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Brain volume reductions in medication-naive patients with schizophrenia in relation to intelligence quotient

Published online by Cambridge University Press:  23 February 2012

M. Rais
Affiliation:
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands
W. Cahn
Affiliation:
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands
H. G. Schnack
Affiliation:
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands
H. E. Hulshoff Pol
Affiliation:
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands
R. S. Kahn
Affiliation:
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands
N. E. M. van Haren*
Affiliation:
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands
*
*Address for correspondence: N. E. M. van Haren, Ph.D., Department of Psychiatry A.01.126, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. (Email: N.E.M.vanHaren@umcutrecht.nl)

Abstract

Background

Global brain abnormalities such as brain volume loss and grey- and white-matter deficits are consistently reported in first-episode schizophrenia patients and may already be detectable in the very early stages of the illness. Whether these changes are dependent on medication use or related to intelligence quotient (IQ) is still debated.

Method

Magnetic resonance imaging scans were obtained for 20 medication-naive patients with first-episode schizophrenia and 26 matched healthy subjects. Volume measures of total brain grey and white matter, third and lateral ventricles and cortical thickness/surface were obtained. Differences between the groups were investigated, taking into account the effect of intelligence.

Results

Medication-naive patients showed statistically significant reductions in whole-brain volume and cerebral grey- and white-matter volume together with lateral ventricle enlargement compared to healthy subjects. IQ was significantly lower in patients compared to controls and was positively associated with brain and white-matter volume in the whole group. No significant differences in cortical thickness were found between the groups but medication-naive patients had a significantly smaller surface in the left superior temporal pole, Heschl's gyrus and insula compared to controls.

Conclusions

Our findings suggest that brain volume loss is present at illness onset, and can be explained by the reduced surface of the temporal and insular cortex. These abnormalities are not related to medication, but IQ.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2012

