CLINICAL HANDBOOK OF SCHIZOPHRENIA

48 I. CORE SCIENCE AND BACKGROUND INFORMATIONThe DLPFC has been shown to demonstrate a decrease in synaptophysin, a markerof postsynaptic density, and this finding is supplemented by a lower density of dendriticspines in this area in patients with schizophrenia. This may represent an excess of synapticpruning in this area, but it may also reflect the loss of dendrites, with resultant increasesin synaptic density due to some other aberrant process that divests these neuronsof trophic or sustaining factors. Magnetic resonance spectroscopic (MRS) investigationshave demonstrated a reduction in N-acetylaspartate (NAA), a marker of neuronal integrity,in the DLPFC, which is present at first break and is consistent with a reduction insynaptic and dendritic density. Furthermore, several studies have demonstrated a state ofrelative hypofunctioning in the frontal cortex in patients with schizophrenia, consistentwith the notion that there is both functional and structural aberration in this region.Temporal LobeLike all investigations into brain pathology in schizophrenia, investigations into the temporallobe have produced conflicting results. Although the majority of studies demonstratereductions in total temporal lobe volume, almost 40% report negative findings.However, like so much of schizophrenia research, these conflicting findings are likely duein part to methodological differences that impact the accuracy of measurement, differencesin the definition of boundaries of the temporal lobe, and sample size limitations. Asmore studies have used more rigorous methods and better instruments, the number ofpositive studies in this area has been increasing. One might question whether the entiretemporal lobe is a sufficiently specific region of interest to capture differences betweenpatients with schizophrenia and controls. Subdividing the temporal lobe has revealed alterationsin three structures within the temporal lobe in schizophrenia: the medial temporallobe, the superior temporal gyrus, and the planum temporale.The medial temporal lobe includes the amygdala (responsible for emotional valence)and the parahippocampal gyrus (involved in aspects of memory), and has been found tobe reduced in volume in the vast majority of imaging studies in schizophrenia, consistentwith postmortem findings in this region and with the common finding of increased volumeof the temporal horn of the lateral ventricles, which surrounds the medial temporallobe. Volume reductions in both substructures—amygdala–hippocampal complex andparahippocampal gyrus—are evident in chronic patients, but volume reductions in theamygdala–hippocampal complex are also present in first-episode patients. However,amygdala–hippocampal complex reductions are also present in mood disorders, someanxiety disorders, and as a function of aging, thus lacking specificity as an aspect ofschizophrenia. And although the meaning of any lateralized differences remains unknown,it is common to find a left-greater-than-right separation between patients withschizophrenia and control subjects. Investigations into the hippocampus specifically,though, have yielded some intriguing results.In healthy subjects, there is an anatomical asymmetry in the hippocampus, with theright hippocampus being somewhat larger. Functionally, the hippocampus is involved inmemory: The right hippocampus is preferentially involved in spatial memory, whereas theleft is concerned with verbal memory. Reductions in hippocampal size and alterations inhippocampal shape have both been demonstrated in patients with schizophrenia. Volumereductions in the hippocampus have generally been found to be greater on the left, whichcoincides with parahippocampal reductions being greater on the left, as well as volumeincreases in the left temporal horn of the lateral ventricle. The cross-sectional area of pyramidalneuron cell bodies has also been found to be reduced in patients with schizophrenia.Again, negative reports have been published as well. Hippocampal neuronal shape