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Lack of progressive gray matter reduction of the superior temporal subregions in chronic schizophrenia
Schizophrenia Research 117 (2010) 101–102
Contents lists available at ScienceDirect
Schizophrenia Research j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / s c h r e s
Letter to the Editor Lack of progressive gray matter reduction of the superior temporal subregions in chronic schizophrenia
Dear Editors Although whether there are progressive brain changes in schizophrenia remains controversial (Borgwardt et al., 2009a), progressive volume reduction of the superior temporal gyrus (STG) has been reported during the early stages of the illness (Kasai et al., 2003; Takahashi et al., 2009b). However, the only region of interest (ROI) based longitudinal magnetic resonance imaging (MRI) study of this region in chronic schizophrenia found no such changes (Yoshida et al., 2009), suggesting a nonlinear pattern of STG reduction. We aimed to replicate this finding and further examine whether specific STG subregions show progressive changes in chronic schizophrenia. Eleven schizophrenia patients (10 males, mean age at baseline = 32.7 ± 7.6 years, mean illness duration = 12.0 ± 7.0 years) meeting Structured Clinical Interview for DSM-IV Disorders criteria (First et al., 1997) and 17 age-matched controls (12 males, mean age = 30.2±8.5 years) were recruited. Patients' symptoms were assessed using the Positive and Negative Syndrome Scale (Kay et al., 1987) at baseline and follow-up (where available). Nine [typical (n = 4) and atypical (n = 5), mean chlorpromazine equivalent dose = 492.5 ± 380.4 mg/day] and eight [typical (n = 4) and atypical (n = 4), 626.0 ± 560.7 mg/day] patients were taking antipsychotics at baseline and follow-up, respectively. Detailed clinical data have been described previously (Takahashi et al., 2009a). Participants were screened for co-morbid medical and psychiatric conditions by clinical assessment, physical and neurological examination. Exclusion criteria were a history of head injury, neurological diseases, impaired thyroid function, steroid use, or alcohol or substance abuse/ dependence. The local Ethics Committees approved this study and written informed consent was obtained for all participants. Subjects underwent MR imaging twice on a 1.5-T GE Signa scanner (GE, Milwaukee, Wisconsin); the patients (mean = 2.4 ± 1.0 years, range = 1.0–4.2) and controls (mean = 2.4 ± 1.1 years, range = 0.9–4.2) were matched for inter-scan interval. A 3D volumetric spoiled gradient recalled echo sequence generated 124 contiguous 1.5-mm coronal slices (TR = 14.3 ms, TE= 3.3 ms, Flip = 30°, FOV= 24× 24 cm, Matrix = 256 × 256, voxel dimension = 0.938 × 0.938 × 1.5 mm). Using the Dr. View software (AJS, Tokyo, Japan), the STG 0920-9964/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2009.12.034
subregions (planum polare, Heschl gyrus, planum temporale, rostral STG, and caudal STG) were traced on reconstructed contiguous coronal images, with a 0.938-mm thickness, perpendicular to the AC-PC line (Takahashi et al., 2009b). Intra- (TT) and inter-rater (TT and YK) intraclass correlation coefficients were N0.88 for all subregions. The absolute STG volume was analyzed using repeatedmeasures ANCOVA with age and intracranial volume (ICV) as covariates, diagnosis as a between-subject factor, and side and subregions as within-subject variables. The longitudinal STG change [100 × (absolute volume at follow-up − absolute volume at baseline) / absolute volume at baseline] was analyzed using the same ANCOVA model but with interscan interval, age at baseline, and ICV as covariates. Spearman's rho was calculated to examine relationships between the annual STG gray matter loss (% volume change/year) and clinical variables (illness duration, medication dosage, and PANSS subscale scores). The patients had a smaller STG compared with controls for both baseline [F (1, 24) = 9.34, p = 0.005] and follow-up [F (1, 24) = 9.99, p = 0.004], but no significant