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References

Andreasen, NC, Flaum, M, Arndt, S (1992). The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. Archives of General Psychiatry 49, 615623.CrossRefGoogle ScholarPubMed
Andreasen, NC, Flaum, M, Swayze, V, O'Leary, DS, Alliger, R, Cohen, G, Ehrhardt, J, Yuh, WT (1993). Intelligence and brain structure in normal individuals. American Journal of Psychiatry 150, 130134.Google ScholarPubMed
Antonova, E, Kumari, V, Morris, R, Halari, R, Anilkumar, A, Mehrotra, R, Sharma, T (2005). The relationship of structural alterations to cognitive deficits in schizophrenia: a voxel-based morphometry study. Biological Psychiatry 58, 457467.CrossRefGoogle ScholarPubMed
Antonova, E, Sharma, T, Morris, R, Kumari, V (2004). The relationship between brain structure and neurocognition in schizophrenia: a selective review. Schizophrenia Research 70, 117145.CrossRefGoogle ScholarPubMed
Baare, WF, Hulshoff Pol, HE, Hijman, R, Mali, WP, Viergever, MA, Kahn, RS (1999). Volumetric analysis of frontal lobe regions in schizophrenia: relation to cognitive function and symptomatology. Biological Psychiatry 45, 15971605.CrossRefGoogle ScholarPubMed
Borgwardt, SJ, Riecher-Rossler, A, Dazzan, P, Chitnis, X, Aston, J, Drewe, M, Gschwandtner, U, Haller, S, Pflüger, M, Rechsteiner, E, D'Souza, M, Stieglitz, RD, Radü, EW, McGuire, PK (2007). Regional gray matter volume abnormalities in the at risk mental state. Biological Psychiatry 61, 11481156.CrossRefGoogle ScholarPubMed
Brouwer, RM, Hulshoff Pol, HE, Schnack, HG (2010). Segmentation of MRI brain scans using non-uniform partial volume densities. Neuroimage 49, 467477.CrossRefGoogle ScholarPubMed
Cahn, W, Hulshoff Pol, HE, Bongers, M, Schnack, HG, Mandl, RC, van Haren, NE, Durston, S, Koning, H, van der Linden, JA, Kahn, RS (2002). Brain morphology in antipsychotic-naive schizophrenia: a study of multiple brain structures. British Journal of Psychiatry Supplement 43, s66s72.CrossRefGoogle ScholarPubMed
Cahn, W, Rais, M, Stigter, FP, van Haren, NE, Caspers, E, Hulshoff Pol, HE, Xu, Z, Schnack, HG, Kahn, RS (2009). Psychosis and brain volume changes during the first five years of schizophrenia. European Neuropsychopharmacology 19, 147151.CrossRefGoogle ScholarPubMed
Chua, SE, Cheung, C, Cheung, V, Tsang, JT, Chen, EY, Wong, JC, Cheung, JPY, Yip, L, Tai, K, Suckling, J (2007). Cerebral grey, white matter and csf in never-medicated, first-episode schizophrenia. Schizophrenia Research 89, 1221.CrossRefGoogle ScholarPubMed
Corson, PW, Nopoulos, P, Andreasen, NC, Heckel, D, Arndt, S (1999). Caudate size in first-episode neuroleptic-naive schizophrenic patients measured using an artificial neural network. Biological Psychiatry 46, 712720.CrossRefGoogle ScholarPubMed
Dorph-Petersen, KA, Pierri, JN, Perel, JM, Sun, Z, Sampson, AR, Lewis, DA (2005). The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychopharmacology 30, 16491661.CrossRefGoogle ScholarPubMed
Ebdrup, BH, Glenthoj, B, Rasmussen, H, Aggernaes, B, Langkilde, AR, Paulson, OB, Lublin, H, Skimminge, A, Baaré, W (2010). Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia. Journal of Psychiatry and Neuroscience 35, 95–104.CrossRefGoogle ScholarPubMed
Eyler, LT, Prom-Wormley, E, Panizzon, MS, Kaup, AR, Fennema-Notestine, C, Neale, MC, Jernigan, TL, Fischl, B, Franz, CE, Lyons, MJ, Grant, M, Stevens, A, Pacheco, J, Perry, ME, Schmitt, JE, Seidman, LJ, Thermenos, HW, Tsuang, MT, Chen, CH, Thompson, WK, Jak, A, Dale, AM, Kremen, WS (2011). Genetic and environmental contributions to regional cortical surface area in humans: a magnetic resonance imaging twin study. Cerebral Cortex 21, 23132321.CrossRefGoogle ScholarPubMed
Fornito, A, Yucel, M, Wood, SJ, Adamson, C, Velakoulis, D, Saling, MM, McGorry, PD, Pantelis, C (2008). Surface-based morphometry of the anterior cingulate cortex in first episode schizophrenia. Human Brain Mapping 29, 478489.CrossRefGoogle ScholarPubMed
