Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked syndrome characterized by pre- and postnatal overgrowth (gigantism), which clinically resembles the autosomal Beckwith-Wiedemann syndrome (BWS). Deletions and translocations involving the glypican-3 gene ( GPC3 ) have been shown to be associated with SGBS. Occasionally, these deletions also include the glypican-4 gene ( GPC4 ). Glypicans are heparan sulfate proteoglycans which have a role in the control of cell growth and cell division. We have examined the mutational status of the GPC3 and GPC4 genes in one patient with Perlman syndrome, three patients with overgrowth without syndrome diagnosis, ten unrelated SGBS-patients and 11 BWS patients. We identified one SGBS patient with a deletion of a GPC3 exon. Six SGBS patients showed point mutations in GPC3. One frameshift, three nonsense, and one splice mutation predict a loss-of-function of the glypican-3 protein. One missense mutation, W296R, changes an amino acid that is conserved in all glypicans identified so far. A GPC3 protein that reproduces this mutation is poorly processed and fails to increase the cell surface expression of heparan sulfate, suggesting that this missense mutation is also a loss-of-function mutation. In three SGBS patients and in all non-SGBS patients, no mutations could be identified. We found three single nucleotide polymorphisms in the GPC4 gene but no evidence for loss-of-function mutations in GPC4 associated with SGBS.

This study was registered in Current Controlled Trials; Nordic Long-term Obsessive-compulsive disorder (OCD) Treatment Study (www.controlled-trials.com ISRCTN66385119).

In the multivariate analysis, only age predicted better treatment outcome. Using univariate analysis, a variety of predictors of poorer treatment outcome after CBT was identified. The high impact of comorbid symptoms on outcome in pediatric OCD suggests that treatment should address comorbidity issues. The lack of a family predictor may be related to high family involvement in this study. Future research strategies should focus on optimizing intervention in the presence of these characteristics to achieve greater benefits for patients with OCD. Clinical trial registration information-Nordic Long-term Obsessive compulsive disorder (OCD) Treatment Study; www.controlled-trials.com; ISRCTN66385119.

Barn og ungdom med tvangslidelse (OCD): Komorbiditet og livskvalitet.OCD er kjennetegnet av ubehagelige tvangstanker og tidskrevende tvangshandlinger og forekommer hos 0,5 -3 % av barnebefolkningen. Ubehandlet får lidelsen et kronisk forløp hos 40 -75 %. Hovedmålsettingen for avhandlingen var å belyse to viktige aspekter av OCD: Samtidig forkommende andre tilstander (komorbiditet) og livskvalitet. Komorbiditet i form av autistiske trekk ble undersøkt hos barn og unge med OCD og sammenliknet med en kontrollgruppe fra den generelle befolkningen. Utvalget er hentet fra en svensk OCD klinikk (Göteborg), kontrollgruppen ble rekruttert i en middels stor by fra samme geografiske området. Autistiske symptomer forekom hos omtrent en femtedel av barn og unge med OCD og var dermed mye hyppigere enn i den generelle befolkningen. Allikevel hadde flertallet ikke slike symptomer som tyder på at kombinasjonen av autistiske symptomer og OCD forekommer i en undergruppe, men er ikke et generelt trekk ved OCD. l den internasjonalt pågående debatten om det er empirisk grunnlag for å betrakte tilstander som OCD, Tourettes syndrom, spiseforstyrrelser og autismespekterforstyrrelser som deler av et såkalt Obsessive-Compulsive Spectrum (OCSD) støtter våre resultater ikke klassifikasjon av autismespekterforstyrrelser som del av dette spektrum. At en undergruppe av barn med OCD har autistiske trekk må dog tas i betraktning når man skal skreddersy individuell tilpasset behandling for barn med OCD.Å utforske livskvalitet hos barn og unge med OCD er relevant, fordi det finnes et stort antall studier av livskvalitet hos voksne med OCD, men veldig få undersøkelser hos barn. Livskvalitet ble undersøkt hos barn og unge med OCD som deltok i NordLOTS studien (Nordic Longterm OCD treatment study) og sammenliknet med livskvalitet av skoleelever i Sør-Trøndelag. NordLOTS-studien er en nordisk multisenterstudie hvor enheter som behandler OCD hos barn og ungdom har anvendt samme prosedyre for utredning, behandling og evaluering. Studien har inkludert 135 barn og ungdom i alder 7-17 år med OCD. Pasientene ble behandlet med kognitiv atferdsterapi (KAT) med eksponering i en "standartdose" på 14 timer og ble deretter evaluert. Livskvalitet og sosial kompetanse var betydelig redusert hos barn og ungdom med OCD sammenlignet med den generelle befolkningen. Hos barn med komorbide lidelser beskrev foreldrene lavere livskvalitet enn hos de med bare OCD. Etter behandlingen rapporterte de som hadde effekt av behandlingen en livskvalitet i samme nivå som i den generelle befolkningen, mens de som ikke hadde effekt beskrev ingen forbedring av livskvaliteten. Basert på våre funn anbefales å anvende livskvalitets evaluering i klinikk og forskning for å få med et mål for barns og foreldrenes subjektive opplevelse i vurderingen og dermed en mer helhetlig forståelse av OCD hos barn og unge. Ovennevnte avhandling er funnet verdig til å forsvares offentlig for graden philosophiae doctor (ph.d.). Disputas finner sted i Auditoriet, Medisinsk Teknisk Forskningssenter, fredag 9...

