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1.
World J Biol Psychiatry ; 21(3): 183-194, 2020 03.
Article in English | MEDLINE | ID: mdl-30295116

ABSTRACT

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: Fifty-three healthy adults (final analyzed sample was N = 49, 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 h. Blood samples were taken before and 6 h after challenge intake.Results: Amino acid concentrations following challenge intake significantly decreased (all P ≤ 0.01). 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 RTs (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 = 0.037), 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.


Subject(s)
Attention , Dopamine , Serotonin , Adult , Attention/drug effects , Cross-Over Studies , Dopamine/metabolism , Double-Blind Method , Humans , Serotonin/metabolism , Tryptophan/physiology , Young Adult
2.
Acta Psychiatr Scand ; 134(2): 161-71, 2016 08.
Article in English | MEDLINE | ID: mdl-27145324

ABSTRACT

OBJECTIVE: Alterations of the default mode network (DMN) have been described in patients with neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), and the neurotransmitter serotonin (5-HT) is known to modulate DMN activity. This study aimed to explore the role of 5-HT on the DMN and its functional connectivity (FC) in young patients with ADHD. METHODS: Young male patients with ADHD (n = 12) and healthy controls (n = 10) (both aged 12-17 years) were subjected to acute tryptophan depletion (ATD) and subsequently diminished brain 5-HT synthesis. Three hours after challenge intake (ATD or a balanced control condition, BAL), resting state fMRI scans were obtained. RESULTS: In patients, ATD led to attenuated FC of the right superior premotor cortex (BA 6) with the DMN, comparable to the extent found in controls after BAL administration. ATD lowered FC of the left somatosensory cortex (BA 3) with the DMN, independently of the factor group, but with stronger effects in controls. CONCLUSIONS: Data reveal a serotonergic modulation of FC between BA 6 and 3, known to be relevant for motor planning and sensory perception, and the DMN, thereby possibly pointing toward ATD acting beneficially on neural planning of motor activity in patients with ADHD.


Subject(s)
Attention Deficit Disorder with Hyperactivity/physiopathology , Brain/physiopathology , Neural Pathways/physiopathology , Tryptophan/deficiency , Adolescent , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Attention Deficit Disorder with Hyperactivity/metabolism , Brain/diagnostic imaging , Brain/metabolism , Brain Mapping/methods , Child , Humans , Magnetic Resonance Imaging/methods , Male , Neural Pathways/diagnostic imaging , Neural Pathways/metabolism , Rest , Serotonin/metabolism
3.
Amino Acids ; 48(4): 1109-1120, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26767373

ABSTRACT

The default mode network (DMN) plays a central role in intrinsic thought processes. Altered DMN connectivity has been linked to diminished cerebral serotonin synthesis. Diminished brain serotonin synthesis is further associated with a lack of impulse control and various psychiatric disorders. Here, we investigated the serotonergic modulation of intrinsic functional connectivity (FC) within the DMN in healthy adult females, controlling for the menstrual cycle phase. Eighteen healthy women in the follicular phase (aged 20-31 years) participated in a double-blind controlled cross-over study of serotonin depletion. Acute tryptophan depletion (ATD) and a balanced amino acid load (BAL), used as the control condition, were applied on two separate days of assessment. Neural resting state data using functional magnetic resonance imaging (fMRI) and individual trait impulsivity scores were obtained. ATD compared with BAL significantly reduced FC with the DMN in the precuneus (associated with self-referential thinking) and enhanced FC with the DMN in the frontal cortex (associated with cognitive reasoning). Connectivity differences with the DMN between BAL and ATD in the precentral gyrus were significantly correlated with the magnitude of serotonin depletion. Right medial frontal gyrus and left superior frontal gyrus connectivity differences with the DMN were inversely correlated with trait impulsivity. These findings partially deviate from previous findings obtained in males and underline the importance of gender-specific studies and controlling for menstrual cycle to further elucidate the mechanism of ATD-induced changes within intrinsic thought processes.


