Person:

Dickey, Chandlee

Background: One of the cardinal features of schizotypal personality disorder (SPD) is language abnormalities. The focus of this study was to determine whether or not there are also processing abnormalities of pure tones differing in pitch and duration in SPD. Methods: Thirteen neuroleptic-naïve male subjects met full criteria for SPD and were group-matched on age and parental socioeconomic status to 13 comparison subjects. Verbal learning was measured with the California Verbal Learning Test. Heschl’s gyrus volumes were measured using structural MRI. Whole-brain fMRI activation patterns in an auditory task of listening to tones including pitch and duration deviants were compared between SPD and control subjects. In a second and separate ROI analysis we found that peak activation in superior temporal gyrus (STG), Brodmann Areas 41 and 42, was correlated with verbal learning and clinical measures derived from the SCID-II interview. Results: In the region of the STG, SPD subjects demonstrated more activation to pitch deviants bilaterally (p<0.001); and to duration deviants in the left hemisphere (p=0.005) (two-sample t). SPD subjects also showed more bilateral parietal cortex activation to duration deviants. In no region did comparison subjects activate more than SPD subjects in either experiment. Exploratory correlations for SPD subjects suggest a relationship between peak activation on the right for deviant tones in the pitch experiment with odd speech and impaired verbal learning. There was no difference between groups on Heschl’s gyrus volume. Conclusions: These data suggest that SPD subjects have inefficient or hyper-responsive processing of pure tones both in terms of pitch and duration deviance that is not attributable to smaller Heschl’s gyrus volumes. Finally, these auditory processing abnormalities may have significance for the odd speech heard in some SPD subjects and downstream language and verbal learning deficits.

Background: The caudate nucleus might contribute to the psychopathological and cognitive deficits observed in schizotypal personality disorder (SPD), a schizophrenia spectrum disorder. Here we focused on female patients, because this group is underrepresented in studies of SPD and schizophrenia, and we might learn more about the caudate and clinical and cognitive impairments that are unique to female patients diagnosed with SPD. Methods: Magnetic resonance imaging scans, obtained on a 1.5-T magnet with 1.5-mm contiguous slices, were used to measure the caudate in 32 neuroleptic-naïve women with SPD and in 29 female normal comparison subjects. Subjects were group-matched for age, parental socioeconomic status, and intelligence quotient. Results: We found significantly reduced left and right caudate relative volume (8.3%, 7.7%) in female SPD subjects compared with normal comparison subjects. In female SPD subjects, we found significant correlations between smaller total caudate relative volume and worse performance on the Wisconsin Card Sorting test (nonperseverative errors) and on the California Verbal Learning Test (verbal memory and learning), and significant correlations between smaller total caudate relative volume and both positive and negative symptoms on the Structured Interview for Schizotypy. Conclusions: These findings demonstrate that, for female SPD subjects, smaller caudate volume is associated with poorer cognitive performance and more schizotypal symptomatology.

The fusiform gyrus is important for face and object recognition, is abnormal in schizophrenia, but has not been studied in schizotypal personality disorder (SPD). Thin-slice MR images showed no differences, either in right, left or total fusiform gyri volumes, between subjects with SPD (N = 21) and normal controls (N = 19). However, there was a correlation between severity of illusions and magical thinking suffered by the SPD subjects and smaller right fusiform gyrus volumes. This suggests that future studies may be useful in determining the functional competence of this gyrus in SPD.

