Repository logo

Longitudinal regional brain volume loss in schizophrenia: Relationship to antipsychotic medication and change in social function.

Change log


Guo, Joyce Y 
Huhtaniska, Sanna 
Miettunen, Jouko 
Jääskeläinen, Erika 
Kiviniemi, Vesa 


BACKGROUND: Progressive brain volume loss in schizophrenia has been reported in previous studies but its cause and regional distribution remains unclear. We investigated progressive regional brain reductions in schizophrenia and correlations with potential mediators. METHOD: Participants were drawn from the Northern Finland Birth Cohort 1966. A total of 33 schizophrenia individuals and 71 controls were MRI scanned at baseline (mean age=34.7, SD=0.77) and at follow-up (mean age=43.4, SD=0.44). Regional brain change differences and associations with clinical mediators were examined using FSL voxelwise SIENA. RESULTS: Schizophrenia cases exhibited greater progressive brain reductions than controls, mainly in the frontal and temporal lobes. The degree of periventricular brain volume reductions were predicted by antipsychotic medication exposure at the fourth ventricular edge and by the number of days in hospital between the scans (a proxy measure of relapse duration) at the thalamic ventricular border. Decline in social and occupational functioning was associated with right supramarginal gyrus reduction. CONCLUSION: Our findings are consistent with the possibility that antipsychotic medication exposure and time spent in relapse partially explain progressive brain reductions in schizophrenia. However, residual confounding could also account for the findings and caution must be applied before drawing causal inferences from associations demonstrated in observational studies of modest size. Less progressive brain volume loss in schizophrenia may indicate better preserved social and occupational functions.



Antipsychotic medication, Longitudinal MRI, Schizophrenia, Adult, Antipsychotic Agents, Brain, Cohort Studies, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Psychiatric Status Rating Scales, Schizophrenia, Schizophrenic Psychology, Statistics, Nonparametric

Journal Title

Schizophr Res

Conference Name

Journal ISSN


Volume Title



Elsevier BV
Medical Research Council (G1000183)
Medical Research Council (G0001354)
Medical Research Council (G0701911)
Wellcome Trust (093875/Z/10/Z)
Medical Research Council (G0701911/1)
Academy of Finland, Medical Research Council, Sigrid Jusélius Foundation and the Signe and Ane Gyllenberg Foundation, Finland, Stanley Foundation, Brain & Behavior Research Foundation. The work was partially completed within the University of Cambridge Behavioural and Clinical Neuroscience Institute, supported by a joint award from the Medical Research Council and Wellcome Trust.