diagnosis-by-subregion interactions were found (Table 1). In the longitudinal comparison, there was no significant effect of diagnosis [diagnosis effect, F (1, 23) = 0.04, p = 0.852]. No significant correlations were found between the progressive STG changes and clinical variables. This longitudinal ROI analysis found no significant progressive volume changes in STG subregions in chronic schizophrenia compared to controls. In contrast, our previous study demonstrated left-sided gray matter reduction (2.6 to 6.6%/year) across most of these subregions during and after the onset of schizophrenic psychosis, which were correlated with severity of delusions (Takahashi et al., 2009b). While DeLisi and Hoff (2005) did not detect progressive STG changes in a 10-year follow-up of first-episode schizophrenia, detailed ROI analyses using high-resolution images by us and another group (Kasai et al., 2003; Yoshida et al., 2009) that directly compared longitudinal STG changes in first-episode and chronic patients suggest a period of intense gray matter reduction during early phases of schizophrenia, which could be a therapeutic target or outcome marker of the illness. Nevertheless, given the small sample sizes of these ROI studies, which could lead to inappropriate statistical models (e.g., too many variables), as well as a voxel-based finding in 96 chronic patients (mean illness duration = 10.95 years) over a 5 - year interval (van Haren et al., 2007), it is possible that chronic schizophrenia also exhibits STG reduction that
102
Letter to the Editor
Table 1 Absolute gray matter volume of the superior temporal sub-regions at baseline and second scan and annual percent change. Brain region
Control subjects (12 males, 5 females) Baseline
Whole gray matter Whole STG Left Right Planum polare Left Right Heschl gyrus Left Right Planum temporale Left Right Rostral STG Left Right Caudal STG Left Right
Schizophrenia patients (10 males, 1 female) % change/year
Baseline
Mean
SD
Second scan Mean
SD
Mean
SD
Mean
SD
Second scan Mean
SD
% change/year Mean
SD
706,325
97,770
672,676
92,698
− 2.4
2.0
652,888
83,707
618,298
79,245
− 1.9
2.7
13,091 11,855
2888 2735
13,001 11,673
3138 2642
− 0.5 − 0.1
2.2 2.9
11,281 9611
2467 1736
10,704 9455
2135 1980
− 1.6 − 0.8
3.7 3.9
1731 1635
448 501
1713 1604
447 474
− 0.1 0.2
3.7 4.5
1586 1324
333 320
1539 1306
326 272
− 0.4 − 0.5
4.2 7.3
2097 1539
750 464
2090 1509
790 477
− 0.7 − 0.4
3.1 5.7
2019 1428
450 481
1946 1396
412 487
− 1.4 − 1.2
3.4 4.7
3286 2959
943 1082
3274 2943
971 1070
− 0.6 0.8
1.7 3.8
2898 2319
910 603
2738 2259
817 651
− 1.6 − 0.9
4.9 5.6
1482 1350
676 636
1460 1308
689 572
− 1.1 − 0.7
2.9 4.0
1021 1053
317 355
999 1046
298 381
− 0.3 − 0.4
4.8 4.7
4448 4332
1235 1300
4440 4259
1332 1271
0.0 − 0.7
3.7 3.6
3677 3432
867 838
3455 3418
752 847
− 2.0 0.0
4.1 2.6
Values indicate absolute volumes (mm3) except % change/year values. STG, superior temporal gyrus. % change/year was calculated as follows: [100 × (absolute volume at follow-up − absolute volume at baseline) / absolute volume at baseline] / inter-scan interval. Negative value indicates decrease in volume.
exceeds the normal aging changes. Moreover, as antipsychotics may act regionally rather than globally on the brain changes including the STG region (Borgwardt et al., 2009b), future studies should evaluate the potential treatment effects on these progressive changes.
Yoshida, T., McCarley, R.W., Nakamura, M., Lee, K., Koo, M.S., Bouix, S., Salisbury, D.F., Morra, L., Shenton, M.E., Niznikiewicz, M.A., 2009. A prospective longitudinal volumetric MRI study of superior temporal gyrus gray matter and amygdala–hippocampal complex in chronic schizophrenia. Schizophr. Res. 113, 84–94.
References
Tsutomu Takahashi⁎ Stephen J. Wood Dennis Velakoulis Christos Pantelis Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Melbourne, Australia ⁎Corresponding author. Department of Neuropsychiatry, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Tel.: +81 76 434 2281; fax: +81 76 434 5030. E-mail address: [email protected] (T. Takahashi).
