Training-induced plasticity of the social brain in autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is linked to social brain activity and facial affect recognition (FAR). AIMS: To examine social brain plasticity in ASD. METHOD: Using FAR tests and functional magnetic resonance imaging tasks for FAR, we compared 32 individuals with ASD and 25 controls. Subsequently, the participants with ASD were assigned to FAR computer-aided cognitive training or a control group. RESULTS: The ASD group performed more poorly than controls on explicit behavioural FAR tests. In the scanner, during implicit FAR, the amygdala, fusiform gyrus and other regions of the social brain were less activated bilaterally. The training group improved on behavioural FAR tests, and cerebral response to implicit affect processing tasks increased bilaterally post-training in the social brain. CONCLUSIONS: Individuals with ASD show FAR impairments associated with hypoactivation of the social brain. Computer-based training improves explicit FAR and neuronal responses during implicit FAR, indicating neuroplasticity in the social brain in ASD.

Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.

Common variants in genes of the postsynaptic FMRP signalling pathway are risk factors for autism spectrum disorders.

Autism spectrum disorders (ASD) are heterogeneous disorders with a high heritability and complex genetic architecture. Due to the central role of the fragile X mental retardation gene 1 protein (FMRP) pathway in ASD we investigated common functional variants of ASD risk genes regulating FMRP. We genotyped ten SNPs in two German patient sets (N = 192 and N = 254 families, respectively) and report association for rs7170637 (CYFIP1; set 1 and combined sets), rs6923492 (GRM1; combined sets), and rs25925 (CAMK4; combined sets). An additional risk score based on variants with an odds ratio (OR) >1.25 in set 1 and weighted by their respective log transmitted/untransmitted ratio revealed a significant effect (OR 1.30, 95 % CI 1.11-1.53; P = 0.0013) in the combined German sample. A subsequent meta-analysis including the two German samples, the "Strict/European" ASD subsample of the Autism Genome Project (1,466 families) and a French case/control (541/366) cohort showed again association of rs7170637-A (OR 0.85, 95 % CI 0.75-0.96; P = 0.007) and rs25925-G (OR 1.31, 95 % CI 1.04-1.64; P = 0.021) with ASD. Functional analyses revealed that these minor alleles predicted to alter splicing factor binding sites significantly increase levels of an alternative mRNA isoform of the respective gene while keeping the overall expression of the gene constant. These findings underpin the role of ASD candidate genes in postsynaptic FMRP regulation suggesting that an imbalance of specific isoforms of CYFIP1, an FMRP interaction partner, and CAMK4, a transcriptional regulator of the FMRP gene, modulates ASD risk. Both gene products are related to neuronal regulation of synaptic plasticity, a pathomechanism underlying ASD and may thus present future targets for pharmacological therapies in ASD.

Neural mechanisms of savant calendar calculating in autism: an MEG-study of few single cases.

This study contrasted the neurological correlates of calendar calculating (CC) between those individuals with autism spectrum disorder (ASD) and typically developing individuals. CC is the ability to correctly and quickly state the day of the week of a given date. Using magnetoencephalography (MEG), we presented 126 calendar tasks with dates of the present, past, and future. Event-related magnetic fields (ERF) of 3000ms duration and brain activation patterns were compared in three savant calendar calculators with ASD (ASDCC) and three typically developing calendar calculators (TYPCC). ASDCC outperformed TYPCC in correct responses, but not in answering speed. Comparing amplitudes of their ERFs, there was a main effect of group between 1000 and 3000ms, but no further effects of hemisphere or sensor location. We conducted CLARA source analysis across the entire CC period in each individual. Both ASDCC and TYPCC exhibited activation maxima in prefrontal areas including the insulae and the left superior temporal gyrus. This is in accordance with verbal fact retrieval and working memory as well as monitoring and coordination processes. In ASDCC, additional activation sites at the right superior occipital gyrus, the right precuneus, and the right putamen point to visual-spatial strategies and are in line with the preference of autistic individuals for engaging posterior regions relatively more strongly in various reasoning and problem solving tasks.

Impaired gamma-band activity during perceptual organization in adults with autism spectrum disorders: evidence for dysfunctional network activity in frontal-posterior cortices.

