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Beate Herpertz-Dahlmann

Publications and source records attributed to Beate Herpertz-Dahlmann.

At least 19 recordsLinked to original sources

Genetic and functional analyses of CTBP2 in anorexia nervosa and body weight regulation.

The C-terminal binding protein 2 (CTBP2) gene (translational isoforms: CTBP2-L/S, RIBEYE) had been identified by a cross-trait analysis of genome-wide association studies for anorexia nervosa (AN) and body mass index (BMI). Here, we did a mutation analysis in CTBP2 by performing polymerase chain reactions with subsequent Sanger-sequencing to identify variants relevant for AN and body weight regulation and ensued functional studies. Analysis of the coding regions of CTBP2 in 462 female patients with AN (acute or recovered), 490 children and adolescents with severe obesity, 445 healthy-lean adult individuals and 168 healthy adult individuals with normal body weight detected 24 variants located in the specific exon of RIBEYE. In the initial analysis, three of these were rare non-synonymous variants (NSVs) detected heterozygously in patients with AN (p.Arg72Trp - rs146900874; p.Val289Met -rs375685611 and p.Gly362Arg - rs202010294). Four NSVs and one heterozygous frameshift variant were exclusively detected in children and adolescents with severe obesity (p.Pro53Ser - rs150867595; p.Gln175ArgfsTer45 - rs141864737; p.Leu310Val - rs769811964; p.Pro397Ala - rs76134089 and p.Pro402Ser - rs113477585). Ribeye mRNA was detected in mouse hypothalamus. No effect of fasting or overfeeding on murine hypothalamic Ribeye expression was determined. Yet, increased Ribeye expression was detected in hypothalami of leptin-treated Lepob/ob mice. This increase was not related to reduced food intake and leptin-induced weight loss. We detected rare and frequent variants in the RIBEYE specific exon in both patients with AN and in children and adolescents with severe obesity. Our data suggest RIBEYE as a relevant gene for weight regulation.

Humans↗

[Phenomenology and co-morbidity of childhood onset obsessive compulsive disorder].

OBJECTIVES: The goal of the study was to investigate the contents and comorbidity features of obsessive-compulsive disorder in children and adolescents. METHOD: 55 patients (29 males, 26 females), mainly inpatients selected from university clinics for child and adolescent psychiatry (95%), were investigated. Structured diagnostic interviews were used to interview patients and their parents. RESULTS: The mean age of onset for obsessive-compulsive disorders was 11.3 years. In males the onset was slightly earlier than among females, but this difference was not significantly significant. Compulsions mostly referred to washing and cleaning, checking, repeating, ordering, and counting. Most frequently, obsessions included thought about contamination, catastrophes, sexuality, and aggression. According to parental reports, the rate of comorbidity was high (lifetime diagnosis: 69%, current diagnosis: 53%), with anxiety, depressive, hyperkinetic, conduct, and eating disorders being the most frequent co-morbid conditions. Obsessive-compulsive symptoms were more intense in those patients who had a greater number of lifetime diagnoses of other psychiatric disorders. Comparing the rates found when structured interviews were carried out according to the study protocol to those for clinicians, clinicians were found to have diagnosed mixed obsessional thoughts and acts (presenting obsessional thoughts, as well as compulsive acts) less frequently. CONCLUSIONS: The results of this investigation are well in line with those of international studies on obsessive-compulsive disorders. The rates of disorders found were dependent on the diagnostic methods used. A potentially promising approach for further investigation is the sub-typing of patients according to symptom dimensions.

Adolescent↗

[Aetiology and life-course of conduct disorder in childhood: risk factors for the development of an antisocial personality disorder].

OBJECTIVES: Conduct disorders are among the most common disorders encountered in child and adolescent psychiatry. They represent a heterogeneous group of disorders, each with a different psychopathology and a different life-course. While antisocial behaviour is only transient in some children, others show increasing criminal behaviour and delinquency, and some even develop an antisocial personality disorder. METHODS: This review presents substantial biological and psychosocial factors, as well as their interaction in the aetiology of conduct disorders. Changes in autonomic responsiveness are emphasized. RESULTS: Especially young children with conduct problems seem to be at greater risk for persistent and more widespread antisocial behaviour. Some of these children have emotional disturbances similar to those of psychopathic individuals. CONCLUSIONS: In order to prevent a negative course of the disorder, the relevance of primary care for children at high risk for antisocial behaviour is emphasized. In this context, the application of psychophysiological methods might be useful, in order to identify these children at an early stage.

