Alterations in hippocampal function in schizophrenia: Its genetic associations and systems implications

Schizophrenia is characterized by a constellation of symptoms that include psychosis, cognitive deficits and negative symptoms. This has been verified in several investigations using factor analysis of large schizophrenic patient populations showing these distinct domains of dysfunction. When clinical symptoms are related to imaging findings, specific brain areas are found to be differentially involved in symptom domains in the illness (Liddle 1987; Carpenter and Buchanan 1989; Kay and Sevy 1990; Arndt et al. 1991; Lenzenweger et al. 1991; Barnes and Liddle 1990; Andreasen et al 1995), with prefrontal (PFC) most involved in executive function and medial temporal lobe (MTL) most associated with declarative memory. Studies defining the anatomy of schizophrenia show delimited regions of brain associated with the symptoms; these include the prefrontal cortex (both dorsolateral prefrontal cortex, DLPFC, and anterior cingulate cortex, ACC) and the MTL as well as the superior temporal gyrus (STG). In this chapter, we review a large and significant body of convergent evidence that demonstrates the importance of the medial temporal lobe as a brain region central to the pathophysiology of schizophrenia.