Klinische kinderpsychiatrie en het cognitief-structurele ontwikkelingsmodel

In dit onderzoeksproject zal worden nagegaan of de ontwikkeling van het klinisch-kinderpsychiatrisch in behandeling zijnde kind vastgelegd kan worden binnen het cognitief-structurele ontwikkel ingsmodel. In het volgen de hoofdstuk zal dit model besproken worden. Binnen het cognitiefstructurele ontwikkelingsmodel staat onderzoek naar de (kinderlijke) denkontwikkeling centraal. Dit project is beperkt tot het naast elkaar en in onderlinge samenhang onderzoeken van het kinderlijk denken over de physische en over de sociale werkelijkheid. Hiervoor werden een aantal tests geselecteerd die erop gericht zijn om aspecten van deze twee soorten denken afzonderlijk te meten. Het gebruik voor behandelingsdoeleinden van het gekozen testinstrumentarium in de kinder- en jeugdpsychiatrische kliniek is eerst mogelijk wanneer de relaties bekend zijn tussen de beide vormen van denken en tussen de diverse tests. In de vorm van een evaluatieonderzoek van een ten aanzien van leerjaar, sexe en school gestratifi ceerde steekproef van zich normaal ontwikkelende kinderen werd onderzocht of en in welke mate de geselecteerde cognitiefstructurele ontwikkelingstests geschikt zijn voor ontwikkelingsregistratie binnen de kinder- en jeugdpsychiatrische kliniek en voor voorspellende doeleinden.Samenvattend valt het onderzoeksproject in een aantal delen uiteen. Allereerst werd de bruikbaarheid en de onderlinge samenhang onderzocht van de geselecteerde cognitief-structurele ontwikkelingstests door deze tests af te nemen bij een ten aanzien van leerjaar en sexe gestratificeerde steekproef van achtenzestig zich normaal ontwikkelende Rotterdamse schoolkinderen met een leeftijdsrange van zes tot en met elf jaar. Vervolgens werd onderzocht of de verkregen gegevens bevestigd werden in longitudinaal onderzoek (een-jaar follow-up met drie afnamen) verricht bij dezelfde groep schoolkinderen. Tenslotte werden de resultaten van de afname van de tests bij klinisch-kinderpsychiatrisch behandelde kinderen vergeleken met de bevindingen verkregen uit de afname van de tests bij de controlegroe

Increased cocaine self-administration in rats lacking the serotonin transporter : a role for glutamatergic signaling in the habenula

Serotonin (5-HT) and the habenula (Hb) contribute to motivational and emotional states such as depression and drug abuse. The dorsal raphe nucleus, where 5-HT neurons originate, and the Hb are anatomically and reciprocally interconnected. Evidence exists that 5-HT influences Hb glutamatergic transmission. Using serotonin transporter knockout (SERT-/- ) rats, which show depression-like behavior and increased cocaine intake, we investigated the effect of SERT reduction on expression of genes involved in glutamate neurotransmission under both baseline conditions as well as after short-access or long-access cocaine (ShA and LgA, respectively) intake. In cocaine-na\uefve animals, SERT removal led to reduced baseline Hb mRNA levels of critical determinants of glutamate transmission, such as SLC1A2, the main glutamate transporter and N-methyl-D-aspartate (Grin1, Grin2A and Grin2B) as well as \u3b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (Gria1 and Gria2) receptor subunits, with no changes in the scaffolding protein Dlg4. In response to ShA and LgA cocaine intake, SLC1A2 and Grin1 mRNA levels decreased in SERT+/+ rats to levels equal of those of SERT-/- rats. Our data reveal that increased extracellular levels of 5-HT modulate glutamate neurotransmission in the Hb, serving as critical neurobiological substrate for vulnerability to cocaine addiction

The Stability of Comorbid Psychiatric Disorders: A 7 Year Follow Up of Children with Pervasive Developmental Disorder-Not Otherwise Specified

The current study was a 7-year follow-up of 74 6–12 year old children with Pervasive Developmental Disorder-Not Otherwise Specified. We examined the rates and 7 year stability of comorbid psychiatric diagnoses as ascertained with the Diagnostic Interview Schedule for Children: Parent version at ages 6–12 and again at ages 12–20. Also, we examined childhood factors that predicted the stability of comorbid psychiatric disorders. The rate of comorbid psychiatric disorders dropped significantly from childhood (81 %) to adolescence (61 %). Higher levels of parent reported stereotyped behaviors and reduced social interest in childhood significantly predicted the stability of psychiatric comorbidity. Re-evaluation of psychiatric comorbidity should be considered in clinical practice, since several individuals shifted in comorbid diagnoses

