- Email: [email protected]
Progressive focal gray matter density changes in speech related areas in schizophrenia
13. Neuroimaging, Structural
191
Luminance of isolated check stimuli was modulated sinusoidally at 12Hz against a constant background to elicit VEPs. In the M condition, low luminance contrast stimuli were used and in the P condition, stimuli were presented around a high contrast (48%) pedestal in order to deep modulation above the low contrast region. Fourier (frequency) analysis was used to extract the amplitude and phase of the response at the stimulus frequency and derive a signal-to-noise ratio. Patients showed significant decreases in fractional anisotropy (FA) and increases in mean diffusivity compared to controls in right and left OR and left IPL. Decreased FA indicates less coherence or integrity of white matter organization. Most of the patients were low functioning, and in this group, deficits were observed in both M and P VEP measures. With groups combined, significant correlations were found between M and P VEP measures and OR FA. These data indicate that primary visual deficits may be detectable using both structural and functional methods in SCZ. The results point to a reduction in integrity of projections from lateral geniculate nucleus to striate cortex in SCZ. Supported by Burroughs Wellcome Fund and RO1 MH49334.
PROGRESSIVE FOCAL GRAY MATTER DENSITY CHANGES IN SPEECH RELATED AREAS IN SCHIZOPHRENIA W. Cahn,* H. E. Hulshoff Pol, H. Schnack, R. C. Mandl, D. L. Collins, A. C. Evans, R. S. Kahn Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, Netherlands Introduction: Schizophrenia is considered to be a brain disorder that mainly affects the gray matter, with recent studies indicating that these changes may be progressive in nature. However, it is not known which brain areas are affected earlier in the disorder than others. Methods: In a one year follow-up study magnetic resonance imaging whole brain scans were obtained from thirty-four first-episode patients with schizophrenia and thirty-six matched healthy comparison subjects. Gray matter density was measured using voxel-based morphometry at base-line and at follow-up. Linear regression analysis was done for each voxel separately. Cumulative antipsychotic medication, clinical symptoms and outcome were related to the significant gray matter density changes. Results: At base-line no significant changes in gray matter density between the groups were found. At one-year follow-up gray matter density was significantly decreased in patients in the left and fight interior frontal gyrus (Broca) and in the right insula. Decreased left and right inferior frontal density were associated with clinical severity and/or outcome. Lower gray matter density in the right insula was associated with a greater amount of cumulative medication. Conclusion: Gray matter density decreases in schizophrenia one year after the first psychotic episode in distinct ~bcal areas of the brain, i.e. in the frontal and insular gyri. These progressive changes are related to disease severity and antipsychotic medication, suggesting that the progressive brain abnormalities in schizophrenia first become evident in speech related areas. Gray matter density ill first-episode schizophrenia at inclusion and after one year Blain A ~ a
Coordinates X
Icft in f,'liOl" frontal - 3 5
Glay [nattel density afte~ one year (T I )
Y
Z
t
Glay matter density at inchLsion (TO)
~
t
13
17
3
-5.41
-0.037
-I.56
0.01l
rightinferiorflontal
37
15
1
6.00
-0.053
1.32
-0015
right insula
37
3
5
5.36
11.(141
1.32
0.[110
MICROSTRUCTURAL WHITE MATTER CHANGES AS CORRELATES OF I M P A I R E D FRONTAL TASK PERFORMANCE IN FIRST EPISODE SCHIZOPHRENIA M. Carbon,* J. Bates, R. M. Bilder, K. O. Lira