Subject(s)
Follicular Phase/physiology , Frontal Lobe/physiology , Nerve Net/physiology , Parietal Lobe/physiology , Rest/physiology , Serotonin/biosynthesis , Adult , Affect/drug effects , Affect/physiology , Amino Acids/administration & dosage , Brain Mapping , Cognition/drug effects , Cognition/physiology , Cross-Over Studies , Double-Blind Method , Female , Frontal Lobe/anatomy & histology , Frontal Lobe/drug effects , Humans , Impulsive Behavior/drug effects , Impulsive Behavior/physiology , Magnetic Resonance Imaging , Nerve Net/anatomy & histology , Nerve Net/drug effects , Parietal Lobe/anatomy & histology , Parietal Lobe/drug effects , Rest/psychology , Thinking/drug effects , Thinking/physiology , Tryptophan/administration & dosage , Tryptophan/deficiency
4.
Acta Psychiatr Scand ; 133(4): 310-23, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26292852

ABSTRACT

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is often linked with impulsive and aggressive behaviour, indexed by high comorbidity rates between ADHD and disruptive behaviour disorders (DBD). The present study aimed to investigate underlying neural activity of reactive aggression in children with ADHD and comorbid DBD using functional neuroimaging techniques (fMRI). METHOD: Eighteen boys with ADHD (age 9-14 years, 10 subjects with comorbid DBD) and 18 healthy controls were administered a modified fMRI-based version of the 'Point Subtraction Aggression Game' to elicit reactive aggressive behaviour. Trials consisted of an 'aggression phase' (punishment for a fictitious opponent) and an 'outcome phase' (presentation of the trial outcome). RESULTS: During the aggression phase, higher aggressive responses of control children were accompanied by higher activation of the ventral anterior cingulate cortex and the temporoparietal junction. Patients displayed inverted results. During the outcome phase, comparison between groups and conditions showed differential activation in the dorsal striatum and bilateral insular when subjects gained points. Losing points was accompanied by differential activation of regions belonging to the insula and the middle temporal sulcus. CONCLUSION: Data support the hypothesis that deficient inhibitory control mechanisms are related to increased impulsive aggressive behaviour in young people with ADHD and comorbid DBD.


Subject(s)
Aggression/psychology , Attention Deficit Disorder with Hyperactivity/psychology , Attention Deficit and Disruptive Behavior Disorders/psychology , Adolescent , Attention Deficit Disorder with Hyperactivity/diagnostic imaging , Attention Deficit and Disruptive Behavior Disorders/diagnostic imaging , Child , Humans , Magnetic Resonance Imaging , Male , Neuroimaging/methods
5.
Int J Neuropsychopharmacol ; 18(10): pyv050, 2015 May 19.
Article in English | MEDLINE | ID: mdl-25991656

ABSTRACT

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.


Subject(s)
Executive Function/physiology , Goals , Habits , Psychomotor Performance/physiology , Serotonin/metabolism , Animals , Humans , Models, Neurological , Models, Psychological
6.
Eur Neuropsychopharmacol ; 25(6): 846-56, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25869157

ABSTRACT

Diminished synthesis of the neurotransmitter serotonin (5-HT) has been linked to disrupted impulse control in aversive contexts. However, the neural correlates underlying a serotonergic modulation of female impulsivity remain unclear. The present study investigated punishment-induced inhibition in healthy young women. Eighteen healthy female subjects (aged 20-31) participated in a double-blinded, counterbalanced, placebo-controlled, within subjects, repeated measures study. They were assessed on two randomly assigned occasions that were controlled for menstrual cycle phase. In a randomized order, one day, acute tryptophan depletion (ATD) was used to reduce 5-HT synthesis in the brain. On the other day, participants received a tryptophan-balanced amino acid load (BAL) as a control condition. Three hours after administration of ATD/BAL, neural activity was recorded during a modified Go/No-Go task implementing reward or punishment processes using functional magnetic resonance imaging (fMRI). Neural activation during No-Go trials in punishment conditions after BAL versus ATD administration correlated positively with the magnitude of central 5-HT depletion in the ventral and subgenual anterior cingulate cortices (ACC). Furthermore, neural activation in the medial orbitofrontal cortex (mOFC) and the dorsal ACC correlated positively with trait impulsivity. The results indicate reduced neural sensitivity to punishment after short-term depletion of 5-HT in brain areas related to emotion regulation (subgenual ACC) increasing with depletion magnitude and in brain areas related to appraisal and expression of emotions (mOFC and dorsal ACC), increasing with trait impulsivity. This suggests a serotonergic modulation of neural circuits related to emotion regulation, impulsive behavior, and punishment processing in females.