Face and emotion recognition in MCDD versus PDD-NOS

Previous studies indicate that Multiple Complex Developmental Disorder (MCDD) children differ from PDD-NOS and autistic children on a symptom level and on psychophysiological functioning. Children with MCDD (n = 21) and PDD-NOS (n = 62) were compared on two facets of social-cognitive functioning: identification of neutral faces and facial expressions. Few significant group differences emerged. Children with PDD-NOS demonstrated a more attention-demanding strategy of face processing, and processed neutral faces more similarly to complex patterns whereas children with MCDD showed an advantage for face recognition compared to complex patterns. Results further suggested that any disadvantage in face recognition was related more to the autistic features of the PDD-NOS group rather than characteristics specific to MCDD. No significant group differences emerged for identifying facial expressions

Formal thought disorder in autism spectrum disorder predicts future symptom severity, but not psychosis prodrome

Formal thought disorder (FTD) is a disruption in the flow of thought, which is inferred from disorganisation of spoken language. FTD in autism spectrum disorders (ASD) might be a precursor of psychotic disorders or a manifestation of ASD symptom severity. The current longitudinal study is a seven-year follow-up of 91 individuals aged 5-12 years with ASD. We tested (1) whether childhood FTD predicted prodromal symptoms of psychosis in adolescence and (2) whether childhood FTD was associated with greater ASD symptom severity in adolescence. ASD symptom severity was assessed in childhood (T1) and 7 years later (T2), using the autism diagnostic observation schedule (ADOS). At T1, the Kiddie-Formal Thought Disorder Rating Scale (KFTDS) was used to measure symptoms of FTD. At T2, the prodromal questionnaire (PQ) was used to assess prodromal symptoms of psychosis. FTD at T1 did not predict prodromal symptoms of psychosis at T2 in children with ASD. FTD symptoms at T1, namely illogical thinking, predicted ASD symptom severity at T2 and this effect remained significant after controlling for T1 ASD symptom severity. In children with ASD, illogical thinking predicts severity of ASD symptoms in adolescence, but FTD does not predict prodromal symptoms of psychosis

Collagen proportionate area correlates with histological stage and predicts clinical events in primary sclerosing cholangitis

Background & Aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease in need of accurate biomarkers for stratification and as surrogates for clinical endpoints in trials. Quantitative liver fibrosis assessment by collagen proportionate area (CPA) measurement has been demonstrated to correlate with clinical outcomes in chronic hepatitis C, alcohol-related and non-alcoholic fatty liver disease. We aimed to investigate the ability of CPA to quantify liver fibrosis and predict clinical events in PSC. Methods: Biopsies from 101 PSC patients from two European centres were retrospectively assessed by two expert pathologists in tandem, using grading (Ishak and Nakanuma) and staging (Ishak, Nakanuma, Ludwig) systems recently validated to predict clinical events in PSC. CPA was determined by image analysis of picro-Sirius red-stained sections following a standard protocol. We assessed the correlations between CPA, staging and grading and their associations with three outcomes: (1) time to PSC-related death, liver transplant or primary liver cancer; (2) liver transplant-free survival; (3) occurrence of cirrhosis-related clinical manifestations. Results: CPA correlated strongly with histological stage determined by each scoring system (P < .001) and was significantly associated with the three endpoints. Median time to endpoint-1, endpoint-2 and endpoint-3 was shorter in patients with higher CPA, on Kaplan-Meier analyses (P = .011, P = .034 and P = .001, respectively). Conclusion: Quantitative fibrosis assessment by CPA has utility in PSC. It correlates with established histological staging systems and predicts clinical events. CPA may be a useful tool for staging fibrosis and for risk stratification in PSC and should be evaluated further within prospective clinical trials

Melken in twee tanks: hoog en laag eiwitgehalte

Uit berekeningen van het PR is gebleken dat het scheiden van de melk in een deel met een hoog en een deel met een laag eiwitgehalte in een aantal gevallen bedrijfseconomisch aantrekkelijk kan zijn

Is green space in the living environment associated with people's feelings of social safety?

