Reduced prolactin response to fenfluramine challenge in personality disorder patients is not due to deficiency of pituitary lactotrophs

Coccaro, Emil F.; Klar, Howard; Siever, Larry J.

doi:10.1016/0006-3223(94)90633-5

Cited by 22 publications

(8 citation statements)

References 7 publications

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“…Thus, aggression and suicidal behaviour may share common regulatory aspects that include a role for serotonin inputs to control or suppress the probability and seriousness of these behaviours. Other indices of serotonergic function in the brain, such as the prolactin response to serotonin release by fenfluramine, correlate with severity of past suicide attempts [37] and aggressive behaviours [38], and predict future suicide attempts [39]. Such findings are consistent with trait low serotonergic activity related to the diathesis for both suicidal behaviour and externally directed aggressive behaviour.…”

Section: A Stress-diathesis Model Of Suicidal Behaviourmentioning

confidence: 59%

The serotonergic system in mood disorders and suicidal behaviour

Mann

2013

Phil. Trans. R. Soc. B

186

117

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A stress-diathesis explanatory model of suicidal behaviour has proved to be of heuristic value, and both clinical and neurobiological components can be integrated into such a model. A trait deficiency in serotonin input to the anterior cingulate and ventromedial prefrontal cortex is found in association with suicide, and more recently non-fatal suicidal behaviour, and is linked to decision-making and suicide intent by imaging and related studies in vivo . The same neural circuitry and serotonin deficiency may contribute to impulsive aggressive traits that are part of the diathesis for suicidal behaviour and are associated with early onset mood disorders and greater risk for suicidal behaviour. Other brain areas manifest deficient serotonin input, that is, a trait related to recurrent major depressive disorder and bipolar disorder. Thus the serotonin system is involved in both the diathesis for suicidal behaviour in terms of decision-making, and to a major stressor, namely episodes of major depression.

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Section: A Stress-diathesis Model Of Suicidal Behaviourmentioning

confidence: 59%

The serotonergic system in mood disorders and suicidal behaviour

Mann

2013

Phil. Trans. R. Soc. B

186

117

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“…However, the functional status of lactotrophs and their tonic inhibition by dopamine, as assessed by prolactin secretion after infusion of thyrotropin-releasing hormone, are unrelated to fenfluramine-induced changes in circulating prolactin levels. 16 Some previous research has suggested that hypertension is associated with elevated basal prolactin concentration 17 and exaggerated prolactin response to the dopaminergic antagonist metaclopramide. 18,19 However, prolactin responses in individuals with a modest BP elevation in this study were blunted and therefore are inconsistent with a general increase in basal and stimulus-evoked prolactin release.…”

Section: Discussionmentioning

confidence: 99%

Inverse Relationship Between Fenfluramine-Induced Prolactin Release and Blood Pressure in Humans