Center for Neuroscience, North-Shore Long Island Research Institute, Manhasset, NY, USA The objective of the current study was to assess whether (i) changes of white matter microstructural integrity occur early in the course of schizophrenia, (ii) the neuropsychological decline in early schizophrenia is related to white matter changes. Thirteen first-episode schizophrenia (FE-SCZ) patients (age 23.8 +/- 3.7 years; 10 mate) and 10 age-matched control subjects (age 24.6 +/- 4.7 years; 7 male; t-test for age p=0.64) were scanned with diffusion-tensor magnetic resonance imaging (DTI-MRI) [1.5T GE]. White matter microstructural measures [fractional anisotropy (FA) and diffusivity (TR)] were calculated from these data. Bilateral regions of interest (ROI) were placed blind to subject state in the frontal white matter on six subsequent axial slices, separated by 5mm, starting at the level of the AC-PC line. Controls and FE-SCZ patients underwent neuropsychological testing within 1 month from the MRI scan date. Seven variables were selected as indices of frontal cortex function from a comprehensive neuropsychological test battery (Bilder et al. 2000), to assess correlations with the imaging measures. Data analysis revealed: t .) FA and TR in FE-SCZ did not differ from controls in 'all tested ROIs (p>0.3). No age correlation with white matter measures was noted. 2.) Patients performed worse than controls (p<0.05) on 5/7 frontal tasks. 3.) The following white matter changes were correlates of diminished cognitive performance: Decreased FA of the left inferior frontal white matter was associated with reduced verbal fluency (R2 =0.44, P= 0.001) and inCreased error rate on the Wisconsin Card Sorting Test (R2=0.34 p=0.04). In FE-SCZ patients, FA in the right centrum semiovale correlated inversely with performance time on the Trail Making Test B (R 2= 0.46 p=0.01) Age was excluded as a contributor to the brain-behavior correlations in a stepwise regression analysis. In contrast to prior studies of chronic schizophrenia (Buchsbanm et aL 1998, Lira et al. t999) no difference in white matter anisotropy or diffusivity was found in this first episode schizophrenia cohort compared to controls. However, subtle decreases in executive function and verbal fluency were related to reduced frontal white matter tract integrity. Further longitudinal studies of white matter microstrueture are needed to deepen our understanding of the development of cognitive deficits during the early course of schizophrenia. (Supported in part by: MH-060662, NARSAD; and MH60374)
CHANGES IN MORPHOLOGY OF THE T H A L A M U S OVER T I M E IN SUBJECTS W I T H NEUROLEPTIC N A I V E SCHIZOPHRENIA: EFFECTS O F NEUROLEPTIC T R E A T M E N T G. Cherascu,* E Nopoulos, N, C. Andreasen
Psychiatry, University of Iowa, Iowa City, IA, USA The thalamus is an important "node" in a circuit that is hypothesized to be abnormal in subjects with schizophrenia, the cortico-cerebellar-thalamic-cortical circuit (CCTCC). Many studies have found both
International Congress on Schizophrenia Research 2003
191
Luminance of isolated check stimuli was modulated sinusoidally at 12Hz against a constant background to elicit VEPs. In the M condition, low luminance contrast stimuli were used and in the P condition, stimuli were presented around a high contrast (48%) pedestal in order to deep modulation above the low contrast region. Fourier (frequency) analysis was used to extract the amplitude and phase of the response at the stimulus frequency and derive a signal-to-noise ratio. Patients showed significant decreases in fractional anisotropy (FA) and increases in mean diffusivity compared to controls in right and left OR and left IPL. Decreased FA indicates less coherence or integrity of white matter organization. Most of the patients were low functioning, and in this group, deficits were observed in both M and P VEP measures. With groups combined, significant correlations were found between M and P VEP measures and OR FA. These data indicate that primary visual deficits may be detectable using both structural and functional methods in SCZ. The results point to a reduction in integrity of projections from lateral geniculate nucleus to striate cortex in SCZ. Supported by Burroughs Wellcome Fund and RO1 MH49334.
