Smaller superior temporal gyrus volume specificity in schizotypal personality disorder

Abstract

Background: Superior temporal gyrus (STG/BA22) volume is reduced in schizophrenia and to a milder degree in schizotypal personality disorder (SPD), representing a less severe disorder in the schizophrenia spectrum. SPD and Borderline personality disorder (BPD) are severe personality disorders characterized by social and cognitive dysfunction. However, while SPD is characterized by social withdrawal/anhedonia, BPD is marked by hyper-reactivity to interpersonal stimuli and hyper-emotionality. This is the first morphometric study to directly compare SPD and BPD patients in temporal lobe volume.

Methods: We compared three age-, sex-, and education-matched groups: 27 unmedicated SPD individuals with no BPD traits, 52 unmedicated BPD individuals with no SPD traits, and 45 healthy controls. We examined gray matter volume of frontal and temporal lobe Brodmann areas (BAs), and dorsal/ventral amygdala from 3-T magnetic resonance imaging.

Results: In the STG, an auditory association area reported to be dysfunctional in SPD and BPD, the SPD patients had significantly smaller volume than healthy controls and BPD patients. No group differences were found between BPD patients and controls. Smaller BA22 volume was associated with greater symptom severity in SPD patients. Reduced STG volume may be an important endophenotype for schizophrenia-spectrum disorders. SPD is distinct from BPD in terms of STG volume abnormalities which may reflect different underlying pathophysiological mechanisms and could help discriminate between them.

Figure 1. Brodmann Area Regions of Interest

Left: Perry Atlas slice showing Brodmann Areas. Middle: BAs morphed to individual participant’s MRI at matching coronal slice level. Right: Gray and white matter and cerebrospinal fluid (CSF) within BAs delineated on individual MRI. Coronal slices perpendicular to the anterior commissure-posterior commissure line were divided into 20 radial sectors on each hemisphere surface and 10 midline sectors. BAs were then assessed for the gray and white matter pixels within all sectors identified in each BA. For quantification, the coronal images are segmented into gray matter, white matter, and CSF using cutoff values individually determined in each subject by examining the within-brain-edge histogram of axial MRI values as validated and assessed for reliability earlier (Mitelman et al., 2003,Mitelman et al., 2005). Every sector was assigned a BA according to the same radial sector division applied to Perry’s drawing of the BA margins. Volume measures were expressed in mm³ and obtained by computing relative size as the ratio of (area of ROI)/(volume of brain) × 1000. The Brodmann methods for our gray/white segmentation have been validated and the intraclass correlation coefficients for gray and white matter components for two tracers were 0.98 and 0.99. The detailed methodology and reliability description can be found in Mitelman et al. (2003,2005).

Figure 2. Amygdala Tracing Method

(A) Left: Coronal MRI: anterior-posterior dimension of amygdala. At this mid-section, the amygdaloid complex is roughly elliptical in shape, and anatomical margins are defined by the cornu ammonis and the white matter of gyrus ambiens in the medial aspect, the cornu inferius of the lateral ventricle in the ventral aspect, the temporal lobe white matter laterally, and the gyrus semilunaris in the dorsal aspect. (B) Middle: Using an edge contrast-enhancing technique (gradient filter) (Haznedar et al., 2000), we were able to better visualize the dentate gyrus of the hippocampus and boundaries between the hippocampus and the amygdala. Tracing procedure: the white line produced by the gradient filter is identified by mouse and the program finds the local maximum for the edge. Outlining of the amygdala began at its largest extent (approximately the center in the antero-posterior dimension) where clear boundaries between gray matter and surrounding white matter are visible and extended to anterior and anterior ends of the amygdaloid complex. The posterior portions of the amygdaloid complex were outlined by using the ventricular recess, hippocampus, and gyrus semilunaris as reference points. Anteriorly, the amygdaloid complex gray matter is more heterogeneous and hard to identify. We outlined from the midsection forward using gradient filtering and excluded the entorhinal cortex, which may include the inferior amygdala. The outlining ended at the first coronal MRI section on which there was visible white matter between the amygdala, ambiens, and white matter of the entorhinal cortex. This procedure may have omitted the very anterior end of the amygdaloid complex, but it had the advantage of excluding other extraneous structures from our analysis. (C) Right: Traced amygdala with division into dorsal and ventral regions. Employing methodology used previously by our group (New et al., 2007), we divided the amygdala into dorsal and ventral portions, based on the vertical distance on the mid-coronal slice. Volume measures for these amygdala regions were expressed in mm³ and relative to whole brain volume. Measurements were obtained by computing relative size as the ratio of (area of dorsal subregion)/(volume of brain) × 1000.

Figure 3. Between-group differences in MRI volume

Differences from the healthy control group in temporal lobe regions are shown for the SPD and BPD groups. Group × Temporal lobe region interaction, F(8, 236)= 2.27, p=0.02, Wilks. Y-axis shows the mean volume difference scores for the patients minus the healthy controls. Volume for the temporal lobe regions is expressed as: (region-of-interest volume/total brain volume) × 1000.* In BA42, BPD>Healthy Controls, p=0.03, Fisher’s LSD test. ** In BA22, Healthy Controls>SPD, p=0.01, and BPD > SPD, p=0.004, Fisher’s LSD test.

Figure 4. Relative STG by Diagnosis

Scatterplot of individual values for relative STG volume averaged over left and right hemisphere for participants within each of the three diagnostic groups. The horizontal bars indicate the mean value for each respective group.

Figure 5. Individual differences in superior temporal gyrus volume and symptom severity

The scatterplot for the correlation between relative superior temporal gyrus volume (STG; Brodmann Area 22; averaged over left and right hemisphere) and clinical symptom severity (DSM-IV) scores for SPD patients is shown (r=-0.48, p=0.01). Among the SPD patients, smaller STG volume was associated with greater symptom severity. Each of the nine DSM-IV criteria for SPD were rated on a 4-point scale (0=absent, 0.5=somewhat present, 1.0=definitely present/prototypic, 2.0=severe, pervasive) and then totaled for the symptom severity score.