Muldoon

Sved²,

Flory³

et al. 1998

Hypertension

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Abstract-Although substantial evidence from experimental animals suggests that augmentation and reduction in serotonergic neurotransmission both affect arterial blood pressure (BP), it is unknown whether "tonic" central serotonergic activity is related to resting BP variability in humans. We tested this hypothesis in a community sample by evaluating the relationship between resting BP and a neuropharmacologic index of brain serotonergic activity (the fenfluramine challenge test). Subjects were 270 generally healthy men and women aged 25 to 60 years who were not receiving prescribed antihypertensive or psychotropic medications. The sample included 216 non-Hispanic whites and 47 blacks. Resting systolic BP ranged from 85 to 161 mm Hg and diastolic from 58 to 98 mm Hg. Each subject received 0.55 to 0.65 mg/kg D,L-fenfluramine hydrochloride, and the plasma prolactin concentration was measured over 3.5 hours. Analyses revealed a linear, inverse relationship between the maximum fenfluramine-induced prolactin rise and systolic and diastolic BP in whites: rϭϪ0.36 and rϭϪ0.29, respectively (PϽ0.001 for both). These relationships were not observed in the black participants. In whites, the prolactin response to fenfluramine remained a significant predictor of systolic and diastolic BPs in multivariate models including age, gender, body mass index, physical activity, smoking, and alcohol consumption (PՅ0.001). When compared with subjects in the highest quartile of prolactin response, individuals whose prolactin responses to fenfluramine comprised the lowest quartile were 2.6 times more likely to have a resting systolic/diastolic BP of Ͼ135/85 mm Hg. These data reveal that in white but not black adults, fenfluramine- Conversely, experimental manipulation of BP has also been found to influence serotonergic neural transmission in certain brain loci. However, it has never been demonstrated whether central serotonergic activity, under resting or basal conditions, is related to individual differences in BP.In the present study, central serotonergic activity was assessed with a neuroendocrine challenge with D,Lfenfluramine hydrochloride. Fenfluramine enhances serotonin neurotransmission by both inducing presynaptic release of serotonin stores and inhibiting synaptic reuptake.2,3 Activation of serotonergic receptors in the hypothalamus in turn promotes the pituitary release of prolactin into the circulation. Therefore, the rise in plasma prolactin concentration after fenfluramine administration reflects "net" serotonergic responsivity, as influenced by variability in presynaptic events (ie, synthesis, storage, release, and reuptake) and activation of hypothalamic 5-HT receptors. In this article we report an inverse correlation between interindividual variability in prolactin response to fenfluramine and resting BP that is independent of traditional risk factors for hypertension. Methods SubjectsThe 270 adult participants described in this report were recruited from the Pittsburgh area through media advertisements and local distrib...

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“…However, the levorotary isomer of fenfluramine may also affect dopaminergic and noradrenergic activity in rodents (46), and PRL release may reflect nonserotonergic influences on the secretory capacity of the lactotroph. Nonetheless, PRL responses to d,l-fenfluramine have been found to correlate highly with responses to the more selective d-fenfluramine (47,48). It has also been reported that PRL responses evoked by d,l-fenfluramine are unrelated to the PRL response to TSH-releasing hormone, thus tending to exclude variability in lactotroph function and dopaminergic inhibition as an explanation for individual differences in the fenfluramine challenge test (48).…”

Section: Discussionmentioning

confidence: 99%

Low Central Nervous System Serotonergic Responsivity Is Associated with the Metabolic Syndrome and Physical Inactivity

Muldoon¹,

Mackey

Williams

et al. 2004

The Journal of Clinical Endocrinology & Metabolism

111

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The metabolic syndrome, recognized by the co-occurrence of general or abdominal obesity, hypertension, dyslipidemia, insulin resistance, and dysglycemia, appears to involve disturbances in metabolism, autonomic function, and health-related behaviors. However, physiological processes linking the components of the metabolic syndrome remain obscure. The current study examined associations of central nervous system serotonergic function with each metabolic syndrome risk variable, the metabolic syndrome, and physical activity. The subjects were 270 adult volunteers who participated in a study of cardiovascular disease risk factors and neurobehavioral functioning. Central serotonergic responsivity was indexed as the prolactin (PRL) response evoked by the serotoninreleasing agent, fenfluramine. Across the sample, low PRL response was associated with greater body mass index, higher concentrations of triglycerides, glucose, and insulin, higher systolic and diastolic blood pressure, greater insulin resistance, and less physical activity (P < 0.03-0.001). There also existed an inverse linear relationship between PRL response and the number of metabolic syndrome risk factors individuals possessed (P for trend ‫؍‬ 0.002). Finally, a 1 SD decline in PRL response was associated with an odds ratio for the metabolic syndrome of 2.05 (95% confidence interval, 1.10 -3.

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Reduced prolactin response to fenfluramine challenge in personality disorder patients is not due to deficiency of pituitary lactotrophs

Cited by 22 publications

References 7 publications

The serotonergic system in mood disorders and suicidal behaviour

The serotonergic system in mood disorders and suicidal behaviour

Inverse Relationship Between Fenfluramine-Induced Prolactin Release and Blood Pressure in Humans

Low Central Nervous System Serotonergic Responsivity Is Associated with the Metabolic Syndrome and Physical Inactivity

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