Cognition,Emotion and Behavior in Children with Tourette’s Syndrome and Children with ADHD-Combined Subtype—A Two-Year Follow-Up Study

Objective

This two-year follow-up study investigates the course of and association among measures of cognitive control, focused attention, decision-making and symptom severity (anxiety, depression and behavior) in children and adolescents with Tourette’s Syndrome (TS) or Attention-Deficit/Hyperactivity Disorder-Combined subtype (ADHD-C).

Method

19 children with TS, 33 with ADHD-C, and 50 typically developing children (TDC) were examined with a battery of psychometric measures and rating forms at baseline and two-years later.

Results

All three groups improved likewise in measures of cognitive control over time, whereas only the TDC improved in focused attention. The group of children with TS with comorbidities performed more similar to the children with ADHD-C in cognitive control at T1 and T2, whereas the children with TS without comorbidities performed more similar to the TDC in cognitive control at T1 and T2. In the decision-making task, the children with TS (with or without comorbidities) preferred a safer strategy in selecting advantageous choices than the children with ADHD-C and the TDC at T2. Children with TS and children with ADHD-C showed higher symptoms of anxiety and depression and more problems with emotional control compared with TDC at both time points. Finally, children with ADHD-C self-reported more depression symptoms than those with TS at both assessments. For the TS group, safer decision-making was related to better emotional control, and this relationship was stronger for the TS subgroup without comorbidities.

Conclusion

This study emphasizes the importance of addressing symptoms of anxiety and depression in children with TS or ADHD-C, identifying the effect of comorbidities in children with TS, and that children with TS or ADHD-C likely differ in their sensitivity to reinforcement contingencies.     

Modulation of the dopamine transporter by interaction with Secretory Carrier Membrane Protein 2

The monoamine transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT) facilitate the homeostatic balance of neurotransmitters in the synaptic cleft and thus, play a fundamental role in regulating neuronal activity. Despite the importance of these monoamine transporters in controlling brain function, only relatively little information is available regarding the cellular and molecular regulation of these proteins. The monoamine transporters have been found to associate with a number of different proteins that regulate the function and subcellular localization of the transporters. We recently reported a functional interaction between SERT and the Secretory Carrier Membrane Protein 2 (SCAMP2). Here, we demonstrate that SCAMP2 also plays a role in the functional regulation of DAT. DAT and SCAMP2 interaction is here verified by co-immunoprecipitation and fluorescence resonance energy transfer (FRET) microscopy. Moreover, co-expression of DAT and SCAMP2 results in a decrease in DAT-mediated dopamine uptake caused by reduced levels of DAT molecules on the cell surface. Our finding that SCAMP2 interacts with and regulates the subcellular distribution of both DAT and SERT suggests that interaction with SCAMP2 may constitute an important mechanism for coordinating cell surface expression of monoamine transporters.     

Osteopontin reduces biofilm formation in a multi-species model of dental biofilm

Background

Combating dental biofilm formation is the most effective means for the prevention of caries, one of the most widespread human diseases. Among the chemical supplements to mechanical tooth cleaning procedures, non-bactericidal adjuncts that target the mechanisms of bacterial biofilm formation have gained increasing interest in recent years. Milk proteins, such as lactoferrin, have been shown to interfere with bacterial colonization of saliva-coated surfaces. We here study the effect of bovine milk osteopontin (OPN), a highly phosphorylated whey glycoprotein, on a multispecies in vitro model of dental biofilm. While considerable research effort focuses on the interaction of OPN with mammalian cells, there are no data investigating the influence of OPN on bacterial biofilms.

Methodology/Principal Findings

Biofilms consisting of Streptococcus oralis, Actinomyces naeslundii, Streptococcus mitis, Streptococcus downei and Streptococcus sanguinis were grown in a flow cell system that permitted in situ microscopic analysis. Crystal violet staining showed significantly less biofilm formation in the presence of OPN, as compared to biofilms grown without OPN or biofilms grown in the presence of caseinoglycomacropeptide, another phosphorylated milk protein. Confocal microscopy revealed that OPN bound to the surface of bacterial cells and reduced mechanical stability of the biofilms without affecting cell viability. The bacterial composition of the biofilms, determined by fluorescence in situ hybridization, changed considerably in the presence of OPN. In particular, colonization of S. mitis, the best biofilm former in the model, was reduced dramatically.

