Hostname: page-component-586b7cd67f-r5fsc Total loading time: 0 Render date: 2024-11-22T14:49:58.516Z Has data issue: false hasContentIssue false
  • English
  • Français

Brain morphometry of individuals with schizophrenia with and without antipsychotic medication – The Northern Finland Birth Cohort 1966 Study

Published online by Cambridge University Press:  15 April 2020

J. Moilanen ,
S. Huhtaniska ,
M. Haapea ,
E. Jääskeläinen ,
J. Veijola ,
M. Isohanni ,
H. Koponen  and
J. Miettunen
J. Moilanen*
Affiliation:
Institute of Clinical Medicine, Department of Psychiatry, University of Oulu and Oulu University Hospital, P.O. Box 5000 90014Oulu, Finland Medical Research Center Oulu, University of Oulu and Oulu University Hospital, P.O. Box 5000 90014Oulu, Finland
S. Huhtaniska
Affiliation:
Institute of Clinical Medicine, Department of Psychiatry, University of Oulu and Oulu University Hospital, P.O. Box 5000 90014Oulu, Finland Medical Research Center Oulu, University of Oulu and Oulu University Hospital, P.O. Box 5000 90014Oulu, Finland
M. Haapea
Affiliation:
Institute of Clinical Medicine, Department of Psychiatry, University of Oulu and Oulu University Hospital, P.O. Box 5000 90014Oulu, Finland Medical Research Center Oulu, University of Oulu and Oulu University Hospital, P.O. Box 5000 90014Oulu, Finland Department of Diagnostic Radiology, Oulu University Hospital, P.O. Box 5000 90014Oulu, Finland
E. Jääskeläinen
Affiliation:
Medical Research Center Oulu, University of Oulu and Oulu University Hospital, P.O. Box 5000 90014Oulu, Finland Institute of Health Sciences, University of Oulu, P.O. Box 5000 90014Oulu, Finland
J. Veijola
Affiliation:
Institute of Clinical Medicine, Department of Psychiatry, University of Oulu and Oulu University Hospital, P.O. Box 5000 90014Oulu, Finland Medical Research Center Oulu, University of Oulu and Oulu University Hospital, P.O. Box 5000 90014Oulu, Finland
M. Isohanni
Affiliation:
Institute of Clinical Medicine, Department of Psychiatry, University of Oulu and Oulu University Hospital, P.O. Box 5000 90014Oulu, Finland
H. Koponen
Affiliation:
University of Helsinki and Helsinki University Hospital, Psychiatry, P.O. Box 22 00014Helsinki, Finland
J. Miettunen
Affiliation:
Institute of Clinical Medicine, Department of Psychiatry, University of Oulu and Oulu University Hospital, P.O. Box 5000 90014Oulu, Finland Medical Research Center Oulu, University of Oulu and Oulu University Hospital, P.O. Box 5000 90014Oulu, Finland Institute of Health Sciences, University of Oulu, P.O. Box 5000 90014Oulu, Finland
*
⁎Corresponding author. Institute of Clinical Medicine, Department of Psychiatry, University of Oulu and Oulu University Hospital, P.O. BOX 5000, 90014 Oulu, Finland. Tel.: +358 440690706; fax: +358 8 336169. E-mail address:[email protected] (J. Moilanen).
Get access

Abstract

Background

In schizophrenia, brain morphometric changes may be associated with antipsychotic medication. Only limited data is available concerning individuals with schizophrenia without antipsychotic medication. We aimed to study the associations of: use versus no use of antipsychotic medication; length of continuous time without antipsychotic medication; cumulative dose of lifetime antipsychotic medication; and type of antipsychotic medication; with brain morphometry in schizophrenia after an average of 10 years of illness.

Methods

Data of 63 individuals with schizophrenia (mean duration of illness 10.4 years) from the Northern Finland Birth Cohort 1966 were gathered by interview and from hospital and outpatient records. Structural MRI data at age 34 years were acquired and grey matter volume maps with voxel-based morphometry were analyzed using FSL tools.

