Lars Wöckel

CBCL-pediatric bipolar disorder phenotype: severe ADHD or bipolar disorder?

SummaryBackground. In children with pediatric bipolar disorder (PBD), a consistent pattern of elevations in hyperactivity, depression/anxiety, and aggression has been identified on the child behavior checklist (CBCL-PBD profile). The aim of the present study was to estimate the prevalence of the CBCL-PBD profile in a child psychiatric sample, and to determine ICD-10 diagnoses in CBCL-PBD patients.Methods. We studied a sample of 939 consecutively referred children and adolescents, aged 4–18 years. ICD-10 discharge diagnoses were established in consensus conferences. The CBCL 4–18 was completed by parents as part of the diagnostic routine.Results. A total of 62 subjects (6.6%; 95% CI=5.2–8.4) met criteria for the CBCL-PBD phenotype. More than 75% of CBCL-PBD subjects were clinically diagnosed with disruptive behavior disorders (ADHD, ODD, and CD). Two patients (0.2% of the total sample) received a formal diagnosis of bipolar disorder, but did not show the CBCL-PBD phenotype.Conclusions. A considerable number of children in Germany are referred to psychiatric care with a mixed phenotype of aggression, anxiety, depression and attention problems. Our study demonstrated a comparable prevalence and similar clinical characteristics as reported from other countries using different diagnostic approaches. However, the CBCL-PBD phenotype does not correspond with clinical consensus diagnoses of bipolar disorder, but with severe disruptive behavior disorders.

Diminished Serotonergic Functioning in Hostile Children with ADHD: Tryptophan Depletion Increases Behavioural Inhibition

INTRODUCTION Serotonergic (5-HT) functioning has been shown to account for a variety of behavioural characteristics, in particular aggressive and impulsive behaviour. This study explored the effects of rapid tryptophan depletion (RTD) and the ensuing reduction of brain 5-HT synthesis on behavioural inhibition in passive avoidance learning assessed in a computerized go/no-go task. METHODS 22 male patients with an ICD-10 diagnosis of ADHD were administered RTD within an amino acid drink lacking tryptophan, the natural precursor of 5-HT, thus lowering the central nervous 5-HT synthesis rate in a placebo-controlled double-blind within-subject crossover-design. 4 hours after RTD/placebo intake the patients were subjected to a go/no-go task for assessment of behavioural inhibition. RESULTS Highly hostile aggressive patients showed increased inhibition errors under RTD compared to placebo. Low hostile aggressive patients showed lower rates of inhibition errors and thus better performance under RTD compared to placebo. DISCUSSION The data suggest that in ADHD levels of trait-aggressive characteristics influence the susceptibility to changed behavioural inhibition after an acute 5-HT dysfunction. The detected influence of 5-HT could also be relevant as regards behavioural inhibition being subject to a developmental change in 5-HT functioning.

Diminished 5-HT functioning in CBCL pediatric bipolar disorder-profiled ADHD patients versus normal ADHD: susceptibility to rapid tryptophan depletion influences reaction time performance†‡

There is a current debate on characterizing children with pediatric bipolar disorder (PBD) through a profile within the child behaviour checklist (CBCL), and on the involvement of the 5‐HT system in the underlying neurobiological processes of PBD. The aim of the present paper was to investigate reaction time performance in patients with CBCL‐PBD and to discriminate ADHD from ADHD with CBCL‐PBD with respect to diminished 5‐HT functioning and reaction time.

Reduced serotonergic functioning changes heart rate in ADHD.

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.

Differences in zinc status and the leptin axis in anorexic and recovered adolescents and young adults: a pilot study

Background Evidence from animal studies suggests that leptin metabolism is associated with zinc (Zn) status. However, research investigating this relationship in adolescents and young adults with anorexia nervosa (AN) is scarce; the present study aims to fill that gap. Methods Serum concentrations of leptin, the soluble leptin receptor (sOB-R) and the free leptin index (FLI) were obtained in healthy control subjects (n=19), acutely ill individuals (n=14) and recovered patients with AN (n=15). Serum Zn concentrations noted in previous research data were also incorporated for all groups. Results Leptin, FLI and Zn concentrations were higher in recovered subjects with AN when compared with acutely ill AN patients. Remitted patients showed higher sOB-R concentrations but no difference in FLI compared with the control group. Leptin and FLI were lower in the acutely ill patients compared with the control subjects, who showed no differences in Zn concentrations. Zn concentrations were not correlated with leptin, sOB-R or FLI concentrations in any of the three investigated subgroups. Conclusions The present investigation does not entirely support an association between Zn, Leptin and FLI concentrations in subjects with AN, possibly due to limited statistical power. Further research and replication of the present findings related to the interaction between leptin and Zn is warranted. However, with respect to serum leptin levels the data of the present investigation indicate that acutely ill and remitted patients with AN differ as regards serum leptin concentrations and FLI, which is in line with previous research.