Current theories of the pathophysiology of autism spectrum disorders (ASD) have focused on abnormal temporal coordination of neural activity in cortical circuits as a core impairment of the disorder. In the current study, we examined the possibility that gamma-band activity may be crucially involved in aberrant brain functioning in ASD. Magneto-encephalographic (MEG) data were recorded from 13 adult human participants with ASD and 16 controls during the presentation of Mooney faces. MEG data were analyzed in the 25-150 Hz frequency range and a beamforming approach was used to identify the sources of spectral power. Participants with ASD showed elevated reaction times and reduced detection rates during the perception of upright Mooney faces, while responses to inverted stimuli were in the normal range. Impaired perceptual organization in the ASD group was accompanied by a reduction in both the amplitude and phase locking of gamma-band activity. A beamforming approach identified distinct networks during perceptual organization in controls and participants with ASD. In controls, perceptual organization of Mooney faces involved increased 60-120 Hz activity in a frontoparietal network, while in the ASD group stronger activation was found in visual regions. These findings highlight the contribution of impaired gamma-band activity toward complex visual processing in ASD, suggesting atypical modulation of high-frequency power in frontoposterior networks.

Differences in serum zn levels in acutely ill and recovered adolescents and young adults with anorexia nervosa--a pilot study.

Preliminary evidence suggests that changes in zinc (Zn) metabolism are associated with anorexia nervosa (AN). However, data are scarce regarding potential differences in serum Zn concentrations in adolescent and young adult patients with AN. It was the aim of the present pilot study to compare serum Zn concentrations between acutely ill and remitted adolescent and young adult female patients with AN and female controls. Zn concentrations were higher in remitted compared with acutely ill patients. Zn concentrations were also higher in remitted patients compared with controls, but there was no significant difference in Zn concentrations between acutely ill patients and controls. The present study provides preliminary evidence for differences in serum Zn status in recovered patients with AN. These differences are likely influenced by reported food preferences, in particular as regards Ca²âº and phosphorus-containing foods. However, because of limited statistical power, future research involving larger samples is necessary.

Severe affective and behavioural dysregulation is associated with significant psychosocial adversity and impairment.

BACKGROUND: Recently, a highly heritable behavioral phenotype of simultaneous deviance on the Anxious/Depressed, Attention Problems, and Aggressive Behavior syndrome scales has been identified on the Child Behavior Checklist (CBCL-Dysregulation Profile, CBCL-DP). This study aims to investigate psychosocial adversity and impairment of the CBCL-DP. METHODS: A total of 9024 patients aged 4-18 years were assessed using the CBCL, and the axes V and VI of ICD-10. RESULTS: ANOVA revealed significant differences regarding psychosocial adversity and impairment between patients with CBCL-DP phenotype and the clinical control group, patients with attention problems, and patients with attention problems and additional anxious/depressed symptoms as assessed by the CBCL. Patients with CBCL-DP showed significant psychosocial adversity and impairment. However, in most cases patients with aggressive behavior showed equal psychosocial adversity as patients with CBCL-DP. CONCLUSIONS: Findings suggest the CBCL-DP phenotype to be associated with significant psychosocial adversity and impairment either as a cause or an effect of the syndrome. Clinicians should carefully address psychosocial adversity and impairment with particular attention to the adversity and impairment of adolescents with CBCL-DP.

No association between a common single nucleotide polymorphism, rs4141463, in the MACROD2 gene and autism spectrum disorder.

The Autism Genome Project (AGP) Consortium recently reported genome-wide significant association between autism and an intronic single nucleotide polymorphism marker, rs4141463, within the MACROD2 gene. In the present study we attempted to replicate this finding using an independent case-control design of 1,170 cases with autism spectrum disorder (ASD) (874 of which fulfilled narrow criteria for Autism (A)) from five centers within Europe (UK, Germany, the Netherlands, Italy, and Iceland), and 35,307 controls. The combined sample size gave us a non-centrality parameter (NCP) of 11.9, with 93% power to detect allelic association of rs4141463 at an alpha of 0.05 with odds ratio of 0.84 (the best odds ratio estimate of the AGP Consortium data), and for the narrow diagnosis of autism, an NCP of 8.9 and power of 85%. Our case-control data were analyzed for association, stratified by each center, and the summary statistics were combined using the meta-analysis program, GWAMA. This resulted in an odds ratio (OR) of 1.03 (95% CI 0.944-1.133), with a P-value of 0.5 for ASD and OR of 0.99 (95% CI 0.88-1.11) with P-value = 0.85 for the Autism (A) sub-group. Therefore, this study does not provide support for the reported association between rs4141463 and autism.

