A PubMed search was conducted including the following keywords: schizophrenia, MRI or CT, longitudinal, or progressive. In addition, earlier works as referenced in the articles that were retrieved using the PubMed procedure were added. To be included in the review, the study was required to include patients with adult-onset chronic schizophrenia, defined as illness duration of longer than 2 years at the time of the first scan. Also, the study had to include a healthy control group of patients. Finally, 10 studies used volumetric brain imaging methodologies, whereas one study applied an area measurement based on CT scans. Both studies reporting on brain tissue changes (eg, in whole brain volume, frontal and temporal lobes, hippocampus etc) as well as those reporting on CSF and lateral and third ventricle volume or density changes were included. Exclusion of articles on patients with an illness duration shorter than 2 years at the time of the first scan considerably reduced the number of articles included in the review because the majority of studies have concentrated on progressive changes in the early stages of the disease. The number of articles initially found using CT scanning was considerably reduced when articles including patients only (ie, excluding a healthy comparison group) were excluded from the search.
The following information was extracted: the number of subjects (males/females) within the chronic schizophrenia group, possible other patient groups, and healthy comparisons; age at first measurement of each group; interval between the 2 imaging scans (mean, range in years); duration of illness (mean, SD, or range, in years); antipsychotic medication taken during the interval; brain imaging methodology that was applied (MRI or CT, Tesla [MRI] slice thickness in millimeters; scan direction; gap in millimeter if applicable); the brain areas in which progressive brain tissue volume changes were measured if any; the percentage change in brain tissue in patients with schizophrenia; the percentage change in brain tissue in healthy comparisons; the progressive CSF and lateral ventricle volume changes that were measured if any; the percentage change in CSF and ventricles in patients with schizophrenia; and the percentage change in CSF and ventricles in healthy comparisons.
Moreover, if available, associations between progressive brain changes in patients and outcome, severity of symptoms, cognitive functioning, and antipsychotic medication intake during the interval were examined. Finally, in case of a direct comparison within a study between progressive brain changes in chronically ill patients and first-episode patients and in case of 3 scans per person, this information was used. Seven studies reported on brain tissue changes over time, and 9 studies reported on ventricle (8) and/or CSF (2) changes over time. In 5 of these studies the measurements overlapped, ie, both brain tissue and ventricle and/or CSF changes over time were measured.
The percentage change in brain tissue and CSF and ventricle volume over time was calculated from the available material if not directly provided in the article, as follows: The average volume at follow-up was subtracted from the average volume at baseline, divided by the baseline volume, and multiplied by 100. Hence, in some instances the percentages change provided in this review have to be considered as an approximation of the actual changes.
The findings are summarized in . Studies were numbered according to the order of appearance in and these identity numbers were included in the text.
Longitudinal structural brain imaging studies in patients with schizophrenia beyond the first episode