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

Abstract

BackgroundProgressive 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.MethodParticipants 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.ResultsSchizophrenia 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.ConclusionOur 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 and benzodiazepine use and brain morphology in schizophrenia and affective psychoses – Systematic reviews and birth cohort study

“…Acknowledging the small sample size and that there are no previous studies on topic regarding benzodiazepine effects on brain volumes, there is a possibility that our findings may be by chance and the results must be interpreted with caution and considered exploratory and hypothesis generating rather than being conclusive. However, the findings regarding schizophrenia cases are in line with our previous longitudinal studies (Guo et al, 2015;Huhtaniska et al, 2017b;Veijola et al, 2014).…”

“…In previous studies of an overlapping NFBC1966 sample, a higher amount of antipsychotic medication predicted total brain volume loss (Veijola et al, 2014) and lateral ventricular volume increase (Huhtaniska et al, 2017b;Veijola et al, 2014), as well as periventricular brain volume reductions at the fourth ventricular edge (Guo et al, 2015) over a 9-year follow-up. In addition to brain findings, higher doses of antipsychotics associated with decline in verbal learning and memory (Husa et al, 2014), and high lifetime doses and antipsychotic polypharmacy associated with poorer outcomes in schizophrenia in the NFBC1966 (Moilanen et al, 2016).…”

“…We have previously published longitudinal findings from NFBC1966 follow-up study performed at ages 34 and 43 years for schizophrenia subjects. In these studies, higher doses of antipsychotic medication over the follow-up was associated with a larger total brain volume loss (Veijola et al, 2014), a degree of periventricular brain reduction at the fourth ventricular edge (Guo et al, 2015), and an increase in lateral ventricles after adjusting for symptom severity (Huhtaniska et al, 2017b). Higher benzodiazepine doses during the follow-up was associated with a volume decrease in the caudate nucleus even after controlling for antipsychotic use and illness severity (Huhtaniska et al, 2017b).…”

Long-term antipsychotic use and brain changes in schizophrenia - a systematic review and meta-analysis

“…Of these subjects, approximately two thirds were male. Six studies from four different samples had follow‐up of over 5 years (Andreasen et al, ; Guo et al, ; Ho, Andreasen, Ziebell, Pierson, & Magnotta, ; Nesvåg et al, ; Saijo et al, ; Veijola et al, ). The main focus of the studies was rarely on antipsychotics and brain volume change but rather the association was studied as a secondary analysis.…”

“…Only 11 of the 34 included studies used covariates in their analyses (e.g., age or total GM). Only four studies took into account illness severity measures (Andreasen, Liu, Ziebell, Vora, & Ho, ; Guo et al, ; Ho et al, ; Veijola et al, ).…”