David C. Jimerson

Abnormal hypothalamic-pituitary-adrenal function in anorexia nervosa: pathophysiologic mechanisms in underweight and weight-corrected patients

To study the pathophysiology of hypercortisolism in patients with anorexia nervosa, we examined plasma ACTH and cortisol responses to ovine corticotropin-releasing hormone before and after correction of weight loss. We also studied patients with bulimia whose weight was normal, since this disorder has been suspected to be a variant of anorexia nervosa. Before their weight loss was corrected, the anorexic patients had marked hypercortisolism but normal basal plasma ACTH. The hypercortisolism was associated with a marked reduction in the plasma ACTH response to corticotropin-releasing hormone. When these patients were studied three to four weeks after their body weight had been restored to normal, the hypercortisolism had resolved but the abnormal response to corticotropin-releasing hormone remained unchanged. On the other hand, at least six months after correction of weight loss their responses were normal. The bulimic patients whose weight was normal also had a normal response to corticotropin-releasing hormone. We conclude that in underweight anorexics, the pituitary responds appropriately to corticotropin-releasing hormone, being restrained in its response by the elevated levels of cortisol. This suggests that hypercortisolism in anorexics reflects a defect at or above the hypothalamus. The return to eucortisolism soon after correction of the weight loss indicates resolution of this central defect despite persistence of abnormalities in adrenal function.

Growth hormone response to clonidine as a probe of noradrenergic receptor responsiveness in affective disorder patients and controls

The growth hormone (GH) response to the alpha-adrenergic agonist clinidine was blunted in 19 depressed patients compared to 20 controls. The difference remained significant when age- and sex-matches pairs of patients and controls were compared from this sample, either including or excluding subjects with elevated GH baseline levels. Plasma levels of free 3-methoxy-4-hydroxyphenyl-glycol (MHPG) were assayed in blood samples drawn just before the clonidine infusion. A modest negative correlation was found between the plasma MHPG values and the magnitude of the GH responses to clonidine, although baseline plasma MHPG levels were not significantly different between patients and controls. The diminished GH response to clonidine observed suggests that many depressed patients may have decreased alpha-adrenoreceptor responsiveness. Decreased responsiveness may in some cases be associated with relatively increased indices of presynaptic noradrenergic availability. Such a model might have implications for understanding the functional status of the noradrenergic neurotransmitter system in depressed patients and the possible subtyping of affective disorder patients.

Effect of dieting on plasma leptin, soluble leptin receptor, adiponectin and resistin levels in healthy volunteers

objective  Recent findings demonstrating important effects of the adipokines on metabolism, energy homeostasis and body weight regulation have prompted research on the possible role of negative energy balance in altering adipocytokine regulation. The goal of this study was to evaluate the effects of a hypocaloric diet in healthy normal‐weight volunteers. An additional goal was to help clarify the contribution of restricted caloric intake to altered plasma adipokine levels in the eating disorders anorexia nervosa and bulimia nervosa.

Dopamine and mania: Behavioral and biochemical effects of the dopamine receptor blocker pimozide

Although recent data suggest that pimozide has effects at other neurotransmitter receptor sites, it is one of the more specific neuroleptics in its effects on dopamine receptors. We report that in manic patients pimozide produces substantial clinical improvement with a magnitude and time course similar to that observed with the more routinely used phenothiazines chlorpromazine and thioridazine. Pimozide did not significantly increase probenecid-induced accumulations of the dopamine metabolite homovanillic acid (HVA) compared to pretreatment values. Higher HVA values were observed in manic than in nonmanic patients, however. These clinical and biochemical data add to a growing body of indirect evidence that a dopaminergic alteration may be associated with some components of the manic syndrome.

