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Biomedical subjects

L R Baxter

Publications and source records attributed to L R Baxter.

At least 19 recordsLinked to original sources

Serial changes of cerebral glucose metabolism and caudate size in persons at risk for Huntington's disease.

OBJECTIVE: To determine the rate of change of glucose metabolism and caudate size in persons at risk for Huntington's disease. DESIGN: Eighteen persons at risk for Huntington's disease had two positron emission tomographic glucose metabolic studies and two magnetic resonance imaging scans separated by 42 (+/- 9) months. SETTING: Ambulatory research subjects at a teaching hospital with magnetic resonance imaging and positron emission tomographic technology. SUBJECTS: Seven of the individuals were Huntington' disease gene negative by testing at the polymorphic DNA loci D4S10, D4S43, and D4S125; the remainder were gene positive by genetic testing or onset of chorea after study entry. INTERVENTIONS: None. OUTCOME MEASURES: Onset of chorea and imaging results. RESULTS: The gene-positive group demonstrated a significant 3.1% loss of glucose metabolic rate per year in the caudate nucleus (95% confidence interval [CI], -4.64, -1.48) compared with the gene-negative group. There was a 3.6% per year increase in the magnetic resonance imaging bicaudate ratio (95% CI, 1.81, 5.37), a linear measure of caudate atrophy. The rate of change in caudate size did not correlate with the rate of change in caudate metabolism, suggesting that metabolic loss and atrophy may develop independently. CONCLUSIONS: The results suggest that a reduction in caudate glucose metabolism and atrophy develop rapidly in Huntington's disease. The findings establish a strategy for using serial positron emission tomographic imaging to monitor experimental pharmacologic interventions in presymptomatic individuals who have developed caudate hypometabolism.

Adult

Psychiatric, genetic, and positron emission tomographic evaluation of persons at risk for Huntington's disease.

We examined chorea-free subjects at risk for Huntington's disease (n = 52) for lifetime psychiatric diagnoses, present mood, genetic marker status, and caudate glucose metabolic rates with positron emission tomography. Based on previous work, a caudate-ipsilateral hemisphere ratio less than 1.15 was defined as abnormal and predictive of Huntington's disease. None of three methods used to segregate subjects into groups more and less likely to develop Huntington's disease gave significant group rate differences for any formal psychiatric diagnoses. On present mood testing, however, subjective "anger/hostility" was significantly higher in those likely, compared with those less likely, to develop Huntington's disease, as determined by all three methods.

Adult

Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder.

We used positron emission tomography to investigate local cerebral metabolic rates for glucose (LCMRG1c) in patients with obsessive-compulsive disorder before and after treatment with either fluoxetine hydrochloride or behavior therapy. After treatment, LCMRG1c in the head of the right caudate nucleus, divided by that in the ipsilateral hemisphere (Cd/hem), was decreased significantly compared with pretreatment values in responders to both drug and behavior therapy. These decreases in responders were also significantly greater than right Cd/hem changes in nonresponders and normal controls, in both of whom values did not change from baseline. Percentage change in obsessive-compulsive disorder symptom ratings correlated significantly with the percent of right Cd/hem change with drug therapy and there was a trend to significance for this same correlation with behavior therapy. By lumping all responders to either treatment, right orbital cortex/hem was significantly correlated with ipsilateral Cd/hem and thalamus/hem before treatment but not after, and the differences before and after treatment were significant. A similar pattern was noted in the left hemisphere. A brain circuit involving these brain regions may mediate obsessive-compulsive disorder symptoms.

Adult

Disruption of social circadian rhythms in major depression: a preliminary report.

While dysregulations of physiological circadian rhythms are common findings in depression and have been posited to be involved in the mediation of depressive episodes, only recently has the role of social circadian rhythms in the pathogenesis of depression been a focus of interest. The Social Rhythm Metric (SRM), designed to describe the regularity of a human subject's social circadian rhythms, was used in this study to compare the social rhythms of depressed patients with those of normal controls and to determine the relationship between SRM scores and depression severity. Depressed patients' SRM scores were significantly lower than those of normal controls. The SRM negatively correlated with scores on the Hamilton Rating Scale for Depression. Overall social activity was negatively correlated with a Hamilton item, social activity impairment. The results of this preliminary study support the hypothesis that social zeitgebers are disrupted in major depression.

Activities of Daily Living

Positron emission tomography and familial Alzheimer's disease: a pilot study.

OBJECTIVE: Local cerebral metabolic rates for glucose were compared between patients with familial Alzheimer's disease (FAD), sporadic Alzheimer's Disease (SAD), and normal controls (NC) to determine if FAD is associated with a unique pattern of brain metabolism. DESIGN: Case-control study matched to convenience sample of FAD. METHODS: Subjects in the three diagnostic groups were scanned using fluorodeoxyglucose and the Positron Emission Tomographic (PET) technique. The criterion standard of a detailed clinical history and examination were compared to scan results. SETTING: Patients in a university hospital. SUBJECTS: Ambulatory controls and Alzheimer's patients, both sporadic (n = 8) and familial (n = 7). The two groups were similar in severity of cognitive dysfunction. RESULTS: FAD and SAD patients did not significantly differ in terms of local cerebral metabolic rates for glucose.

