At the whole-organism level, two recent studies have associated rs1344706 with variation in function. Esslinger and colleagues (2009) reported that the schizophrenia risk allele at this locus was associated with reduced connectivity both within dorsolateral pre-frontal cortex (DLPFC) and between the right and left DLPFC as indexed by the extent to which activation of those brain structures was temporally correlated during the N-back task (a probe for executive function). In contrast, connectivity was increased between the DLPFC and the hippocampal formation as well between a number of other structures. More recently, Walters and colleagues found that the schizophrenia risk allele at rs1344706 was associated with better episodic and working memory in individuals with schizophrenia, but not controls, a finding they replicated in a German sample. Given that schizophrenia is associated with reduced cognitive function, association with better function seems counter-intuitive. However, given the absence of association with better function in controls, rather than being associated with cognitive ability, ZNF804A may be associated with a subtype of schizophrenia in which cognition is relatively spared. This hypothesis is in keeping with association
