Table 1.

Approaches to constructing animal models of neuropsychiatric disorders

General approach	Specific method	Strengths	Weaknesses
Genetics	Selective breeding	Focus on phenotypes of interest	May produce a phenocopy of human disorder
	Random mutation and screening	Focus on phenotypes of interest	May produce a phenocopy of human disorder
	Transgenic animals (e.g., knock-outs, knock-ins, overexpressors)	Recapitulates genetic abnormality in human disorder; Focus on gene of interest	Variable penetrance of genetic abnormality in rodents. Human relevance of phenotype may be difficult to establish
	Virally mediated gene delivery to brain	Spatial and temporal control over genetic change; Focus on gene of interest	Does not recapitulate genetic cause of human disorder
Pharmacological	Administration of neurotransmitter agonist or antagonist	Temporal and some spatial (with intracranial delivery) control; Focus on neurotransmitter system of interest	Lack of evidence that common mental disorders involve selective lesions of a single neurotransmitter system
Environmental	Chronic social stress (adult or during development)	May recapitulate risk factors in humans	Lack of specificity for a given human disorder
	Chronic physical stress	Easy to administer	Lack of construct validity for most human disorders
Electrical stimulation and lesions	Brain stimulation, including optogenetic approaches	Spatial and temporal control over neural circuit function; May recapitulate some findings in humans with DBS	Current limitations in knowledge of neural circuit abnormalities in human disorder
	Anatomical lesions	May produce behavioral abnormalities reminiscent of human disorder	Lack of evidence for anatomical lesions as cause of human disorder