Prolactin response to d-fenfluramine is blunted in people with anorexia nervosa

Monteleone, Palmiero; Brambilla, Frăncesca; Bortolotti, Francesca; Rocca, Antonietta La; Maj, Mario

doi:10.1192/bjp.172.5.439

Cited by 43 publications

(26 citation statements)

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“…However, in our patients and controls, no correlation was observed between PRL values in basal conditions or after placebo administration and BMI scores, which casts doubts on the hypothesis that the hormonal pathology is only a starva-Brambilla/Bellodi/Arancio/Limonta/ Ferrari/Solerte tion-related phenomenon. Since 5-HT stimulates PRL secretion, it is possible that the reduced hormonal levels are linked to a secretory deficiency of the neurotransmitter [52]. The blunted PRL responses to D-Fen stimulation agree with the data of our previous study in another group of anorexics [52] and with those in the literature, being expression of a reduced 5-HT function [45][46][47][48][49][50][51].…”

Section: Discussionsupporting

confidence: 82%

“…Basal PRL secretion has been repeatedly reported to be reduced in AN during the phase of starvation and to return to normal after weight recovery, suggesting that the hormonal impairment is due to reduced food consumption and weight loss [50,52,67]. However, in our patients and controls, no correlation was observed between PRL values in basal conditions or after placebo administration and BMI scores, which casts doubts on the hypothesis that the hormonal pathology is only a starva-Brambilla/Bellodi/Arancio/Limonta/ Ferrari/Solerte tion-related phenomenon.…”

Section: Discussionmentioning

confidence: 99%

“…Impairments of central 5-HT function have been reported in AN, with reduced 5-HT secretion during the active phase of the disease, a return to normal during refeeding and an increase to higher than normal activity after recovery [45][46][47][48][49][50][51][52], but their relation to aggressiveness has never been considered.…”

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confidence: 99%

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Neurotransmitter and Hormonal Background of Hostility in Anorexia nervosa

et al. 2001

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Marked hostility toward relatives, therapists and friends is very frequently observed in anorexia nervosa (AN) as expression of outward-directed aggressiveness which interferes with the therapeutic programs of the patients. With the purpose to investigate this aspect of the disorder and its biological background, we studied in anorexics some neurotransmitter-hormonal secretions which are known to modulate aggressivity-hostility by measuring plasma concentrations of total (TT) and free testosterone (FT), total estrogens (TE), the TT/E and FT/TE ratios, and the serotonergic function by measuring basal prolactin (PRL) levels and responses to stimulation with the specific serotonin (5-HT)-releasing agent D-fenfluramine (D-Fen). In 13 women with AN, 5 of the restricted (AN-R) and 8 of the bingeing/purging type (AN-BP) in an active phase of the disease, and in 13 healthy controls matched for sex and age, we measured hostility by the SCL-90 scale (subscale items 11, 24, 63, 67, 74, 81). Basal TT, FT, TE, TT/TE, FT/TE, PRL values and PRL responses to D-Fen and to saline administration were measured radioimmunologically in AN patients and controls. Hostility was significantly higher in AN patients than in controls, TT, FT and TE concentrations were significantly lower in AN patients than in controls, TT/TE ratio was significantly higher in AN patients than in controls, and FT/TE ratio was not different in the two groups. In AN patients and controls, hostility correlated positively with TT and FT values. Basal PRL values and responses to D-Fen administration were significantly lower in anorexics than in controls, but they did not correlate with the degree of hostility in either patients or controls. In conclusion, hostility is higher than normal in anorexics, and its severity seems to be linked to the secretion of FT and not to the alterations in the 5-HT function.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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Neurotransmitter and Hormonal Background of Hostility in Anorexia nervosa

et al. 2001

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“…Systematic brain imaging of patients with OCPD has yet to be performed. Blunted fenfluramine-mediated prolactin responses have been reported in OCPD and in several other disorders, including depression, anorexia nervosa, and binge-eating disorder, [113][114][115] suggesting similarities in serotonergic processing. Blunted fenfluramine responses have also been reported for OCD, but increased responses have also been reported (reviewed in Fineberg et al).…”

Section: Neurocognitive Endophenotypesmentioning

confidence: 97%

Obsessive-compulsive (anankastic) personality disorder: toward the ICD-11 classification

Fineberg

Reghunandanan

Kolli

et al. 2014

Rev. Bras. Psiquiatr.

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Obsessive-compulsive personality disorder (OCPD) is an early-onset disorder characterized by perfectionism, need for control, and cognitive rigidity. Its nosological status is currently under review. Historically, OCPD has been conceptualized as bearing a close relationship with obsessivecompulsive disorder (OCD). In this article, we discuss the diagnosis of OCPD in anticipation of its review for the ICD-11, from the perspective of clinical utility, global applicability, and research planning. Considering the recent establishment of an obsessive-compulsive and related disorders (OCRD) category in DSM-5, we focus on the relationship between OCPD and the disorders that are currently thought to bear a close relationship with OCD, including DSM-5 OCRD, and other compulsive disorders such as eating disorder and autistic spectrum disorder (that were not included in the DSM-5 OCRD category), as well as with the personality disorders, focusing on nosological determinants such as phenomenology, course of illness, heritability, environmental risk factors, comorbidity, neurocognitive endophenotypes, and treatment response. Based on this analysis, we attempt to draw conclusions as to its optimal placement in diagnostic systems and draw attention to key research questions that could be explored in field trials.

