Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression.

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

Increasing association between a neuropeptide Y promoter polymorphism and body mass index during the course of development.

OBJECTIVE: To investigate the association of the neuropeptide Y (NPY) promoter polymorphism rs16147 with body mass index (BMI) during the course of development from infancy to adulthood. DESIGN: Longitudinal, prospective study of a German community sample. SUBJECTS: n = 306 young adults (139 males, 167 females). MEASUREMENTS: Participants' body weight and height were assessed at the ages of 3 months and 2, 4.5, 8, 11, 15 and 19 years. NPY rs16147 was genotyped. RESULTS: Controlling for a number of possible confounders, homozygote carriers of the rs16147 C allele exhibited significantly lower BMI scores when compared with individuals carrying the T allele. In addition, a significant genotype by age interaction emerged, indicating that the genotype effect increased during the course of development. CONCLUSIONS: This is the first longitudinal study to report an association between rs16147 and BMI during childhood and adolescence. The finding that this effect increased during the course of development may either be due to age-dependent alterations in gene expression or to maturation processes within the weight regulation circuits of the central nervous system.

A new approach to sample size calculation for reference interval studies.

A new criterion is proposed for determining the sample size required for a study performed for the purpose of establishing reference intervals. The basic idea behind the criterion is to compare the empirical coverage (i.e. the probability content) of the reference region obtained from the sample with its target value (e.g. 95 per cent) and to set suitable limits delta1, delta2 to the difference between both quantities which must not be exceeded with sufficiently large probability beta (e.g. beta=90 per cent). For the most frequently used parametric and distribution-free methods of estimating univariate reference limits, implicit formulae are derived relating the sample size to the design parameters delta1, delta2 and beta. For symmetric specification of (delta1, delta2), explicit approximation formulae for the computation of n are given. Exact values obtained by means of suitable numerical techniques are presented in a set of tables covering specifications of delta1, delta2 and beta which can be recommended for real applications. The tables can be used both for one- and two-sided reference intervals.

[How effective are interventions in children and adolescents with antisocial behavior? A utilization study]. / Wie effektiv sind Interventionen bei Kindern und Jugendlichen mit Störungen des Sozialverhaltens? eine Inanspruchnahmestudie.

OBJECTIVE: Anti-social behavior in childhood and adolescence represents a frequent behavior disorder in this age group and its prognosis is predominantly unfavourable. The purpose of this study was to analyze the outcome and predictors of outpatients and inpatients with conduct disorders and internalizing disorders. METHOD: We compared a 10 year follow-up history of in- and outpatients with conduct disorders and internalizing disorders. The sample of patients with conduct disorders was divided into three groups ("I": F90.1; "E": F91.2, F92; "D": F91.1, F91.3). The outcome was defined as an improvement of psychosocial functioning (SGKJ). Statistical analysis consisted of Fisher exact test and logistical regression. RESULTS: Our findings showed the best results in patients with the ICD 10 diagnosis F90.1. Inpatient treatment was superior to outpatient treatment. Cooperation of parents and children, severeness of disease, psychosocial risk factors and pharmacotherapy were found to be the most important predictors. CONCLUSIONS: Effectiveness of an outpatient treatment of children and adolescents with conduct disorders can be increased by training of parents, home treatment or pharmacotherapy.

Differential regulation of synaptic vesicle proteins by antidepressant drugs.

Synaptic vesicle proteins (SVP) play a critical role in neurotransmitter release and neural plasticity, and have been implicated in the pathophysiology of psychiatric disorders such as depression. Antidepressant drugs not only alter the level of neurotransmitters, but also modulate de novo gene transcription and synthesis of proteins involved in neural plasticity. In order to investigate the effects of antidepressant compounds on SVP-mRNA levels, the expressions of synaptophysin, synaptotagmin, VAMP, and synapsin-I were analysed by in situ hybridization in rats which had been treated with desipramine, fluoxetine, tranylcypromine, or saline. The results demonstrate that chronic treatment with fluoxetine and tranylcypromine leads to an increased expression of synaptophysin, but decreased expression of synaptotagmin and VAMP in the hippocampus and cerebral cortex. Additionally, synapsin I-mRNA levels in the hippocampus and cerebral cortex are significantly reduced in tranylcypromine-treated animals. This identifies SVP genes as target genes of antidepressant treatment.

