Neuroendocrine Response to Fenfluramine Challenge in Boys

Pine, Daniel S.; Coplan, Jeremy D.; Wasserman, Gail A.; Miller, Linda B.; Fried, Jane; Davies, Mark; Cooper, Thomas B.; Greenhill, Laurence L.; Shaffer, David; Parsons, Bruce

doi:10.1001/archpsyc.1997.01830210083010

Cited by 115 publications

(33 citation statements)

References 55 publications

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“…Likewise, increased prolactin responses to fenfluramine were observed in boys with adverse rearing environment (Pine et al 1997). Since prolactin but not cortisol release is mediated via 5-HT 1A receptors, these findings suggest sensitization of these receptors due to early life stress.…”

Section: Studies In Childrenmentioning

confidence: 70%

The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies

Heim

Nemeroff

2001

Biological Psychiatry

2,420

1,506

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Section: Studies In Childrenmentioning

confidence: 70%

The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies

Heim

Nemeroff

2001

Biological Psychiatry

2,420

1,506

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“…9 Several lines of evidence have indicated abnormal serotonergic function in children with disruptive behaviour disorders (ADHD, ODD, CD) who display marked problems with hyperactivity, impulsivity, and aggression. [10][11][12][13][14] Animal models of ADHD have also been useful in implicating a role for serotonin in the control of attention, impulsivity, and hyperactivity. Rodents that had poorer performance on a task measuring attention and impulsivity had a greater index of serotonin utilization in the frontal cortex.…”

Section: Using the Transmission Disequilibrium Test (Tdt)mentioning

confidence: 99%

Evidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHD)

et al. 2000

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A recent study demonstrated that treatment of hyperactive mice with psychostimulants and serotonergic agents produced a calming effect that was dependent on serotonergic neurotransmission and was not associated with any changes in extracellular dopamine levels. 1 The complex interaction between the serotonergic and dopaminergic neurotransmitter systems suggests that a balance between the two systems may be necessary for mediating hyperactive behaviour. Defects in serotonin system genes, therefore, may disrupt normal brain serotonin function causing an imbalance between these neurotransmitter systems leading to the development of attention deficit hyperactivity disorder (ADHD). Attention deficit hyperactivity disorder (ADHD) is a common childhood disruptive behavioral disorder affecting between 3-5% of school age children who display persistent patterns of inattention and hyperactivity/impulsivity causing impairment in academic, social, and emotional development. 2 ADHD children frequently exhibit a variety of other comorbid conditions such as learning disorder, mood disorder, and other disruptive behavior disorders including oppositional defiant disorder (ODD) and conduct disorder (CD).While the exact mechanisms for the disorder are unknown, research has suggested abnormalities in the catecholaminergic and serotonergic systems. Support for a catecholaminergic hypothesis has been based on evidence from neuroimaging studies which have suggested reduced functioning in frontal-striatal regions, whose pathways are rich in catecholamines, notably dopamine. 3 Furthermore, stimulant medications, such as methylphenidate (Ritalin™), whose primary site of action is the dopamine transporter, have shown widespread clinical success in the treatment of ADHD. The significant interaction between the dopaminergic and serotonergic systems, 4 however, suggests that dopamine dysfunction may not be the sole basis for the development of ADHD.Evidence for the serotonergic hypothesis began two decades ago when it was found that whole blood and serum serotonin (5-HT) concentrations were decreased in children with ADHD. 5,6 These results have been further supported by a recent study that also found a tendency towards low platelet serotonin in a sample of children with severe ADHD. 7 Additional support for a serotonin hypothesis is demonstrated by the moderate efficacy of several serotonin enhancing agents in the treatment of ADHD including selective serotonin reuptake inhibitors (SSRIs) 8 and certain selective monoamine oxidase inhibitors. 9 Several lines of evidence have indicated abnormal serotonergic function in children with disruptive behaviour disorders (ADHD, ODD, CD) who display marked problems with hyperactivity, impulsivity, and aggression. [10][11][12][13][14] Animal models of ADHD have also been useful in implicating a role for serotonin in the control of attention, impulsivity, and hyperactivity. Rodents that had poorer performance on a task measuring attention and impulsivity had a greater index of serotonin utilization in t...

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“…Pharmacological challenge studies, which assess 5-HT function by measuring the prolactin response to the 5-HT-release/reuptake inhibitor fenfluramine, have yielded conflicting results. The prolactin-fenfluramine response was found to be significantly enhanced in aggressive boys with ADHD, when compared with non-aggressive ADHD boys [16] ; however, this relationship was only true for younger ADHD boys [17,18] , and was found to be unrelated to aggression in older ADHD boys [19] . It has been suggested that aggressive ADHD children who initially have an enhanced prolactin-fenfluramine response, fail to undergo normal developmental changes in 5-HT function and subsequently might have a blunted response.…”

Section: Introductionmentioning

confidence: 99%

Influence of Rapid Tryptophan Depletion on Laboratory-Provoked Aggression in Children with ADHD

et al. 2007

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Background: The present study investigated the effects of rapid tryptophan depletion (RTD), and the ensuing reduction of central nervous system levels of serotonin (5-HT), upon reactive aggression in patients with attention deficit/hyperactivity disorder (ADHD). Furthermore, it was asked whether the relation between 5-HT function and behavioural aggression in patients is influenced by their age, the intensity of their attention problems or their comorbid symptoms. Methods: The study employed a double-blind, within-subject crossover design. On day 1, 22 male adolescent patients with ADHD were subjected to RTD and the subsequent reduction of central 5-HT levels. On day 2, they received a tryptophan-balanced amino acid mixture (BAL), which acted as a placebo. On both days, 4.5 h after the intake of the RTD/BAL amino acids, reactive aggressive behaviour was provoked using a competitive reaction time game, which consisted of both high and low provocation conditions. Results: The number of aggressive responses was significantly higher after low provocation during acute tryptophan depletion, in comparison to the placebo. Furthermore, this study provides evidence that neither age nor the intensity of attention symptoms in ADHD patients had an impact on the relation between 5-HT and reactive aggression. Conclusion: This study indicates that in children with ADHD, there is an inverse relationship between 5-HT and aggression.

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Neuroendocrine Response to Fenfluramine Challenge in Boys

Abstract: In young boys, aggressive behavior and social circumstances that are conducive to the development of aggressive behavior are positively correlated with a marker of central serotonergic activity.

Cited by 115 publications

References 55 publications

The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies

The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies

Evidence for the serotonin HTR2A receptor gene as a susceptibility factor in attention deficit hyperactivity disorder (ADHD)

Influence of Rapid Tryptophan Depletion on Laboratory-Provoked Aggression in Children with ADHD

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