psychiatry from a study comparing olanzapine with haloperidol in first - episode patients and comparing any brain changes to control changes over time . they claim that , over a 2-year period , whole gray matter volume decreases significantly more in patients administered haloperidol than in controls or patients on olanzapine . however , the time of the follow - up mri scans was short ; there were many dropout subjects in this study and disproportionately among the groups ; and some time periods were missing in one group entirely , thus hampering interpretation of these results . there have now been several other studies attempting to examine the question of neuroleptic effects on brain structure . while it , appears consistently in most , but , not all , studies that the caudate enlarges with typical neuroleptics , the changes seen with respect , to other cortical regions and ventricular enlargement have yet to be shown to be due to medication ( table iv ) . there are two large and interesting independent , studies of people with a prodromal syndrome that , is high likely to lead to schizophrenia - one in scotland-  and another in melbourne , australia ( table iii ) . initially during the prodrome , a change in brain structure seems to be present in the temporal lobe volume and cingulated . on follow - up in those who have gone onto a psychotic episode , further changes can be seen in the cingulate , temporal lobe , and parahippocampal gyrus . these two independent studies have results that are not entirely consistent with each other , but it is interesting that neither show ventricular enlargement , or its progression at this stage . in general , while both research groups see initial changes in temporal and frontal lobes in people who later develop schizophrenia and progressive change in the time interval from prodrome to onset , of clinical illness , the specific changes that are clearly predictive of illness need to be further delineated . the underlying basis for the changes detected by imaging could be related to abnormalities in axonal integrity and organization that begin to take place during the normal adolescent neuronal pruning and reorganizational process , and continue through out , the lifetime of the individual during aging and brain response to normal stresses . in some individuals , it , may even begin prenatally , but last , a lifetime . perhaps examining white matter integrity we now have the techniques in mri , ie , diffusion tensor imaging ( dti ) and magnetization transfer ( mt ) . two measurements based on dti images are the apparent , diffusion coefficient ( adc ) , which measures the water content and reflects the amount of cerebrospinal fluid ( csf ) , and fractional anisotropy ( fa ) , which measures the direction of flow or , indirectly , the lining up of fibers . the fa is high when fibers are orientated in one direction and low when there is diffusion and the fibers are more disorganized . the adc is high when the water content , is high and low when the water content , is low . magnetization transfer ( mt ) is a proton - weighted mri image that can give information about the integrity of myelin , in particular with the quantification of the magnetization transfer ratio ( mtr ) . the most , recent , focus of our research group has been to extend the previous longitudinal studies back in time from the first , episode to the study of individuals at high genetic risk for schizophrenia who arc in the age range for peak incidence of developing the disorder . current preliminary data are illustrated on 15 such adolescents , 15 controls , and 15 of their siblings with chronic schizophrenia ( figures 2 to 6 ) . figure 2 shows a dti comparison of fa in high - risk subjects with controls illustrating evidence of reduced fa ( or directional axonal organization ) already taking place in the left , posterior superior temporal gyrus . figure 3 shows evidence of higher adc ( or water content , ic , csf ) already evident in the left parahippocampal gyrus and right , superior temporal gyrus in the high - risk patients . this is more widespread in those with schizophrenia , suggesting that atrophic changes occur early and could be progressing into later stages of illness . figure 4andfigure 5 show that mt changes are also present , ie , changes in fiber membranes in the superior frontal gyrus and posterior cingulate . in additionne have been performing functional mri ( fmri ) lexical decision task , as previously developed , which has the ability to show lateralized activation in the superior temporal gyrus in normal individuals . in our preliminary analyses , less lateralized activation is seen in the individuals at , high - risk for schizophrenia than controls , similar but to a lesser extent , than what , is seen in the patients with chronic schizophrenia ( figure 6 ) . these studies taken together indicate that changes are occurring early in the brains of people who are likely to later develop schizophrenia , and that these changes are relevant to those regions of the brain that are involved in language processing . it appears that brain structural change is detectable in both gray and white matter prior to illness onset , that , active progression of the changes may also begin prior to the onset of clinical symptoms , that progressive brain changes may account , for the brain structural anomalies seen in chronic schizophrenia , and that the structures involved in language processing are affected . white - matter anomalies in the anatomical connections relevant to language and/or myelination of these connections could be involved . the ability to have specific mri predictors of who will develop schizophrenia among those at high risk appears hopeful for the near future . having the ability to predict , the development , of illness will then lead to studies to determine whether early pharmacological treatment , will prevent , the cortical progressive brain cortical change and , in doing so , have a significant effect , on clinical outcome .
schizophrenia is a chronic progressive disorder that has at its origin structural brain changes in both white and gray matter . 
 it is likely that these changes begin prior to the onset of clinical symptoms in cortical regions , particularly those concerned with language processing . 
 later , they can be detected by progressive ventricular enlargement . 
 current magnetic resonance imaging ( mri ) technology can provide a valuable tool for detecting early changes in cortical atrophy and anomalous language processing , which may be predictive of who will develop schizophrenia .