CLINICAL HANDBOOK OF SCHIZOPHRENIA

4. Brain Imaging 37yet to be strong evidence to support any single theory; however, investigations usingnewer techniques, such as functional neuroimaging and diffusion tensor imaging (DTI),which can be used to visualize integrity of white matter tracts, are likely to provide amore direct means of testing disconnection theories. The idea that structural deficits maybe neurodevelopmental in origin is supported to some degree by the fact that MRI abnormalitieshave generally been found among both first-episode patients and chronically illindividuals. Longitudinal studies, however, suggest that there may also be additional factorsthat lead to patients’ somewhat steeper decline in cortical volume with age comparedto healthy individuals. Many studies of structural deficits in schizophrenia have attemptedto relate these abnormalities to clinical and, particularly, cognitive features of thedisorder. Although methodological inconsistencies between studies make it difficult todraw strong conclusions, it does appear that structure–function relationships are commonto patients and controls (e.g., positive association between whole-brain volume andgeneral cognitive ability, and between IQ and dorsal prefrontal cortex gray matter volume),and that some relationships are specific to schizophrenia (e.g., positive associationsbetween cognitive flexibility and prefrontal cortex volume, and between language functioningand volumes of superior temporal gyrus and parahippocampal gyrus). Other importantissues that deserve further study include the relationship of structural deficits togenetic risk for schizophrenia and whether volume deficits predict course or outcome. Recentimaging studies that have focused on individuals at high genetic risk or those showingprodromal symptoms of schizophrenia are promising first steps toward addressingboth of these issues. In addition, not much is known about the potential effects ofantipsychotic medication and the specificity of the findings to schizophrenia compared toother psychiatric disorders. As automated or semiautomated techniques to parcel thebrain into regions of interest become more established, larger studies with the power toexamine such questions should be feasible.Magnetic Resonance SpectroscopyAnother method for examining the integrity of the brain involves examination of chemicalsrelated to metabolic activity. MRS uses nuclear magnetic resonance principles to generatea spectrum of peaks related to the biochemical composition of a region of the brain.The most common form of MRS is sensitive to hydrogen protons and can measure levelsof compounds such as amino acids and sugars. The strength of this technique is its uniqueability to measure in vivo neurochemistry. The weaknesses include low spatial resolutioncompared to MRI, and, as yet, no ability to measure neurochemical change due to cognitiveactivity.The majority of MRS studies in schizophrenia have focused on measuring levels ofN-acetylaspartate (NAA), which is hypothesized to be a marker of neuronal integrity.NAA levels appear to be reduced in the hippocampus and in the gray and white matter ofthe frontal lobe among patients with schizophrenia. Fewer studies have examined phosphorus-containingmetabolites, such as phosphomonoesters and phosphodiesters, butthese studies have also revealed temporal lobe and frontal abnormalities in patterns thatmay be reflective of synaptic pruning failures.FUNCTIONAL BRAIN IMAGINGThe functional significance of the subtle but well-documented structural brain abnormalitiesin schizophrenia is not completely understood. Because the distribution of brain volumesand neurochemical levels among patients and healthy individuals seems to overlap,