Understanding the pathophysiology of postpartum psychosis: Challenges and new approaches

Table 1 The advantages and limitations of methods for investigating biological risk factors in individuals with postpartum psychosis

Investigational method	Advantages of method	Limitations of method
Clinical biochemistry or gene expression analyses	Direct assessment in patient or “at risk” groups	Difficult to access central nervous system; peripheral changes may not reflect central functional abnormalities
	Possibility of identifying peripheral biomarkers for PP risk	Potential issues with obtaining consent for samples
		Substantial fluctuation of markers with participant demographics, experiences and treatments
		Possible issues related to reverse causation, i.e., are abnormalities a cause or consequence of the disorder?
Neuroimaging	Direct assessment of brain structure, function or chemistry in patient or “at risk” groups	Cannot easily be performed during psychotic episodes
		Substantial exclusion criteria for procedure
		Limited resolution; cannot provide information on most neurochemical, cellular or molecular abnormalities
		Substantial fluctuation of measures with participant demographics, experiences and treatments
		Possible issues related to reverse causation, i.e., are abnormalities a cause or consequence of the disorder?
Genetics	DNA can be readily obtained from patient or “at risk” groups from peripheral tissues	Low power of genome-wide studies as a consequence of low prevalence of the condition; possibility of false positives and negatives
	DNA sequence is stable and unaffected by variability in patient’s circumstances
	Possibility of identifying biomarkers that can predict risk at an early stage
	Few issues with reverse causation
Porcine infanticide model	Some degree of face validity	Questionable relevance of animal behavioural phenotypes to PP symptoms
	Direct access to brain tissue for detailed examination and DNA for genetic studies	Difficult and expensive to breed and maintain
		Not readily amenable to pharmacological studies; predictive validity unclear
		Difficult to systematically assess all brain regions
STS-inhibition mouse model	Some degree of face and predictive validity	Questionable relevance of animal behavioural phenotypes to PP symptoms
	Direct access to brain tissue for detailed examination	Face and predictive validity require further confirmation
		STS deficiency unconfirmed in PP cases, hence construct validity unsubstantiated
	Relatively cheap to breed and maintain
	Amenable to pharmacological and genomic studies

PP: Postpartum psychosis; STS: Steroid sulfatase.