Gur, RE, Maany, V, Mozley, PD, Swanson, C, Bilker, W, Gur, RC (1998). Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia. American Journal of Psychiatry 155, 17111717.CrossRefGoogle ScholarPubMed
Gutiérrez-Galve, L, Wheeler-Kingshott, CA, Altmann, DR, Price, G, Chu, EM, Leeson, VC, Lobo, A, Barker, GJ, Barnes, TR, Joyce, EM, Ron, MA (2010). Changes in the frontotemporal cortex and cognitive correlates in first-episode psychosis. Biological Psychiatry 68, 5160.CrossRefGoogle ScholarPubMed
Joyal, CC, Laakso, MP, Tiihonen, J, Syvalahti, E, Vilkman, H, Laakso, A, Alakare, B, Räkköläinen, V, Salokangas, RK, Hietala, J (2002). A volumetric MRI study of the entorhinal cortex in first episode neuroleptic-naive schizophrenia. Biological Psychiatry 51, 10051007.CrossRefGoogle ScholarPubMed
Joyal, CC, Laakso, MP, Tiihonen, J, Syvalahti, E, Vilkman, H, Laakso, A, Alakare, B, Räkköläinen, V, Salokangas, RK, Hietala, J (2003). The amygdala and schizophrenia: a volumetric magnetic resonance imaging study in first-episode, neuroleptic-naive patients. Biological Psychiatry 54, 13021304.CrossRefGoogle ScholarPubMed
Kabani, N, Le Goualher, G, MacDonald, D, Evans, AC (2001). Measurement of cortical thickness using an automated 3-D algorithm: a validation study. Neuroimage 13, 375380.CrossRefGoogle ScholarPubMed
Kay, SR, Fiszbein, A, Opler, LA (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261276.CrossRefGoogle ScholarPubMed
Keshavan, MS, Diwadkar, VA, Harenski, K, Rosenberg, DR, Sweeney, JA, Pettegrew, JW (2002). Abnormalities of the corpus callosum in first episode, treatment naive schizophrenia. Journal of Neurology, Neurosurgery and Psychiatry 72, 757760.CrossRefGoogle ScholarPubMed
Keshavan, MS, Rosenberg, D, Sweeney, JA, Pettegrew, JW (1998). Decreased caudate volume in neuroleptic-naive psychotic patients. American Journal of Psychiatry 155, 774778.Google ScholarPubMed
Kim, JS, Singh, V, Lee, JK, Lerch, J, Ad-Dab'bagh, Y, MacDonald, D, Lee, JM, Kim, SI, Evans, AC (2005). Automated 3-D extraction and evaluation of the inner and outer cortical surfaces using a Laplacian map and partial volume effect classification. Neuroimage 27, 210221.CrossRefGoogle ScholarPubMed
Lyttelton, O, Boucher, M, Robbins, S, Evans, A (2007). An unbiased iterative group registration template for cortical surface analysis. Neuroimage 34, 15351544.CrossRefGoogle ScholarPubMed
MacDonald, D, Kabani, N, Avis, D, Evans, AC (2000). Automated 3-D extraction of inner and outer surfaces of cerebral cortex from MRI. Neuroimage 12, 340356.CrossRefGoogle ScholarPubMed
Maes, F, Collignon, A, Vandermeulen, D, Marchal, G, Suetens, P (1997). Multimodality image registration by maximization of mutual information. IEEE Transactions on Medical Imaging 16, 187198.CrossRefGoogle ScholarPubMed
Moncrieff, J, Leo, J (2010). A systematic review of the effects of antipsychotic drugs on brain volume. Psychological Medicine 40, 14091422.CrossRefGoogle ScholarPubMed
Narr, KL, Bilder, RM, Toga, AW, Woods, RP, Rex, DE, Szeszko, PR, Robinson, D, Sevy, S, Gunduz-Bruce, H, Wang, YP, DeLuca, H, Thompson, PM (2005 a). Mapping cortical thickness and gray matter concentration in first episode schizophrenia. Cerebral Cortex 15, 708719.CrossRefGoogle ScholarPubMed
Narr, KL, Toga, AW, Szeszko, P, Thompson, PM, Woods, RP, Robinson, D, Sevy, S, Wang, Y, Schrock, K, Bilder, RM (2005 b). Cortical thinning in cingulate and occipital cortices in first episode schizophrenia. Biological Psychiatry 58, 3240.CrossRefGoogle ScholarPubMed
Narr, KL, Woods, RP, Thompson, PM, Szeszko, P, Robinson, D, Dimtcheva, T, Gurbani, M, Toga, AW, Bilder, RM (2007). Relationships between IQ and regional cortical gray matter thickness in healthy adults. Cerebral Cortex 17, 21632171.CrossRefGoogle ScholarPubMed
