Longitudinal Changes in Total Brain Volume in Schizophrenia: Relation to Symptom Severity, Cognition and Antipsychotic Medication

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.

Neuroimaging findings from childhood onset schizophrenia patients and their non-psychotic siblings

“…In the case of adult-onset schizophrenia, decreased intracranial volume in adulthood (Haijma et al, 2013; Kahn and Sommer, 2014) and longitudinal decrease in total cerebral volume are well documented (Veijola et al, 2014). In adult patients, it is predicted that brain growth is stunted even before the onset of illness (Haijma et al, 2013).…”

Long-term antipsychotic use and its association with outcomes in schizophrenia – the Northern Finland Birth Cohort 1966

“…The data on antipsychotic medication has been used in earlier studies with shorter periods of follow-up[27,31,32].…”

Peptidomic analysis of the anterior temporal lobe and corpus callosum from schizophrenia patients

“…In schizophrenia, studies describe a volume reduction especially in the temporal lobe and periventricular area. Despite the volume loss, no direct correlation was found with symptom severity, functioning level, or decline in cognition [8]. Proteomic analysis of the ATL of schizophrenia patients revealed several altered, negatively regulated proteins related to the myelin sheath and OLs such as 2',3'-cyclic-nucleotide 30-phosphodiesterase (CNP); glial fibrillary acidic protein (GFAP); myelin oligodendrocyte glycoprotein (MOG); myelin basic protein (MBP), the main component of the myelin sheath; and ermin (a myelinating oligodendrocytespecific protein) [9].…”