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“…An involvement of serotonin in the pathophysiology of AN gains support from the observations of altered cerebrospinal fluid serotonin metabolite levels (Gillberg 1983;Kaye et al 1984;Kaye and Weltzin 1991) and abnormal hormonal responses to serotonergic probes (Brewerton and Jimerson 1996;Goodwin et al 1989;Hadigan et al 1995;Monteleone et al 1998;Ward et al 1998; see also O'Dwyer et al 1996) in AN subjects, as well as from the fact that treatment with serotonin reuptake inhibitors may prevent relapse in weight-restored AN subjects Mayer and Walsh 1998;Kaye et al 2001). …”

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confidence: 99%

Association between a Polymorphism of the 5-HT2C Receptor and Weight Loss in Teenage Girls

Westberg

Bah

Råstam

et al. 2002

Neuropsychopharmacology

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Receptors of the 5-HT2C subtype are assumed to be involved in the influence of serotonin on food intake. A polymorphism in the coding region of the gene for this receptor, resulting inData from family and twin studies suggest that genetic factors may contribute to the development of eating disorders such as anorexia nervosa (AN) (Holland et al. 1988;Gorwood et al. 1998;Lilenfeld et al. 1998;Bulik et al. 2000;Strober et al. 2000;Kortegaard et al. 2001). As yet, no consistent findings regarding associations between specific candidate genes and eating behavior have however been reported.Serotonin appears to exert an important inhibitory influence on food intake in experimental animals, and serotonin-facilitating compounds are known to reduce food intake also in humans (Leibowitz and Alexander 1998). An involvement of serotonin in the pathophysiology of AN gains support from the observations of altered cerebrospinal fluid serotonin metabolite levels (Gillberg 1983;Kaye et al. 1984;Kaye and Weltzin 1991) and abnormal hormonal responses to serotonergic probes (Brewerton and Jimerson 1996;Goodwin et al. 1989;Hadigan et al. 1995;Monteleone et al. 1998;Ward et al. 1998; see also O'Dwyer et al. 1996) in AN subjects, as well as from the fact that treatment with serotonin reuptake inhibitors may prevent relapse in weight-restored AN subjects Mayer and Walsh 1998;Kaye et al. 2001 NO . 6 Pharmacological studies in rats (Dourish et al. 1989;Kennett and Curzon 1991), and experiments using knockout mice (Tecott et al. 1995), suggest that the influence of serotonin on food intake is partly mediated by 5-HT2C receptors. This notion gains support from the observation that weight gain is a common side-effect of antidepressant and antipsychotic drugs acting as antagonists at 5-HT2C receptors, and by preliminary data suggesting that 5-HT2C-blocking compounds may be effective for the treatment of AN (Goldberg et al. 1979;Halmi et al. 1986;La Via et al. 2000). Of interest in this context is also the finding that dieting may increase 5-HT2C receptor responsiveness in humans (Cowen et al. 1996). Previous studies have suggested that AN may be associated with a polymorphism in the gene coding for another 5-HT2 receptor-the 5-HT2A subtype-but subsequent studies on this issue have yielded conflicting data (Collier et al. 1997;Ziegler et al. 1999). With respect to a possible relationship between the 5-HT2C receptor gene and AN, the literature is as yet sparse.The 5-HT2C receptor gene is located on the X chromosome, at q24, and contains a single nucleotide polymorphism, resulting in a cysteine to serine substitution at position 23 (cys23ser) of the receptor (Lappalainen et al. 1995). The aim of this study was to examine the possible association between this polymorphism and weight loss (regardless of underlying diagnosis) in teenage girls. METHOD SubjectsThe original purpose of this investigation was to establish the rate of AN in 16-year-old girls in Göteborg, and to compare AN girls and age-, sex-, and school-matched controls with respec...

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Prolactin response to d-fenfluramine is blunted in people with anorexia nervosa

Abstract: These results support a dysfunction of 5-HT transmission in anorexia nervosa. This dysfunction does not seem to be related to concomitant depressive or obsessive--compulsive symptoms or to the level of aggressiveness of the patients.

Cited by 43 publications

References 17 publications

Neurotransmitter and Hormonal Background of Hostility in Anorexia nervosa

Neurotransmitter and Hormonal Background of Hostility in Anorexia nervosa

Obsessive-compulsive (anankastic) personality disorder: toward the ICD-11 classification

Association between a Polymorphism of the 5-HT2C Receptor and Weight Loss in Teenage Girls

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