The Effects of Acute Tryptophan Depletion on Reactive Aggression in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and Healthy Controls

Background: 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. Methodology/Principal Findings: 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 TRPbalanced 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

Effects of serotonin depletion and dopamine depletion on bimodal divided attention.

OBJECTIVES:This study aimed to explore the effects of acute phenylalanine-tyrosine depletion (APTD) and acute tryptophan depletion (ATD) on bimodal divided attention. A balanced amino acid mixture (BAL) served as control condition. METHODS:54 healthy adults (age: M = 23.8 years) were randomly assigned to APTD, ATD or BAL in a double-blind, between-subject approach. Divided attention was assessed after 4 hours. Blood samples were taken before and 6 hours after challenge intake. RESULTS:Amino acid concentrations following challenge intake significantly decreased (all p ≤ .01). There was a significant difference in the mean reaction time (RT) towards auditory stimuli, but not towards visual stimuli between the groups. Post-hoc comparison of mean RT's (auditory stimuli) showed a significant difference between ATD (RT = 604.0 ms, SD = 56.9 ms) and APTD (RT = 556.4 ms, SD = 54.2 ms; p = .037), but no RT-difference between ATD and BAL or APTD and BAL (RT = 573.6 ms, SD = 45.7 ms). CONCLUSIONS:The results indicate a possible dissociation between the effects of a diminished brain 5-HT and DA synthesis on the performance in a bimodal divided attention task. The difference was exclusively observed within the RT towards auditory signals. This is an Accepted Manuscript of an article published by Taylor & Francis in the World Journal of Biological Psychiatry on 08 October 2018, available online: http://www.tandfonline.com/10.1080/15622975.2018.153211

Effects of Acute Tryptophan Depletion on Brain Serotonin Function and Concentrations of Dopamine and Norepinephrine in C57BL/6J and BALB/cJ Mice

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

Serotonergic Contribution to Boys' Behavioral Regulation

Animal and human adult studies reveal a contribution of serotonin to behavior regulation. Whether these findings apply to children is unclear. The present study investigated serotonergic functioning in boys with a history of behavior regulation difficulties through a double-blind, acute tryptophan supplementation procedure.Participants were 23 boys (age 10 years) with a history of elevated physical aggression, recruited from a community sample. Eleven were given a chocolate milkshake supplemented with 500 mg tryptophan, and 12 received a chocolate milkshake without tryptophan. Boys engaged in a competitive reaction time game against a fictitious opponent, which assessed response to provocation, impulsivity, perspective taking, and sharing. Impulsivity was further assessed through a Go/No-Go paradigm. A computerized emotion recognition task and a staged instrumental help incident were also administered.Boys, regardless of group, responded similarly to high provocation by the fictitious opponent. However, boys in the tryptophan group adjusted their level of responding optimally as a function of the level of provocation, whereas boys in the control group significantly decreased their level of responding towards the end of the competition. Boys in the tryptophan group tended to show greater perspective taking, tended to better distinguish facial expressions of fear and happiness, and tended to provide greater instrumental help to the experimenter.The present study provides initial evidence for the feasibility of acute tryptophan supplementation in children and some effect of tryptophan supplementation on children's behaviors. Further studies are warranted to explore the potential impact of increased serotonergic functioning on boys' dominant and affiliative behaviors