Adolescent↗

[Neuroimaging data of ADHD, tic-disorder and obsessive-compulsive-disorder in children and adolescents].

ADHD, Tic Disorder, Tourette's Syndrome, and Obsessive-Compulsive Disorder are all characterised by an impairment of executive functioning and often occur together. There are thus indications of a similar neurobiological basis. This review presents an overview of neuroimaging studies of these disorders in childhood and adolescence, focusing thereby on magnet resonance imaging data. Studies provide concurring data about structural changes in the basal ganglia and the prefrontal cortex, and abnormal activation in the fronto-striatal circuitry in patients as compared to healthy controls. ADHD and Tourette's Syndrome are both associated with prefrontal aberrations. However, variances in Tourette's Syndrome are less pronounced, which might be due to compensation mechanisms. ADHD children show small, but more global, morphological alterations in the cortex and cerebellum, while Tourette's Syndrome seems to be linked additionally to differences in the occipital cortex. Furthermore, structural and functional data for obsessive-compulsive disorder indicate aberrations in the amygdala and thalamus, and functional changes in the orbito-frontal cortex. By comparison, findings in children with ADHD point towards abnormal activity in the ventral prefrontal cortex. To summarise, the data display an impairment of cortico-striato-thalamic circuits which appears to be associated with dysfunctioning motor inhibition, and impulsive behaviour and objectionable thoughts. Since the majority of the studies reviewed are characterised by small and heterogeneous samples, and since the studies differ in their methods, comparability is limited and general conclusions can not be drawn.

Adolescent↗

Acquired dyslexia after stroke in the prereading stage: a single case treatment study with f MRI.

The authors report a treatment study of a child (CK) who suffered a left-hemisphere stroke at age 6.3 years, a few months before beginning school. Despite complete recovery of spoken language abilities, CK failed to acquire written language abilities. Neurolinguistic assessment 2 years after the stroke revealed marked impairments in working memory, deficits in acquiring a sublexical reading strategy, and a very rudimentary orthographic network. Functional imaging demonstrated activation in posterior language areas during reading of familiar words while the attempt to read unfamiliar words activated peri- and contralesional structures of the anterior language areas. It was assumed that despite sufficient neural plasticity, the acquisition of a sublexical reading strategy was prevented by severe working memory deficits. Therefore, a specific treatment intervention was developed, choosing a compensatory strategy for reading remediation. Reading development was monitored over three months before and three months after an intensive training was conducted. Data showed significant gains in reading performance only after the specific intervention. These gains remained stable in a catamnesis 2 years later.

Child↗

Clinical drug monitoring in child and adolescent psychiatry: side effects of atypical neuroleptics.

OBJECTIVE: The aim of this study was to improve and evaluate the practibility of a method for the assessment of drug-associated side effects, and we implemented a clinical drug monitoring for atypical neuroleptics. METHODS: Side effects of initially hospitalized patients treated with clozapine (n = 16), olanzapine (n = 16), and risperidone (n = 19) were prospectively monitored on a weekly basis for the first 3 weeks. In the case of stable medication, measurements of all variables were made every 4 weeks or upon discharge. We used the Dosage Record Treatment Emergent Symptom Scale (DOTES) in a supplemented version to measure the presence and severity of side effects. RESULTS: Drowsiness and decreased motor activity were common, especially in the first 2 weeks. Orthostatic hypotension, increased salivation, constipation, and nasal congestion were seen in more than 30% to 60% of patients treated with clozapine and were less common in adolescents treated with olanzapine and risperidone. Rigidity, tremor, and dystonia were seen in 5% to 15% of patients treated with risperidone and olanzapine. The average weight gain after 6 weeks of treatment with the atypical neuroleptics was significantly higher for the olanzapine group (4.6 +/- 1.9 kg) than for the risperidone (2.8 +/- 1.3 kg) and clozapine (2.5 +/- 2.9 kg) groups. CONCLUSIONS: The authors' supplemented DOTES version is generally applicable to clinical use in mental health centers. The differences among the side effects of these three agents may affect compliance with medication and medical risks of metabolic syndrome, diabetes, and cardiovascular disease. More research on the short- and long-term safety of psychotropic drugs in children and adolescents, using standardized methods, should be considered.

