Erik Lykke Mortensen

The Danish National Birth Cohort - its background, structure and aim

Background: It is well known that the time from conception to early childhood has importance for health conditions that reach into later stages of life. Recent research supports this view, and diseases such as cardiovascular morbidity, cancer, mental illnesses, asthma, and allergy may all have component causes that act early in life. Exposures in this period, which infl uence fetal growth, cell divisions, and organ functioning, may have long-lasting impact on health and disease susceptibility. Methods: To investigate these issues the Danish National Birth Cohort (Better health for mother and child) was established. A large cohort of pregnant women with long-term follow-up of the offspring was the obvious choice because many of the exposures of interest cannot be reconstructed with sufficient validity back in time. The study needs to be large, and it is aimed to recruit 100,000 women early in pregnancy, and to continue follow-up for decades. The Nordic countries are better suited for this kind of research than most other countries because of their population-based registers on diseases, demography and social conditions, linkable at the individual level by means of the unique ID-number given to all citizens. Exposure information is mainly collected by computer-assisted telephone interviews with the women twice during pregnancy and when their children are six and 18 months old. Participants are also asked to fill in a self-administered food frequency questionnaire in mid-pregnancy. Furthermore, a biological bank has been set up with blood taken from the mother twice during pregnancy and blood from the umbilical cord taken shortly after birth. Data collection started in 1996 and the project covered all regions in Denmark in 1999. By August 2000, a total of 60,000 pregnant women had been recruited to the study. It is expected that a large number of gene-environmental hypotheses need to be based on case-control analyses within a cohort like this.

Fish manipulation as a lake restoration tool in shallow, eutrophic, temperate lakes 2: threshold levels, long-term stability and conclusions

In order to evaluate short-term and long-term effects of fish manipulation in shallow, eutrophic lakes, empirical studies on relationships between lake water concentration of total phosphorus (P) and the occurrence of phytoplankton, submerged macrophytes and fish in Danish lakes are combined with results from three whole-lake fish manipulation experiments. After removal of less than 80 per cent of the planktivorous fish stock a short-term trophic cascade was obtained in the nutrient regimes, where large cyanobacteria were not strongly dominant and persistent. In shallow Danish lakes cyanobacteria were the most often dominating phytoplankton class in the P-range between 200 and 1000 pg P 1−1. Long-term effects are suggested to be closely related to the ability of the lake to establish a permanent and wide distribution of submerged macrophytes and to create self-perpetuating increases in the ratio of piscivorous to planktivorous fish. The maximum depth at which submerged macrophytes occurred, decreased exponentially with increasing P concentration. Submerged macrophytes were absent in lakes > 10 ha and with P levels above 250−300 μg P 1−1, but still abundant in some lakes 10 cm numerically contributed more than 80 per cent of the total planktivorous and piscivorous fish (> 10 cm) in the pelagical of lakes with concentrations above 100 μg P 1−1. Below this threshold level the proportion of planktivores decreased markedly to ca. 50 per cent at 22 μg P 1−1. The extent of the shift in depth colonization of submerged macrophytes and fish stock composition in the three whole-lake fish manipulations follows closely the predictions from the relationships derived from the empirical study. We conclude that a long-term effect of a reduction in the density of planktivorous fish can be expected only when the external phosphorus loading is reduced to below 0.5−2.0 g m −2 y −1. This loading is equivalent to an in-lake summer concentration below 80−150 μg P 1−1. Furthermore, fish manipulation as a restoration tool seems most efficient in shallow lakes.

Effect of dietary counseling on food intake, body weight, response rate, survival, and quality of life in cancer patients undergoing chemotherapy: a prospective, randomized study.

PURPOSE This study examined the effect of frequent nutritional counseling on oral intake, body weight, response rate, survival, and quality of life in patients with cancer of the lung (small-cell), ovary, or breast undergoing cyclic chemotherapy. PATIENTS AND METHODS Of 105 assessable patients, 57 were randomized to receive nutritional counseling, and 48 to receive no nutritional counseling and consumption of an ad lib oral intake. The intervention group was counseled to achieve a daily energy and protein intake according to recommended dietary allowances. Counseling was standardized and performed by a trained dietitian, and took place twice monthly during a 5-month period from start of chemotherapy. RESULTS Dietary counseling increased daily energy intake by approximately 1 MJ and protein intake by 10 g over the entire study period. There was no change in the control group. Counseling led to an insignificant increase in body weight, but triceps skinfold measurement increased significantly after 5 months. Response rate and overall survival did not differ between the groups. Quality of life measured by the Quality-of-Life index (QL-index) increased significantly in both groups, but did not differ between groups. CONCLUSION No clinical benefit could be demonstrated despite long-term and continuous improved food intake in cancer patients with solid tumors undergoing aggressive chemotherapy.

Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: a longitudinal study

BACKGROUND White-matter hyperintensities are commonly found on magnetic resonance imaging (MRI) of elderly people with or without dementia. Studies of the relation between severity of white-matter hyperintensities and cognitive impairment have had conflicting results. We undertook a longitudinal study of age-related decline in intellectual function and MRI at age 80 years. METHODS From a cohort of 698 people born in 1914 and living in seven municipalities in Denmark, 68 healthy non-demented individuals had been tested with the Wechsler adult intelligence scale (WAIS) at ages 50, 60, and 70, and they agreed to further WAIS testing at age 80, and cerebral MRI at age 80-82 (mean age 82.3 years). We scored separately the numbers of periventricular and deep white-matter hyperintensities. FINDINGS Scores for periventricular hyperintensities in this sample included all possible degrees of severity, but no participant scored more than 75% of maximum for deep white-matter hyperintensities. Neither type was related to the WAIS IQs of the 80-year assessment, but both were significantly associated with decline in performance IQ from age 50 to age 80 years (bivariate correlation coefficients 0.32, p=0.0087, and 0.28, p=0.0227, respectively). An analysis based on two WAIS subtests showed that the association between white-matter hyperintensities and cognitive impairment was significant only for cognitive decline in the decade 70-80 years. INTERPRETATION Both periventricular and deep white-matter hyperintensities are related to decline in intelligence but, in healthy octogenarians, the cumulative effect of these features alone explains only a small part of the large differences among individuals in age-related decline in intelligence. Interpretation of the presence and severity of white-matter hyperintensities in a diagnostic context must be done cautiously.

Prevalence of major depression and stress indicators in the Danish general population

Objective:  To estimate the prevalence rate of major depression in the Danish general population by using the Major Depression Inventory (MDI), a validated self‐rating scale fulfilling the symptomatic criteria in DSM‐IV and ICD‐10 for a depressive episode.

The SCL‐90 and SCL‐90R versions validated by item response models in a Danish community sample

Objective:  To evaluate the internal validity of the subscales of the combined SCL‐90 and SCL‐90R, the SCL‐92, by item response analyses as compared with several previously reported factor analyses of this questionnaire in the literature.

Association Between Prenatal Exposure to Bacterial Infection and Risk of Schizophrenia

Recent research suggests that prenatal exposure to nonviral infection may be associated with increased risk of schizophrenia, and we hypothesized an association between maternal bacterial infection during pregnancy and elevated offspring risk of schizophrenia. Data on maternal infections from the Copenhagen Perinatal Cohort were linked with the Danish National Psychiatric Register. Offspring cases of narrowly defined schizophrenia (International Classification of Diseases, Eighth Revision [ICD-8]) and more broadly defined schizophrenia (ICD-8 and ICD-10) were identified before the ages of 32-34 and 45-47 years, respectively. The effect of prenatal exposure to bacterial infections was adjusted for prenatal exposure to analgesics and parental social status. In a risk set of 7941 individuals, 85 cases (1.1%) of ICD-8 schizophrenia were identified by the age of 32-34 years and 153 cases (1.9%) of more broadly defined schizophrenia by the age of 45-47 years. First-trimester exposure conferred an elevated risk of ICD-8 schizophrenia (odds ratio 2.53; 95% confidence interval [CI] 1.07-5.96) and also of broadly defined schizophrenia (odds ratio 2.14; 95% CI 1.06-4.31). Second-trimester exposure also conferred a significantly elevated risk of schizophrenia but only in unadjusted analyses. These findings suggest a relationship between maternal bacterial infection in pregnancy and offspring risk of schizophrenia, and this effect was somewhat stronger for ICD-8 schizophrenia with earlier onset. Post hoc analyses showed that upper respiratory tract and gonococcal infections were associated with elevated risk of the disease. An association between risk of schizophrenia and prenatal exposure to bacterial infections might be mediated through transplacental passage of maternally produced cytokines in response to bacterial infections.

