Efficacy of psychodynamic short-term psychotherapy for children and adolescents with depression

Depression is highly prevalent in children and adolescents. Psychodynamic therapies are only insufficiently evaluated in this field although many children and adolescents suffering from depression are treated using this approach. Therefore, the aim of our study was to evaluate the efficacy of psychodynamic short-term psychotherapy (PSTP) for the treatment of depression in children and adolescents. In a waiting-list controlled study, 20 children and adolescents fulfilling diagnosis of major depression or dysthymia were included. The treatment group received 25 sessions of psychodynamic psychotherapy. Main outcome criterion was the Impairment-Score for Children and Adolescents (IS-CA) as well as the Psychic and Social-Communicative Findings Sheet for Children and Adolescents (PSCFS-CA) and the Child Behavior Checklist (CBCL), which were assessed at the beginning and the end of treatment. The statistical and clinical significance of changes in these measures were evaluated. There was a significant advantage of the treatment group compared to the waiting group for the IS-CA. The effect size of the IS-CA total score was 1,3. In contrast to the treatment group, where 20% of the children showed clinically significant and reliable improvement, no subject in the waiting-list control group met this criterion. Comparable results were found for the PSCFS-CA and for the internalising score assessed with the CBCL. The results show that psychodynamic short-term psychotherapy (PSTP) is an effective treatment for depressed children and adolescents. Still, some of the children surely require more intensive treatment.     

Efficacy of psychodynamic short-term psychotherapy for children and adolescents with behavioral disorders

Behavioral disorders represent one of the most frequent mental disorders in children and adolescents. Even though psychodynamic psychotherapies are often used to treat behavioral disorders, to date, its efficacy has rarely been empirically evaluated. The aim of the study therefore was to evaluate psychodynamic short-term psychotherapy (PSTP) for children and adolescents with behavioral disorders. By means of a waiting-list controlled study, 26 children and adolescents fulfilling diagnosis of behavioral disorders were examined. The treatment group received 25 sessions of psychodynamic psychotherapy. Primary criterion of outcome was the Impairment-Score for Children and Adolescents (IS-CA). Furthermore, the Child Behavior Checklist (CBCL) and the Psychic and Social-Communicative Findings Sheet for Children and Adolescents (PSCFS-CA) were administered at the beginning and end of the treatment. The statistical as well as the clinical significance of changes during treatment were analysed. It could be shown, that the treatment group improved significantly more in the Impairment-Score for children and adolescents (IS-CA) compared to the waiting group. The effect size of the IS-CA total score was 0,6. 31% of the children in the treatment group improved clinically significantly or according to the criterion of Reliable Change, whereas that was the case only for 8 % of the subject in the waiting list condition. A significant advantage was found for the therapy group in the PSCFS-CA. Effect sizes were between 0.8 and 1.4. In the CBCL significant improvement could be shown for the treatment and control group however only with small effects. These results substantiate that psychodynamic short-term psychotherapy (PSTP) is an effective intervention for children and adolescents with behavioral disorders. However, the findings also show that some of the children and adolescents are in need of a more intensive or long-term treatment.     

Prospects and limits of pharmacogenetics: the thiopurine methyl transferase (TPMT) experience

Thiopurine drug metabolism is a quintessential case of pharmacogenetics. A wealth of experimental and clinical data on polymorphisms in the thiopurine metabolizing enzyme thiopurine methyl transferase (TPMT) has been generated in the past decade. Pharmacogenetic testing prior to thiopurine treatment is already being practiced to some extent in the clinical context, and it is likely that it will be among the first pharmacogenetic tests applied on a regular basis. We analyzed the published TPMT data and identified some lessons to be learned for the future implementation of pharmacogenetics for thiopurines as well as in other fields. These include the need for comprehensive and unbiased data on allele frequencies relevant to a broad range of populations worldwide. The nature and frequency of TPMT gene polymorphisms in some ethnic groups is still a matter of speculation, as the vast majority of studies on TPMT allele distribution are limited to only a small subset of alleles and populations. Secondly, an appreciation of the limits of pharmacogenetics is warranted, as pharmacogenetic testing can help in avoiding some, but by far not all adverse effects of drug therapy. An analysis of six clinical studies correlating adverse thiopurine effects and TPMT genotype revealed that an average of 78% of adverse drug reactions were not associated with TPMT polymorphisms. Pharmacogenetic testing will thus not eliminate the need for careful clinical monitoring of adverse drug reactions. Finally, a careful approach toward dose increases for patients with high enzyme activity is necessary, as TPMT-mediated methylation of thiopurines generates a possibly hepatotoxic byproduct.     

Modifiable risk factors for SIDS in Germany: results of GeSID

Background: The incidence of sudden infant death syndrome (SIDS) has been falling in Germany over the last decade. However, little is known about the prevalence and the importance of well-known risk factors in Germany since a local prevention campaign in 1992. Design: A 3-y, population-based, case-control study was conducted in half of Germany, consisting of 333 cases. All sudden and unexpected deaths in infancy, if they fitted the inclusion criteria, were included in the study. Parental interview was carried out soon after the death, and three living control infants, matched for age, gender, region and sleep time, were recruited. Results: The prevalence of placing infants prone to sleep was only 4% in the control group, but this was associated with a markedly increased risk of SIDS (adjusted odds ration, aOR=6.08). Other modifiable risk factors for SIDS were: maternal smoking during pregnancy, breastfeeding for less than 2 wk (aOR=1.71) and co-sleeping (aOR=2.71), while using a pacifier during the last sleep reduced the risk (aOR=0.39).