Borgwardt, S.J., Dickey, C., Hulshoff Pol, H., Whitford, T.J., DeLisi, L.E., 2009a. Workshop on defining the significance of progressive brain change in schizophrenia: December 12, 2008 American College of Neuropsychopharmacology (ACNP) all-day satellite, Scottsdale, Arizona: the rapporteurs' report. Schizophr. Res. 112, 32–45. Borgwardt, S.J., Riecher-Rössler, A., Smieskova, R., McGuire, P.K., Fusar-Poli, P., 2009b. Superior temporal gray and white matter changes in schizophrenia or antipsychotic related effects? Schizophr. Res. 113, 109–110. DeLisi, L.E., Hoff, A.L., 2005. Failure to find progressive temporal lobe volume decreases 10 years subsequent to a first episode of schizophrenia. Psychiatry Res. 138, 265–268. First, M.B., Spitzer, R.L., Gibbon, M., Williams, J.B., 1997. Structured Clinical Interview for DSM-IV Axis I Disorders. American Psychiatric Association, Washington, DC. Kasai, K., Shenton, M.E., Salisbury, D.F., Hirayasu, Y., Onitsuka, T., Spencer, M. H., Yurgelun-Todd, D.A., Kikinis, R., Jolesz, F.A., McCarley, R.W., 2003. Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Arch. Gen. Psychiatry 60, 766–775. Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull. 13, 261–276. Takahashi, T., Wood, S.J., Soulsby, B., McGorry, P.D., Tanino, R., Suzuki, M., Velakoulis, D., Pantelis, C., 2009a. Follow-up MRI study of the insular cortex in first-episode psychosis and chronic schizophrenia. Schizophr. Res. 108, 49–56. Takahashi, T., Wood, S.J., Yung, A.R., Soulsby, B., McGorry, P.D., Suzuki, M., Kawasaki, Y., Phillips, L.J., Velakoulis, D., Pantelis, C., 2009b. Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis. Arch. Gen. Psychiatry 66, 366–376. van Haren, N.E., Hulshoff Pol, H.E., Schnack, H.G., Cahn, W., Mandl, R.C., Collins, D.L., Evans, A.C., Kahn, R.S., 2007. Focal gray matter changes in schizophrenia across the course of the illness: a 5-year follow-up study. Neuropsychopharmacology 32, 2057–2066.
Tsutomu Takahashi Yasuhiro Kawasaki Michio Suzuki Department of Neuropsychiatry, The University of Toyama, Toyama, Japan Tsutomu Takahashi Yasuhiro Kawasaki Michio Suzuki Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo, Japan 16 September 2009
Contents lists available at ScienceDirect
Schizophrenia Research j o u r n a l h o m e p a g e : w w w. e l s e v i e r. c o m / l o c a t e / s c h r e s
Letter to the Editor Lack of progressive gray matter reduction of the superior temporal subregions in chronic schizophrenia
Dear Editors Although whether there are progressive brain changes in schizophrenia remains controversial (Borgwardt et al., 2009a), progressive volume reduction of the superior temporal gyrus (STG) has been reported during the early stages of the illness (Kasai et al., 2003; Takahashi et al., 2009b). However, the only region of interest (ROI) based longitudinal magnetic resonance imaging (MRI) study of this region in chronic schizophrenia found no such changes (Yoshida et al., 2009), suggesting a nonlinear pattern of STG reduction. We aimed to replicate this finding and further examine whether specific STG subregions show progressive changes in chronic schizophrenia. Eleven schizophrenia patients (10 males, mean age at baseline = 32.7 ± 7.6 years, mean illness duration = 12.0 ± 7.0 years) meeting Structured Clinical Interview for DSM-IV Disorders criteria (First et al., 1997) and 17 age-matched controls (12 males, mean age = 30.2±8.5 years) were recruited. Patients' symptoms were assessed using the Positive and Negative Syndrome Scale (Kay et al., 1987) at baseline and follow-up (where available). Nine [typical (n = 4) and atypical (n = 5), mean chlorpromazine equivalent dose = 492.5 ± 380.4 mg/day] and eight [typical (n = 4) and atypical (n = 4), 626.0 ± 560.7 mg/day] patients were taking antipsychotics at baseline and follow-up, respectively. Detailed clinical data have been described previously (Takahashi et al., 2009a). Participants were screened for co-morbid medical and psychiatric conditions by clinical assessment, physical and neurological examination. Exclusion criteria were a history of head injury, neurological diseases, impaired thyroid function, steroid use, or alcohol or substance abuse/ dependence. The local Ethics Committees approved this study and written informed consent was obtained for all participants. Subjects underwent MR imaging twice on a 1.5-T GE Signa scanner (GE, Milwaukee, Wisconsin); the patients (mean = 2.4 ± 1.0 years, range = 1.0–4.2) and controls (mean = 2.4 ± 1.1 years, range = 0.9–4.2) were matched for inter-scan interval. A 3D volumetric spoiled gradient recalled echo sequence generated 124 contiguous 1.5-mm coronal slices (TR = 14.3 ms, TE= 3.3 ms, Flip = 30°, FOV= 24× 24 cm, Matrix = 256 × 256, voxel dimension = 0.938 × 0.938 × 1.5 mm). Using the Dr. View software (AJS, Tokyo, Japan), the STG 0920-9964/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2009.12.034