Results

Of the individuals studied, 15 (24%) had taken no antipsychotic medication during the previous year. Individuals with antipsychotic medication had lower total grey matter (TGM) volume compared with non-medicated subjects, although this association was not statistically significant (Cohen's d = –0.51, P = 0.078). Time without antipsychotic medication associated with increased TGM (P = 0.028). Longer time without antipsychotic medication associated with increased regional volume in right precentral gyrus and right middle frontal gyrus. There were no associations between cumulative dose of lifetime antipsychotic medication or type of antipsychotic medication and brain morphometry.

Conclusions

Unlike some previous investigators, we found no association between cumulative dose of lifetime antipsychotic medication and brain morphological changes in this population-based sample. However, longer continuous time without antipsychotic medication preceding the MRI scan associated with increased gray matter volume.

Keywords

AntipsychoticsMedicatedNon-medicatedMRISchizophrenia
Type
Original article
Information
European Psychiatry , Volume 30 , Issue 5 , July 2015 , pp. 598 - 605
Copyright
Copyright © Elsevier Masson SAS 2015

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Ahuja, N.Antipsychotic drugs. In: Vyas, A.J., Ahuja, N. editors. Textbook of Postgraduate Psychiatry Jaypee Brothers Medical Publishers (P) Ltd; 1999. p.737–752.Google Scholar
Andersson, J.L.R., Jenkinson, M., Smith, S.Non-linear optimisation. 2007, FMRIB technical report TR07JA1 from http://www.fmrib.ox.ac.uk/analysis/techrep.Google Scholar
Andersson, J.L.R., Jenkinson, M., Smith, S.Non-linear registration, aka spatial normalisation. 2007, FMRIB technical report TR07JA2 from http://www.fmrib.ox.ac.uk/analysis/techrep.Google Scholar
Andreasen, N.C., Carpenter, W.T., Kane, J.M., Lasser, R.A., Marder, S.R., Weinberger, D.R.. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry 2005;162:441–449.CrossRefGoogle ScholarPubMed
Andreasen, N.C., Nopoulos, P., Magnotta, V., Pierson, R., Ziebell, S., Ho, B.C.. Progressive brain change in schizophrenia: a prospective longitudinal study of first-episode schizophrenia. Biol Psychiatry 2011;70(7):672–679.CrossRefGoogle ScholarPubMed
Artigas, F.. The prefrontal cortex: a target for antipsychotic drugs. Acta Psychiatr Scand 2010;121(1):11–21.CrossRefGoogle ScholarPubMed
Ashburner, J., Friston, K.J.. Voxel-based morphometry – the methods. Neuroimage 2000;11:805–821.CrossRefGoogle ScholarPubMed
Bazire, S., Bazire, S. editor. Psychotropic Drug Directory 2003/2004. Fivepin Publishing; 2003. p. 179–180.Google Scholar
Cohen, J.. A power primer. Psychol Bull 1992;112(1):155–159.CrossRefGoogle ScholarPubMed
Dorph-Petersen, K.A., Pierri, J.N., Perel, J.M., Sun, Z., Sampson, A.R., Lewis, D.A.. 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 2005;30:1649–1661.CrossRefGoogle ScholarPubMed
Emsley, R., Fleischhacker, W.W.. Is the ongoing use of placebo in relapse-prevention clinical trials in schizophrenia justified?. Schizophr Res 2013;150(2–3):427–433.CrossRefGoogle ScholarPubMed
Fusar-Poli, P., Smieskova, R., Kempton, M.J., Ho, B.C., Andreasen, N.C., Borgwardt, S.. Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neurosci Biobehav Rev 2013;37(8):1680–1691.CrossRefGoogle ScholarPubMed
Good, C.D., Johnsrude, I.S., Ashburner, J., Henson, R.N.A., Friston, K.J., Frackowiak, R.S.J.. Voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage 2001;14:21–36.CrossRefGoogle ScholarPubMed