Gas flows, star formation and galaxy evolution

In the first part of this article we show how observations of the chemical evolution of the Galaxy: G- and K-dwarf numbers as functions of metallicity, and abundances of the light elements, D, Li, Be and B, in both stars and the interstellar medium (ISM), lead to the conclusion that metal poor HI gas has been accreting to the Galactic disc during the whole of its lifetime, and is accreting today at a measurable rate, ~2 Msun per year across the full disc. Estimates of the local star formation rate (SFR) using methods based on stellar activity, support this picture. The best fits to all these data are for models where the accretion rate is constant, or slowly rising with epoch. We explain here how this conclusion, for a galaxy in a small bound group, is not in conflict with graphs such as the Madau plot, which show that the universal SFR has declined steadily from z=1 to the present day. We also show that a model in which disc galaxies in general evolve by accreting major clouds of low metallicity gas from their surroundings can explain many observations, notably that the SFR for whole galaxies tends to show obvious variability, and fractionally more for early than for late types, and yields lower dark to baryonic matter ratios for large disc galaxies than for dwarfs. In the second part of the article we use NGC 1530 as a template object, showing from Fabry-Perot observations of its Halpha emission how strong shear in this strongly barred galaxy acts to inhibit star formation, while compression acts to stimulate it.Comment: 20 pages, 10 figures, to be presented at the "Penetrating Bars through Masks of Cosmic Dust" conference in South Africa, proceedings published by Kluwer, Eds. D.L. Block, K.C. Freeman, I. Puerari, & R. Groes

Effects of a structured 20-session slow-cortical-potential-based neurofeedback program on attentional performance in children and adolescents with attention-deficit hyperactivity disorder: retrospective analysis of an open-label pilot-approach and 6-month follow-up

Johanna S Albrecht,1–3 Sarah Bubenzer-Busch,1,2 Anne Gallien,1,4 Eva Lotte Knospe,1,2 Tilman J Gaber,1,2,5 Florian D Zepf1,2,6,7 1Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University, Aachen, 2JARA Translational Brain Medicine, Aachen & Jülich, 3Center for Pediatrics and Adolescent Medicine Elisabeth Hospital Rheydt, Mönchengladbach, 4Clinic for Neurology, Medical Center City Region Aachen, Würselen, 5NeuroCare Group, Munich, Germany; 6Centre and Discipline of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, School of Paediatrics and Child Health & School of Psychiatry and Clinical Neurosciences, Faculty of Medicine, Dentistry and Health Sciences, The University of Western Australia, 7Department of Health in Western Australia, Specialised Child and Adolescent Mental Health Services, Perth, WA, Australia Objective: The aim of this approach was to conduct a structured electroencephalography-based neurofeedback training program for children and adolescents with attention-deficit hyperactivity disorder (ADHD) using slow cortical potentials with an intensive first (almost daily sessions) and second phase of training (two sessions per week) and to assess aspects of attentional performance. Patients and methods: A total of 24 young patients with ADHD participated in the 20-session training program. During phase I of training (2 weeks, 10 sessions), participants were trained on weekdays. During phase II, neurofeedback training occurred twice per week (5 weeks). The patients’ inattention problems were measured at three assessment time points before (pre, T0) and after (post, T1) the training and at a 6-month follow-up (T2); the assessments included neuropsychological tests (Alertness and Divided Attention subtests of the Test for Attentional Performance; Sustained Attention Dots and Shifting Attentional Set subtests of the Amsterdam Neuropsychological Test) and questionnaire data (inattention subscales of the so-called Fremdbeurteilungsbogen für Hyperkinetische Störungen and Child Behavior Checklist/4–18 [CBCL/4–18]). All data were analyzed retrospectively. Results: The mean auditive reaction time in a Divided Attention task decreased significantly from T0 to T1 (medium effect), which was persistent over time and also found for a T0–T2 comparison (larger effects). In the Sustained Attention Dots task, the mean reaction time was reduced from T0–T1 and T1–T2 (small effects), whereas in the Shifting Attentional Set task, patients were able to increase the number of trials from T1–T2 and significantly diminished the number of errors (T1–T2 & T0–T2, large effects). Conclusion: First positive but very small effects and preliminary results regarding different parameters of attentional performance were detected in young individuals with ADHD. The limitations of the obtained preliminary data are the rather small sample size, the lack of a control group/a placebo condition and the open-label approach because of the clinical setting and retrospective analysis. The value of the current approach lies in providing pilot data for future studies involving larger samples. Keywords: SCP, neurofeedback, ADHD, children, adolescents, attentio