CLINICAL HANDBOOK OF SCHIZOPHRENIA

5. Neuropathology 51also been demonstrated to be decreased in patients with schizophrenia, as measured bydiffusion tensor imaging (DTI), a method by which the organization of white mattertracts can be determined (discussed below). The anteroventral nucleus, which projectslargely to the prefrontal cortex, has also been found to have a decrease in the number ofaxons present. This is not to say that other areas of the thalamus do not have irregularities;rather, the lack of information regarding other thalamic nuclei reflects a paucity ofinvestigation into these areas. Importantly, a reduction in synaptic protein rab3a has alsobeen found in studies utilizing a substantial sample of subjects with schizophrenia.Basal GangliaAn increase in the volume of the basal ganglia has repeatedly been demonstrated in patientswith schizophrenia. However, this increase has been determined to be largely amedication effect. Interestingly, it may be that typical neuroleptics are more responsiblefor this effect, because in one study, switching patients to an atypical neuroleptic for 1year led to a decrease in caudate nucleus size. In contrast, medication-naive patients withschizophrenia have been shown to have reduced caudate size in several studies, althoughthis finding is, of course, contradicted in a study that noted no significant size differencebetween basal ganglia volume in treated and never-treated patients. Finally, reduced volumeof the basal ganglia has been demonstrated in patients with depression as well, makingthe specificity of this finding to schizophrenia somewhat suspect.DYSCONNECTIVITY AND THE POSSIBLE ROLEOF WHITE MATTER IN SCHIZOPHRENIAThe theory of dysconnectivity suggests that the inability of different brain regions to communicateeffectively with each other has a causal impact on the symptoms, course, andneuropathology of schizophrenia. Disorganized or poorly insulated neurotransmissionmay explain at least some of the observable psychophenomena of the disease. Proposedneuroanatomical consequences include the idea that areas that should receive ongoing,function-maintaining trophic signaling fall into disrepair when the tracts that connectthese regions are not communicating optimally, and that this might explain some of theregional evidence we presented in earlier sections. In addition, if disconnectivity is part ofthe neuropathology of schizophrenia, then the components of these connections, particularlywhite matter, should be somehow aberrant in the brains of patients with schizophrenia.Over the past several years, multiple lines of evidence have converged in support of theidea that, indeed, white matter—specifically oligodendrocytes and myelin—is involved inpatients with schizophrenia. Increased cell density has been found in the deep white matterin patients with schizophrenia, along with maldistribution of neurons in white matter of theprefrontal cortex (PFC), although both of these findings have not been universally demonstrated.Microarray studies have found decreased expression of myelin-related genes in severalbrain regions, and quantification and qualification of oligodendrocytes in postmortemsamples have found a deficit of close to 25% in the PFC of patients with schizophrenia,along with altered spacing and distribution. Other postmortem examinations have revealedabnormal changes in both myelin and oligodendrocytes in the PFC and caudate nucleus ofpatients with schizophrenia. DTI (a special type of MRI analysis that is well suited to the examinationof white matter) has found decreased organization and coherence of white matterin widespread brain regions, including the PFC, temporoparietal and parieto-occipitalregions, splenium, cingulum, posterior capsule, medial temporal cortex, and frontal white