Subject(s)
Gyrus Cinguli/physiology , Prefrontal Cortex/physiology , Punishment , Serotonin/deficiency , Adult , Decision Making/physiology , Double-Blind Method , Estradiol/blood , Female , Follicle Stimulating Hormone/blood , Gyrus Cinguli/blood supply , Humans , Impulsive Behavior/physiology , Luteinizing Hormone/blood , Neuropsychological Tests , Oxygen/blood , Prefrontal Cortex/blood supply , Psychiatric Status Rating Scales , Psychological Tests , Surveys and Questionnaires , Tryptophan/deficiency , Young Adult
7.
J Neural Transm (Vienna) ; 122(3): 343-8, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25204277

ABSTRACT

Serotonin (5-HT) and the hormone leptin have been linked to the underlying neurobiology of appetite regulation with evidence coming from animal and cellular research, but direct evidence linking these two pathways in humans is lacking. We examined the effects of reduced brain 5-HT synthesis due to acute tryptophan depletion (ATD) on levels of soluble leptin receptor (sOb-R), the main high-affinity leptin binding protein, in healthy adults using an exploratory approach. Women, but not men, showed reduced sOb-R concentrations after ATD administration. With females showing reduced baseline levels of central 5-HT synthesis compared to males diminished brain 5-HT synthesis affected the leptin axis through the sOb-R in females, thereby potentially influencing their vulnerability to dysfunctional appetite regulation and co-morbid mood symptoms.


Subject(s)
Brain/metabolism , Receptors, Leptin/metabolism , Serotonin/metabolism , Adult , Analysis of Variance , Cohort Studies , Double-Blind Method , Female , Food, Formulated , Humans , Leptin/blood , Male , Time Factors , Tryptophan/deficiency , Young Adult
9.
J Neural Transm (Vienna) ; 121(4): 451-5, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24292894

ABSTRACT

We investigated the impact of acute tryptophan depletion (ATD) and reduced brain serotonin synthesis on physiological arousal in 15 young people with ADHD participating in an aggression-inducing game. ATD was not associated with altered physiological arousal, as indexed by electrodermal activity (EDA). Baseline aggression was negatively correlated with the mean ATD effect on EDA. In accordance with the low arousal theory related to aggressive behavior, subjects with reduced physiological responsiveness/lower electrodermal reactivity to ATD tended to display elevated externalizing behavior.


Subject(s)
Aggression , Attention Deficit Disorder with Hyperactivity/physiopathology , Attention Deficit Disorder with Hyperactivity/psychology , Galvanic Skin Response/physiology , Tryptophan/deficiency , Adolescent , Analysis of Variance , Child , Double-Blind Method , Female , Humans , Male , Pilot Projects , Psychometrics , Serotonin/metabolism , Statistics, Nonparametric , Tryptophan/blood
10.
Amino Acids ; 45(5): 1207-19, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24072504

ABSTRACT

Diminished synthesis of the neurotransmitter serotonin (5-HT) in the brain has been linked to disturbed memory processes. The present study investigated the effects of diminished central nervous 5-HT synthesis as achieved by an acute dietary tryptophan depletion (ATD) on verbal declarative episodic memory in young women while controlling for the effects of female sex hormones. Eighteen healthy females (aged 20-31 years) participated in a within-subject repeated measures study, with two separate days of assessment spaced at least one individual menstrual cycle apart. On one day, participants were subjected to ATD, thus lowering central nervous 5-HT synthesis. The other day participants received a tryptophan-balanced amino acid load (BAL = control condition). The study was randomized, counterbalanced and double blind in terms of ATD/BAL administration. Measurements took place in the early follicular phase of the participants' menstrual cycle. Estrogen, FSH and LH levels were assessed at baseline. Verbal declarative episodic memory was assessed using a structured word-learning task. Short-term memory, as indexed by immediate recall, was reduced after ATD intake, whereas delayed recall and recognition after a 25-min delay did not show any differences after intake of ATD or BAL. In young women, verbal short-term memory function was more vulnerable to ATD than consolidation processes. In light of the possible interplay between female sex hormones and 5-HT, further studies comparing different menstrual cycle phases are needed.


