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Biomedical subjects

L R Baxter

Publications and source records attributed to L R Baxter.

At least 55 records · Page 3Linked to original sources

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↗

[18F]-fluorodeoxyglucose (FDG) and positron emission tomography (PET) in aging and dementia. A decade of studies.

Alzheimer's disease (AD) is becoming an increasingly important public health problem. The clinical diagnosis of AD continues to be problematic and costly. [18F]-fluorodeoxyglucose-position emission tomography (FDG-PET) can assist with the diagnosis of AD at an early stage. The utility of FDG-PET in AD may also be extremely useful in the future when objective physiologic monitoring of drug effects and therapy are required.

Adolescent↗

Poor interrater reliability of MECTA EEG recordings of ECT seizure duration.

The electroencephalogram (EEG) tracings of seizure durations recorded by the MECTA SR-1 for 24 patients undergoing right unilateral electroconvulsive therapy (ECT) were estimated independently by four psychiatrists and a neurologist. Differences among raters were often large and, overall, were statistically significant. The literature on interrater reliability for the MECTA EEG remains contradictory, and caution in MECTA EEG use appears warranted.

Depressive Disorder↗

Urinary phenylacetate and response to methylphenidate.

Phenylacetate (PAA) is the metabolic end-product of phenylalanine, a catecholamine precursor, and of phenylethylamine, a centrally active neurochemical substance which has been implicated in the actions of stimulant medications. PAA has been reported to be low in unipolar depression. We measured 24-h urinary PAA in normal controls (N = 21) and in-patients with unipolar depression (N = 33; 12 drug-free) and did subsequent dexamethasome suppression tests (DST). We also gave patients methylphenidate challenges, examining mood response. There were no significant differences between depressed patients and controls in 24-h urinary PAA excretion (P greater than 0.9). However, the variance in PAA excretion was higher in patients than normals and 5 patients had values at or above the 99% confidence limits for the normal control group. There was no association of DST results with PAA excretion (P greater than 0.4). Patients with a worsened mood after taking methylphenidate excreted less PAA than those with an improved mood, however (P less than 0.025). The clinical and theoretical significance of these results is discussed.

Adult↗

Cerebral glucose metabolic rates in nondepressed patients with obsessive-compulsive disorder.

The authors compared 10 nondepressed patients with obsessive-compulsive disorder with 10 normal control subjects of the same sex and similar age for cerebral glucose metabolic rates obtained using positron emission tomography. Obsessive-compulsive patients showed significantly elevated metabolic rates in the whole cerebral hemispheres, heads of the caudate nuclei, orbital gyri, and the orbital gyri relative to the ipsilateral hemisphere (the orbital-hemisphere ratio). These results are similar to those the authors reported previously for another group of obsessive-compulsive patients and normal control subjects.

Adult↗

Localization of neurochemical effects of cocaine and other stimulants in the human brain.

The cocaine epidemic is a complex problem that has defied conventional medical, psychological, and legal interventions. A better understanding of the brain mechanisms that lead to cocaine's unsurpassed euphoric and reinforcing effects, as well as to associated physical brain damage, will be needed to develop new treatment strategies. Although much work has been done on cocaine's effects in the brains of animals, most techniques used have not been safe for human subjects. Positron emission tomography (PET) offers a unique opportunity for studying the cerebral biochemistry of cocaine abuse in humans. The authors present preliminary data from their ongoing studies of the effects of cocaine and related psychostimulants on the brain's energy requirements and on catecholamine neurotransmitter systems.

Bipolar Disorder↗

Reduced cerebral glucose metabolism in asymptomatic subjects at risk for Huntington's disease.

Symptomatic patients with Huntington's disease may have reduced glucose metabolism in the caudate nuclei. We used positron emission tomography and [18F]fluorodeoxyglucose to study cerebral glucose metabolism in 95 subjects: 58 clinically asymptomatic (chorea-free) subjects at risk for Huntington's disease, 10 symptomatic patients with the disease, and 27 controls. All the symptomatic patients had marked reductions in caudate glucose metabolism. Despite a normal structural appearance on computed tomography, caudate glucose metabolism was bilaterally reduced in 31 percent of the subjects at risk (18 of 58). Using each at-risk subject's age and the sex of the affected parent, we averaged individual risk estimates for the development of Huntington's disease for this group and predicted that the probability of having the clinically unexpressed Huntington's disease gene should be 33.9 +/- 6.0 percent for the group. Thus, there was excellent agreement between the predicted percentage of carriers of the Huntington's disease gene (33.9 +/- 6.0 percent) and the percentage with metabolic abnormalities of the caudate nuclei (31 percent). These results indicate that the measurement of glucose metabolism may allow the observation of the pathophysiologic effects of the Huntington's disease gene during the natural development of the disease. It may also provide a direct means to monitor the response to experimental treatments during both the clinically asymptomatic and the symptomatic phases of the disorder.

