Reduced serotonergic functioning changes heart rate in ADHD
ABSTRACT Reduced mean heart rate (HR) was shown to be a biophysiological marker for aggression, which in turn was proven to be related to changed serotonergic neurotransmission. A total of 16 ADHD-diagnosed boys were subjected to rapid tryptophan depletion (RTD) and a placebo in a double-blind within-subject crossover-design. Mean HR was assessed under RTD/placebo. Low impulsive patients behaving aggressively under RTD showed a lowered HR under RTD versus placebo. Diminished 5-HT functioning was associated with lowered HR and aggressive behaviour.
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- "Paradoxically, however, starting early in life, children with conduct problems, and adults with antisocial personality disorder, both of which groups are prone to episodic violence, are found to have lower mean heart rates than controls . Similar findings have been reported in children with ADHD [114, 115]. Conversely, healthy children who secrete relatively higher levels of adrenaline tend to be less aggressive, less restless, more emotionally stable, and better able to concentrate than children who secrete less adrenaline . "
ABSTRACT: Learning disorders are often associated with persistent hyperactivity and aggression and are part of a spectrum of neurodevelopmental disorders. A potential clue to understanding these linked phenomena is that physical exercise and passive forms of stimulation are calming, enhance cognitive functions and learning, and are recommended as complementary treatments for these problems. The theory is proposed that hyperactivity and aggression are intense stimulation-seeking behaviors (SSBs) driven by increased brain retinergic activity, and the stimulation thus obtained activates opposing nitrergic systems which inhibit retinergic activity, induce a state of calm, and enhance cognition and learning. In persons with cognitive deficits and associated behavioral disorders, the retinergic system may be chronically overactivated and the nitrergic system chronically underactivated due to environmental exposures occurring pre- and/or postnatally that affect retinoid metabolism or expression. For such individuals, the intensity of stimulation generated by SSB may be insufficient to activate the inhibitory nitrergic system. A multidisciplinary research program is needed to test the model and, in particular, to determine the extent to which applied physical treatments can activate the nitrergic system directly, providing the necessary level of intensity of sensory stimulation to substitute for that obtained in maladaptive and harmful ways by SSB, thereby reducing SSB and enhancing cognitive skills and performance.09/2012; 2012:589792. DOI:10.5402/2012/589792
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- "A modified mixture, ATD Moja-De, involves a body weight adapted administration of amino acids and lower concentration of methionine relative to conventional mixtures, which makes it less nauseating in humans. Its use has proven to be a safe and effective method of TRP depletion even in children and adolescents , , , , , , . It has been shown that ATD Moja-De significantly lowers influx of TRP into the brain in humans , but its specific effect on brain 5-HT has not yet been established, which was the aim of this study. "
ABSTRACT: Acute tryptophan depletion (ATD) is a method of lowering brain serotonin (5-HT). Administration of large neutral amino acids (LNAA) limits the transport of endogenous tryptophan (TRP) across the blood brain barrier by competition with other LNAAs and subsequently decreases serotonergic neurotransmission. A recent discussion on the specificity and efficacy of the ATD paradigm for inhibition of central nervous 5-HT has arisen. Moreover, side effects such as vomiting and nausea after intake of amino acids (AA) still limit its use. ATD Moja-De is a revised mixture of AAs which is less nauseating than conventional protocols. It has been used in preliminary clinical studies but its effects on central 5-HT mechanisms and other neurotransmitter systems have not been validated in an animal model. We tested ATD Moja-De (TRP-) in two strains of mice: C57BL/6J, and BALB/cJ, which are reported to have impaired 5-HT synthesis and a more anxious phenotype relative to other strains of mice. ATD Moja-De lowered brain TRP, significantly decreased 5-HT synthesis as indexed by 5-HTP levels after decarboxlyase inhibition, and lowered 5-HT and 5-HIAA in both strains of mice, however more so in C57BL/6J than in BALB/cJ. Dopamine and its metabolites as well as norepinephrine were not affected. A balanced (TRP+) control mixture did not raise 5-HT or 5-HIAA. The present findings suggest that ATD Moja-De effectively and specifically suppresses central serotonergic function. These results also demonstrate a strain-specific effect of ATD Moja-De on anxiety-like behavior.PLoS ONE 05/2012; 7(5):e35916. DOI:10.1371/journal.pone.0035916 · 3.23 Impact Factor
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- "This finding is of particular relevance as it suggests that both adolescent and adult low trait-impulsive patients with ADHD may respond with increased reactive aggression under ATD after a low provocation . In addition, low-impulsive patients in particular showed a lowered heart rate under ATD  while behaving aggressively . This is consistent with previous findings showing that the low provocation condition in the used behavioral paradigm is the most effective to assess anger reactive responses , . "
ABSTRACT: The neurotransmitter serotonin (5-HT) has been linked to the underlying neurobiology of aggressive behavior, particularly with evidence from studies in animals and humans. However, the underlying neurobiology of aggression remains unclear in the context of attention-deficit/hyperactivity disorder (ADHD), a disorder known to be associated with aggression and impulsivity. We investigated the effects of acute tryptophan depletion (ATD), and the resulting diminished central nervous serotonergic neurotransmission, on reactive aggression in healthy controls and adults with ADHD. Twenty male patients with ADHD and twenty healthy male controls were subjected to ATD with an amino acid (AA) beverage that lacked tryptophan (TRP, the physiological precursor of 5-HT) and a TRP-balanced AA beverage (BAL) in a double-blind, within-subject crossover-study over two study days. We assessed reactive aggression 3.25 hours after ATD/BAL intake using a point-subtraction aggression game (PSAG) in which participants played for points against a fictitious opponent. Point subtraction was taken as a measure for reactive aggression. Lowered rates of reactive aggression were found in the ADHD group under ATD after low provocation (LP), with controls showing the opposite effect. In patients with ADHD, trait-impulsivity was negatively correlated with the ATD effect on reactive aggression after LP. Statistical power was limited due to large standard deviations observed in the data on point subtraction, which may limit the use of this particular paradigm in adults with ADHD. Together with previous findings, the data provide preliminary evidence of an inverse association between trait-impulsivity and the ATD effect on reactive aggression after LP (as assessed by the PSAG) in patients with ADHD and that this relationship can be found in both adolescents and adults. Because of limited statistical power larger sample sizes are needed to find main effects of ATD/BAL administration on reactive aggression in adults with ADHD.PLoS ONE 03/2012; 7(3):e32023. DOI:10.1371/journal.pone.0032023 · 3.23 Impact Factor