subregions (planum polare, Heschl gyrus, planum temporale, rostral STG, and caudal STG) were traced on reconstructed contiguous coronal images, with a 0.938-mm thickness, perpendicular to the AC-PC line (Takahashi et al., 2009b). Intra- (TT) and inter-rater (TT and YK) intraclass correlation coefficients were N0.88 for all subregions. The absolute STG volume was analyzed using repeatedmeasures ANCOVA with age and intracranial volume (ICV) as covariates, diagnosis as a between-subject factor, and side and subregions as within-subject variables. The longitudinal STG change [100 × (absolute volume at follow-up − absolute volume at baseline) / absolute volume at baseline] was analyzed using the same ANCOVA model but with interscan interval, age at baseline, and ICV as covariates. Spearman's rho was calculated to examine relationships between the annual STG gray matter loss (% volume change/year) and clinical variables (illness duration, medication dosage, and PANSS subscale scores). The patients had a smaller STG compared with controls for both baseline [F (1, 24) = 9.34, p = 0.005] and follow-up [F (1, 24) = 9.99, p = 0.004], but no significant diagnosis-by-subregion interactions were found (Table 1). In the longitudinal comparison, there was no significant effect of diagnosis [diagnosis effect, F (1, 23) = 0.04, p = 0.852]. No significant correlations were found between the progressive STG changes and clinical variables. This longitudinal ROI analysis found no significant progressive volume changes in STG subregions in chronic schizophrenia compared to controls. In contrast, our previous study demonstrated left-sided gray matter reduction (2.6 to 6.6%/year) across most of these subregions during and after the onset of schizophrenic psychosis, which were correlated with severity of delusions (Takahashi et al., 2009b). While DeLisi and Hoff (2005) did not detect progressive STG changes in a 10-year follow-up of first-episode schizophrenia, detailed ROI analyses using high-resolution images by us and another group (Kasai et al., 2003; Yoshida et al., 2009) that directly compared longitudinal STG changes in first-episode and chronic patients suggest a period of intense gray matter reduction during early phases of schizophrenia, which could be a therapeutic target or outcome marker of the illness. Nevertheless, given the small sample sizes of these ROI studies, which could lead to inappropriate statistical models (e.g., too many variables), as well as a voxel-based finding in 96 chronic patients (mean illness duration = 10.95 years) over a 5 - year interval (van Haren et al., 2007), it is possible that chronic schizophrenia also exhibits STG reduction that
102
Letter to the Editor
Table 1 Absolute gray matter volume of the superior temporal sub-regions at baseline and second scan and annual percent change. Brain region
Control subjects (12 males, 5 females) Baseline
Whole gray matter Whole STG Left Right Planum polare Left Right Heschl gyrus Left Right Planum temporale Left Right Rostral STG Left Right Caudal STG Left Right
Schizophrenia patients (10 males, 1 female) % change/year
Baseline
Mean
SD
Second scan Mean
SD
Mean
SD
Mean
SD
Second scan Mean
SD
% change/year Mean
SD
706,325
97,770
672,676
92,698
− 2.4
2.0
652,888
83,707
618,298
79,245
− 1.9
2.7
13,091 11,855
2888 2735
13,001 11,673
3138 2642
− 0.5 − 0.1
2.2 2.9
11,281 9611
2467 1736
10,704 9455
2135 1980
− 1.6 − 0.8
3.7 3.9
1731 1635
448 501
1713 1604
447 474
− 0.1 0.2
3.7 4.5
1586 1324
333 320
1539 1306
326 272
− 0.4 − 0.5
4.2 7.3
2097 1539
750 464
2090 1509
790 477
− 0.7 − 0.4
3.1 5.7
2019 1428
450 481
1946 1396
412 487
− 1.4 − 1.2
3.4 4.7
3286 2959
943 1082
3274 2943
971 1070
− 0.6 0.8
1.7 3.8
2898 2319
910 603
2738 2259
817 651
− 1.6 − 0.9
4.9 5.6
1482 1350
676 636
1460 1308
689 572
− 1.1 − 0.7
2.9 4.0
1021 1053
317 355
999 1046
298 381
− 0.3 − 0.4
4.8 4.7
4448 4332
1235 1300
4440 4259
1332 1271
0.0 − 0.7
3.7 3.6
3677 3432
867 838
3455 3418
752 847
− 2.0 0.0
4.1 2.6
Values indicate absolute volumes (mm3) except % change/year values. STG, superior temporal gyrus. % change/year was calculated as follows: [100 × (absolute volume at follow-up − absolute volume at baseline) / absolute volume at baseline] / inter-scan interval. Negative value indicates decrease in volume.