Navari, S, Dazzan, P (2009). Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings. Psychological Medicine 39, 17631777.CrossRefGoogle ScholarPubMed
Panizzon, MS, Fennema-Notestine, C, Eyler, LT, Jernigan, TL, Prom-Wormley, E, Neale, M, Jacobson, K, Lyons, MJ, Grant, MD, Franz, CE, Xian, H, Tsuang, M, Fischl, B, Seidman, L, Dale, A, Kremen, WS (2009). Distinct genetic influences on cortical surface area and cortical thickness. Cerebral Cortex 19, 27282735.CrossRefGoogle ScholarPubMed
Pantelis, C, Velakoulis, D, McGorry, PD, Wood, SJ, Suckling, J, Phillips, LJ, Yung, AR, Bullmore, ET, Brewer, W, Soulsby, B, Desmond, P, McGuire, PK (2003). Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 361, 281288.CrossRefGoogle ScholarPubMed
Pantelis, C, Yucel, M, Wood, SJ, Velakoulis, D, Sun, D, Berger, G, Stuart, GW, Yung, A, Phillips, L, McGorry, PD (2005). Structural brain imaging evidence for multiple pathological processes at different stages of brain development in schizophrenia. Schizophrenia Bulletin 31, 672696.CrossRefGoogle ScholarPubMed
Peper, JS, Brouwer, RM, Schnack, HG, van Baal, GC, van Leeuwen, M, van den Berg, SM, Delemarre-Van de Waal, HA, Janke, AL, Collins, DL, Evans, AC, Boomsma, DI, Kahn, RS, Hulshoff Pol, HE (2008). Cerebral white matter in early puberty is associated with luteinizing hormone concentrations. Psychoneuroendocrinology 33, 909915.CrossRefGoogle ScholarPubMed
Posthuma, D, De Geus, EJ, Baare, WF, Hulshoff Pol, HE, Kahn, RS, Boomsma, DI (2002). The association between brain volume and intelligence is of genetic origin. Nature Neuroscience 5, 8384.CrossRefGoogle ScholarPubMed
Prasad, KM, Goradia, D, Eack, S, Rajagopalan, M, Nutche, J, Magge, T, Rajarethinam, R, Keshavan, MS (2010). Cortical surface characteristics among offspring of schizophrenia subjects. Schizophrenia Research 116, 143151.CrossRefGoogle ScholarPubMed
Prasad, KM, Patel, AR, Muddasani, S, Sweeney, J, Keshavan, MS (2004 a). The entorhinal cortex in first-episode psychotic disorders: a structural magnetic resonance imaging study. American Journal of Psychiatry 161, 16121619.CrossRefGoogle ScholarPubMed
Prasad, KM, Rohm, BR, Keshavan, MS (2004 b). Parahippocampal gyrus in first episode psychotic disorders: a structural magnetic resonance imaging study. Progress in Neuropsychopharmacology and Biological Psychiatry 28, 651658.CrossRefGoogle ScholarPubMed
Rais, M, van Haren, NE, Cahn, W, Schnack, HG, Lepage, C, Collins, L, Evans, AC, Hulshoff Pol, HE, Kahn, RS (2010). Cannabis use and progressive cortical thickness loss in areas rich in CB1 receptors during the first five years of schizophrenia. European Neuropsychopharmacology 20, 855865.CrossRefGoogle Scholar
Rajput, S, Hassiotis, A, Richards, M, Hatch, SL, Stewart, R (2011). Associations between IQ and common mental disorders: the 2000 British National Survey of Psychiatric Morbidity. European Psychiatry 26, 390395.CrossRefGoogle ScholarPubMed
Rakic, P (1988). Specification of cerebral cortical areas. Science 241, 170176.CrossRefGoogle ScholarPubMed
Reichenberg, A, Caspi, A, Harrington, H, Houts, R, Keefe, RS, Murray, RM, Poulton, R, Moffit, TE (2010). Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: a 30-year study. American Journal of Psychiatry 167, 160169.CrossRefGoogle ScholarPubMed
Robins, LN, Wing, J, Wittchen, HU, Helzer, JE, Babor, TF, Burke, J, Farmer, A, Jablenski, A, Pickens, R, Regier, DA, Sartorius, N, Towle, LH (1988). The Composite International Diagnostic Interview. An epidemiologic instrument suitable for use in conjunction with different diagnostic systems and in different cultures. Archives of General Psychiatry 45, 10691077.CrossRefGoogle ScholarPubMed
Roiz-Santianez, R, Perez-Iglesias, R, Quintero, C, Tordesillas-Gutierrez, D, Mata, I, Ayesa, R, Sánchez, JM, Gutiérrez, A, Sanchez, E, Vázquez-Barquero, JL, Crespo-Facorro, B (2010). Insular cortex thinning in first episode schizophrenia patients. Psychiatry Research 182, 216222.CrossRefGoogle ScholarPubMed