Aged

Neuroimaging studies of obsessive compulsive disorder.

In the last 5 years, there has been an explosion of neuroimaging studies of obsessive compulsive disorder. This work is now beginning to suggest dysfunctional brain regions and circuits that may mediate some of the symptoms of this classic neuropsychiatric illness.

Blood Glucose

Response to sleep deprivation in three women with postpartum psychosis.

BACKGROUND: Postpartum psychotic disorders are rare and poorly understood phenomena occurring after approximately 1 in 2000 births. Increasing attention has been given to the concept of postpartum psychosis as an affective spectrum disorder. We sought to characterize the responses to sleep deprivation of three women with postpartum psychotic and mood symptoms. METHOD: Three hospitalized postpartum women with no prior history of psychotic disorder were treated according to a partial sleep deprivation protocol. Each patient was awakened at 2:00 a.m. and kept awake until 9:00 p.m. the following night. A full and an abbreviated Hamilton Rating Scale for Depression (HAM-D) were completed for each patient before and after partial sleep deprivation. RESULTS: Two of the three patients became transiently manic and the third became hypomanic after sleep deprivation. HAM-D scores decreased drastically for each patient. After recovery sleep, each patient de-escalated but required further treatment with mood-stabilizing agents. CONCLUSION: These findings suggest that postpartum psychosis in our patients may represent a variant of bipolar affective disorder.

Adult

Effects of partial sleep deprivation on the diurnal variation of mood and motor activity in major depression.

Partial sleep deprivation (PSD), keeping a subject awake from 2 AM to 9 PM produces an acute mood improvement in 60% of patients with major depression. We sought to characterize the timing, subcomponent mood, and motor activity changes of this response. Thirty-seven subjects with major depression were rated with the 6-item Hamilton Depression Scale (HAM-6) at 1 PM and completed the Profile of Mood States (POMS) every 2 hr on the day before and day of PSD. Locomotor activity was monitored continuously during the trial with an automated device. Bipolar I patients responded more frequently than other groups. Positive mood responders had greater improvement than nonresponders in POMS subscales of depression, tension, confusion, and anger. The mood improvement increased steadily during the day, peaked in late afternoon, and declined thereafter. Responders showed significantly higher levels of locomotor activity on the baseline pre-PSD day than did nonresponders. All subjects increased motor activity following sleep deprivation, however.

Adult

Clinical and biochemical aspects of depressive disorders: I. Introduction, classification, and research techniques.

The present review focuses on recent data from clinical and animal research concerning the biochemical bases of depressive disorders, diagnosis, and treatment. In addition to integrating these data, problems and future directions in this research are discussed. The review is presented in three parts. This study, Part I, describes diagnostic classification schemes for depressive disorders, some epidemiological and biological correlates of the classifications, and research techniques for investigating depressive disorders. Research techniques include animal models, human biochemical techniques, and Positron Emission Tomography. In a future issue, Part II will discuss various transmitter/receptor theories of depressive disorders, e.g., noradrenergic, serotonergic, cholinergic, and dopaminergic, GABAergic, and peptidergic theories. Also in a future issue, Part III will discuss treatments for depression and some of the controversies in the field.

Depressive Disorder

Changes in glucose metabolism in dementia of the Alzheimer type compared with depression: a preliminary report.

We evaluated positron emission tomography (PET) in the differential diagnosis of depression and Alzheimer's disease. The local cerebral metabolic rate for glucose (LCMRGlc) in the parahippocampal gyrus-hippocampus and the dorsolateral prefrontal cortex were determined. The ratio of the LCMRGlc in those two regions was examined in patients with unipolar depression, bipolar depression, and Alzheimer's dementia. An analysis of variance revealed significant overall intergroup differences in values for both hemispheres. Student's t test showed significant differences in LCMRGlc for both unipolar and bipolar depression as compared with Alzheimer's dementia. These data indicate that PET may be useful in the differential diagnosis of dementia vs. depression.

Aged

Functional brain imaging and Alzheimer-type dementia.

Alzheimer disease is a common neurodegenerative disorder consisting of memory impairment and intellectual function that produces not only profound disabilities in the patient, but a significant cost to society as well. The biochemical basis for Alzheimer disease is not completely understood, but both positron-emission tomography and single-photon-emission computed tomography provide insights into the in vivo biochemistry associated with this disease. Both techniques show characteristic brain abnormalities, which consist of reductions in temporal-parietal metabolism that progress in severity and extent as the disease itself shows clinical progression. Such noninvasive biochemical assays may ultimately prove to be of assistance in clinical management, and are clearly helpful in understanding the pathophysiologic mechanisms associated with the production of this disease.

