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Biomedical subjects

D C Jimerson

Publications and source records attributed to D C Jimerson.

At least 55 records · Page 3Linked to original sources
PubMed1989

Contribution of CNS neuropeptide (NPY, CRH, and beta-endorphin) alterations to psychophysiological abnormalities in anorexia nervosa.

Patients with anorexia nervosa have neuroendocrine and behavioral alterations that starvation and weight loss are thought to cause, or contribute to, since they are reversed by weight restoration. We have found that anorexics have starvation-related disturbances of neuropeptide Y (NPY), corticotropin-releasing hormone (CRH), and beta-endorphin, as determined by their measurements in cerebrospinal fluid. The relationship between these neuropeptides and several symptoms in anorexia, together with findings in experimental animals, raise a possibility that changes in the activity of these neuropeptides contribute to neuroendocrine and behavioral alterations in anorexia. Specifically, a disturbance of central nervous system CRH activity is likely to be responsible for hypercortisolemia, while a disturbance of central nervous system NPY may contribute to amenorrhea. In addition, disturbances of these neuropeptides could contribute to other symptoms such as increased physical activity, hypotension, reduced sexual interest, depression, and pathological feeding behavior.

Adult↗
PubMed1989

Neurohypophyseal dysfunction: implications for the pathophysiology of eating disorders.

Vasopressin (AVP) and oxytocin (OT) are hypothalamic neuropeptides having distinct peripherally and centrally directed cell populations. While principally responsible for the regulation of osmotic equilibrium, AVP also participates in stress-mediated adrenocorticotropic hormone (ACTH) release, and in consolidation and retrieval of aversively conditioned behaviors. OT is principally known for its role in parturition and lactation, but also has effects opposite of AVP, antagonizing stress-mediated ACTH release and impairing the consolidation and retrieval of aversively conditioned behaviors. Our group has demonstrated novel peripheral osmoregulatory defects in underweight anorexics, coupled with hypersecretion of AVP into the cerebrospinal fluid (CSF). Conversely, a relative reduction of CSF OT is seen in underweight anorexics. Speculatively, these reciprocal changes in neurohypophyseal peptides in the underweight anorexic may enhance the observed neuroendocrine and cognitive abnormalities. In addition, the alterations in CSF OT may occur as a consequence of the abnormal gastrointestinal function present during the acute stages of anorexia nervosa.

Feeding and Eating Disorders↗
PubMed1988

Normal urinary free cortisol and plasma MHPG in panic disorder: clinical and theoretical implications.

Abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and noradrenergic function have been reported in patients with panic disorder. Mean urinary free cortisol and plasma MHPG were measured in 12 medication-free panic disorder patients and 12 normal controls. No significant difference in urinary free cortisol and plasma MHPG was observed between the patients and controls. There was no relationship between plasma MHPG and urinary free cortisol in the panic patients or normal controls. These findings are described within the context of current concepts of stress and noradrenergic dysfunction in panic disorder.

Adult↗
PubMed1988

Lymphocyte beta-adrenergic receptor modification in bulimia.

beta-Adrenergic receptor binding on circulating lymphocytes was evaluated in young female bulimic patients (n = 12) and age- and sex-matched normal control volunteers (n = 10). Using iodine 125-labeled cyanopindolol, antagonist binding was evaluated (number of receptors [Bmax] and dissociation constant [KD]), and using isoproterenol competition of cyanopindolol binding, the concentration required to inhibit binding by 50% (IC50) for isoproterenol and the agonist affinity measure of KL/KH (ratio of dissociation constants for the low- and high-affinity states of the receptor) were determined. Plasma norepinephrine (NE) level was also measured. There was a trend toward lower plasma NE levels in the bulimic patients. The KL/KH ratio in bulimic patients was significantly greater than that for the normal volunteers, indicating increased receptor coupling. The KL/KH ratio was not significantly correlated with plasma NE level. Neither Bmax nor KD was different between the two groups. These findings suggest that beta-adrenergic receptors in bulimic patients may be more responsive than in normal subjects, without alteration of the traditional measures of receptor responses, a difference that cannot be explained on the basis of plasma NE. These findings provide another line of evidence for altered regulation of the noradrenergic system in bulimic patients during a controlled phase of their illness.