Schnack, HG, Hulshoff, HE, Baare, WF, Viergever, MA, Kahn, RS (2001). Automatic segmentation of the ventricular system from MR images of the human brain. Neuroimage 14, 95–104.CrossRefGoogle ScholarPubMed
Schultz, CC, Koch, K, Wagner, G, Roebel, M, Schachtzabel, C, Gaser, C, Nenadic, I, Reichenbach, JR, Sauer, H, Schlösser, RG (2010). Reduced cortical thickness in first episode schizophrenia. Schizophrenia Research 116, 204209.CrossRefGoogle ScholarPubMed
Sled, JG, Zijdenbos, AP, Evans, AC (1998). A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Transactions on Medical Imaging 17, 8797.CrossRefGoogle ScholarPubMed
Smieskova, R, Fusar-Poli, P, Allen, P, Bendfeldt, K, Stieglitz, RD, Drewe, J, Radue, EW, McGuire, PK, Riecher-Rössler, A, Borgwardt, SJ (2010). Neuroimaging predictors of transition to psychosis – a systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews 34, 12071222.CrossRefGoogle ScholarPubMed
Steen, RG, Mull, C, McClure, R, Hamer, RM, Lieberman, JA (2006). Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies. British Journal of Psychiatry 188, 510518.CrossRefGoogle ScholarPubMed
Toulopoulou, T, Grech, A, Morris, RG, Schulze, K, McDonald, C, Chapple, B, Rabe-Hesketh, S, Murray, RM (2004). The relationship between volumetric brain changes and cognitive function: a family study on schizophrenia. Biological Psychiatry 56, 447453.CrossRefGoogle Scholar
Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, Crivello, F, Etard, O, Delcroix, N, Mazoyer, B, Joliot, M (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15, 273289.CrossRefGoogle ScholarPubMed
Upadhyaya, AR, El-Sheikh, R, MacMaster, FP, Diwadkar, VA, Keshavan, MS (2007). Pituitary volume in neuroleptic-naive schizophrenia: a structural MRI study. Schizophrenia Research 90, 266273.CrossRefGoogle ScholarPubMed
van Haren, NE, Schnack, HG, Cahn, W, van den Heuvel, MP, Lepage, C, Collins, L, Evans, AC, Hulshoff Pol, HE, Kahn, RS (2011). Changes in cortical thickness during the course of illness in schizophrenia. Archives of General Psychiatry 68, 871880.CrossRefGoogle ScholarPubMed
van Oel, CJ, Sitskoorn, MM, Cremer, MP, Kahn, RS (2002). School performance as a premorbid marker for schizophrenia: a twin study. Schizophrenia Bulletin 28, 401414.CrossRefGoogle ScholarPubMed
Venkatasubramanian, G, Jayakumar, PN, Gangadhar, BN, Keshavan, MS (2008). Automated MRI parcellation study of regional volume and thickness of prefrontal cortex (PFC) in antipsychotic-naive schizophrenia. Acta Psychiatrica Scandinavica 117, 420431.CrossRefGoogle ScholarPubMed
Vita, A, de Peri, L, Silenzi, C, Dieci, M (2006). Brain morphology in first-episode schizophrenia: a meta-analysis of quantitative magnetic resonance imaging studies. Schizophrenia Research 82, 7588.CrossRefGoogle ScholarPubMed
Walterfang, M, McGuire, PK, Yung, AR, Phillips, LJ, Velakoulis, D, Wood, SJ, Suckling, J, Bullmore, ET, Brewer, W, Soulsby, B, Desmond, P, McGorry, PD, Pantelis, C (2008). White matter volume changes in people who develop psychosis. British Journal of Psychiatry 193, 210215.CrossRefGoogle ScholarPubMed
Winkler, AM, Kochunov, P, Blangero, J, Almasy, L, Zilles, K, Fox, PT, Duggirala, R, Glahn, DC (2010). Cortical thickness or grey matter volume? The importance of selecting the phenotype for imaging genetics studies. Neuroimage 53, 11351146.CrossRefGoogle ScholarPubMed
Woodberry, KA, Giuliano, AJ, Seidman, LJ (2008). Premorbid IQ in schizophrenia: a meta-analytic review. American Journal of Psychiatry 165, 579587.CrossRefGoogle ScholarPubMed
Ziermans, TB, Schothorst, PF, Schnack, HG, Koolschijn, PC, Kahn, RS, van Engeland, H, Durston, S (2010). Progressive structural brain changes during development of psychosis. Schizophrenia Bulletin. Published online 7 October 2010. doi:10.1093/schbul/sbq113.Google ScholarPubMed