human conditions Amenable to dosing, timing and routes of exposure	Artificial immune activation Wide-spread effects	Shi et al., 2009 Xu et al., 2013
Altered thyroid production	Early postnatal hypothyroidism in rats	Hyperactivity Decreased habituation Deficient learning and memory	Retarded granular cell migration in the external granular layer	Relevance to human conditions	Responsible for limited numbers of cases Widespread effects on the brain and whole body	Sadamatsu and Watanabe, 2005; Sadamatsu et al., 2006 Akaike et al., 1991; Akaike and Kato, 1997