5‐HT functioning and aggression in children with ADHD and disruptive behaviour disorders
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ABSTRACT: Acute tryptophan depletion (ATD) is a method of reducing central nervous serotonin (5-HT) synthesis in humans by administering an amino acid (AA) beverage lacking in tryptophan (TRP), the physiological precursor of 5-HT. However, to date, the use of conventional ATD protocols in children and adolescents was limited due to frequently observed side effects (e.g., vomiting and nausea). This study investigated the effects of diminished central nervous system 5-HT synthesis on plasma concentrations of relevant AAs and TRP influx into the brain in 24 healthy young adults using the ATD procedure Moja-De, a test protocol that has been used in preliminary research in youths. Twenty-four healthy participants received ATD and a TRP-balanced amino acid load (BAL) using a randomized double-blind within-subject crossover design. Plasma concentrations of the relevant AAs that compete with TRP on the same transport system were assessed at baseline and 90, 180, and 240 min after ATD/BAL intake. TRP influx across the blood–brain barrier was calculated using Michaelis–Menten kinetics with a correction for multiple substrate competition, indicating a significant decrease in TRP influx into the central nervous system under Moja-De. ATD Moja-De decreased TRP influx into the brain and central nervous system 5-HT synthesis safely and effectively and was well tolerated, allowing it to be used in children and adolescents. Future research into other secondary, compensatory effects induced by ATD in patients with neuropsychiatric disorders and healthy populations is needed. ATD Moja-De allows this type of research with a focus on a developmental viewpoint. Electronic supplementary material The online version of this article (doi:10.1007/s00702-012-0793-z) contains supplementary material, which is available to authorized users.Journal of Neural Transmission 05/2012; 119(9):1037-45. DOI:10.1007/s00702-012-0793-z · 2.87 Impact Factor
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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.Journal of Neural Transmission 12/2008; 116(1):105-8. DOI:10.1007/s00702-008-0146-0 · 2.87 Impact Factor
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ABSTRACT: Early-onset bipolar disorder (BD) and attention-deficit-hyperactivity disorder (ADHD) have recently been the subject of highly controversial debate, due to theories regarding underlying pathophysiological processes and a clinical overlap of symptoms. Epidemiological data, clinical aspects neuroimaging, neurochemical, and genetic studies suggest that there may be a possible relationship between biological factors and clinical characteristics in the development of symptoms. However, longitudinal data supporting the hypothesis of a diagnostic shift from BD to ADHD symptoms and vice versa are currently not available. These would be essential to enable further investigations into whether these two disorders possibly represent two different aspects of an underlying common psychopathophysiological entity.Dialogues in clinical neuroscience 02/2009; 11(1):63-72.