William E. Semple

Cerebral glucose metabolic rates in obsessive compulsive disorder

Brain metabolism was measured with positron emission tomography and [18F] 2-fluoro-2-deoxyglucose in normal subjects and in patients with obsessive compulsive disorder (OCD) while they performed a continuous auditory discrimination task designed to evaluate the functional localization of sustained attention. Data on 8 nondepressed patients with OCD were compared with 30 normal volunteers. We observed significantly higher normalized regional metabolism both in the right orbital frontal cortex (p = 0.002, two-tailed t test) and in the left anterior orbital frontal cortex (p = 0.017, one-tailed t test) and in patients with OCD as compared to normal controls. We observed no normalized glucose metabolic differences in basal ganglia structures in patients with OCD as compared to our normal controls. There were no statistical differences in global glucose metabolic values between the OCD and the control group. Our findings are consistent with the findings of Baxter et al. (Arch Gen Psychiatry 44:211-218, 1987). Regions in the parietal cortex also appear to show differences in this preliminary study.

Positron-Emission Tomography and Personality Disorders

This study used positron-emission tomography to examine cerebral metabolic rates of glucose (CMRG) in 17 patients with DSM III-R diagnoses of personality disorder. Within the group of 17 personality disorder patients, there was a significant inverse correlation between a life history of aggressive impulse difficulties and regional CMRG in the frontal cortex of the transaxial plane approximately 40 mm above the canthomeatal line (CML) (r = −.56, p = 0.17). Diagnostic groups included antisocial (n = 6), borderline (n = 6), dependent (n = 2), and narcissistic (n = 3). Regional CMRG in the six antisocial patients and in the six borderline patients was compared to a control group of 43 subjects using an analysis of covariance with age and sex as covariates. In the borderline personality disorder group, there was a significant decrease in frontal cortex metabolism in the transaxial plane approximately 81 mm above the CML and a significant increase in the transaxial plane approximately 53 mm above the CML (F[1,45] = 8.65, p = .005; and F[1,45] = 7.68, p = .008, respectively).

Comparing the mental health needs of female and male incarcerated juvenile delinquents

The present study was undertaken to survey the prevalence of mental disorder in juvenile justice facilities and to compare the mental health needs for females and males. Girls displayed significantly more mental health needs than boys. The estimated prevalence of mental disorder for boys was 27%, compared with 84% for girls. The difference is highly significant and is discussed in terms of service system issues in juvenile justice that affect males and females differently.

Dysfunction in a prefrontal substrate of sustained attention in schizophrenia

Regional brain metabolism was measured in normal subjects and patients with schizophrenia while they performed an auditory discrimination task designed to emphasize sustained attention. A direct relationship was found in the normal subjects between metabolic rate in the middle prefrontal cortex and accuracy of performance. The metabolic rate in the middle prefrontal cortex of patients with schizophrenia, even those who performed as well as normals, was found to be significantly lower than normal and unrelated to performance. The findings point to a role of the mid-prefrontal region in sustained attention and to dysfunction of this region in schizophrenia.

Evidence for common alterations in cerebral glucose metabolism in major affective disorders and schizophrenia

Regional glucose metabolic rates were measured in affectively disordered patients during the performance of auditory discrimination. Those regions previously observed as abnormal in schizophrenia were examined to see if similar alterations might be associated with affective disorder. The abnormalities observed in the mid-prefrontal cortex, an area that appears to be an important biologic determinant of the sustained attention required of subjects in this task, are similar to those previously observed in schizophrenia. Moreover, the abnormalities do not appear to relate directly to symptomatology or the subjects performance. The authors discuss the possibility that this abnormality may reflect dysfunction in the integrating component of the attention network critical for the maintenance of goal-directed behavior and thus represent a psychosis vulnerability factor in some patients.