Adult↗
PubMed1988

Plasma 3-methoxy-4-hydroxyphenylglycol changes associated with clinical state and schizophrenic subtype.

In a study of 14 drug-free schizophrenic patients and 22 healthy control subjects, the plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) level appeared to be altered by changes in clinical state. Repeated sampling in schizophrenic patients showed that plasma MHPG values were elevated in high-psychosis phases in comparison with metabolite levels at times of lower psychosis. There was a nonsignificant trend toward higher MHPG levels in paranoid schizophrenic patients in comparison with patients who had undifferentiated schizophrenia. Paranoid schizophrenic patients had significantly elevated plasma MHPG levels in comparison with previously studied healthy controls. These findings suggested that alterations in the plasma MHPG level may reflect psychosis-related changes in norepinephrine function in schizophrenia.

Adult↗
PubMed1988

CSF somatostatin in anorexia nervosa and bulimia: relationship to the hypothalamic pituitary-adrenal cortical axis.

The eating disorders, anorexia nervosa and normal weight bulimia, are associated with disturbances of hypothalamic-pituitary-adrenal cortical (HPA) and growth hormone function. Because somatostatin (SRIF) is one of the neuropeptides known to modulate feeding behavior and neuroendocrine systems, we measured cerebrospinal fluid (CSF) concentrations of this peptide in patients with eating disorders. CSF SRIF concentrations in patients with anorexia nervosa, both at low weight and after weight recovery, were similar to those in controls. When normal weight bulimic women stopped binging, they had a modest but significant increase in CSF SRIF. CSF SRIF was not related to plasma growth hormone concentrations but did show relationships to HPA axis hormones. Healthy volunteer women had a significant positive relationship between CSF SRIF and CSF corticotropin releasing hormone (CRH). In underweight anorectics, CSF SRIF was negatively related to both 24-hr urinary free cortisol and plasma cortisol concentrations after dexamethasone, but it was not significantly related to CSF CRH. These relationships more closely resembled those of healthy controls after weight correction. In bulimics, CSF SRIF was positively related to CSF CRH and negatively related to plasma cortisol. Our findings support a previously described relationship between CSF SRIF and HPA axis activity. The differences in SRIF-HPA relationships in anorectics and bulimics may constitute or reflect pathophysiological distinctions between these disorders.

Adult↗
PubMed1988

Induction of migrainelike headaches by the serotonin agonist m-chlorophenylpiperazine.

In a study of serotonin (5-HT) function in patients with eating disorders and healthy control subjects, severe headaches with features of common migraine occurred unexpectedly in 28 of 52 subjects (54%) 8 to 12 hours after receiving a single oral dose of the 5-HT receptor agonist m-chlorophenylpiperazine (m-CPP), 0.5 mg/kg. None of the same subjects developed similar late-occurring headaches after placebo or the 5-HT precursor, L-tryptophan, 100 mg/kg given intravenously. The frequency of these migrainelike headaches was not significantly different between patients with bulimia or anorexia nervosa and control subjects, but incidence of headaches was significantly greater in subjects with a personal or family history of migraine, with almost all predisposed individuals (18 of 20, 90%) developing severe symptoms. Headache ratings were also significantly correlated (rho = 0.70; p less than 0.0001) with peak concentrations of m-CPP in plasma. These observations indicate that m-CPP may provide a novel probe for studies of the pathophysiology of migraine headaches.

Adult↗
PubMed1988

Pattern of onset of bulimic symptoms in anorexia nervosa.

Among patients with anorexia nervosa in a research program, the proportion of those who had developed bulimia before anorexia increased between 1976 and 1987. These preliminary results may reflect a new symptom pattern with important clinical and research implications.

Adult↗
PubMed1987

Reduced cerebrospinal fluid levels of immunoreactive pro-opiomelanocortin related peptides (including beta-endorphin) in anorexia nervosa.