Epidemiology and prognosis of specific disorders of language and scholastic skills.

Data from a prospective longitudinal study on the development of children born at biological and psychosocial risk were utilised to examine language and learning abilities of 320 children at ages 4.5 and 8 years. Following the research criteria of the ICD-10, specific developmental disorders of speech and language and specific developmental disorders of scholastic skills were diagnosed. Data were also provided for a clinical and general low achievement group according to less stringent criteria. Frequencies in the risk population were low for specific disorders (ICD-10) (0.6%-3.7% depending on age and type of disorder). Higher frequencies were found when a clinical definition (0.6%-13.6%) or overall low achievement score (0.6%-18.6%) was chosen. The impact of well-documented organic and psychosocial risks was analysed. Organic risk affected language abilities at 4.5 years of age but neither language nor learning abilities at 8 years of age. Psychosocial aspects of a child's environment proved to be associated with both specific language and learning abilities. Stability of language disorders, association between language and reading/spelling disorders as well as gender effects were investigated.

At risk for language disorders? Correlates and course of language disorders in preschool children born at risk.

The language abilities of 324 children of an at-risk population were investigated at age 2 and 4.5 y. Modified research criteria of the ICD-10 for specific developmental disorders of speech and language were applied. Frequencies between 4% and 7%, depending on age and type of disorder, were diagnosed among children whose performance on the language measure was only 1 instead of ICD-10's 2 SD below group mean, but the discrepancy measure of 1 SD between non-verbal language score and language measure was retained. Psychosocial aspects of a child's environment proved to be better predictors of later language disorders than obstetric complications. Stability of specific language disorders was on the whole fairly low, but children who perform below age level on language measures remained at risk. Gender differences are almost compensated by the age 4.5 y.

Development of the EEG of school-age children and adolescents. II. Topography.

Topographic aspects of EEG development of normal children and adolescents from 6 to 17 years are investigated with respect to various spectral parameters. The topographic distribution of spectral band power does not change between hemispheres across age. Changes take place, however, in the antero-posterior dimension. For the bands theta, alpha 1 and alpha 2 (and less so for delta) maturation starts at posterior derivations and ends at anterior derivations. For the band beta 2 (and to some extent also for beta 1), development progresses from Cz to Pz and further to occipital, lateral, central and frontal derivations. Principal component analysis (PCA) leads to a more parsimonious and better interpretable description of broad-band power and of its topographic distribution. Broad-band coherences increase with age, though to a modest degree. The different magnitudes of coherence between different regions can be largely accounted for by the interelectrode distances. Coherences, too, can be described in a more parsimonious and better interpretable way via PCA. The 3 components extracted reflect firstly the overall level of coherence, secondly the coherences of the occipital regions with all other regions and thirdly antero-posterior versus left-right coherences.

EEG coherence at rest and during a visual task in two groups of children.

EEG coherence was studied in a group of n = 31 normal children (NG) and in a group of n = 25 mildly mentally retarded children (EG), 10-13 years old. This was done for a recording at rest, eyes closed, and one during which a visual matching task was presented. Coherence showed little structure across frequency, apart from a slow decline towards higher frequencies. For the EEG at rest, coherence was higher for the EG and a slight increase with age was found. The visual task changed the coherence pattern in a complex way, and differently for the two groups. Coherence decreased in the fronto-central region (about the same in both groups) and increased in occipito-parietal central combinations (more so for the NG). The delta band showed predominantly an increase for the NG.