Guy, W., EDCEU Assessment Manual for Psychopharmacology – Revised (DHEW Pupl No ADM 76 338). Rockville, MD, U.S.: Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976. p. 534–537.Google Scholar
Haapea, M., Miettunen, J., Veijola, J., Lauronen, E., Tanskanen, P., Isohanni, M.Non-participation may bias the results of a psychiatric survey: an analysis from the survey including magnetic resonance imaging within the Northern Finland 1966 Birth Cohort. Soc Psychiatry Psychiatric Epidemiol 2007;42:403–409.CrossRefGoogle ScholarPubMed
Haijma, S.V., Van Haren, N., Cahn, W., Koolschijn, P.C., Hulshoff Pol, H.E., Kahn, R.S.Brain volumes in schizophrenia: a meta-analysis in over 18 000 subjects. Schizophr Bull 2013;39(5):1129–1138.CrossRefGoogle ScholarPubMed
Ho, B.C., Andreasen, N.C., Ziebell, S., Pierson, R., Magnotta, V.Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Arch Gen Psychiatry 2011;68(2):128–137.CrossRefGoogle ScholarPubMed
Honea, R., Crow, T.J., Passingham, D., Mackay, C.E.Regional deficits in brain volume in schizophrenia: a meta-analysis of voxel-based morphometry studies. Am J Psychiatry 2005;162(12):2233–2245.CrossRefGoogle ScholarPubMed
Isohanni, M., Mäkikyrö, T., Moring, J., Räsänen, P., Hakko, H., Partanen, U., et al.A comparison of clinical and research DSM-III-R diagnoses of schizophrenia in a Finnish national birth cohort. Soc Psychiatry Psychiatr Epidemiol 1997;32:303–308.CrossRefGoogle Scholar
Janssen, B., Weinnmann, S., Berger, M., Gaebel, W.Validation of polypharmacy process measures in inpatient schizophrenia care. Schizophr Bull 2004;30:1023–1033.CrossRefGoogle ScholarPubMed
Jenkinson, M., Smith, S.A global optimisation method for robust affine registration of brain images. Med Image Anal 2001;5(2):143–156.CrossRefGoogle ScholarPubMed
Jenkinson, M., Bannister, P.R., Brady, J.M., Smith, S.M.Improved optimisation for the robust and accurate linear registration and motion correction of brain images. Neuroimage 2002;17(2):825–841.CrossRefGoogle Scholar
Kay, S.R., Fiszbein, A., Opler, L.A.The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261–276.CrossRefGoogle Scholar
Konopaske, G.T., Dorph-Petersen, K.A., Sweet, R.A., Pierri, J.N., Zhang, W., Sampson, A.R., et al.Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys. Biol Psychiatry 2008;63(8):759–765.CrossRefGoogle ScholarPubMed
Kroken, R.A., Johnsen, E., Ruud, T., Wentzel-Larsen, T., Jørgensen, H.A.Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study. BMC Psychiatry 2009;9:24.CrossRefGoogle ScholarPubMed
Leung, M., Cheung, C., Yu, K., Yip, B., Sham, P., Li, Q., et al.Gray matter in first-episode schizophrenia before and after antipsychotic drug treatment. Anatomical likelihood estimation meta-analyses with sample size weighting. Schizophr Bull 2011;37(1):199–211.CrossRefGoogle ScholarPubMed
Moilanen, K., Veijola, J., Läksy, K., Mäkikyrö, T., Miettunen, J., Kantojärvi, L., et al.Reasons for the diagnostic discordance between clinicians and researchers in schizophrenia in the Northern Finland 1966 Birth Cohort. Soc Psychiatry Psychiatric Epidemiol 2003;38:305–310.CrossRefGoogle ScholarPubMed
Moilanen, J., Haapea, M., Miettunen, J., Jääskeläinen, E., Veijola, J., Isohanni, M., et al.Characteristics of subjects with schizophrenia spectrum disorder with and without antipsychotic medication – a 10-year follow-up of the Northern Finland 1966 Birth Cohort study. Eur Psychiatry 2013;28(1):53–58.CrossRefGoogle ScholarPubMed
Moncrieff, J., Leo, J.A systematic review of the effects of antipsychotic drugs on brain volume. Psychol Med 2010;40(9):1409–1422.CrossRefGoogle ScholarPubMed
Navari, S., Dazzan, P.Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings. Psychol Med 2009;39(11):1763–1777.CrossRefGoogle ScholarPubMed