The discovery that the endogenous opioid peptides contribute to the modulation of appetitive behavior and neuroendocrine function has raised questions as to whether disturbances of opioids contributes to the pathophysiology of eating disorders. To assess central nervous system (CNS) beta-endorphin in patients with anorexia nervosa we measured cerebrospinal fluid (CSF) beta-endorphin concentrations before, and at intervals after weight correction. In addition, we measured three sister peptides (beta-lipotropin, adrenocorticotropic hormone (ACTH), and the N-terminal fragment) derived from the same precursor molecule, pro-opiomelanocortin (POMC) to determine whether possible disturbances might extend to sister peptides. Underweight anorectics (58 +/- 5% of average body weight (ABW), n = 10) had significantly lower CSF concentrations of all 4 peptides compared to healthy controls (102 +/- 10% ABW, n = 11). CSF concentrations of all 4 POMC-related peptides were found to be significantly increased when the same anorectics were restudied 4 to 6 weeks after weight gain (83 +/- 4% ABW). After weight gain, levels of CSF beta-endorphin, beta-lipotropin, and ACTH were similar to controls, whereas levels of CSF N-POMC remained significantly less than controls. Another group of women, previously underweight with anorexia nervosa, but weight-restored (93 +/- 11% ABW, n = 12) for greater than 1 year had CSF concentrations of all 4 POMC-related peptides that were similar to controls. We conclude that underweight anorectics have state-associated disturbances of CNS beta-endorphin as well as other POMC-related peptides. These abnormalities are part of the neurobiological syndrome of anorexia nervosa and may contribute to the characteristic alterations in behavior and neuroendocrine function.

Adrenocorticotropic Hormone↗
PubMed1987

The effects of dexamethasone on plasma homovanillic acid and 3-methoxy-4-hydroxyphenylglycol. Evidence for abnormal corticosteroid-catecholamine interactions in major depression.

We investigated the possible interactions between corticosteroids and catecholamines in depression by studying the effects of the synthetic glucocorticoid dexamethasone on plasma levels of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) in a group of depressed patients and normal controls. In comparison with metabolite levels on a control day, normal controls showed a significant dexamethasone-induced increase in the plasma HVA level and a trend toward a decrease in the plasma MHPG level at 4 PM following dexamethasone administration (1 mg orally at 11 PM). Conversely, depressed patients, particularly those with psychotic features, showed a significant dexamethasone-induced increase in the plasma MHPG level and a blunting of the plasma HVA response relative to the normal controls. Dexamethasone-induced increases in the plasma MHPG level were directly correlated with the severity of depressive symptoms and with postdexamethasone cortisol levels in the depressed patients. These data suggest abnormal corticosteroid-catecholamine interactions in depression and, specifically, in depressed patients with psychotic features.

Adult↗
PubMed1987

Comparison of lactate-induced anxiety in bulimic patients and healthy controls.

Clinical symptomatology and diagnostic interview studies suggest that patients with bulimic disorder have some characteristics in common with patients with generalized anxiety disorder or panic disorder. The purpose of this study was to compare sodium lactate-induced physiological responses and anxiety symptoms in hospitalized normal weight bulimic patients and healthy controls. Bulimic patients had significantly elevated anxiety ratings at baseline, and showed a trend toward greater increases in anxiety ratings after lactate administration. Lactate-induced anxiety did not provoke an urge to binge in the bulimic patients. In keeping with the specificity of lactate-induced panic attacks in panic disorder, none of the bulimic subjects experienced a panic attack during lactate infusion.

Adult↗
PubMed1987

Elevated cerebrospinal fluid levels of immunoreactive corticotropin-releasing hormone in anorexia nervosa: relation to state of nutrition, adrenal function, and intensity of depression.