Effects of Acute Stimulant Medication on Cerebral Metabolism in Adults with Hyperactivity

Recent work in our laboratory has demonstrated both global and regional reductions in cerebral glucose metabolism in adult subjects with attention-deficit typeractivity disorder (ADHD). The purpose of the present study was to examine the effects of an acute dose of stimulant medication on cerebral metabolism in adults with ADHD using positron emission tomography with flurodeoxyglucose-18 as the tracer. Each subject underwent scanning twice, once off-drug and again after receiving a single oral dose of either dextroamphetamine (0.25 mg/kg) or methylphenidate (0.35 mg/kg). Subjects completed behavioral self-report measures before and after the scan and performed an auditory continuous performance task during the tracer uptake period. Neither drug changed global metabolism. Both drugs increased systolic blood pressure, and dextroamphetamine improved performance on the auditory attention task. Each stimulant produced a differential pattern of increases and decreases in regional metabolism throughout the regions of interest that were sampled. Rather than increasing glucose utilization in specific brain regions with lowered metabolic rates in adults with ADHD, stimulants may act by altering glucose use throughout the brain.

Metabolic brain pattern of sustained auditory discrimination

SummaryPositron emission tomography of [18F]-2-fluorodeoxyglucose was used to assess the functional brain activity of normal subjects while performing auditory discrimination (CPT), while receiving an identical set of tones as in CPT, but with the instructions that they were background noise, or while at rest. The present study: (1) confirms earlier findings of an association between the functional activity of the right midprefrontal cortex and the performance of auditory discrimination, (2) localizes this increase in right prefrontal cortex activity to the middle prefrontal gyrus; and (3) provides a framework of specific testable hypotheses for the evaluation of the importance of certain limbic and paralimbic areas in the biological determination of sustained attention to be addressed in future studies. The framework accounts for the now confirmed finding that the middle cingulate has lower metabolic activity in CPT than at rest, and new findings of alterations in temporal lobe processing of tones in response to attention.

The brain metabolic patterns of clozapine- and fluphenazine-treated female patients with schizophrenia: evidence of a sex effect.

The regional cerebral glucose metabolic rates of clozapine-treated and fluphenazine-treated women with schizophrenia and normal controls were obtained by positron emission tomography (PET) using [18F]-2-fluoro-2-deoxy-D-glucose (FDG) as the tracer. The regional metabolic patterns were compared to each other and to the changes previously observed in men. In women, as in men, both clozapine- and fluphenazine-treatment were associated with lower metabolism in the superior prefrontal cortex and higher metabolism in the medial temporal lobe. In both men and women, clozapine treatment led to a greater lowering of inferior prefrontal cortex activity than fluphenazine, which was statistically significant in the larger male cohort. Fluphenazine led to higher metabolic rates in the lateral temporal lobe than clozapine did, but the differences between the two neuroleptics were not statistically significant in either group. The greatest differences in the female as compared to the male responses to fluphenazine and clozapine were in the cingulate and striatum. As compared to controls, the cingulate metabolic rates of women were reduced by 9.1% and 11.4% on clozapine and fluphenazine, respectively; whereas, men have a statistically nonsignificant reduction of 0.1% with clozapine and a 3.2% increase with fluphenazine. In men, fluphenazine was associated with a much greater elevation in basal ganglia metabolic rates than was clozapine, 23.5 % as compared to 3.75%; whereas, in women, basal ganglia metabolic rates are nearly equally increased by fluphenazine (21.6%) and clozapine (15.1%).

The metabolic brain pattern of young subjects given scopolamine

The effect of an intravenous dose of 0.5 mg of scopolamine on the functional brain activity of normal subjects performing auditory discrimination (CPT) was determined in two independent positron emission tomography studies with [18F] 2-fluoro-deoxyglucose. In the first preliminary study, the most significant effect found was a reduction in the functional activity of the thalamus. In the second “hypothesis-testing” study, an equally prominent effect on thalamic functional activity was seen. Because the second study was performed on a high-resolution scanner with improved methodology, we re-examined scopolamines effects on those brain regions established as determinants of CPT. Of the regions affected, the reduction in cingulate and the increase in basal ganglia metabolic rates were the most notable. We concluded that scopolamines effects on the functions of thalamic, cingulate and basal ganglia are the likely causes of scopolamines well-described attention-altering properties. Alterations in these same brain structures could be responsible for scopolamines effects on other cognitive functions, e.g., memory. Alternatively, scopolamines effects on other brain structures such as the hippocampus and frontal cortex could underlie scopolamines effects on these other cognitive functions. Studies of scopolamines regional metabolic effects in subjects performing these other cognitive tasks at more than a single dose and at more than one post-drug time are needed to discriminate between these two possibilities.