Adolescent↗

The influence of risperidone on attentional functions in children and adolescents with attention-deficit/hyperactivity disorder and co-morbid disruptive behavior disorder.

This study aims to examine the influence of risperidone on various attentional functions, including intensity and selectivity aspects of attention plus inhibitory control in children with attention deficit/hyperactivity disorder (ADHD) with co-morbid Disruptive Behavior Disorders (DBD) and normal IQ. Children with ADHD and DBD, aged 8-15 years, were treated with risperidone (mean daily dose: 1.5 mg; n = 23) and examined with three attentional paradigms before and after a 4-week treatment period. Age- and IQ-matched normal controls (n = 23) were also tested without medication on the same two occasions. No influence of the medication could be detected for any neuropsychological variable, neither as a positive enhancement nor as adverse side effects. However, clinical symptoms of ADHD and DBD assessed on the IOWA Conners Scale significantly improved after the 4-week treatment period. Divergent behavioral and cognitive effects of risperidone on ADHD symptoms were observed, with a significant reduction in behavioral symptoms, whereas no positive treatment effects were found on laboratory tasks of impulsivity. Thus, the cognitive effects of risperidone seem to differ from the cognitive effects of stimulant treatments in children with ADHD + DBD. However, no negative impact of risperidone was observed on attentional functions either, i.e., there was no slowing of cognitive speed.

Adolescent↗

Metacognitive therapy versus exposure and response prevention for pediatric obsessive-compulsive disorder. A case series with randomized allocation.

BACKGROUND: Exposure with ritual prevention (ERP) is the psychotherapeutic treatment of choice for pediatric obsessive-compulsive disorder (OCD). In the present study, a new treatment rationale - metacognitive therapy (MCT) for children - was developed and evaluated. METHODS: Ten children and adolescents with OCD were randomly assigned to either MCT or ERP therapy condition. Patients were assessed before and after treatment and at the 3-month and 2-year follow-up by means of symptom severity interviews. Depressive symptoms were also assessed. Manualized treatment involved up to 20 sessions on a weekly basis. RESULTS: We found clinically and statistically significant improvements in symptom severity after treatment. At the 3-month and 2-year follow-up, the attained improvements during treatment were retained. CONCLUSIONS: Despite some methodological limitations, results showed that MCT proved to be a promising psychotherapeutic alternative to the well-established ERP in the treatment of pediatric OCD. Further investigations into the efficacy of MCT are necessary to answer questions as to the working mechanisms underlying therapy for OCD.

Adolescent↗

Physical activity and restlessness correlate with leptin levels in patients with adolescent anorexia nervosa.

BACKGROUND: In food-restricted rats, leptin suppresses semistarvation-induced hyperactivity (SIH) and decreases exploratory behavior. Leptin ameliorates anxiety-related movement in ob/ob mice. In this study, we assessed the relationship between leptin and qualities of physical activity and restlessness in acute anorexia nervosa (AN). METHODS: Serum leptin, body mass index (BMI), % body fat, and self- and expert-ratings of qualities of physical activity and restlessness were assessed in 26 inpatients with acute AN. Accelerometry was also performed. Regression analyses were used to predict activity and restlessness using BMI, % body fat, and leptin levels as predictor variables. RESULTS: Leptin levels significantly contributed to the prediction of all measures of activity and restlessness. CONCLUSIONS: This is the first study linking hypoleptinemia in AN patients to subjective and objective measures of higher physical activity and motor and inner restlessness. Leptin may directly or indirectly (or both) influence behaviors and cognitions contributing to hyperactivity and motor restlessness.