Alzheimer Disease

A comparison of neurological, metabolic, structural, and genetic evaluations in persons at risk for Huntington's disease.

We compared four diagnostic data sets for the assessment of individuals at risk for Huntington's disease. Fifty-four chorea-free persons were evaluated by neurological examination, positron emission tomography measurement of glucose metabolism, radiographic computerized tomographic measurement of caudate size, and genetic testing at the polymorphic DNA loci D4S10, D4S43, and D4S125. Twelve (22%) persons had abnormal caudate metabolism, 6 (11%) had subtle abnormalities of motor control, and 7 (13%) had computed tomographic evidence of caudate atrophy, compared with an expected gene frequency of 34% for this population. In 20 persons with unambiguous genetic test results or the subsequent phenotypic expression of Huntington's disease (chorea), there was a greater sensitivity of the positron emission tomographic measurement of caudate metabolism (75%) relative to computed tomography (33%) or the clinical examination (17%) for the determination of a subpopulation of probable Huntington's disease gene carriers. Hypometabolism of the putamen and globus pallidus, and hypermetabolism of the precentral gyrus were also associated with a high probability of carrying the Huntington's disease gene. The findings support the hypothesis that abnormalities of cerebral metabolism precede clinical or structural (computed tomographic) abnormalities in gene-positive individuals at risk for Huntington's disease.

Atrophy

PET imaging in obsessive compulsive disorder with and without depression.

Obsessive compulsive disorder (OCD) is a classic psychoneurosis which is frequently complicated by major depression. Recent positron emission tomography neuroimaging studies, when taken in the context of a variety of other data, implicate a brain dysfunction involving the orbital prefrontal cortex and the striatum in the mediation of OCD behaviors and those of the related Gilles de la Tourette's syndrome. The anterolateral prefrontal cortex is implicated in the secondary major depressions often complicating OCD.

Brain

Brain imaging as a tool in establishing a theory of brain pathology in obsessive compulsive disorder.

Positron emission tomography (PET) studies using 18F-2-deoxy-2-fluoro-D-glucose (FDG) to determine glucose metabolic rates have been used recently to correlate the symptoms of obsessive compulsive disorder (OCD) with neuroanatomically localized brain dysfunctions. These studies, as well as data from other techniques and other disease states, suggest that the orbital cortex and the striatum are dysfunctional in OCD. This information can be used to construct a theory of how the symptoms of OCD and the related Gilles de la Tourette's syndrome and chronic motor tics are mediated by the central nervous system.

Brain

Reduction of prefrontal cortex glucose metabolism common to three types of depression.

Using positron emission tomography, we studied cerebral glucose metabolism in drug-free, age- and sex-matched, right-handed patients with unipolar depression (n = 10), bipolar depression (n = 10), obsessive-compulsive disorder (OCD) with secondary depression (n = 10), OCD without major depression (n = 14), and normal controls (n = 12). Depressed patients were matched for depression on the Hamilton Depression Rating Scale, and subjects with OCD without depression and OCD with depression had similar levels of OCD without depression and OCD with depression had similar levels of OCD pathology. We also studied six non-sex-matched patients with mania. Mean (+/- SD) glucose metabolic rates for the left dorsal anterolateral prefrontal cortex, divided by the rate for the ipsilateral hemisphere as a whole (ALPFC/hem), were similar in the primary depressions (unipolar depression = 1.05 +/- 0.05; bipolar depression = 1.04 +/- 0.05), and were significantly lower than those in normal controls (1.12 +/- 0.06) or OCD without depression (1.15 +/- 0.05). Results for the right hemisphere were similar. Values in subjects with OCD with depression (1.10 +/- 0.05) were also significantly lower than in subjects with OCD without depression, and values in subjects with bipolar depression were lower than those in manic subjects (1.12 +/- 0.03) on this measure in the left hemisphere, although results were not significant in the right hemisphere. There was a significant correlation between the HAM-D score and the left ALPFC/hem. With medication for depression (n = 12), the left ALPFC/hem increased significantly and the percentage change in the Hamilton scale score correlated with the percentage change in the left ALPFC/hem.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Lymphocyte function in major depression.

Immunologic function as measured by lymphocyte response to phytohemagglutinin (PHA) mitogen was evaluated in 8 psychiatric inpatients. All were less than 45 years of age and had a DSM-III diagnosis of major depression. When patient's immunologic responses were compared with healthy age- and sex-matched controls, a significant increase in PHA mitogen stimulation was observed in the depressed group. Further, a significantly greater variance in PHA response was observed in the patients compared with controls. The literature on depression and immunity is reviewed and the clinical implications of our findings are discussed.

Adult