exceeds the normal aging changes. Moreover, as antipsychotics may act regionally rather than globally on the brain changes including the STG region (Borgwardt et al., 2009b), future studies should evaluate the potential treatment effects on these progressive changes.
Yoshida, T., McCarley, R.W., Nakamura, M., Lee, K., Koo, M.S., Bouix, S., Salisbury, D.F., Morra, L., Shenton, M.E., Niznikiewicz, M.A., 2009. A prospective longitudinal volumetric MRI study of superior temporal gyrus gray matter and amygdala–hippocampal complex in chronic schizophrenia. Schizophr. Res. 113, 84–94.
References
Tsutomu Takahashi⁎ Stephen J. Wood Dennis Velakoulis Christos Pantelis Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Melbourne, Australia ⁎Corresponding author. Department of Neuropsychiatry, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Tel.: +81 76 434 2281; fax: +81 76 434 5030. E-mail address: [email protected] (T. Takahashi).
Borgwardt, S.J., Dickey, C., Hulshoff Pol, H., Whitford, T.J., DeLisi, L.E., 2009a. Workshop on defining the significance of progressive brain change in schizophrenia: December 12, 2008 American College of Neuropsychopharmacology (ACNP) all-day satellite, Scottsdale, Arizona: the rapporteurs' report. Schizophr. Res. 112, 32–45. Borgwardt, S.J., Riecher-Rössler, A., Smieskova, R., McGuire, P.K., Fusar-Poli, P., 2009b. Superior temporal gray and white matter changes in schizophrenia or antipsychotic related effects? Schizophr. Res. 113, 109–110. DeLisi, L.E., Hoff, A.L., 2005. Failure to find progressive temporal lobe volume decreases 10 years subsequent to a first episode of schizophrenia. Psychiatry Res. 138, 265–268. First, M.B., Spitzer, R.L., Gibbon, M., Williams, J.B., 1997. Structured Clinical Interview for DSM-IV Axis I Disorders. American Psychiatric Association, Washington, DC. Kasai, K., Shenton, M.E., Salisbury, D.F., Hirayasu, Y., Onitsuka, T., Spencer, M. H., Yurgelun-Todd, D.A., Kikinis, R., Jolesz, F.A., McCarley, R.W., 2003. Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Arch. Gen. Psychiatry 60, 766–775. Kay, S.R., Fiszbein, A., Opler, L.A., 1987. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr. Bull. 13, 261–276. Takahashi, T., Wood, S.J., Soulsby, B., McGorry, P.D., Tanino, R., Suzuki, M., Velakoulis, D., Pantelis, C., 2009a. Follow-up MRI study of the insular cortex in first-episode psychosis and chronic schizophrenia. Schizophr. Res. 108, 49–56. Takahashi, T., Wood, S.J., Yung, A.R., Soulsby, B., McGorry, P.D., Suzuki, M., Kawasaki, Y., Phillips, L.J., Velakoulis, D., Pantelis, C., 2009b. Progressive gray matter reduction of the superior temporal gyrus during transition to psychosis. Arch. Gen. Psychiatry 66, 366–376. van Haren, N.E., Hulshoff Pol, H.E., Schnack, H.G., Cahn, W., Mandl, R.C., Collins, D.L., Evans, A.C., Kahn, R.S., 2007. Focal gray matter changes in schizophrenia across the course of the illness: a 5-year follow-up study. Neuropsychopharmacology 32, 2057–2066.
Tsutomu Takahashi Yasuhiro Kawasaki Michio Suzuki Department of Neuropsychiatry, The University of Toyama, Toyama, Japan Tsutomu Takahashi Yasuhiro Kawasaki Michio Suzuki Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo, Japan 16 September 2009