To study the pathophysiology of hypercortisolism in anorexia nervosa, we measured the cerebrospinal fluid (CSF) levels of corticotropin-releasing hormone (CRH) in patients when they were underweight and at intervals after weight restoration. CSF CRH levels were significantly elevated in hypercortisolemic underweight patients. Both CSF CRH levels and pituitary-adrenal function normalized after weight recovery. A significant positive correlation was found between CSF CRH levels and depression ratings in weight-corrected patients. We conclude that the hypercortisolism of anorexia nervosa reflects a defect at or above the hypothalamus which results in the hypersecretion of endogenous CRH. The positive correlation between CSF CRH and depression in the weight-restored patients is compatible with previous data indicating increased CRH secretion in the depressed phase of primary affective disorder and supports the notion of a relationship between CRH and depressive symptomatology. Moreover, these data are compatible with observations that depression is part of the anorexia nervosa syndrome.

Adrenal Glands↗
PubMed1986

Indices of noradrenergic output in depression.

Concentrations of plasma norepinephrine (NE) and plasma-3-methoxy-4-hydroxyphenylglycol (MHPG), blood pressure, and heart rate were measured on 2 days in 25 depressed patients and 25 controls. Comparisons were made between patients and controls, and also between days for both groups, to determine the short-term stability of these measures. The means of the plasma and urinary noradrenergic metabolite measures were not significantly different between groups. The variance of plasma MHPG, plasma NE, and mean blood pressure was greater in the depressed patients than in controls. Blood pressure, plasma MHPG, and plasma NE were relatively stable as suggested by the significant correlations between the 2 days for each of these variables. Plasma NE, plasma MHPG, and the sum of the deaminated urinary metabolites (MHPG and vanillylmandelic acid) were significantly intercorrelated. These results support other data in suggesting that plasma concentrations of NE and MHPG may be useful measures of noradrenergic activity, but may not consistently distinguish depressed patients from controls.

Adult↗
PubMed1986

Caloric intake necessary for weight maintenance in anorexia nervosa: nonbulimics require greater caloric intake than bulimics.

In the past decade, patients with anorexia nervosa have been subdivided by the presence or absence of binging-and-purging behavior. Psychologic, physiologic, and premorbid weight differences have also been discovered between these subgroups. We now report that nonbulimic anorectics required 30-50% more caloric intake than bulimic anorectics to maintain a stable weight. This difference in caloric intake was independent of phase of illness; it was present at low weight and at intervals after weight restoration. Subjects were closely supervised on an inpatient hospital ward so that they could not binge or purge. Motor activity did not appear to explain these alterations in caloric requirements. Such differences in caloric intake could be trait related or a consequence of many years of starving or binging behavior. These findings are clinically relevant for advising eating disorder patients of caloric requirements necessary to maintain a normal weight.

Adult↗
PubMed1986

Plasma MHPG in depressive disorders and relationship to the dexamethasone suppression test.

Plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in 51 depressed patients and 43 normal control subjects. There were significantly higher plasma MHPG levels in the combined patient group with current or past melancholia (N = 28) than in nonmelancholic (N = 12) or dysthymic (N = 11) patients, in unipolar melancholic (N = 16) versus bipolar melancholic (N = 4) patients, and in patients with a major depressive episode who failed to suppress cortisol after the dexamethasone suppression test (N = 24) versus patients with normal suppression (N = 16). Anxiety symptoms correlated significantly with plasma MHPG levels. These results substantiate previous evidence that dysregulation of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system occur together in a subgroup of depressed patients.

Adult↗
PubMed1986

Relationship of mood alterations to bingeing behaviour in bulimia.

Twelve women with bulimia participated in a study in which they binged and vomited on the day after hospital admission. Caloric intake, time spent bingeing and vomiting, and self-reported mood ratings demonstrated much variation from subject to subject. Both subjective and objective ratings of mood indicated that anxiety decreased more frequently and to a greater extent than depression, both during and after bingeing and vomiting. The present data, obtained in a controlled setting, tend to confirm previous information on binge episodes obtained by self-report from bulimic patients. Bingeing and vomiting episodes may provide bulimic patients with a physiological mechanism for temporarily relieving a dysphoric mood state.

Adult↗