Campbell M. Clark

Olfactory deficits in neuroleptic naive patients with schizophrenia

Because previous studies have shown deficits in olfactory identification for male patients with schizophrenia, either withdrawn from or receiving neuroleptic medication, the purpose of the current study was to determine if such deficits occurred in male patients who had never received neuroleptics. A sample of male (n = 30) and female (n = 10) patients as well as age appropriate controls (males, n = 28, females, n = 30) was assessed in terms of olfactory acuity and identification ability. No differences were found in olfactory acuity, but an olfactory identification deficit was present in 31% of the male patients with schizophrenia. As the olfactory pathways project through the limbic system and to the orbitofrontal cortex, odour identification may be a measure of the functional integrity of these structures. Therefore, these results suggest that for a sub-sample of male patients, the functional integrity of these structures is compromised.

The Brain at High Altitude: Hypometabolism as a Defense against Chronic Hypoxia?:

The brain of hypoxia-tolerant vertebrates is known to survive extreme limitations of oxygen in part because of very low rates of energy production and utilization. To assess if similar adaptations may be involved in humans during hypoxia adaptation over generational time, volunteer Quechua natives, indigenous to the high Andes between about 3,700 and 4,900 m altitude, served as subjects in positron emission tomographic measurements of brain regional glucose metabolic rates. Two metabolic states were analyzed: (a) the presumed normal (high altitude-adapted) state monitored as soon as possible after leaving the Andes and (b) the deacclimated state monitored after 3 weeks at low altitudes. Proton nuclear magnetic resonance spectroscopy studies of the Quechua brain found normal spectra, with no indication of any unusual lactate accumulation; in contrast, in hypoxia-tolerant species, a relatively large fraction of the glucose taken up by the brain is released as lactate. Positron emission tomographic measurements of [18F]2-deoxy-2-fluoro-d-glucose (FDG) uptake rates, quantified in 26 regions of the brain, indicated systematically lower region-by-region glucose metabolic rates in Quechuas than in lowlanders. The metabolic reductions were least pronounced in primitive brain structures (e.g., cerebellum) and most pronounced in regions classically associated with higher cortical functions (e.g., frontal cortex). These differences between Quechuas with lifetime exposure to hypobaric hypoxia and lowlanders, which seem to be expressed to some degree in most brain regions examined, may be the result of a defense adaptation against chronic hypoxia.

REGIONAL CEREBRAL GLUCOSE METABOLISM IN MAJOR DEPRESSIVE DISORDER

Six subjects with DSM-III defined unipolar major depressive disorder had positron emission tomography scans using 18F-2-fluoro-2-deoxy-D-glucose (2FDG) before and after treatment with imipramine. Their 12 scans were compared to the scans of six controls matched for age. Significant reductions in metabolism for subjects in the depressed group were found on scans for both the anterior and right frontal regions. Significant reductions in metabolism occurred more often in the right hemisphere than the left. No significant changes in metabolism could be attributed to imipramine. In addition, absolute metabolic rates were not related to the degree of depression pre- and post-treatment. The findings suggest that hypometabolism in the frontal cortex and right hemisphere may occur in major depressive disorders.

Olfactory deficits in schizophrenia

Olfactory discrimination was measured in patients with schizophrenia who were on neuroleptic medication and was compared with other psychiatric patients receiving neuroleptics and normal controls. The performance of the patients with schizophrenia was significantly lower than the psychiatric and normal controls. The latter two groups performed at equivalent levels. The findings are discussed with respect to olfactory deficits found in patients with cerebral lesions and with abnormalities of specific neurotransmitter systems.

Regional cerebral glucose metabolism in turner syndrome

Regional cerebral glucose metabolism was examined in females with Turner syndrome, a sex chromosome abnormality. Previous studies have found a visual/spatial cognitive anomaly in these women but, to date, no abnormalities in brain structure or function have been associated with the condition. In the present study, decreases in regional metabolism were found in the occipital and parietal cortex. The involvement of the occipital cortex, although consistent with the observed cognitive anomalies, has not been suggested previously as an area dysfunction. Because the occipital cortex is a primary sensory cortex, the reduction of glucose metabolism in the parietal cortex may reflect a lack of innervation from the occipital cortex. Besides insight into the functional specialization of the brain, these findings are also consistent with previous reports on animals regarding the effects of estrogen in brain maturation.