Adolescent↗

Dysfunctional attentional networks in children with attention deficit/hyperactivity disorder: evidence from an event-related functional magnetic resonance imaging study.

BACKGROUND: Although there is evidence for attentional dysfunction in children with attention deficit/hyperactivity disorder (ADHD), the neural basis of these deficits remains poorly understood. METHODS: We used event-related functional magnetic resonance imaging (fMRI) to investigate brain activations related to three particular aspects of attention: alerting, reorienting, and executive control. Sixteen medication-naive boys with ADHD and 16 healthy boys, aged 8 to 12 years, were studied. RESULTS: Behaviorally, children with ADHD showed a significant impairment only in their executive control system compared to healthy subjects. Neurally, children with ADHD (relative to controls) recruited deviant brain regions for all three attentional networks: less right-sided activation in the anterior cingulate gyrus during alerting, more fronto-striatal-insular activation during reorienting, and less fronto-striatal activation for executive control. ADHD symptom severity was associated with dysregulation of the blood oxygen level dependent (BOLD) signal within the putamen during reorienting and executive control. CONCLUSIONS: Our results demonstrated altered brain mechanism in ADHD associated with all three attentional networks investigated. For alerting and executive attention, our data indicate a deviant mechanism of cortical control, while ADHD children may have adopted altered strategies for reorienting of attention. Our results also stress the etiological role of functional abnormalities in the putamen in medication-naive ADHD.

Attention Deficit Disorder with Hyperactivity↗

Transmission disequilibrium of polymorphic variants in the tryptophan hydroxylase-2 gene in children and adolescents with obsessive-compulsive disorder.

Dysfunction of the central serotonergic system has been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). The genetic contribution to the development of OCD is particularly high in early-onset OCD. The aim of this study was to investigate the effect of polymorphic variants in the gene of the novel brain-specific tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme of serotonin (5-HT) synthesis in the brain, in OCD with disease onset in childhood and adolescence. We analysed two common single nucleotide polymorphisms (SNPs) of TPH2 in the putative transcriptional control region and in intron 2 of the TPH2 gene in a unique family-based sample of OCD patients with onset of the disease in childhood and adolescence comprising 71 complete, independent trios. The transmission disequilibrium test was used to determine transmission of alleles and haplotypes from parents to offspring. In this first study of TPH2 in OCD, analysis of the SNPs, rs4570625 and rs4565946, revealed a significant preferential transmission of haplotype G-C to children and adolescents with OCD. Moreover, a trend towards preferential transmission of the C allele of SNP rs4565946 to the patients was found. The genotype relative-risk estimate for homozygous C allele carriers of SNP rs4565946 was 2.58 (95% CI 0.98-6.82). In conclusion, the results link TPH2 variations to the pathogenesis of early-onset OCD and further support the aetiological relevance of 5-HT signalling in OCD.

Adolescent↗

Development of attentional networks: an fMRI study with children and adults.

Data on the development of the attentional systems remain scarce. We used structural and event-related functional magnetic resonance imaging to investigate differences in the neural mechanisms associated with alerting, reorienting, and executive control of attention between children (ages 8 to 12 years) and adults, while controlling for effects of performance and brain morphology. Behaviorally, children exhibited a numerically smaller alerting effect and significantly larger invalidity (reorienting) and interference (executive control of attention) effects. Neurally, children showed significantly reduced brain activation in a priori defined regions-of-interest in right-sided frontal-midbrain regions during alerting, in the right-sided temporo-parietal junction during reorienting of attention, and in the dorsolateral prefrontal cortex during executive control of attention. In addition, children activated significantly more brain regions outside the a priori defined regions-of-interest, such as the superior frontal gyrus during reorienting and the superior temporal gyrus during executive control of attention. Functional group differences overlapped with structural group differences in gray matter volume in particular within the frontopolar areas. The data suggest that there is a transition from functional yet immature systems supporting attentional functions in children to the more definitive adult networks and that the differences observed may reflect both developmental changes in cognitive strategies and morphology.

