Striatal size and relative glucose metabolic rate in schizotypal personality disorder and schizophrenia.

BACKGROUND: Schizotypal personality disorder (SPD) shares social deficits and cognitive impairment with schizophrenia, but is not typically characterized by frank psychosis. Because striatal size and functional activity have both been shown to be associated with psychotic symptoms, we carried out the first study of SPD to assess the caudate and putamen for comparison with findings in schizophrenia. METHODS: Patients with SPD (n = 16), schizophrenic patients (n = 42), and age- and sex-matched normal control subjects (n = 47) were assessed with magnetic resonance imaging. All of the patients with SPD and subsamples of the schizophrenic patients (n = 27) and control subjects (n = 32) were also assessed with positron emission tomography using fluorodeoxyglucose F-18. RESULTS: The relative size of the putamen in controls was significantly larger than in patients with SPD and significantly smaller than in schizophrenic patients, while the relative size of the caudate was similar in all 3 groups. Compared with control values, relative glucose metabolic rate in the ventral putamen was significantly elevated in patients with SPD and reduced in schizophrenic patients. When subsamples of schizophrenic patients (n = 10) and patients with SPD (n = 10) both of whom never received medication were compared, this pattern was more marked, with the highest value for the putamen being found in patients with SPD for the ventral slice and the lowest value for the right dorsal putamen. CONCLUSIONS: Patients with SPD showed reduced volume and elevated relative glucose metabolic rate of the putamen compared with both schizophrenic patients and controls. These alterations in volume and activity may be related to the sparing of patients with SPD from frank psychosis.

Thalamic activation during an attention-to-prepulse startle modification paradigm: a functional MRI study.

BACKGROUND: Prepulse inhibition (PPI) of the startle reflex reflects early stages of information processing and is modulated by selective attention. Animal models indicate medial frontal-thalamic circuitry is important in PPI modulation. We report data from the first functional magnetic resonance imaging (fMRI) study examining whether attending to or ignoring a prepulse differentially activates brain areas within this circuitry. METHODS: Ten healthy subjects received structural and functional MRI. During fMRI acquisition, subjects heard intermixed attended and ignored tones serving as prepulses to the startle stimulus. Regions of interest were traced on structural MRI and coregistered to fMRI images. RESULTS: Greater amplitude fMRI blood-oxygen-level-dependent response to attended than ignored PPI conditions occurred in the right thalamus, and bilaterally in the anterior and mediodorsal thalamic nuclei, whereas the startle-alone condition showed deactivation. In transitional medial cortex (Brodmann Area 32), which is involved in affective processing of noxious stimuli, the startle-alone condition elicited the greatest response, the attended-PPI condition showed the smallest response, and the ignored-PPI condition was intermediate. CONCLUSIONS: These findings extend animal models to humans by indicating thalamic involvement in the modulation of PPI. Further fMRI investigations may elucidate other key structures in the circuitry underlying normal and disordered modulation of PPI.

Hypofrontality in unmedicated schizophrenia patients studied with PET during performance of a serial verbal learning task.

Previous research indicates that verbal learning and memory deficits are among the most severe cognitive deficits observed in schizophrenia. However, the concomitant patterns of regional brain function associated with these deficits in schizophrenia are not well understood. The present study examined verbal-memory performance and simultaneous relative glucose metabolic rates (rGMR) with FDG PET in 20 unmedicated schizophrenia patients who met stringent memory-performance criteria and 32 age- and sex-matched normal volunteers. On a modified version of the California Verbal Learning Test, patients recalled fewer correct words using a semantic-clustering strategy and exhibited more intrusions compared with normal subjects. However, patients had higher serial-ordering strategy scores, indicating their use of a less efficient organizational strategy. Among patients, greater use of the serial-ordering strategy was associated with decreased rGMR in frontal cortex and increased rGMR in temporal cortex. Patients had lower rGMR primarily in frontal and temporal cortex, but not parietal and occipital lobe regions. Patients also exhibited hypofrontality (lower ratio of frontal to occipital rGMR) compared with normal subjects. Among the patients, more severe hypofrontality was associated with increased perseveration errors.