Alexithymia ratings in bulimia nervosa : clinical correlates

&NA; Previous reports indicate that some patients with eating disorders have alexithymic characteristics, including affect deficit states and paucity of imagination. This study evaluated whether nonhospitalized patients with bulimia nervosa had elevated ratings of alexithymia in comparison to age‐matched controls, and whether severity of bulimic symptoms was correlated with elevations in alexithymia ratings. Because alexithymia may be secondary to concurrent depression, this study was limited to patients with bulimia nervosa who were free of major depression. The authors compared alexithymia ratings for nonhospitalized normal weight women meeting DSM‐III‐R criteria for bulimia nervosa (N = 20) to healthy female volunteers (N = 20), utilizing the Toronto Alexithymia Scale (TAS) as the primary assessment instrument. Subjects also completed standardized rating scales for bulimic symptoms, depression, and anxiety. Alexithymia rating scale scores were significantly higher for patients with bulimia nervosa than for controls. In comparison to controls, patients had significant elevations on TAS factors reflecting affect deficit states, but normal scores for factors reflecting imagination and abstract thinking. Frequency of binge eating or purging behaviors was not correlated with alexithymia ratings. These data indicate that some patients with bulimia nervosa have alexithymic characteristics. Affect dysregulation was more prominent than limitation in fantasy or metaphorical thought. Additional studies are needed to assess whether presence of alexithymic characteristics may be predictive of response to treatment in patients with bulimia nervosa.

Urinary melatonin rhythms during sleep deprivation in depressed patients and normals

Abstract Melatonin excretion was measured in 8 hour urine aliquots for eight healthy controls and six depressed patients. Both groups had similar diurnal rhythms, with increased melatonin excretion during the night. When subjects were sleep deprived, remaining awake and active in continuous light from 7 a.m. one morning until 11 p.m. the following day, the diurnal rhythm in melatonin excretion remained unchanged. These data in man appear to be inconsistent with previous studies in rats showing rapid light-induced suppression of the nocturnal rise in pineal melatonin synthesis.

Biochemical correlates of personality traits in normals: An exploratory study

Abstract This study attempted to identify biochemical systems associated with the personality dimensions of Extraversion (E), Neuroticism (N), Psychoticism (P), Sensation Seeking (SS) and Impulsivity (Imp). The subjects were 43 normal volunteers who volunteered to take a battery of psychological tests and allow investigators to obtain samples of blood, urine and cerebrospinal fluid (CSF) for biochemical assessment. Substantial positive correlations were found between CSF norepinephrine (NE), MHPG (the principal metabolite of NE), DBH (an enzyme involved in the production of NE) and plasma MHPG and DBH; all of these are regarded, in some part, as putative indicators of central noradrenergic activity. After partialling out the influences of age, height and weight, a number of significant relationships were found between psychological traits and biochemical variables. Extraversion correlated positively and introversion and neuroticism correlated negatively with CSF Ca. Neuroticism also correlated negatively with plasma MHPG. Ego Strength (inversely related to Neurotic Introversion), P and Disinhibitory SS correlated negatively with CSF cort. General SS correlated negatively with CSF NE and plasma DBH, and these correlations were significant in both males and females, as well as in the total group. The results are consistent with some biological models of personality, but suggest the need for modification in others.

CSF 5-HIAA concentrations in anorexia nervosa: reduced values in underweight subjects normalize after weight gain

introduction It has been uncertain whether or not underweight anorectics have reduced concentrations of cerebrospinal fluid (CSF) 5hydroxyindolacetic acid (5HIAA) concentrations compared to controls. We previously reported that CSF 5-HIAA concentrations were significantly lower in eight underweight anorectics compared to the same patients after weight restoration (Kaye et al. 1984a). In that study, CSF S-HIAA levels for both underweight patients (as well as the same patients after weight correction) were similar to healthy control women. Gillberg ( 1983) reported that two underweight anorectics had CSF 5-HIAA levels that were below the range of age-matched controls. In contrast, Gemer et al. C 1984) found that underweight anorectics had normal basal CSF 5-HIAA levels. In our previous study. the number of under-

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 < 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.

Eating disorders and depression: Is there a serotonin connection?

Central serotonin pathways modulate eating patterns, and may also participate in the regulation of behavioral impulsivity and mood. Recent studies lend support to the hypothesis that impaired postingestive satiety in bulimia nervosa is associated with reduced hypothalamic serotonergic responsiveness. Serotonin dysregulation has been implicated in major depression, and may play a role in the increased prevalence of depressive episodes in patients with eating disorders. This review compares evidence for alterations in central serotonin regulation in patients with anorexia nervosa, bulimia nervosa, and depression. It is proposed that impaired synaptic transmission in functionally distinct serotonin pathways may result in concurrent or sequential periods of binge eating, behavioral impulsivity, and depression in patients with eating disorders.