Adult↗

Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls.

We studied 14 patients with obsessive-compulsive disorder (OCD) by positron emission tomography and the fluorodeoxyglucose method, looking for abnormalities in local cerebral metabolic rates for glucose in brain structures that have been hypothesized to function abnormally in OCD. These patients were compared with 14 normal controls and 14 patients with unipolar depression. The patients with unipolar depression and OCD did not differ in levels of anxiety, tension, or depression. In OCD, metabolic rates were significantly increased in the left orbital gyrus and bilaterally in the caudate nuclei. This was apparent on all statistical comparisons with both controls and unipolar depression. The right orbital gyrus showed at least a trend to an increased metabolic rate in all comparisons. The metabolic rate in the left orbital gyrus, relative to that in the ipsilateral hemisphere (orbital gyrus/hemisphere ratio), was significantly elevated compared to controls and subjects with unipolar depression, and stayed high even with successful drug treatment. Though it was in the normal range in the morbid state, with improvement in OCD symptoms after drug treatment, the caudate/hemisphere metabolic ratio increased uniformly and significantly bilaterally. This ratio did not increase in patients who did not respond to treatment. Thus, OCD showed cerebral glucose metabolic patterns that differed from controls in both the symptomatic and recovered states.

Adult↗

Cerebral glucose metabolic rates in normal human females versus normal males.

Sex-related differences have been reported for some brain neuroanatomical structures and several measures of brain function. We studied the cerebral glucose metabolic rates of normal men (n = 7) and women (n = 7) with positron emission tomography and the fluorodeoxyglucose method. Women were studied between days 5 and 15 of the menstrual cycle. Women had whole brain glucose metabolic rates that were 19% higher than those of men. All neuroanatomical structures surveyed showed significant female greater than male rates, with no particular regions being outstanding. The higher cerebral glucose metabolic rates we observed in women may have been related to the effects of the high estrogen levels that can obtain in the phase of the menstrual cycle during which we tested our female subjects.

Adult↗

Effect of interrupted sleep patterns and partial sleep deprivation on DST and mood in psychiatric house officers.

To gain further insight into clinical associations seen in depression, the authors investigated the effect of interrupted night-time sleep on the HPA axis and mood in 20 psychiatric house officers taking overnight call. Specific interest was in whether multiple awakenings could induce a positive DST. No statistically significant association emerged between number of nocturnal awakenings, number of hours of sleep deprivation or temporal occurrence of sleep deprivation and cortisol, DST or mood. The results suggest that cortisol and DST changes are not likely to be causally linked to, or epiphenomenon of disrupted sleep. The implications of these findings for major depression are discussed.

Adult↗

Trazodone treatment response in obsessive-compulsive disorder--correlated with shifts in glucose metabolism in the caudate nuclei.

Obsessive-compulsive disorder (OCD) is a severe psychiatric illness that is difficult to treat. The effects of trazodone hydrochloride treatment were studied, both with and without the addition of a monoamine oxidase inhibitor, in OCD patients. Changes in symptoms correlated with changes in local cerebral metabolic rates for glucose (LCMRGlc), as measured by positron emission tomography and the 18F-fluorodeoxyglucose method. All patients whose OCD responded favorably to drug treatment showed a relative increase in glucose metabolism in the heads of the caudate nuclei compared with the metabolic rate in the ipsilateral hemisphere as a whole (ratio LCMRGlc caudate/LCMRGlc hemisphere). Patients who did not respond to treatment did not show an increase in this ratio, and the difference between responders and nonresponders was significant (p less than 0.03). Changes in the ratio LCMRGlc caudate/LCMRGlc hemisphere correlated with changes on OCD and depression rating scales.

Adult↗

Refractory depression treated with high doses of monoamine oxidase inhibitor.

Two treatment-refractory cases of depression were treated with doses of monoamine oxidase inhibitors (MAOIs) that exceeded the recommended therapeutic range. Both patients improved without any side effects. It appears that high doses of MAOIs when used with caution in responsible patients may be another method for treating refractory depression.

Adult↗

Prolongation of the antidepressant response to partial sleep deprivation by lithium.

Depressed patients given a loading dose of lithium on the first of 2 successive days of partial sleep deprivation (PSD), and kept at maintenance levels thereafter, showed significantly greater prolongation of the antidepressant effects of PSD than patients treated with PSD and placebo, even though the acute elevation in mood derived from PSD was as great on placebo as on lithium. Depression was assessed 3 days after PSD with an augmented version of the Hamilton Rating Scale for Depression. Patients on lithium alone, without PSD, did not have the acute elevation in mood seen in the two PSD groups and had significantly less improvement in depression than those who received PSD with lithium.

Adult↗