Schizophrenia unfolds during the late period of brain maturation, while myelination is still continuing. In the present study, we used MRI and T2 relaxation analysis to measure the myelin water fraction in schizophrenia. In schizophrenia (n ¼ 30) compared with healthy subjects (n ¼ 27), overall white matter showed 12% lower myelin water fraction (P ¼ 0.031), with the most prominent effects on the left genu of the corpus callosum (36% lower, P ¼ 0.002). The left anterior genu was affected in both first-episode (P ¼ 0.035) and chronic patients (P ¼ 0.011). In healthy subjects, myelin water fraction in total white matter and in frontal white matter increased with age, and with years of education, indicating ongoing maturation. In patients with schizophrenia, neither relation was statistically significant. Post-mortem studies of anterior frontal cortex demonstrated less immunoreactivity of two oligodendrocyte-associated proteins in schizophrenia (2 0 ,3 0 -cyclic nucleotide 3'-phosphodiesterase by 33%, P ¼ 0.05; myelin-associated glycoprotein by 27%, P ¼ 0.14). Impaired myelination in schizophrenia could contribute to abnormalities of neural connectivity and persistent functional impairment in the illness. Molecular Psychiatry (2003) 8, 811-820. doi:10.1038/sj.mp.4001337Keywords: myelin-associated glycoprotein; 2 0 ,3 0 -cyclic nucleotide 3 0 -phosphodiesterase; frontal lobe; T2 relaxation; schizophrenia; oligodendrocyte Schizophrenia is one of the most disabling mental disorders, yet the mechanism of illness remains unclear. Abnormalities of dopaminergic neurotransmission contribute to acute exacerbations of illness; 1 however, factors related to illness onset and subsequent disability are less certain. Clinical, neuroimaging, and neuropathological evidence indicates disturbances of early brain development may predispose to schizophrenia. However, the period of brain maturation in adolescence and early adulthood is the window of time during which the illness is first expressed. During this period of maturation, changes in white matter tracts are relatively prominent. [2][3][4][5][6] Diseases of white matter such as leukodystrophies, which may have their onset at this age, frequently present with psychosis as an early feature, 7,8 and multiple sclerosis (MS) may also be associated with psychosis. 9 Abnormalities of white matter in schizophrenia are detected with a range of MRI techniques including image averaging, 10-12 magnetization transfer imaging, 13 diffusion tensor imaging, 14-17 and measurement of transverse relaxation time. [18][19][20][21] The cellular or molecular implications of these findings are not clear. Magnetic resonance spectroscopy (MRS) does detect chemical differences in white matter in schizophrenia. [22][23][24] The observation of lower levels of the neuronspecific maker N-acetylaspartate in white matter suggests abnormalities of axons in schizophrenia.A complementary MRI technique allows analysis of myelin. MRI can detect a signal related to water distribution in tissue. This MRI signal can b...

One of the fundamental goals in understanding schizophrenia is linking the observable symptoms to the underlying unobservable pathophysiology. Given recent advances in medical imaging, researchers are increasingly investigating brain-behavior relationships to better understand the neural substrates of negative, positive, and disorganization symptoms in schizophrenia. This review focused on 25 task-related functional magnetic resonance imaging studies and found meaningful small to moderate associations between specific symptom dimensions and regional brain activity. Negative symptoms were related to the functioning of the ventrolateral prefrontal cortex and ventral striatum. Positive symptoms, particularly persecutory ideation, were related to functioning of the medial prefrontal cortex, amygdala, and hippocampus/parahippocampal region. Disorganization symptoms, although less frequently evaluated, were related to functioning of the dorsolateral prefrontal cortex. Surprisingly, no symptom domain had a consistent relationship with the middle or superior temporal regions. While a number of adaptations in experimental design and reporting standards can facilitate this work, current neuroimaging approaches appear to provide a number of consistent links between the manifest symptoms of schizophrenia and brain dysfunction.

Accumulated evidence suggests that schizophrenia is associated with subtle gray matter deficits throughout the cerebral cortex and regional cortical thinning. Although findings are not entirely consistent, healthy relatives of schizophrenia patients also show abnormalities in cortical gray matter volume, suggesting that this may be one aspect of an unexpressed genetic liability to the disorder. Cortical thickness and surface area are additional indicators of cortical cytoarchitectural integrity. To investigate the nature of cortical abnormalities in the healthy relatives of patients, this study used magnetic resonance imaging to evaluate gray matter volume, surface area, and thickness of 13 regions using an automated parcellation methodology. Compared with controls (n = 22), relatives (n = 19) had decreased volume and surface area in the right cingulate gyrus, a bilateral decrease in cingulate thickness, and decreased surface area in the superior temporal lobe. In addition, relatives had a subtle increase in gray matter volume and surface area in the left hemisphere, bilaterally in the parahippocampal gyri, and in the left middle temporal lobe. The results of this study suggest that the cortical regions most affected by the unexpressed genetic liability to schizophrenia may be the cingulate and temporal regions--regions associated with higher level cognitive, affective, and memory functions.

Convergent and divergent validity are critically important in developing psychological measures that reveal interpretable deficits in disordered populations. This article reports on 2 studies that evaluated the validity of context processing measures. In Experiment 1, a confirmatory factor analysis of data from 481 healthy adults established the convergent validity of 2 context processing measures and showed that context processing accounted for significant amounts of variance in standard IQ and working memory measures. In Experiment 2, 20 schizophrenia patients, 16 of their healthy siblings, and 28 controls were evaluated using a novel, short context processing measure, the dot pattern expectancy (DPX) task. The DPX was sensitive to specific deficits in schizophrenia patients and their healthy siblings. These findings support the construct validity of context processing measures, suggest context processing is a component of intellectual functioning, and demonstrate that brief context processing measures remain sensitive to psychopathological deficits.