Dietary tryptophan depletion according to body weight - a new treatment option in acute mania?

Decreased neurotransmission of serotonin (5-HT) was shown to be related to the development of depressive symptoms, whereas recent preliminary evidence suggests that acute mania may be related to a hyperserotonergic state. The reduction of central nervous 5-HT synthesis achieved by a new modification of the dietary rapid tryptophan depletion technique, with the relevant amino acids dosed according to body weight, is hypothesized by the authors to be a further option of treatment during acute mania, in particular in view of a decrease in adverse reactions, a reduced amount of amino acids needed for sufficient depletion, but also improved tolerability. However, ethical issues may limit such studies investigating this relationship in acutely manic patients, in particular in view of informed consent.

Serotonergic neurotransmission and lapses of attention in children and adolescents with attention deficit hyperactivity disorder:availability of tryptophan influences attentional performance

Deficiencies in serotonergic (5-HT) neurotransmission have frequently been linked to altered attention and memory processes. With attention deficit hyperactivity disorder (ADHD) being associated with impaired attention and working memory, this study investigated the effects of a diminished 5-HT turnover achieved by rapid tryptophan depletion (RTD) on attentional performance in children and adolescents with ADHD. Twenty-two male patients with ADHD (aged 9-15 yr) received the RTD procedure Moja-De and a tryptophan (Trp)-balanced placebo (Pla) in a randomized, double-blind, within-subject crossover design on two separate study days. Lapses of attention (LA) and phasic alertness (PA) were assessed within the test battery for attentional performance under depleted and sham-depleted conditions 120 (T1), 220 (T2) and 300 (T3) min after intake of RTD/Pla. At T1 there was a significant main effect for RTD, indicating more LA under intake of a Trp-balanced Pla compared to diminished 5-HT neurotransmission. For T2/T3 there were no such effects. PA was not affected by the factors RTD/Pla and time. Interactions of 5-HT with other neurotransmitters as possible underlying neurochemical processes could be subject to further investigations involving healthy controls as regards altered attentional performance in children and adolescents.

No effect of acute tryptophan depletion on verbal declarative memory in young persons with ADHD

Animal experiments and studies in adults have shown that the neurotransmitter serotonin (5‐HT) plays an important role in learning and memory processes. However, data on this relationship in young persons are scarce, and neurodietary research in this age group is limited compared with the extensive literature on adults. Here, we aimed to explore the effects of a diminished central nervous 5‐HT synthesis, which is achieved by acute tryptophan depletion (ATD) Moja‐De , on memory function in young males with attention deficit hyperactivity disorder (ADHD).

Diminished central nervous 5-HT neurotransmission and mood self-ratings in children and adolescents with ADHD: no clear effect of rapid tryptophan depletion

Research on 5‐HT‐functioning in adult patients and healthy subjects using rapid tryptophan depletion (RTD) has indicated weak but stable effects on mood ratings. Altered mood in children and adolescents with attention‐deficit/hyperactivity disorder (ADHD) can confound the differential diagnosis between severe ADHD and mood disorders such as pediatric bipolar disorder. The present study investigated the effects of RTD induced lowered central nervous 5‐HT‐levels on mood self‐ratings in children with ADHD.

Reduced number of taste papillae in patients with eating disorders

Summary.Taste affects dietary behavior and in turn taste response and food preferences are altered in eating disorders. Fungiform papillae on the tongue are the first line of the gustatory apparatus to provide information about taste. Aim of this study is determination of their number in patients with eating disorders. Twenty-seven female adolescents with eating disorders and 16 age-matched healthy female controls were examined. Tongues were stained with blue food coloring and the number of fungiform papillae was quantified using digital photography and image processing. Patients with restrictive type eating disorders showed a more distinct reduction (p < 0.001) of fungiform papillae than patients with vomiting and/or binge eating (p < 0.05), compared with those of healthy control subjects. Causes may be an initially disturbed development of fungiform papillae or secondary to changes in eating behavior which may be mutually causative.