J.H.D.A. van Beek

Stability in symptoms of anxiety and depression as a function of genotype and environment: a longitudinal twin study from ages 3 to 63 years.

BACKGROUNDnThe influence of genetic factors on major depressive disorder is lower than on other psychiatric disorders. Heritability estimates mainly derive from cross-sectional studies, and knowledge on the longitudinal aetiology of symptoms of anxiety and depression (SxAnxDep) across the lifespan is limited. We aimed to assess phenotypic, genetic and environmental stability in SxAnxDep between ages 3 and 63 years.nnnMETHODnWe used a cohort-sequential design combining data from 49 524 twins followed from birth to age ⩾20 years, and from adolescence into adulthood. SxAnxDep were assessed repeatedly with a maximum of eight assessments over a 25-year period. Data were ordered in 30 age groups and analysed with longitudinal genetic models.nnnRESULTSnOver age, there was a significant increase during adolescence in mean scores with sex differences (women>men) emerging. Heritability was high in childhood and decreased to 30-40% during adulthood. This decrease in heritability was due to an increase in environmental variance. Phenotypic stability was moderate in children (correlations across ages ~0.5) and high in adolescents (r = 0.6), young adults (r = 0.7), and adults (r = 0.8). Longitudinal stability was mostly attributable to genetic factors. During childhood and adolescence there was also significant genetic innovation, which was absent in adults. Environmental effects contributed to short-term stability.nnnCONCLUSIONSnThe substantial stability in SxAnxDep is mainly due to genetic effects. The importance of environmental effects increases with age and explains the relatively low heritability of depression in adults. The environmental effects are transient, but the contribution to stability increases with age.

Associations between ADH glene variants and alcohol phenotypes in Dutch adults

Recently, Macgregor et al. (2009) demonstrated significant associations of ADH polymorphisms with reactions to alcohol and alcohol consumption measures in an Australian sample. The aim of the present study was to replicate these findings in a Dutch sample. Survey data on alcohol phenotypes came from 1,754 unrelated individuals registered with the Netherlands Twin Register. SNPs in the ADH gene cluster located on chromosome 4q (n = 491) were subdivided in seven gene sets: ADH5, ADH4, ADH6, ADH1A, ADH1B, ADH1C and ADH7. Within these sets associations of SNPs with alcohol consumption measures, age at onset variables, reactions to alcohol and problem drinking liability were examined. Of the original 38 SNPs studied by Macgregor et al. (2009), six SNPs were not available in our dataset, because one of them had a minor allele frequency < .01 (rs1229984) and five could not be imputed. The remaining SNP associations with alcohol phenotypes as identified by Macgregor et al. (2009) were not replicated in the Dutch sample, after correcting for multiple genotype and phenotype testing. Significant associations were found however, for reactions to alcohol with a SNP in ADH5 (rs6827292, p = .001) and a SNP just upstream of ADH5 (rs6819724, p = .0007) that is in strong LD with rs6827292. Furthermore, an association between age at onset of regular alcohol use and a SNP just upstream of ADH7 (rs2654849, p = .003) was observed. No significant associations were found for alcohol consumption and problem drinking liability. Although these findings do not replicate the earlier findings at the SNP level, the results confirm the role of the ADH gene cluster in alcohol phenotypes.

Measuring non-steady-state metabolic fluxes in starch-converting faecal microbiota in vitro

This paper explores human gut bacterial metabolism of starch using a combined analytical and computational modelling approach for metabolite and flux analysis. Non-steady-state isotopic labelling experiments were performed with human faecal microbiota in a well-established in vitro model of the human colon. After culture stabilisation, [U-13C] starch was added and samples were taken at regular intervals. Metabolite concentrations and 13C isotopomeric distributions were measured amongst other things for acetate, propionate and butyrate by mass spectrometry and NMR. The vast majority of metabolic flux analysis methods based on isotopomer analysis published to date are not applicable to metabolic non-steady-state experiments. We therefore developed a new ordinary differential equation-based representation of a metabolic model of human faecal microbiota to determine eleven metabolic parameters that characterised the metabolic flux distribution in the isotope labelling experiment. The feasibility of the model parameter quantification was demonstrated on noisy in silico data using a downhill simplex optimisation, matching simulated labelling patterns of isotopically labelled metabolites with measured metabolite and isotope labelling data. Using the experimental data, we determined an increasing net label influx from starch during the experiment from 94±1 µmol/l/min to 133±3 µmol/l/min. Only about 12% of the total carbon flux from starch reached propionate. Propionate production mainly proceeded via succinate with a small contribution via acrylate. The remaining flux from starch yielded acetate (35%) and butyrate (53%). Interpretation of 13C NMR multiplet signals further revealed that butyrate, valerate and caproate were mainly synthesised via cross-feeding, using acetate as a co-substrate. This study demonstrates for the first time that the experimental design and the analysis of the results by computational modelling allows the determination of time-resolved effects of nutrition on the flux distribution within human faecal microbiota in metabolic non-steady-state.

Symptom Profile of Psychiatric Patients With Psychosis or Psychotic Mood Disorder in Prison

There is evidence that psychiatric patients with psychotic or manic disorders who are incarcerated suffer from the same symptoms as psychiatric patients who are treated in the community. There are also indications that their symptoms might be more severe. The aim of this study was to examine the severity of psychotic and manic symptoms, as well as to collect information about the emotional functioning of patients admitted to a prison psychiatric ward. Incarcerated patients with a diagnosis of psychotic or a manic disorder were examined with the Brief Psychiatric Rating Scale–Expanded (BPRS-E). With the scores of 140 assessments, a symptom profile was created using the domains of the BPRS-E. This profile was compared with the clinical profile of three nonincarcerated patient groups described in literature with a diagnosis in the same spectrum. We found high scores on positive and manic psychotic symptoms and hostility, and low scores on guilt, depression, and negative symptoms. High scores on manic and psychotic symptoms are often accompanied by violent behavior. Low scores on guilt, depression, and negative symptoms could be indicative of externalizing coping skills. These characteristics could complicate treatment in the community and warrant further research along with clinical consideration.