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.

Bipolar disorder in children and adolescents in Germany: national trends in the rates of inpatients, 2000-2007.

OBJECTIVES: Increasing admission and prevalence rates of bipolar disorder (BD) are a matter of controversy in international child and adolescent psychiatry. We seek to contribute to this discussion by presenting data obtained in a population of German children and adolescents. METHODS: Nationwide, whole population changes in inpatient admissions of BD and other psychiatric disorders between 2000 and 2007 were analyzed in individuals aged up to 19 years using registry data from the German Federal Health Monitoring System. RESULTS: Inpatient admissions for BD in individuals aged up to 19 years increased from 1.13 to 1.91 per 100,000 or 68.5% between 2000 and 2007 (odds ratio: 1.69; 95% confidence interval: 1.41-2.02), with a nonsignificant decline in children less than 15 years and the largest relative increase in adolescents aged 15-19 years. Inpatient rates for depressive disorders increased by 219.6% and for hyperkinetic disorder by 111.3%. Conduct disorders increased by 18.1%, considerably less than the 38.1% general rise for all mental disorders in children and adolescents. The only significant decline in a diagnostic category occurred for psychotic disorders (-11.8%). BD inpatient admission represented only 0.22% of all mental disorder admissions in 2000 and 0.27% in 2007. CONCLUSIONS: An elevation of inpatient admissions of BD in Germany in adolescents was detected, exceeding the general trend for increased mental disorder admissions. The results may indicate a higher clinical awareness and appreciation of mood symptoms at earlier ages and, in part, a reconceptualization of previously diagnosed psychotic disorders in youth. However, a diagnosis of BD in youngsters is still extremely rare in Germany. Diagnoses were based on the judgment of the treating physician. A correction for multiple admissions in the data set is not possible.

Peer-victimization and mental health problems in adolescents: are parental and school support protective?

The aim of this study was to investigate the frequency and effects of peer-victimization on mental health problems among adolescents. Parental and school support were assumed as protective factors that might interact with one another in acting as buffers for adolescents against the risk of peer-victimization. Besides these protective factors, age and gender were additionally considered as moderating factors. The Social and Health Assessment survey was conducted among 986 students aged 11-18 years in order to assess peer-victimization, risk and protective factors and mental health problems. For mental health problems, the Strengths and Difficulties Questionnaire (SDQ) was used. Effects of peer-victimization on mental health problems were additionally compared with normative SDQ data in order to obtain information about clinically relevant psychopathology in our study sample. Results of this study show that peer-victimization carries a serious risk for mental health problems in adolescents. School support is effective in both male and female adolescents by acting as a buffer against the effect of victimization, and school support gains increasing importance in more senior students. Parental support seems to be protective against maladjustment, especially in peer-victimized girls entering secondary school. Since the effect of peer-victimization can be reduced by parental and school support, educational interventions are of great importance in cases of peer-victimization.

[Psychopharmacotherapy in adolescents with borderline personality disorder in inpatient and outpatient psychiatric treatment]. / Psychopharmakotherapie einer ambulanten und stationären Inanspruchnahmepopulation adoleszenter Patienten mit Borderline-Persönlichkeitsstörung.

OBJECTIVE: The majority of adult patients with borderline personality disorder (BPD) are treated with psychotropic drugs. However, there are no data on psychotropic therapy in adolescents. This study examines the prevalence of BPD in an adolescent population undergoing either inpatient or outpatient psychiatric treatment and assesses psychotropic prescription patterns in adolescent in- and outpatients with BPD. METHODS: Out of a population of adolescents undergoing psychiatric treatment over a seven-year observation period, 58 adolescent patients with BPD (16.7 +/- 2.5 years) were investigated retrospectively with regard to their first episode of treatment, type of medication, and different risk variables. RESULTS: Out of the investigated population, 37 inpatients and 21 outpatients received treatment. Inpatients were shown to have higher rates of risk variables (approx. 68% with co-morbid disorders and approx. 49% with self-harmful behaviour, significantly (p < .001) more attempted suicides in their patient history) and higher rates of psychotropic treatment (p < .001). Antidepressants (SSRI and NaSSA) were most commonly prescribed, followed by neuroleptics. More than 50% of the medicated patients were treated with multiple psychotropic drugs administered simultaneously. CONCLUSIONS: Pharmacotherapy in BPD has a high and increasing therapeutic value, with the prescription of psychotropic drugs being primarily symptom-orientated. Pharmacotherapy of co-morbid disorders should be accorded equal treatment priority. In line with this, psychotropic treatment of BPD in adolescents is increasingly important. Inpatient adolescents are more burdened in terms of psychiatric risk variables, and also receive medication more often.