Adult↗

[Relevance and results of Theory of Mind research for autism and other psychiatric disorders].

OBJECTIVES: Disorders of the autistic spectrum are basically characterised by a triad of symptoms: dysfunction of social interaction, communication deficits, and stereotyped behaviour patterns and interests. One of the most prominent approaches to explaining these abnormalities is the "Theory of Mind" (Baron-Cohen et al., 1885). METHODS: The present review discusses and critically examines the ongoing research and recapitulates the essential findings of the last ten years, focussing on their methodological quality and utility to explain other psychiatric disorders. RESULTS: Despite considerable research efforts in this field, the existing concepts do not constitute a consistent framework for analysing the development of autism spectrum disorders. CONCLUSIONS: Future research should aim to verify the impact of the existing theoretical models and to emphasise the similarities of the different concepts in order to gain specific information about potential causal factors of autism.

Adolescent↗

[Reliability of attention and verbal memory tests with normal children and adolescents--clinical implications].

OBJECTIVES: Neurological assessment is an intriguing tool for the characterisation of cognitive dysfunctions associated with childhood psychiatric disorders. The current article gives a short theoretical overview on neuropsychological functions such as attention and verbal memory. Selected clinical findings are summarised. Neuropsychological attention and memory tasks that are suited for the examination of children and adolescents are described. METHODS: The retest-reliability of these tasks was examined in a group of 33 healthy children within six weeks after the original test. RESULTS: It was shown that reliability was generally high, albeit differing between some of the dependent variables. The greatest learning effects were found in younger children. CONCLUSIONS: The selected neuropsychological tests seem suitable for clinical applications such as the assessment of cognitive deficits or the evaluation of psychopharmacological treatment. However, age-dependent confidence intervals should be considered if retesting is required.

Adolescent↗

Clinical evaluation of subjective and objective changes in motor activity and attention in children with attention-deficit/hyperactivity disorder in a double-blind methylphenidate trial.

The aim of this study was to determine drug-dependent effects on attention and motor activity in children with attention-deficit/hyperactivity disorder (ADHD) in a double-blind methylphenidate (MPH) trial using both subjective behavior ratings and objective measures of function. In particular, we were interested in the relationship between changes of those subjective and objective measures. A total of 44 ADHD children with the combined subtype completed a randomized, double-blind, placebo-controlled, crossover trial with 2 doses of MPH (0.25; 0.5 mg/kg body weight) and placebo. In each condition, computerized attention tasks were performed, teacher-behavior ratings were obtained, and actigraph data were collected in both clinical and naturalistic settings. Trend tests revealed linear effects of MPH dose on actigraph data in the test session (p = 0.02) and at school (p = 0.001), as well as on sustained attention (p < 0.001), while inhibitory control showed a quadratic dose-response curve (p < 0.001). Multivariate regression analyses revealed that changes of both, hyperactive-impulsive symptoms (28%) and inattentive symptoms (23%) could be explained by objective changes of motor activity. Thus, for clinical practice, it should be taken into account that behavior ratings of ADHD symptoms seemed to be predominantly influenced by changes of motor activity.

Analysis of Variance↗

The influence of sertraline on attention and verbal memory in children and adolescents with anxiety disorders.

This study investigated the cognitive side effects of a 6-week course of sertraline treatment on verbal memory and attention in children and adolescents. Children with various anxiety disorders (social phobia, generalized and separation anxiety disorder; n = 28), between 8 and 17 years of age, received a standardized, computerized neuropsychological assessment before treatment and another 6 weeks after treatment onset with sertraline (daily dose range between 25 and 100 mg). The patient group was compared to healthy controls (n = 28), who were matched for age and IQ and were also tested twice over a 6-week period. Sertraline did not have any negative effects on attentional performance (p > 0.05) but did increase response speed in a divided attention paradigm (p = 0.02). By contrast, performance of the interference part of a verbal memory task decreased (p = 0.05). The described results also remained stable over a 12-week period after treatment onset. Thus, the cognitive side effects of sertraline seemed to differ slightly between pediatric patients and those described in adult patient groups, should, therefore, be carefully assessed.

Adolescent↗