PROGRESSIVE FOCAL GRAY MATTER DENSITY CHANGES IN SPEECH RELATED AREAS IN SCHIZOPHRENIA W. Cahn,* H. E. Hulshoff Pol, H. Schnack, R. C. Mandl, D. L. Collins, A. C. Evans, R. S. Kahn Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, Netherlands Introduction: Schizophrenia is considered to be a brain disorder that mainly affects the gray matter, with recent studies indicating that these changes may be progressive in nature. However, it is not known which brain areas are affected earlier in the disorder than others. Methods: In a one year follow-up study magnetic resonance imaging whole brain scans were obtained from thirty-four first-episode patients with schizophrenia and thirty-six matched healthy comparison subjects. Gray matter density was measured using voxel-based morphometry at base-line and at follow-up. Linear regression analysis was done for each voxel separately. Cumulative antipsychotic medication, clinical symptoms and outcome were related to the significant gray matter density changes. Results: At base-line no significant changes in gray matter density between the groups were found. At one-year follow-up gray matter density was significantly decreased in patients in the left and fight interior frontal gyrus (Broca) and in the right insula. Decreased left and right inferior frontal density were associated with clinical severity and/or outcome. Lower gray matter density in the right insula was associated with a greater amount of cumulative medication. Conclusion: Gray matter density decreases in schizophrenia one year after the first psychotic episode in distinct ~bcal areas of the brain, i.e. in the frontal and insular gyri. These progressive changes are related to disease severity and antipsychotic medication, suggesting that the progressive brain abnormalities in schizophrenia first become evident in speech related areas. Gray matter density ill first-episode schizophrenia at inclusion and after one year Blain A ~ a
Coordinates X
Icft in f,'liOl" frontal - 3 5
Glay [nattel density afte~ one year (T I )
Y
Z
t
Glay matter density at inchLsion (TO)
~
t
13
17
3
-5.41
-0.037
-I.56
0.01l
rightinferiorflontal
37
15
1
6.00
-0.053
1.32
-0015
right insula
37
3
5
5.36
11.(141
1.32
0.[110
MICROSTRUCTURAL WHITE MATTER CHANGES AS CORRELATES OF I M P A I R E D FRONTAL TASK PERFORMANCE IN FIRST EPISODE SCHIZOPHRENIA M. Carbon,* J. Bates, R. M. Bilder, K. O. Lira
Center for Neuroscience, North-Shore Long Island Research Institute, Manhasset, NY, USA The objective of the current study was to assess whether (i) changes of white matter microstructural integrity occur early in the course of schizophrenia, (ii) the neuropsychological decline in early schizophrenia is related to white matter changes. Thirteen first-episode schizophrenia (FE-SCZ) patients (age 23.8 +/- 3.7 years; 10 mate) and 10 age-matched control subjects (age 24.6 +/- 4.7 years; 7 male; t-test for age p=0.64) were scanned with diffusion-tensor magnetic resonance imaging (DTI-MRI) [1.5T GE]. White matter microstructural measures [fractional anisotropy (FA) and diffusivity (TR)] were calculated from these data. Bilateral regions of interest (ROI) were placed blind to subject state in the frontal white matter on six subsequent axial slices, separated by 5mm, starting at the level of the AC-PC line. Controls and FE-SCZ patients underwent neuropsychological testing within 1 month from the MRI scan date. Seven variables were selected as indices of frontal cortex function from a comprehensive neuropsychological test battery (Bilder et al. 2000), to assess correlations with the imaging measures. Data analysis revealed: t .) FA and TR in FE-SCZ did not differ from controls in 'all tested ROIs (p>0.3). No age correlation with white matter measures was noted. 2.) Patients performed worse than controls (p<0.05) on 5/7 frontal tasks. 3.) The following white matter changes were correlates of diminished cognitive performance: Decreased FA of the left inferior frontal white matter was associated with reduced verbal fluency (R2 =0.44, P= 0.001) and inCreased error rate on the Wisconsin Card Sorting Test (R2=0.34 p=0.04). In FE-SCZ patients, FA in the right centrum semiovale correlated inversely with performance time on the Trail Making Test B (R 2= 0.46 p=0.01) Age was excluded as a contributor to the brain-behavior correlations in a stepwise regression analysis. In contrast to prior studies of chronic schizophrenia (Buchsbanm et aL 1998, Lira et al. t999) no difference in white matter anisotropy or diffusivity was found in this first episode schizophrenia cohort compared to controls. However, subtle decreases in executive function and verbal fluency were related to reduced frontal white matter tract integrity. Further longitudinal studies of white matter microstrueture are needed to deepen our understanding of the development of cognitive deficits during the early course of schizophrenia. (Supported in part by: MH-060662, NARSAD; and MH60374)
CHANGES IN MORPHOLOGY OF THE T H A L A M U S OVER T I M E IN SUBJECTS W I T H NEUROLEPTIC N A I V E SCHIZOPHRENIA: EFFECTS O F NEUROLEPTIC T R E A T M E N T G. Cherascu,* E Nopoulos, N, C. Andreasen
Psychiatry, University of Iowa, Iowa City, IA, USA The thalamus is an important "node" in a circuit that is hypothesized to be abnormal in subjects with schizophrenia, the cortico-cerebellar-thalamic-cortical circuit (CCTCC). Many studies have found both
International Congress on Schizophrenia Research 2003