Biomedical subjects

D Keator

Publications and source records attributed to D Keator.

7 recordsLinked to original sources

PubMed2003

D1 receptor alleles predict PET metabolic correlates of clinical response to clozapine.

A goal of pharmacogenetics is to clarify associations between allelic variation and risk factors in psychiatric illness. We report changes in regional brain metabolism based on dopamine alleles. Treatment-resistant schizophrenic subjects were positron emission tomography scanned with 18F-fluorodeoxyglucose after 5 weeks each of placebo and clozapine treatment. Significant regional brain metabolic effects were found for the D1 receptor genotypes (P < 0.05), adjusted for multiple comparisons. Metabolic decreases for the 2,2 genotype but not the 1,2 genotype were observed in all major sectors of the brain, with the exception of the ventral parts of the caudate and putamen. Frontal, temporal, parietal, and occipital neocortices showed decreased metabolism as did the cingulate juxta-allocortex and the parahippocampal allocortex. Decreases were also observed in the thalamus, amygdala, and cerebellum bilaterally. No significant metabolic differences by genotype were observed for D3, 5HT(2A), and 5HT(2C) polymorphisms. In terms of clinical response, the DRD1 2,2 genotype significantly improved with clozapine treatment, demonstrating a 30% decrease in the Brief Psychiatric Rating Scale positive symptoms in contrast to a 7% worsening for the 1,2 genotype (P < 0.05). In this preliminary study, brain metabolic and clinical response to clozapine are related to the D1 receptor genotype.

Adult↗

PubMed2001

Brain metabolic and clinical effects of rivastigmine in Alzheimer's disease.

In-vivo metabolic measures with positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET) have demonstrated hypometabolism in temporal, frontal, and hippocampal areas during the early stages of Alzheimer's disease (AD). Progression of the dementia in AD involves compromised cholinergic functioning. Cholinesterase inhibitors have demonstrated efficacy in improving cognition and behaviour in AD. In this study, we demonstrate the usefulness of FDG-PET in measuring the progression of untreated AD and its modification by treatment with rivastigmine (Exelon, Novartis Pharmaceuticals, East Hanover, New Jersey, USA), a centrally selective cholinesterase inhibitor of the carbamate type. Patients with mild to moderate probable AD (Mini-Mental Status Exam scores of 10-26, inclusive) were enrolled in a double-blind, placebo controlled comparison of three fixed daily doses of rivastigmine (3, 6, or 9 mg/d) or placebo for 26 wk. FDG-PET scans were obtained on 27 patients at baseline and following 26 wk of treatment using the Snodgrass Picture Naming activation task. A total of 71.4% of the patients treated with placebo deteriorated clinically compared to only 25.0% of the patients treated with rivastigmine (chi2 = 4.8; p & 0.03). Rivastigmine-responders (i.e. those who clinically improved or remained clinically stable as measured by the Clinicianaposs Interview-Based Impression of Change-plus) showed a marked increase in brain metabolism (p <0.01) involving, but not limited to, structures comprising the memory-related cortices and the prefrontal system. These metabolic changes were not observed in the placebo-treated patients or the rivastigmine non-responders. Of note is that responders increased hippocampal metabolism by 32.5% (p < 0.03) compared to a non-significant decrease in the non-responders (6.4%) and placebo-treated patients (4.1%). These results are consistent with the literature suggesting that FDG-PET can sensitively measure the progression of AD and its improvement with cholinesterase inhibitors. Rivastigmine prevented the expected deterioration in clinical status and dramatically increased brain metabolic activity in a majority of patients.

Aged↗

PubMed2000

Correlation of intellectual impairment in Parkinson's disease with FDG PET scan.

This study investigated the relationship between regional glucose metabolism with intellectual impairment in patients with Parkinson's disease using statistical parametric mapping. Regional cerebral glucose metabolism using [18F]deoxyglucose (FDG) PET scans were performed on 10 patients with Parkinson's disease. We used the intellectual impairment score from the UPDRS. PET scans were analyzed with SPM96. Patients showed significant positive correlations with left limbic structures such as the cingulate gyrus, parahippocampal gyrus, and medial frontal gyrus. Patients showed significant negative correlations with associative neocortical posterior structures such as bilateral parietal and occipital gyrus. There were significant relationships between regional glucose metabolism and intellectual impairment.

