Longitudinal changes in total brain volume in schizophrenia: relation to symptom severity, cognition and antipsychotic medication.

Juha Veijola,Sanna Huhtaniska,John Suckling,Pirjo Mäki,Vesa Kiviniemi,Merja Kyllönen,Matti Isohanni,Jennifer H Barnett,Antti Alaräisänen,Anna Barnes,Juha Nikkinen,Hiroyuki Kobayashi,Jouko Miettunen,Erika Jääskeläinen,Marianne Haapea,Peter B Jones,Tuomo Starck,Graham K Murray,Osmo Tervonen,Angie A Kehagia ,Hannu Koponen ,Jukka Remes ,Jani Moilanen ,Jing Guo ,Alle Meije Wink ,Pekka Tanskanen

doi:10.1371/journal.pone.0101689

Abstract

Studies show evidence of longitudinal brain volume decreases in schizophrenia. We studied brain volume changes and their relation to symptom severity, level of function, cognition, and antipsychotic medication in participants with schizophrenia and control participants from a general population based birth cohort sample in a relatively long follow-up period of almost a decade. All members of the Northern Finland Birth Cohort 1966 with any psychotic disorder and a random sample not having psychosis were invited for a MRI brain scan, and clinical and cognitive assessment during 1999–2001 at the age of 33–35 years. A follow-up was conducted 9 years later during 2008–2010. Brain scans at both time points were obtained from 33 participants with schizophrenia and 71 control participants. Regression models were used to examine whether brain volume changes predicted clinical and cognitive changes over time, and whether antipsychotic medication predicted brain volume changes. The mean annual whole brain volume reduction was 0.69% in schizophrenia, and 0.49% in controls (p = 0.003, adjusted for gender, educational level, alcohol use and weight gain). The brain volume reduction in schizophrenia patients was found especially in the temporal lobe and periventricular area. Symptom severity, functioning level, and decline in cognition were not associated with brain volume reduction in schizophrenia. The amount of antipsychotic medication (dose years of equivalent to 100 mg daily chlorpromazine) over the follow-up period predicted brain volume loss (p = 0.003 adjusted for symptom level, alcohol use and weight gain). In this population based sample, brain volume reduction continues in schizophrenia patients after the onset of illness, and antipsychotic medications may contribute to these reductions.

Highlights

Over a century after Emil Kraepelin [1] used the term dementia praecox to describe schizophrenia, it remains debatable whether there are progressive neuroanatomical changes in schizophrenia
The mean annual total brain volume reduction was 0.69% in participants with schizophrenia and 0.49% in control participants (Figure 2)
In seven participants (21%) with schizophrenia the annual total brain volume reduction was lower than the mean of total brain volume reduction in control participants

Summary

Introduction

Over a century after Emil Kraepelin [1] used the term dementia praecox (early dementia) to describe schizophrenia, it remains debatable whether there are progressive neuroanatomical changes in schizophrenia. According to two meta-analyses, there is, on average, greater loss of brain volume over time in schizophrenia compared to controls [2,3]. The cause for progressive brain tissue loss in schizophrenia remains unknown. It is crucial to examine the significance of brain volume change in schizophrenia in terms of impact, if any, to the patient. Compared to the control group, the schizophrenia group had a lower level of educational attainment and were more likely to be single (unmarried, divorced, widowed and not cohabiting) rather than married or cohabiting. In both groups, more than 90% were right-handed

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Discussion

Conclusion