Melatonin suppression in bipolar and unipolar mood disorders

Nocturnal melatonin suppression to 500 lux light was studied during an acute episode of illness in 8 patients with bipolar disorder, 7 patients with unipolar depression, and 15 age-, sex-, and season-matched normal controls. Unipolar patients did not differ from controls in melatonin suppression. In contrast to previous studies, controls showed greater melatonin suppression than bipolar patients. Baseline melatonin concentration, however, was significantly lower in the bipolar group compared to the unipolar and control groups.

Neuropsychological performance in patients with mild multiple sclerosis

Although changes in cognitive function in patients with multiple sclerosis (MS) have been reported, these changes have been traditionally associated with the later stages of the disease. In the current study, a comprehensive neuropsychological battery was administered to MS patients (N= 86) in whom the disease progression was relatively mild and in remission and a demographically well-matched control group (N=46). Besides the expected differences in tests of motor function, the two groups also differed on a number of cognitive tests with no motor demands. The two cognitive functions that appear impaired were learning and memory. Given that similar deficits have been found in MS patients with more severe symptoms, it is argued that changes in cognitive function can occur in the mild stages of the disease.

The neuropsychological, psychiatric, and physical effects of prolonged and severe stress: 30 years later.

This study investigates the long term or residual effects resulting from severe and extended exposure to stress. The samples were prisoners of war who were interned in Japan (high stress group) or Europe (low stress group) during the Second World War. They were examined in the following three areas: neuropsychological, psychiatric, and physical/neurological. Significant differences were found in all three spheres between the two groups. Second, to examine further the effect of length of internment on these variables, the low stress group was divided into long term and short term internment duration groups, and then the three groups were compared. Significant differences were found among these three groups. These results are discussed in relation to a traditional model of explanation.

Regional metabolism in microsmic patients with schizophrenia.

The cerebral glucose metabolism of eight patients with schizophrenia and an olfactory agnosia was compared with that of eight normosmic patients with schizophrenia and eight normal controls. Since all patients were scanned while on their current medication regimen, the duration and dosage of the medication of the two patient groups were compared. Similarly, duration and dosage were correlated with absolute regional metabolic rates. No significant effects were found in these analyses. The patients with schizophrenia had significantly lower rates of frontal metabolism than the normal controls. However, the patients with schizophrenia and an olfactory agnosia had a lower right basal ganglia and thalamic metabolism than the normosmic patients with schizophrenia.

Electroconvulsive shock decreases binding to 5-HT2 receptors in nonhuman primates: An in vivo positron emission tomography study with [18F]setoperone

BACKGROUND Dysfunction within the serotonin (5-HT) system plays a major role in the etiology of human depression, and treatment with antidepressant drugs downregulates 5-HT(2) receptors in rodents and humans. The consequences of another effective antidepressant treatment, electroconvulsive therapy (ECT), on 5-HT(2) receptors are less established. METHODS We studied the effects of a course of electroconvulsive shock (ECS) on 5-HT(2) receptor binding in nonhuman primates in vivo using positron emission tomography (PET) and the radiotracer [(18)F]setoperone. Seven adult male rhesus monkeys received two bilateral ECS treatments per week for 3 weeks; PET scans were performed before treatment, and 24 hours, 1 week, and 4-6 weeks after completion of the course of ECS. Regions of interest were placed throughout the cortex, and the data analyzed as the ratio of specific:nonspecific radioactivity accumulation, with the cerebellum used as a measure of nonspecific binding. RESULTS Serotonin 5-HT(2) binding was significantly decreased at 24 hours and 1 week post-ECS, but returned to baseline 4-6 weeks posttreatment. CONCLUSIONS These results show for the first time in a primate species that chronic ECS decreases binding to 5-HT(2) receptors and indicate that 5-HT(2) receptor downregulation may be a common effect of both pharmacologic and nonpharmacologic antidepressant treatments.