Olabi, B., Ellison-Wright, I., McIntosh, A.M., Woods, S.J., Bullmore, E., Lawrie, S.M.Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies. Biol Psychiatry 2011;70(1):88–96.CrossRefGoogle ScholarPubMed
Perälä, J., Suvisaari, J., Saarni, S.I., Kuoppasalmi, K., Isometsä, E., Pirkola, S., et al.Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry 2007;64(1):19–28.CrossRefGoogle Scholar
Ridler, K., Veijola, J.M., Tanskanen, P., Miettunen, J., Chitnis, X., Suckling, J., et al.Frontocerebellar systems are associated with infant motor and adult executive functions in healthy but not in schizophrenia. Proc Natl Acad Sci U S A 2006;103(42):15651–15656.CrossRefGoogle Scholar
Rueckert, D., Sonoda, L.I., Hayes, C., Hill, D.L.G., Leach, M.O., Hawkes, D.J.Non-rigid registration using free-form deformations: application to breast MR images. IEEE Trans Med Imaging 1999;18(8):712–721.CrossRefGoogle Scholar
Scherk, H., Falkai, P.Effects of antipsychotics on brain structure. Curr Opin Psychiatry 2006;19(2):145–150.CrossRefGoogle ScholarPubMed
Semple, D., Smyth, R., Semple, D., Smyth, R., editor Oxford Handbook of Psychiatry 2nd ed. Oxford University Press; 2009.[Table 6.3]CrossRefGoogle Scholar
Shepherd, A.M., Laurens, K.R., Matheson, S.L., Carr, V.J., Green, M.J.Systematic meta-review and quality assessment of the structural brain alterations in schizophrenia. Neurosci Biobehav Rev 2012;36(4):1342–1356.CrossRefGoogle Scholar
Smith, S.Fast robust automated brain extraction. Hum Brain Mapp 2002;17(3):143–155.CrossRefGoogle ScholarPubMed
Smith, S.M., Jenkinson, M., Woolrich, M., Beckmann, C.F., Behrens, T.E.J., Johansen-Berg, H., et al.Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 2004;23:208–219.CrossRefGoogle ScholarPubMed
Spitzer, R.L., Gibbon, M., Endicott, J.Global Assessment Scale (GAS), Global Assessment of Functioning (GAF) scale, Social and Occupational Functional Assessment Scale (SOFAS). Rush, J.A., et, al., Handbook of psychiatric measures Washington: American Psychiatric Association; 2000. p. 96–100.Google Scholar
Tanskanen, P., Ridler, K., Murray, G., Haapea, M., Veijola, J., Jääskeläinen, E., et al.Morphometric brain abnormalities in schizophrenia in a population-based sample: relationship to duration of illness. Schizophr Bull 2010;36(4):766–777.CrossRefGoogle Scholar
Torres, U.S., Portela-Oliveira, E., Borgwardt, S., Busatto, G.F.Structural brain changes associated with antipsychotic treatment in schizophrenia as revealed by voxel-based morphometric MRI: an activation likelihood estimation meta-analysis. BMC Psychiatry 2013 13:342.CrossRefGoogle ScholarPubMed
van der Gaag, M., Hoffman, T., Remijsen, M., Hijman, R., de Haan, L., van Meijel, B., et al.The five-factor model of the Positive and Negative Syndrome Scale II: a ten-fold cross-validation of a revised model. Schicophr Res 2006;85(1–3):280–287.CrossRefGoogle ScholarPubMed
Veijola, J., Guo, J.Y., Moilanen, J.S., Jääskeläinen, E., Miettunen, J., Kyllönen, M., et al.Longitudinal changes in total brain volume in schizophrenia: relation to symptom severity, cognition and antipsychotic medication. PLoS One 2014;9:e101689.CrossRefGoogle ScholarPubMed
Vita, A., De Peri, L., Deste, G., Sacchetti, E.Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies. Transl Psychiatry 2012;2:e190.CrossRefGoogle ScholarPubMed
Zhang, Y., Brady, M., Smith, S.Segmentation of brain MR images through a hidden Markov random field model and the expectation maximization algorithm. IEEE Trans Med Imaging 2001;20:45–57.CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.