Aged↗

PubMed1999

Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex.

OBJECTIVE: Sleep deprivation has been shown to have an antidepressant benefit in a subgroup of depressed patients. Functional imaging studies by the authors and others have suggested that patients with elevated metabolic rates in the anterior cingulate gyrus at baseline are more likely to respond to either sleep deprivation or antidepressant medications than patients with normal metabolic rates. The authors extend their earlier work in a larger group of patients and explore additional brain areas with statistical probability mapping. METHOD: Thirty-six patients with unipolar depression and 26 normal volunteers were studied with positron emission tomography before and after sleep deprivation. Response to sleep deprivation was defined as a 40% or larger decrease in total scores on the Hamilton Depression Rating Scale. RESULTS: One-third of the depressed patients had a significant response to sleep deprivation. Responders had higher relative metabolic rates in the medial prefrontal cortex, ventral anterior cingulate, and posterior subcallosal gyrus at baseline than depressed patients who did not respond to sleep deprivation and normal volunteers. Lower Hamilton depression scores correlated significantly with lower metabolic rates in the left medial prefrontal cortex. After sleep deprivation, significant decreases in metabolic rates occurred in the medial prefrontal cortex and frontal pole in the patients who responded positively to sleep deprivation. CONCLUSIONS: High pretreatment metabolic rates and decreases in metabolic rates after treatment in the medial prefrontal cortex may characterize a subgroup of depressed patients who improve following sleep deprivation and, perhaps, other antidepressant treatments.

Adolescent↗

PubMed1997

Increased dopamine activity associated with stuttering.

Position emission tomography using 6-FDOPA as a marker of presynaptic dopaminergic activity was used to investigate the role of the dopamine system in stuttering. Three patients with moderate to severe developmental stuttering were compared with six normal controls. Stuttering subjects showed significantly higher 6-FDOPA uptake than normal controls in medial prefrontal cortex, deep orbital cortex, insular cortex, extended amygdala, auditory cortex and caudate tail. Elevated 6-FDOPA uptake in ventral limbic cortical and subcortical regions is compatible with the hypothesis that stuttering is associated with an overactive presynaptic dopamine system in brain regions that modulate verbalization.

Adult↗

PubMed1997

Decreasing striatal 6-FDOPA uptake with increasing duration of cocaine withdrawal.

It has been hypothesized that a decrease in dopaminergic presynaptic activity during abstinence or withdrawal is related to relapse in cocaine-dependent subjects (Dackis and Gold 1985; Markou and Koob 1991). This study measured striatal 6-fluorodopa (6-FDOPA) uptake, an index of dopaminergic presynaptic activity, using positron emission tomography (PET) in 11 drug-free cocaine addicts compared to eight normal subjects. Middle abstinence cocaine addicts (n = 5, off cocaine 11-30 days) had significantly lower striatal 6-FDOPA uptake compared to normal controls or early abstinence cocaine addicts (n = 6, off cocaine 1-10 days). The cocaine-dependent subjects (n = 11) showed a significant negative correlation between days off cocaine and striatal 6-FDOPA uptake. The results suggest that during abstinence from cocaine there is a delayed decrease in dopamine terminal activity in the striatum.

Adult↗

PubMed1996

Amygdala activity at encoding correlated with long-term, free recall of emotional information.

Positron emission tomography of cerebral glucose metabolism in adult human subjects was used to investigate amygdaloid complex (AC) activity associated with the storage of long-term memory for emotionally arousing events. Subjects viewed two videos (one in each of two separate positron emission tomography sessions, separated by 3-7 days) consisting either of 12 emotionally arousing film clips ("E" film session) or of 12 relatively emotionally neutral film clips ("N" film session), and rated their emotional reaction to each film clip immediately after viewing it. Three weeks after the second session, memory for the videos was assessed in a free recall test. As expected, the subjects' average emotional reaction to the E films was higher than that for the N films. In addition, the subjects recalled significantly more E films than N films. Glucose metabolic rate of the right AC while viewing the E films was highly correlated with the number of E films recalled. AC activity was not significantly correlated with the number of N films recalled. The findings support the view derived from both animal and human investigations that the AC is selectively involved with the formation of enhanced long-term memory associated with emotionally arousing events.

Adult↗