Cascading trophic interactions from fish to bacteria and nutrients after reduced sewage loading: An 18-year study of a shallow hypertrophic lake

ABSTRACT The effects of major reductions in organic matter, total phosphorus (TP), and total nitrogen (TN) loading on the chemical environment, trophic structure, and dynamics of the hypertrophic, shallow Lake Søbygård were followed for 18 years. After the reduction in organic matter loading in 1976, the lake initially shifted from a summer clear-water state, most likely reflecting high grazing pressure by large Daphniaspecies, to a turbid state with extremely high summer mean chlorophyll a (up to 1400 μg L−1), high pH (up to 10.2), and low zooplankton grazing. Subsequently, a more variable state with periodically high grazing rates on phytoplankton and bacteria was established. Changes in zooplankton abundance and grazing could be attributed to variations in cyprinid abundance due to a fish kill (probably as a consequence of oxygen depletion) and pH-induced variations in fish recruitment and fry survival. The results suggest strong cascading effects of fish on the abundance and size of zooplankton and phytoplankton and on phytoplankton production. A comparatively weak cascading effect on ciliates and bacterioplankton is suggested. Due to high internal loading, only minor changes were observed in lake-water TP after a reduction in external TP loading of approximately 80% in 1982; net retention of TP was still negative 13 years after the loading reduction, despite a short hydraulic retention time of a few weeks. TN, however, decreased proportionally to the TN-loading reduction in 1987, suggesting a fast N equilibration. Only minor improvement in the environmental state of the lake has been observed. We suggest that another decade will be required before the lake is in equilibrium with present external P loading.

Frontolimbic Serotonin 2A Receptor Binding in Healthy Subjects Is Associated with Personality Risk Factors for Affective Disorder

BACKGROUND Serotonergic dysfunction has been associated with affective disorders. High trait neuroticism, as measured on personality inventories, is a risk factor for major depression. In this study we investigated whether neuroticism is associated with serotonin 2A receptor binding in brain regions of relevance for affective disorders. METHODS Eighty-three healthy volunteers completed the standardized personality questionnaire NEO-PI-R (Revised NEO Personality Inventory) and underwent [(18)F]altanserin positron emission tomography imaging for assessment of serotonin 2A receptor binding. The correlation between the neuroticism score and frontolimbic serotonin 2A receptor binding was evaluated by multiple linear regression analysis with adjustment for age and gender. RESULTS Neuroticism correlated positively with frontolimbic serotonin 2A receptor binding [r(79) = .24, p = .028]. Post hoc analysis of the contributions from the six constituent traits of neuroticism showed that the correlation was primarily driven by two of them: vulnerability and anxiety. Indeed, vulnerability, defined as a persons difficulties in coping with stress, displayed the strongest positive correlation, which remained significant after correction for multiple comparisons (r = .35, p = .009). CONCLUSIONS In healthy subjects the personality dimension neuroticism and particularly its constituent trait, vulnerability, are positively associated with frontolimbic serotonin 2A binding. Our findings point to a neurobiological link between personality risk factors for affective disorder and the serotonergic transmitter system and identify the serotonin 2A receptor as a biomarker for vulnerability to affective disorder.

Fish manipulation as a lake restoration tool in shallow, eutrophic temperate lakes 1: cross-analysis of three Danish case-studies

The use of fish manipulation as a tool for lake restoration in eutrophic lakes has been investigated since 1986 in three shallow, eutrophic Danish lakes. The lakes differ with respect to nutrient loading and nutrient levels (130–1000 µg P l−1, 1–6 mg N l−1). A 50% removal of planktivorous fish in the less eutrophic cyanobacteria-diatom dominated Lake Vaeng caused marked changes in lower trophic levels, phosphorus concentration and transparency. Only minor changes occurred after a 78% removal of planktivorous fish in eutrophic cyanobacteria dominated Frederiksborg Castle Lake. In the hypertrophic, green algae dominated Lake Sobygard a low recruitment of all fish species and a 16% removal of fish biomass created substantial changes in trophic structure, but no decrease in phosphorus concentration. The different response pattern is interpreted as (1) a difference in density and persistence of bloomforming cyanobacteria caused by between-lake variations in nutrient levels and probably also mixing- and flushing rates, (2) a difference in specific loss rates through sedimentation of the algal community prevaling after the fish manipulation, (3) a decreased impact of planktivorous fish with increasing mean depth and (4) a lake specific difference in ability to create a self-increasing reduction in the phosphorus level in the lake water. This in turn seems related to the phosphorus loading.