Abstract. The authors investigate whether the percentage of green space in people's living environ- ment affects their feelings of social safety positively or negatively. More specifically they investigate the extent to which this relationship varies between urban and rural areas, between groups in the community that can be identified as more or less vulnerable, and the extent to which different types of green space exert different influences. The study includes 83736 Dutch citizens who were interviewed about their feelings of social safety. The percentage of green space in the living environment of each respondent was calculated, and data analysed by use of a three-level latent variable model, controlled for individual and environmental background characteristics. The analyses suggest that more green space in people's living environment is associated with enhanced feelings of social safetyöexcept in very strongly urban areas, where enclosed green spaces are associated with reduced feelings of social safety. Contrary to the common image of green space as a dangerous hiding place for criminal activity which causes feelings of insecurity, the results suggest that green space generally enhances feelings of social safety. The results also suggest, however, that green space in the most urban areas is a matter of concern with respect to social safety.

Is there still a role for nuchal translucency measurement in the changing paradigm of first trimester screening?

Objectives To give an overview of the genetic and structural abnormalities occurring in fetuses with nuchal translucency (NT) measurement exceeding the 95th percentile at first-trimester screening and to investigate which of these abnormalities would be missed if cell-free fetal DNA (cfDNA) were used as a first-tier screening test for chromosomal abnormalities. Methods This is a national study including 1901 pregnancies with NT &gt;= 95th percentile referred to seven university hospitals in the Netherlands between 1 January 2010 and 1 January 2016. All cases with unknown pregnancy outcome were excluded. Results of detailed ultrasound examinations, karyotyping, genotyping, pregnancy and neonatal outcomes, investigation by a clinical geneticist and post-mortem investigations were collected. Results In total, 821 (43%) pregnancies had at least one abnormality. The rate of abnormalities was 21% for fetuses with NT between 95(th) and 99(th) percentile and 62% for fetuses with NT &gt;= 99(th) percentile. Prevalence of single-gene disorders, submicroscopic, chromosomal and structural abnormalities was 2%, 2%, 30% and 9%, respectively. Conclusion Although cfDNA is superior to the combined test, especially for the detection of trisomy 21, 34% of the congenital abnormalities occurring in fetuses with increased NT may remain undetected in the first trimester of pregnancy, unless cfDNA is used in combination with fetal sonographic assessment, including NT measurement.</p

AT-101, a small molecule inhibitor of anti-apoptotic Bcl-2 family members, activates the SAPK/JNK pathway and enhances radiation-induced apoptosis

<p>Abstract</p> <p>Background</p> <p>Gossypol, a naturally occurring polyphenolic compound has been identified as a small molecule inhibitor of anti-apoptotic Bcl-2 family proteins. It induces apoptosis in a wide range of tumor cell lines and enhances chemotherapy- and radiation-induced cytotoxicity both <it>in vitro </it>and <it>in vivo</it>. Bcl-2 and related proteins are important inhibitors of apoptosis and frequently overexpressed in human tumors. Increased levels of these proteins confer radio- and chemoresistance and may be associated with poor prognosis. Consequently, inhibition of the anti-apoptotic functions of Bcl-2 family members represents a promising strategy to overcome resistance to anticancer therapies.</p> <p>Methods</p> <p>We tested the effect of (-)-gossypol, also denominated as AT-101, radiation and the combination of both on apoptosis induction in human leukemic cells, Jurkat T and U937. Because activation of the SAPK/JNK pathway is important for apoptosis induction by many different stress stimuli, and Bcl-X_Lis known to inhibit activation of SAPK/JNK, we also investigated the role of this signaling cascade in AT-101-induced apoptosis using a pharmacologic and genetic approach.</p> <p>Results</p> <p>AT-101 induced apoptosis in a time- and dose-dependent fashion, with ED₅₀values of 1.9 and 2.4 μM in Jurkat T and U937 cells, respectively. Isobolographic analysis revealed a synergistic interaction between AT-101 and radiation, which also appeared to be sequence-dependent. Like radiation, AT-101 activated SAPK/JNK which was blocked by the kinase inhibitor SP600125. In cells overexpressing a dominant-negative mutant of c-Jun, AT-101-induced apoptosis was significantly reduced.</p> <p>Conclusion</p> <p>Our data show that AT-101 strongly enhances radiation-induced apoptosis in human leukemic cells and indicate a requirement for the SAPK/JNK pathway in AT-101-induced apoptosis. This type of apoptosis modulation may overcome treatment resistance and lead to the development of new effective combination therapies.</p