After more than 100 years of research, the neuropathology of schizophrenia remains unknown and this is despite the fact that both Kraepelin (1919/1971: Kraepelin,E., 1919/1971. Dementia praecox. Churchill Livingston Inc., New York) and Bleuler (1911/1950: Bleuler, E., 1911/1950. Dementia praecox or the group of schizophrenias. International Universities Press, New York), who first described ‘dementia praecox’ and the ‘ schizophrenias’, were convinced that schizophrenia would ultimately be linked to an organic brain disorder. Alzheimer (1897: Alzheimer, A., 1897. Beitrage zur pathologischen anatomie der hirnrinde und zur anatomischen grundlage einiger psychosen. Monatsschrift fur Psychiarie und Neurologie. 2, 82–120) was the first to investigate the neuropathology of schizophrenia, though he went on to study more tractable brain diseases. The results of subsequent neuropathological studies were disappointing because of conflicting findings. Research interest thus waned and did not flourish again until 1976, following the pivotal computer assisted tomography (CT) finding of lateral ventricular enlargement in schizophrenia by Johnstone and colleagues. Since that time significant progress has been made in brain imaging, particularly with the advent of magnetic resonance imaging (MRI), beginning with the first MRI study of schizophrenia by Smith and coworkers in 1984 (Smith, R.C., Calderon, M., Ravichandran, G.K., et al. (1984). Nuclear magnetic resonance in schizophrenia: A preliminary study. Psychiatry Res. 12, 137–147). MR in vivo imaging of the brain now confirms brain abnormalities in schizophrenia. The 193 peer reviewed MRI studies reported in the current review span the period from 1988 to August, 2000. This 12 year period has witnessed a burgeoning of MRI studies and has led to more definitive findings of brain abnormalities in schizophrenia than any other time period in the history of schizophrenia research. Such progress in defining the neuropathology of schizophrenia is largely due to advances in in vivo MRI techniques. These advances have now led to the identification of a number of brain abnormalities in schizophrenia. Some of these abnormalities confirm earlier post-mortem findings, and most are small and subtle, rather than large, thus necessitating more advanced and accurate measurement tools. These findings include ventricular enlargement (80% of studies reviewed) and third ventricle enlargement (73% of studies reviewed). There is also preferential involvement of medial temporal lobe structures (74% of studies reviewed), which include the amygdala, hippocampus, and parahippocampal gyrus, and neocortical temporal lobe regions (superior temporal gyrus) (100% of studies reviewed). When gray and white matter of superior temporal gyrus was combined, 67% of studies reported abnormalities. There was also moderate evidence for frontal lobe abnormalities (59% of studies reviewed), particularly prefrontal gray matter and orbitofrontal regions. Similarly, there was moderate evidence for parietal lobe abnormalities (60% of studies reviewed), particularly of the inferior parietal lobule which includes both supramarginal and angular gyri. Additionally, there was strong to moderate evidence for subcortical abnormalities (i.e. cavum septi pellucidi—92% of studies reviewed, basal ganglia—68% of studies reviewed, corpus callosum—63% of studies reviewed, and thalamus—42% of studies reviewed), but more equivocal evidence for cerebellar abnormalities (31% of studies reviewed). The timing of such abnormalities has not yet been determined, although many are evident when a patient first becomes symptomatic. There is, however, also evidence that a subset of brain abnormalities may change over the course of the illness. The most parsimonious explanation is that some brain abnormalities are neurodevelopmental in origin but unfold later in development, thus setting the stage for the development of the symptoms of schizophrenia. Or there may be additional factors, such as stress or neurotoxicity, that occur during adolescence or early adulthood and are necessary for the development of schizophrenia, and may be associated with neurodegenerative changes. Importantly, as several different brain regions are involved in the neuropathology of schizophrenia, new models need to be developed and tested that explain neural circuitry abnormalities effecting brain regions not necessarily structurally proximal to each other but nonetheless functionally interrelated. Future studies will likely benefit from: (1) studying more homogeneous patient groups so that the relationship between MRI findings and clinical symptoms become more meaningful; (2) studying at risk populations such as family members of patients diagnosed with schizophrenia and subjects diagnosed with schizotypal personality disorder in order to define which abnormalities are specific to schizophrenia spectrum disorders, which are the result of epiphenomena such as medication effects and chronic institutionalization, and which are needed for the development of frank psychosis; (3) examining shape differences not detectable from measuring volume alone; (4) applying newer methods such as diffusion tensor imaging to investigate abnormalities in brain connectivity and white matter fiber tracts; and, (5) using methods that analyze brain function (fMRI) and structure simultaneously.

Background: Previously, we reported abnormal volume and global shape in the caudate nucleus in schizotypal personality disorder (SPD). Here, we use a new shape measure which importantly permits local in addition to global shape analysis, as well as local correlations with behavioral measures. Methods: Thirty-two female and 15 male SPDs, and 29 female and 14 male normal controls (NCLs), underwent brain magnetic resonance imaging (MRI). We assessed caudate shape measures using spherical harmonic-point distribution model (SPHARM-PDM) methodology. Results: We found more pronounced global shape differences in the right caudate in male and female SPD, compared with NCLs. Local shape differences, principally in the caudate head, survived statistical correction on the right. Also, we performed correlations between local surface deformations with clinical measures and found significant correlations between local shape deflated deformations in the anterior medial surface of the caudate with verbal learning capacity in female SPD. Conclusions: Using SPHARM-PDM methodology, we found both global and local caudate shape abnormalities in male and female SPD, particularly right-sided, and largely restricted to limbic and cognitive anterior caudate. The most important and novel findings were bilateral statistically significant correlations between local surface deflations in the anterior medial surface of the head of the caudate and verbal learning capacity in female SPD. By extension, these local caudate correlation findings implicate the ventromedial prefrontal cortex (vmPFC), which innervates that area of the caudate, and demonstrate the utility of local shape analysis to investigate the relationship between specific subcortical and cortical brain structures in neuropsychiatric conditions.