[Does the Fragmented Images Test measure locally oriented visual processing in autism spectrum disorders?]. / Erfasst der FBT lokale visuelle Informationsverarbeitung bei Autismus-Spektrum-Störungen?

OBJECTIVE: The cognitive phenotype of autism spectrum disorders (ASD) is characterized among other things by local processing (weak central coherence). It was examined whether a test that measures identification of fragmented pictures (FBT) is able to seize this preference for local processing. METHOD: The FBT performance of 15 patients with ASD, 16 with depression, 16 with schizophrenia and of 16 control subjects was compared. In addition, two tests well known to be sensitive to local processing were assessed, namely the Embedded Figures Test (EFT) and the Block Design Test (BDT). RESULTS: ASD patients demonstrated a preference for local processing. Difficulties in global processing, or more specifically in gestalt perception (FBT), were accompanied by good performance on the EFT and BDT as expected. Controlling for age and nonverbal intelligence (ANCOVA) reduced differences to trends. However, the calculation of difference scores (i.e., subtraction of FBT from EFT performance) resulted in significant differences between ASD and control groups even after controlling for of age and intelligence. CONCLUSIONS: The FBT is a suitable exploratory test of local visual processing in ASD. In particular, a difference criterion can be generated (FBT vs. EFT) that discriminates between ASD and clinical as well as healthy control groups.

[Psychopharmacotherapy improves psychosocial functioning in adolescents with borderline personality disorder]. / Psychopharmakotherapie verbessert das psychosoziale Funktionsniveau bei adoleszenten Patienten mit Borderline-Persönlichkeitsstörung.

Treatment of patients with borderline personality disorder (BPD) has undergone significant changes within the last decades. Although there is no specific pharmacological treatment approach for BPD per se, there is evidence for a beneficial effect of psychopharmacological treatment in adults. As there is a significant lack of data regarding such treatment in adolescents we aim to investigate the effects of psychopharmacological treatment retrospectively focusing on the first period of treatment. The study sample comprised 2,778 subjects (inpatients and outpatients) from a population on demand of psychiatric services referred to our department, with 39 patients (aged 16,2 +/- 1,7 yrs.) having a diagnosis of BPD. Psychosocial functioning as indexed on axis VI was assessed within the BADO documentation algorithm before and after treatment. Effects of treatment in terms of improved psychosocial functioning under different medications as well as different risk variables were assessed. Moreover, medicated and un-medicated patients were compared as regards effects of treatment. Upon admission inpatients showed a significantly higher impairment in their psychosocial functioning compared with outpatients. There was no significant difference between medicated and un-medicated patients with respect to the different risk variables assessed. Psychosocial functioning improved under pharmacological treatment, with this effect being unrelated to in- or outpatient status. About 80% of the prescribed medications were antidepressants and neuroleptics, with a combination of two drugs being the most frequent treatment approach to be observed. The data of the present study indicate that psychopharmacological treatment of adolescents with BPD can improve psychosocial functioning.

FARP2, HDLBP and PASK are downregulated in a patient with autism and 2q37.3 deletion syndrome.

We describe a patient with autism and brachymetaphalangy, meeting criteria for 2q37 deletion syndrome (also called Albright Hereditary Osteodystrophy-like syndrome or Brachydactyly-Mental Retardation syndrome, OMIM 600430). Our molecular cytogenetic studies, including array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH), define the extent of the de novo deletion to a 3.5 Mb region on 2q37.3. Although a number of reports of patients with 2q37 deletion syndrome have been published, it remains unclear if gene expression and/or translation are altered by the deletion, thus contributing to the observed phenotypes. To address this question, we selected several candidate genes for the neuropsychiatric and skeletal anomalies found in this patient (autism and brachymetaphalangy). The deleted region in 2q37.3 includes the FERM, RhoGEF and pleckstrin domain protein 2 (FARP2), glypican 1 (GPC1), vigilin (HDLBP), kinesin family member 1A (KIF1A) and proline-alanine-rich STE20-related kinase (PASK), all of which are involved in skeletal or neural differentiation processes. Expression analyses of these genes were performed using RNA from lymphoblastoid cell lines of the patient and his family members. Here we demonstrate that three of these genes, FARP2, HDLBP, and PASK, are considerably downregulated in the patient's cell line. We hypothesize that haploinsufficiency of these genes may have contributed to the patient's clinical phenotype.

