Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia

Abstract

Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule.

Fig. 1

Anatomical methods: stereotaxic and Manual tracings. Upper panel Left Coronal MRI showing application of 20 lateral and 10 medial sectors. Center and Right Perry atlas with same sector algorithm applied (see “Methods”). Lower Panel a Axial view of an MRI slice before (above) and after (below) applying the Sobel filter. This method allows distinguishing the boundaries of the different subcortical structures, especially the thalamus, whose tracing is shown. Yellow arrow indicates lateral edge of thalamus and blue arrow enhanced anterior horn of ventricle. b Three-dimensional model merged from the manual tracings of the lateral ventricles. The anterior horn is depicted in blue (note blue arrow indicating edge in a), the lateral horn is in green, and the temporal horn appears in yellow. c Location of the centers of mass of the caudate nucleus and thalamus, and vectors showing their position regarding to the anterior commissure in the midline of the brain (yellow arrow for orientation to a)

Fig. 2

Relative volume proportions in the human brain in controls compared with schizophrenics. The dimension of the boxes represents the percentage of every cortical or subcortical subdivision in the brain of the control sample. Colors indicate whether relative volumes of these subdivisions are bigger in controls (orange), in patients (blue), or do not differ (white). Note how, in general, the relative volume of cortical gray matter and caudate nucleus is bigger in controls, but most aspects of cortical white matter, ventricles, and putamen are bigger in schizophrenics. The values in the color legend (−14.9 and 7.5) are expressed in percentage. Cg cingulate cortex, FC frontal cortex, T temporal cortex