Subject(s)
Memory, Episodic , Menstrual Cycle/metabolism , Menstrual Cycle/psychology , Tryptophan/deficiency , Verbal Behavior , Adult , Estrogens/metabolism , Female , Humans , Serotonin/metabolism , Young Adult
11.
Acta Psychiatr Scand ; 128(2): 114-23, 2013 Aug.
Article in English | MEDLINE | ID: mdl-22913430

ABSTRACT

OBJECTIVE: The neurotransmitter serotonin (5-HT) has been linked to the underlying biological processes related to aggressive behaviour. However, only a few studies on this subject involving young people have been published so far. METHOD: We aimed to investigate the effects of acute tryptophan depletion (ATD) on reactive aggression and decision-time for aggressive responses in a sample of young people with Attention deficit hyperactivity disorder (n = 20), a population at risk for aggressive behaviour. The study design was a double-blind within-subject crossover design. Aggression was assessed using a Point subtraction aggression game (PSAG) with high (HP) and low provocation (LP) trials 2.5 h after the intake of ATD and a tryptophan-balanced control condition. RESULTS: A chi-square comparison was used to identify the effect of ATD on increased aggression after LP. Boys were more likely to respond with an increased aggressive response after HP under ATD as represented by an increased relative risk and odds ratios. Girls had a higher relative risk than boys of an increased point subtraction under ATD after LP. No significant gender differences in decision-time were detected. CONCLUSION: An effect of ATD on increased aggression was found in the whole sample after LP. Research involving larger samples is needed to confirm the present preliminary findings.


Subject(s)
Aggression/drug effects , Attention Deficit Disorder with Hyperactivity , Serotonin/biosynthesis , Tryptophan , Adolescent , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/metabolism , Attention Deficit Disorder with Hyperactivity/psychology , Attention Deficit Disorder with Hyperactivity/therapy , Child , Child Behavior/drug effects , Cross-Over Studies , Decision Making/drug effects , Diet Therapy/methods , Double-Blind Method , Female , Humans , Male , Psychological Techniques , Psychotropic Drugs/metabolism , Psychotropic Drugs/pharmacology , Sex Factors , Synaptic Transmission/drug effects , Synaptic Transmission/physiology , Treatment Outcome , Tryptophan/metabolism , Tryptophan/pharmacology
12.
J Neural Transm (Vienna) ; 119(9): 1037-45, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22622364

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.


Subject(s)
Amino Acids/blood , Blood-Brain Barrier/metabolism , Brain/metabolism , Tryptophan/deficiency , Adult , Amino Acids/pharmacology , Analysis of Variance , Body Weight/drug effects , Brain/drug effects , Chromatography, High Pressure Liquid , Double-Blind Method , Female , Humans , Male , Time Factors , Tryptophan/blood , Young Adult
13.
J Affect Disord ; 134(1-3): 478-82, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21715014

ABSTRACT

OBJECTIVE: Evidence from adults suggests that changes in thyroid function are associated with the development of bipolar disorder (BD) and severe mood dysregulation. A dysregulation profile based on the Child Behavior Checklist (CBCL-DP) describes a phenotype with severe mood problems in youth. The present study investigated whether altered thyroid functioning in youths is associated with the severe mood dysregulation symptoms characterized by the CBCL-DP. METHODS: We analyzed the thyroid function data from 262 children and adolescents (n = 262 for serum TSH, n = 148 for free triiodothyronine [fT3] and n = 153 for free thyroxine [fT4]) with their CBCL-DP composite score. We created and compared high CBCL-DP and low CBCL-DP subgroups with regard to their serum TSH, fT3 and fT4 concentrations as well as the presence or absence of subclinical hypothyroidism. RESULTS: We did not detect between-group differences in serum TSH, fT3 and fT4 concentrations, nor were there significant correlations between youths' CBCL-DP scores and their serum TSH, fT3 and fT4 concentrations for either the whole sample or any subgroup. Post-hoc power analyses indicated that adequate to moderate power existed to detect between-group differences in fT3 and fT4 concentrations, respectively, but that larger TSH samples would be required to detect the same differences in those concentrations. LIMITATIONS: This study had a retrospective design, fewer females than males, and reduced power with respect to TSH concentrations. CONCLUSIONS: The present investigation does not support the association between elevated serum-TSH concentrations and severe mood dysregulation in youths. However, these findings should be confirmed in future large-scale studies.


Subject(s)
Hyperthyroidism/psychology , Mood Disorders/blood , Thyroid Gland/physiopathology , Adolescent , Adult , Bipolar Disorder , Child , Female , Humans , Hyperthyroidism/blood , Hypothyroidism/blood , Hypothyroidism/psychology , Male , Retrospective Studies , Thyroid Function Tests , Thyrotropin/blood , Thyroxine/blood , Triiodothyronine/blood
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