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

INTRODUCTION: 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. METHODS: Seventeen boys with ADHD participated in the study in a double-blind within-subject crossover-design. They were administered RTD within an amino acid drink lacking tryptophan, thus lowering central nervous 5-HT-synthesis. On another day they received a placebo. Self-rated mood was assessed on both days at baseline conditions and at three different post-drink time-points. RESULTS: RTD had no clear effect on mood within the whole sample. Low scorers on venturesomeness were more strongly affected by RTD in terms of feelings of inactivity and negative feelings compared to high venture patients. CONCLUSIONS: Our data did not show a significant effect of RTD on mood self-ratings. However, the findings must be considered as preliminary and require further replication, in particular as they could be due to sampling bias.

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.

Covariation, co-occurrence and epiphenomenal correlation of empirically based syndromes in children and adolescents.

BACKGROUND: This paper determines the co-occurrence and correlations of different problem behaviours in children and adolescents in German clinical and general population samples. SAMPLING AND METHODS: The 2 samples were matched by age and gender (each sample n = 1,760). Including both categorical and dimensional models, rates of co-occurrence, relative risks, odds ratios and Pearson correlations were calculated. RESULTS: The bidirectional comorbidity rates ranged from 7.3 to 34.3% (epidemiological sample) and from 22.5 to 54.8% (clinical sample). Most correlations between syndrome scales show medium or large effects. Many can be identified as 'epiphenomenal'; partial correlations from each pair, excluding influences of other syndromes, are much lower. CONCLUSIONS: This study shows the cross-cultural generalizability of comorbidity rates. The epiphenomenal nature of some comorbidities warrants future attention.

Pilot evaluation of the Frankfurt Social Skills Training for children and adolescents with autism spectrum disorder.

The objective of this pilot study was to evaluate the effectiveness of a group-based intervention aiming at improving social and communication skills in individuals with autism spectrum disorder. Over a period of 11 months, N = 17 children and adolescents received treatment according to the manualised Frankfurt Social Skills Training (KONTAKT). Parent, teacher, expert and blind expert ratings were assessed to judge outcome regarding peer interaction, autistic behaviours, adaptive functioning and family burden. The participants exhibited improvements pre to follow-up treatment, particularly in the area of autistic symptomatology. Effect sizes (partial eta squared) ranged from 0.02 to 0.69. Among other things, regression models showed a positive influence of IQ and language skills on gains in social skills. Findings indicate that KONTAKT might be useful for enhancing social skills and reducing autism-related psychopathology over time in different contexts. Nevertheless, controlled trials are needed to reassure its effectiveness.

[Withdrawal syndrome after abuse of GHB (Gamma-Hydroxybutyrate) and its physiological precursors - its relevance for child and adolescent psychiatrists]. / Entzugsdelir nach Missbrauch von GHB-(Gamma-Hydroxybutyrat) und seiner Vorstufen: Grundlagen und Bedeutung für die Kinder- und Jugendpsychiatrie.

BACKGROUND: The chronic abuse of Gamma-Hydroxybutyrate (GHB) as a designer drug as well as it's physiological precursors Gamma-Butyrolactone (GBL) and 1,4-Butandiole (1,4-BD) confronts child and adolescent psychiatrists with new challenges. The acute withdrawal of GHB with its cardiovascular and delirant symptoms is of particular importance for child and adolescent psychiatrists. METHODS: In the present paper theoretical and biological aspects of acute GHB-/GBL-/1,4-BD-withdrawal syndrome are presented, and selected cases are discussed as regards potential treatment. RESULTS: High dose treatment with benzodiazepines was successful in some cases of acute GHB-/GBL-/1,4-BD-withdrawal syndrome. Complications were severe dystonia under neuroleptic treatment, and also side-effects of treatment with benzodiazepines. Further problems were vegetative symptoms, electrocardiographic changes, rhabdomyolysis, acute renal failure, and death. CONCLUSION: Acute GHB-withdrawal syndrome is a life-threatening condition which requires immediate intensive care treatment along with continuous monitoring of vital parameters. As acute GHB-withdrawal syndrome can present with symptoms close to psychotic episodes or acute alcohol withdrawal this condition is relevant for child and adolescent psychiatrists.