Expert guidelines recommend cognitive-behavior therapy (CBT) as a first-line treatment in pediatric obsessive–compulsive disorder (OCD) and the addition of selective serotonin reuptake inhibitors when CBT is not effective. However, the recommendations for CBT non-responders are not supported by empirical data. Our objective was to investigate the effectiveness of sertraline (SRT) versus continued CBT in children and adolescents that did not respond to an initial course of CBT. Randomized controlled trial conducted in five sites in Denmark, Sweden and Norway, 54 children and adolescents, age 7–17 years, with DSM-IV primary OCD were randomized to SRT or continued CBT for 16 weeks. These participants had been classified as non-responders to CBT following 14 weekly sessions. Primary outcomes were the CY-BOCS total score and clinical response (CY-BOCS <16). The study was a part of the Nordic Long-Term OCD Treatment Study (NordLOTS). Intent-to-treat sample included 50 participants, mean age 14.0 (SD = 2.7) and 48 % (n = 24) males. Twenty-one of 28 participants (75 %) completed continued CBT and 15 of 22 participants (69.2 %) completed SRT. Planned pairwise comparison of the CY-BOCS total score did not reveal a significant difference between the treatments (p = .351), the response rate was 50.0 % in the CBT group and 45.4 % in the SRT group. The multivariate χ2 test suggested that there were no statistically significant differences between groups (p = .727). Within-group effect sizes were large and significant across both treatments. These large within-group effect sizes suggest that continued treatment for CBT non-responders is beneficial. However, there was no significant between-group differences in SRT or continued CBT at post-treatment.

BackgroundThis paper describes and discusses the methodology of the Nordic long-term OCD-treatment study (NordLOTS). The purpose of this effectiveness study was to study treatment outcome of CBT, to identify CBT non- or partial responders and to investigate whether an increased number of CBT-sessions or sertraline treatment gives the best outcome; to identify treatment refractory patients and to investigate the outcome of aripiprazole augmentation; to study the outcome over a three year period for each responder including the risk of relapse, and finally to study predictors, moderators and mediators of treatment response.MethodsStep 1 was an open and uncontrolled clinical trial with CBT, step 2 was a controlled, randomised non-blinded study of CBT non-responders from step 1. Patients were randomized to receive either sertraline plus CBT-support or continued and modified CBT. In step 3 patients who did not respond to either CBT or sertraline were treated with aripiprazole augmentation to sertraline.ConclusionsThis multicenter trial covering three Scandinavian countries is going to be the largest CBT-study for paediatric OCD to date. It is not funded by industry and tries in the short and long-term to answer the question whether further CBT or SSRI is better in CBT non-responders.

BackgroundQuality of life (QoL) is a well-established outcome measure. However, in contrast to adult obsessive-compulsive disorder (OCD), little is known about QoL in children with OCD. This study aimed to assess QoL, social competence and school functioning of paediatric patients with OCD by comparing them with the general population and assessing the relations between comorbidity, duration and severity of symptoms, family accommodation and QoL.MethodsChildren and adolescents (n = 135), aged 7–17 (mean 13 [SD 2.7] years; 48.1% female) were assessed at baseline for treatment. QoL was assessed by self-report and caregiver’s proxy report on the Questionnaire for Measuring Health-related Quality of Life in Children and Adolescents (KINDL-R) and compared with an age- and sex-matched sample from the general population. Social competence and school functioning were assessed with the Child Behavior Checklist, comorbidity with the Kiddie Schedule for Affective Disorders and Schizophrenia (Present and Lifetime Version), severity of OCD with the Children’s Yale-Brown Obsessive Compulsive Scale and the families’ involvement with the child’s OCD symptoms with the Family Accommodation Scale.ResultsQoL and social competence were reduced (p < .001) in patients with OCD compared with controls (KINDL-R mean score 62.40 [SD 13.00] versus 69.72 [12.38] in self-reports and 61.63 [SD 13.27] versus 74.68 [9.97] in parent reports). Patients with comorbidity had lower QoL (p = .001) in proxy ratings than those with OCD only (mean score 56.26 [SD 12.47] versus 64.30 [SD 12.75]). In parent proxy reports, severity of OCD (r = −.28) and family accommodation (r = −.40) correlated moderately negatively with QoL.ConclusionsTo our knowledge, this is the largest QoL study of paediatric OCD. QoL was markedly reduced in children with OCD, especially in those with comorbid psychiatric disorders. Based on our findings, we suggest employing QoL assessment in order to have a more comprehensive understanding of childhood OCD.Clinical trials registration informationThis study was registered in Current Controlled Trials; Nordic Long-term Obsessive Compulsive disorder (OCD) Treatment Study (ISRCTN66385119).

Pragmatic language impairments are common in neurodevelopmental disorders, especially in autism spectrum disorder (ASD). The relationship between structural language skills and pragmatic competence in children with autistic symptoms, however, is largely unknown. We investigated this relationship based on the Children’s Communication Checklist-2 and early language delay among children (N = 177, 19% females) clinically evaluated for ASD, differentiated into ASD (n = 148) and non-ASD (n = 29). Structural language deficits were common and associated with reduced pragmatic competence in both groups. Pragmatic language impairments were most profound in children with ASD. Early language delay and structural language deficits were less common in females. Our findings suggest that assessment of structural language skills should be included in the evaluation of children with suspected ASD.