Conclusions/Significance

OPN strongly reduces the amount of biofilm formed in a well-defined laboratory model of acidogenic dental biofilm. If a similar effect can be observed in vivo, OPN might serve as a valuable adjunct to mechanical tooth cleaning procedures.     

DEMO-II Trial. Aerobic Exercise versus Stretching Exercise in Patients with Major Depression—A Randomised Clinical Trial

Background

The effect of referring patients from a clinical setting to a pragmatic exercise intervention for depressive symptoms, cognitive function, and metabolic variables has yet to be determined.

Methods

Outpatients with major depression (DSM-IV) were allocated to supervised aerobic or stretching exercise groups during a three months period. The primary outcome was the Hamilton depression score (HAM-D₁₇). Secondary outcomes were cognitive function, cardiovascular risk markers, and employment related outcomes.

Results

56 participants were allocated to the aerobic exercise intervention versus 59 participants to the stretching exercise group. Post intervention the mean difference between groups was −0.78 points on the HAM-D₁₇ (95% CI −3.2 to 1.6; P = .52). At follow-up, the participants in the aerobic exercise group had higher maximal oxygen uptake (mean difference 4.4 l/kg/min; 95% CI 1.7 to 7.0; P = .001) and visuospatial memory on Rey’s Complex Figure Test (mean difference 3.2 points; 95% CI 0.9 to 5.5; P = .007) and lower blood glucose levels (mean difference 0.2 mmol/l; 95% CI 0.0 to 0.5; P = .04) and waist circumference (mean difference 2.2 cm; 95% CI 0.3 to 4.1; P = .02) compared with the stretching exercise group.

Conclusions

The results of this trial does not support any antidepressant effect of referring patients with major depression to a three months aerobic exercise program. Due to lower recruitment than anticipated, the trial was terminated prior to reaching the pre-defined sample size of 212 participants; therefore the results should be interpreted in that context. However, the DEMO-II trial does suggest that an exercise program for patients with depression offer positive short-term effects on maximal oxygen uptake, visuospatial memory, fasting glucose levels, and waist circumference.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00695552","term_id":"NCT00695552"}}NCT00695552     

High-Quality Exome Sequencing of Whole-Genome Amplified Neonatal Dried Blood Spot DNA

Stored neonatal dried blood spot (DBS) samples from neonatal screening programmes are a valuable diagnostic and research resource. Combined with information from national health registries they can be used in population-based studies of genetic diseases. DNA extracted from neonatal DBSs can be amplified to obtain micrograms of an otherwise limited resource, referred to as whole-genome amplified DNA (wgaDNA). Here we investigate the robustness of exome sequencing of wgaDNA of neonatal DBS samples. We conducted three pilot studies of seven, eight and seven subjects, respectively. For each subject we analysed a neonatal DBS sample and corresponding adult whole-blood (WB) reference sample. Different DNA sample types were prepared for each of the subjects. Pilot 1: wgaDNA of 2x3.2mm neonatal DBSs (DBS_2x3.2) and raw DNA extract of the WB reference sample (WB_ref). Pilot 2: DBS_2x3.2, WB_ref and a WB_ref replica sharing DNA extract with the WB_ref sample. Pilot 3: DBS_2x3.2, WB_ref, wgaDNA of 2x1.6 mm neonatal DBSs and wgaDNA of the WB reference sample. Following sequencing and data analysis, we compared pairwise variant calls to obtain a measure of similarity—the concordance rate. Concordance rates were slightly lower when comparing DBS vs WB sample types than for any two WB sample types of the same subject before filtering of the variant calls. The overall concordance rates were dependent on the variant type, with SNPs performing best. Post-filtering, the comparisons of DBS vs WB and WB vs WB sample types yielded similar concordance rates, with values close to 100%. WgaDNA of neonatal DBS samples performs with great accuracy and efficiency in exome sequencing. The wgaDNA performed similarly to matched high-quality reference—whole-blood DNA—based on concordance rates calculated from variant calls. No differences were observed substituting 2x3.2 with 2x1.6 mm discs, allowing for additional reduction of sample material in future projects.