Biomedical subjects
Publications and source records attributed to K R Krishnan.
1. The authors investigated the role of serotonin in the hypothalamo pituitary adrenal escape from depression. 2. Maximal dose of fenfluramine was administered to normal individuals pretreated with dexamethasone. 3. Fenfluramine had only a minimal and inconsistent effect on the hypothalamo pituitary adrenal axis in the presence of dexamethasone.
1. The frequent occurrence of hypothalamo-pituitary dysfunction in patients with eating disorders as well as prior reports that nutritional and endocrine status influence pituitary morphology, led us to hypothesize that pituitary size and shape may be altered in patients with eating disorders. 2. Magnetic resonance imaging (MRI) does not use ionizing radiation and is currently one of the most feasible modalities available to study the pituitary gland in vivo. Using MRI, we have previously reported in a preliminary study that female patients with eating disorders had significantly smaller pituitary glands than controls. In addition MRI excluded any pituitary mass lesions. 3. In this report, we confirm our previous MRI findings and provide further evidence of pituitary abnormalities in an expanded sample of eating disorder patients. Preliminary data on pituitary volume estimates from MRI scans are provided for a subset of patients and controls.
The basal ganglia are recognized as putative mediators of certain cognitive and behavioral symptoms of major depression. Moreover, patients with basal ganglia lesions have repeatedly exhibited significant affective symptomatology, including apathy, depressive mood, and psychosis. Using high resolution, axial T2 intermediate magnetic resonance images, and a systematic sampling stereologic method, we assessed putamen nuclei volumes in 41 patients with major depression (DSM-III) and 44 healthy volunteer controls of similar age. Depressed patients had significantly smaller putamen nuclei compared with controls. Age was negatively correlated with putamen size in both groups. These results are the first demonstration of diminished putamen volumes in depression and further support a role for basal ganglia structures in the etiopathogenesis of depression.
In a retrospective study, brain magnetic resonance images of 12 patients with the onset of manic symptoms after the age of 50 years were compared to age- and sex-matched control subjects for the incidence, size, and location of subcortical hyperintensities. Compared with controls, the patients demonstrated a significantly greater number of large subcortical hyperintensities, particularly in the middle third of the brain parenchyma. The lesions occurred with equal frequency in the right and left hemisphere. There were no differences between the two groups in the size of the ventricles or the presence of periventricular hyperintensities.
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An observer measure of social phobic symptoms, referred to as the Brief Social Phobia Scale, consists of 11 items, 7 evaluating commonly feared or avoided situations and 4 additional items measuring autonomic distress. Symptoms represented by the scale items are found frequently in social phobia, and the instrument demonstrates acceptable interrater and test-retest reliability, internal consistency, concurrent validity against other measures of social phobia, and the ability of patients to change as a result of treatment. It can also detect differences between active treatment and placebo treatment. A comparison of the sensitivity of this scale with other scales in detection of size of effect also is presented.
The psychological effects of spinal cord injury on patients themselves have been discussed in a number of articles, but few studies have been made of patients and staff, perceptions of the effectiveness of the treatment they receive and supply. An earlier investigation by the present authors showed that there were differences between the views of staff and of patients in terms of their understanding of rehabilitation. As a consequence, a number of procedural changes were implemented in the Spinal Unit, in an attempt to improve the information provided for patients and their relatives, and the selection and support of staff. Reanalysis of the staff and patients views of rehabilitation were carried out 12 months later using a standardised questionnaire and any changes in response were noted. The present findings are analysed, and the potential implications for other units are noted.
Putamen nuclei were assessed in 36 normal volunteers using magnetic resonance imaging and a systematic sampling method. There was a significant decrease in the volume of the putamen nuclei with advancing age (r = -0.74, p less than 0.0001), and an associated decline in the volume of the caudate nuclei (r = 0.60, p less than 0.0001). The implications of these findings in age-associated motor abnormalities are discussed.
Early studies suggested that cerebrovascular change may be an etiological factor in the development of late-life depression. With the advent of magnetic resonance imaging (MRI), it has become possible to examine this hypothesis. MRI studies have demonstrated that patients with late-onset depression have more severe and frequent patchy lesions in the frontal deep white matter and basal ganglia than do controls or patients with early-onset depression. Patients with basal ganglia lesions, primarily caudate, are more likely to develop delirium with antidepressants and electroshock treatment (EST). The prognostic significance and the relationship of these lesions to cognitive impairment is unclear.
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Bipolar disorder has been reported to occur frequently in a number of subcortical diseases. This suggests that subcortical structures may be involved in the etiology of bipolar disorder in some patients. With the advent of brain magnetic resonance imaging (MRI), in vivo visualization of the subcortical white and gray matter is now possible, allowing the examination of these structures. The authors report a higher occurrence of deep white matter lesions in bipolar patients (44%) compared with age-matched controls (6%). The neuroanatomic and clinical correlates of these lesions will be discussed, along with their potential pathophysiologic significance.
A quantitative magnetic resonance imaging study of regional brain T1 spin-lattice relaxation times in 29 normal volunteers and in 20 patients with major depression revealed significantly shortened T1 relaxation times for the hippocampus in depressed patients. These differences were particularly prominent in elderly depressed patients. T1 relaxation times are reflective of the content and macromolecular environment of tissue water protons; shorter hippocampal T1 values may reflect differences in the content or organizational properties of hippocampal water protons. These findings are consistent with several lines of evidence that have implicated a role for the hippocampus in the regulation of mood and in the pathophysiology of the stress response, and they suggest that major depression may be associated with biophysical tissue changes in the aging hippocampus.
A brain magnetic resonance imaging (MRI) study of the corpus callosum in 36 normal volunteers, ages 26-79 years, revealed that age was positively correlated with the T1 spin-lattice relaxation time of the corpus callosum and was negatively correlated with the corpus callosum cross-sectional area. T1 relaxation times are sensitive to the content and macromolecular environment of tissue water, and variations in callosal T1 may reflect differences in the content or relaxation properties of callosal water. Such changes also potentially could occur secondary to alterations in the composition of callosal myelin. This study confirms and extends prior morphological studies that have reported age-related dimensional changes in the corpus callosum and, in addition, provides evidence of age-related biophysical tissue differences in the human corpus callosum.
In this pilot study, a prolonged (interictal) delirium was induced by electroconvulsive therapy (ECT) in seven out of seven depressed patients with Parkinson's disease. This occurrence of delirium appears much higher than what has been reported in other patient populations. These findings are consistent with several lines of data that have implicated the basal ganglia in the development of delirium from other causes, and they suggest that structural changes in these areas may predispose individuals to develop an interictal delirium during a course of ECT.
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Magnetic resonance images centered at the pituitary stalk were used to measure pituitary gland size in 19 patients with major depression compared with that in age- and sex-matched controls. Depressed patients had significantly greater pituitary cross-sectional area (P = 0.0009) and volume (P = 0.007) than the controls. This difference was particularly prominent in elderly depressed patients compared to elderly controls. These results provide the first demonstration of structural alterations in the pituitary gland in major depression.
Levels of urinary free cortisol were measured in 10 patients with social phobias and in 15 age- and sex-matched normal controls. No differences were found either in cortisol levels or in the ratio of free cortisol to creatinine. These nonsignificant differences between groups do not necessarily rule out the possibility that the hypothalamic-pituitary-adrenal axis may be altered in individuals with social phobia.