Conclusions: Previously recognized risk factors for SIDS also occur in Germany. Despite knowledge about the major modifiable risk factors for SIDS, these factors are still present in Germany. To reduce the incidence of SIDS in Germany, a continued effort is needed to inform all parents about preventable risk factors for SIDS.     

Reanalyses of case-control studies examining the temporal association between sudden infant death syndrome and vaccination

In this paper we examine different time periods after vaccinations and investigate whether the risk of sudden infant death is different during the post-vaccination period than at other times. Three already published case-control studies are re-examined in this context. Several evaluation approaches are presented. The recently developed self-controled case series (SCCS) method for terminal events, which only takes the cases into account, is used in addition. There is no increased or reduced risk of sudden infant death during the period after the vaccination. The previously reported protective effect seen in case contol studies is based on the inclusion of unvaccinated cases. The results of the case-control analysis of one study is affected by two confounders. The SCCS method for terminal events, in which all time-independent confounders are eliminated, is an alternative to case-control analysis when it comes to the temporal association between exposed time periods and SIDS after vaccination.     

Calvarial “doughnut lesions”: Clinical spectrum of the syndrome,report on a case,and review of the literature

Many pathologic fractures, lumps on the head, elevated serum alkaline phosphatase (ALP) levels, and dental caries are the main characteristics of the rare autosomal dominantly inherited calvarial “doughnut lesions” (MIM 126550). We report the sporadic case of a 16‐year‐old patient who has had 10 pathologic fractures between age 6 weeks and 15 years. An elevated serum ALP level was found at age 11 and skull lumps at age 15; radiography showed frontal and parietal round radiolucencies surrounded by sclerotic bone comparable to doughnuts. Magnetic resonance imaging (MRI) showed skull lesions at an early stage. Because the findings are reminiscent of osteogenesis imperfecta (OI), collagen types I, III, and V were analyzed in fibroblasts and shown to be normal in terms of quantities, proportions, electrophoretic mobility, and thermostability. Thus, this rare syndrome can be distinguished from OI by collagen analysis and MRI of the skull at an early stage, even before palpable skull lesions appear. © 2001 Wiley‐Liss. Inc.     

Sudden infant death syndrome (SIDS) and polymorphisms in Monoamine Oxidase A gene (MAOA): a revisit

Literature describes multiple possible links between genetic variations in the neuroadrenergic system and the occurrence of sudden infant death syndrome. The X-chromosomal Monoamine oxidase A (MAOA) is one of the genes with regulatory activity in the noradrenergic and serotonergic neuronal systems and a polymorphism of the promoter which affects the activity of this gene has been proclaimed to contribute significantly to the prevalence of sudden infant death syndrome (SIDS) in three studies from 2009, 2012 and 2013. However, these studies described different significant correlations regarding gender or age of children. Since several studies, suggesting associations between genetic variations and SIDS, were disproved by follow-up analysis, this study was conducted to take a closer look at the MAOA gene and its polymorphisms. The functional MAOA promoter length polymorphism was investigated in 261 SIDS cases and 93 control subjects. Moreover, the allele distribution of 12 coding and non-coding single nucleotide polymorphisms (SNPs) of the MAOA gene was examined in 285 SIDS cases and 93 controls by a minisequencing technique. In contrast to prior studies with fewer individuals, no significant correlations between the occurrence of SIDS and the frequency of allele variants of the promoter polymorphism could be demonstrated, even including the results from the abovementioned previous studies. Regarding the SNPs, three statistically significant associations were observed which had not been described before. This study clearly disproves interactions between MAOA promoter polymorphisms and SIDS, even if variations in single nucleotide polymorphisms of MAOA should be subjected to further analysis to clarify their impact on SIDS.     

Cytokines and sudden infant death

Background

It has been hypothesised that inflammatory reactions could play an important role in the pathway(s) leading to sudden and unexpected death in infancy. On a molecular level, these reactions are regulated by various cytokines.

Methods

To characterise the role of IL-1?, IL-6 and TNF?? more precisely, the concentrations of these cytokines were determined quantitatively using specific ELISA techniques in serum and cerebrospinal fluid (CSF) in 119 cases of sudden infant death. The infants were grouped into four categories (SIDS, SIDS with infection, natural death due to infection and unnatural death).

Results

A good correlation was found between CSF and serum for IL-6 (Spearman correlation coefficients (SCC), 0.73) and also for TNF?? (SCC, 0.57), although the CSF concentrations were lower than that from the serum. There were no significant differences between the categories of death for any of the serum or CSF cytokines. Compared with normal values, increased serum concentrations of IL-1?, IL-6 and TNF?? were found in 70%, 69% and 38% of the cases respectively, indicating possible agonal or post-mortem changes of cytokine concentrations. In three cases very high cytokine concentrations were found (mainly for IL-6). This may have contributed to the mechanism of death (cytokine storm) in two of the cases.

Conclusions

In a small group of patients, very high cytokine concentrations are a possible explanation for the cause of death (??cytokine storm??).