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Biomedical subjects

David Gunnell

Publications and source records attributed to David Gunnell.

At least 19 recordsLinked to original sources
PubMed2006

Depressed mood and n-3 polyunsaturated fatty acid intake from fish: non-linear or confounded association?

There is increasing evidence of an association between low dietary intake of essential n-3 long chain polyunsaturated fatty acids (n-3 EFAs) and depressed mood. This study aimed to evaluate this association in a large population-based sample of UK individuals. N-3 EFA intake (intake from fish alone, and from all sources (fish and supplements)), depressed mood (assessed using the short-form Depression, Anxiety and Stress Scales) and demographic variables (sex, age, Index of Multiple Deprivation (IMD) based on postal code, and date of questionnaire completion) were obtained simultaneously by self-report questionnaire (N = 2982). Using polynomial regression, a non-linear relationship between depressed mood and n-3 EFA intake from fish was found, with the incremental decrease in depressed mood diminishing as n-3 EFA intake increased. However, this relationship was attenuated by adjustment for age and IMD. No relationship between depression and n-3 EFA intake from all sources was found. These findings suggest that higher levels of n-3 EFA intake from fish are associated with lower levels of depressed mood, but the association disappears after adjustment for age and social deprivation, and after inclusion of n-3 EFA intake from supplements. This study does have a number of limitations, but the findings available suggest that the apparent associations between depressed mood and n-3 EFA intake from fish may simply reflect a wider association between depressed mood and lifestyle.

Adult↗
PubMed2006

Social inequalities in antidepressant treatment and mortality: a longitudinal register study.

BACKGROUND: Despite an increased prevalence of depression among people of low socio-economic position, it remains unclear whether their treatment with antidepressants appropriately matches their increased need compared with people from more affluent backgrounds. This study examined socio-economic differences in antidepressant prescriptions and mortality related to depressive disorders. METHOD: A longitudinal register study of 17947 male and 47458 female local government employees with linked information on socio-economic indicators (education and occupational status) and data on antidepressant use and mortality associated with depressive disorder (suicide, alcohol-related deaths) during the years 1994 to 2000. RESULTS: In men, antidepressant treatment was less common among low educational groups than among high educational groups (OR 0.87, 95% CI 0.76-0.99) and a corresponding difference was seen between occupational statuses (OR for manual v. upper non-manual 0.72, 95% CI 0.62-0.84). In women, socio-economic position was not associated with antidepressant use. However, both among the men and women, employees with low socio-economic position had increased risk for mental-health-related mortality, as indicated by suicides, deaths from alcohol-related causes, and all-cause mortality. CONCLUSIONS: These data suggest a mismatch in the treatment of depression relative to apparent clinical need, with the lowest levels of treatment concentrated in the lower socio-economic groups, despite evidence of their increased prevalence of depression and suicide.

Adult↗
PubMed2006

Adult height and lung function as markers of life course exposures: associations with risk factors and cause-specific mortality.

BACKGROUND AND OBJECTIVE: Pulmonary function and height may be regarded as adult indices of exposures accumulated across the entire life course and in early life, respectively. As such, we hypothesised that pulmonary function would be more strongly related to mortality than height. Studies of the association of height and lung function with mortality--which are currently modest in number--will clarify the relative utility of these risk indices and the mechanisms underlying observed patterns of disease risk. DESIGN, SETTING, AND PARTICIPANTS: Data were drawn from the Whitehall study, a prospective cohort study of 18,403 middle-aged non-industrial London-based male government employees conducted in the late 1960s. Data were collected on stature, spirometry measures (including forced expiratory volume in one second [FEV1]) and a range of covariates. These analyses are based on the 3083 non-smoking men with complete data. MAIN OUTCOME MEASURES: Mortality ascribed to all-causes, cardiovascular disease, respiratory disease and site-specific cancers. RESULTS: Both height and FEV1 were associated with a range of physiological, behavioural and socio-economic risk factors. Relations with these risk factors were seen more frequently for FEV1 and, where they occurred, were of somewhat higher magnitude. During a maximum of 35 years follow-up, half the non-smokers had died (n = 1545). FEV1 (HR(per one SD increase); 0.89; 0.84, 0.95) was somewhat more strongly related to total mortality than height (0.96; 0.91, 1.01) in a fully adjusted model, but this difference did not attain statistical significance at conventional levels (p-value for difference = 0.15). Of the eight independent disease-specific outcomes examined, the only convincing evidence of a differential effect was for deaths from respiratory causes which was unsurprisingly more strongly related to FEV1 than height (p-value for difference = 0.03). CONCLUSIONS: In the present study, height and FEV1 were essentially similarly related to both risk factors and mortality outcomes, thus not providing support for our hypothesis. Both factors would appear to have some utility as markers of early life exposures.

Body Height↗
PubMed2006

Schizophrenia and neural tube defects: comparisons from an epidemiological perspective.

In this review, we examine and compare epidemiological studies of schizophrenia and neural tube defects (NTDs). Although there is no apparent link between these 2 disparate disorders in terms of clinical manifestation or phenotypes, overlapping patterns in the variation of incidence of schizophrenia with that of NTDs indicate the existence of one or more shared etiological risk factors. Evidence in support of such a phenomenon may enhance our understanding of underlying pathological mechanisms and may guide future studies of etiology and prevention. The similarities that occur in a number of epidemiological observations for these disorders are in keeping with a hypothesis of nutritional deficiencies in utero acting as a risk factor for both schizophrenia and NTDs. Programes of periconceptual folate and multivitamin supplementation aimed to reduce the risk of NTDs are already in place in many countries. Nevertheless, evidence of additional effects of specific maternal micronutrient deficiency on risk of schizophrenia may not only increase enthusiasm for expansion of such programes but also enhance understanding of etiology of this disorder and offer the potential for targeted interventions in high-risk groups.

Birth Intervals↗
PubMed2006

Risk of schizophrenia and other non-affective psychosis among individuals exposed to head injury: case control study.

Studies of the risk of schizophrenia and related non-affective psychoses among individuals exposed to head injury have reported conflicting findings. The diagnostic specificity of reported associations remains unclear and the effects of sex, genetic vulnerability and timing of exposures are also uncertain. The authors used a comprehensive range of data derived from the linkage of several Swedish registers to investigate associations of head injury with schizophrenia and other non-affective psychoses. We carried out a nested case control study drawn from a cohort of 785,051 men and women born between 1973 and 1980. After head injury exposure, there was a small increase in the risk (OR 1.37 (CI 1.14-1.66)) of non-schizophrenic, non-affective psychoses but not schizophrenic disorder (OR 1.10 CI 0.82 to 1.47). There was no critical period effect for exposures in early childhood, the association with non-affective psychosis being observed only in those exposed to head injury after age 10. There was no evidence that associations differed in males and females or in those with, and those without, a family history of psychosis. We conclude that it is unlikely that head injury causes schizophrenia. There is a small but significant risk of non-schizophrenic psychotic disorders but this is not associated with early age of injury or family history of psychosis. Further research is needed to clarify the potential roles of social and biological intermediary factors.

Adult↗
PubMed2006

Associations of adiposity from childhood into adulthood with insulin resistance and the insulin-like growth factor system: 65-year follow-up of the Boyd Orr Cohort.

CONTEXT: One metabolic pathway through which adiposity influences disease risk may be via alterations in insulin and IGF metabolism. OBJECTIVE: Our objective was to investigate associations of adiposity at different stages of life with insulin and the IGF system. DESIGN, SETTING, AND PARTICIPANTS: The study was a 65-yr follow-up of 728 Boyd Orr cohort participants (mean age, 71 yr) originally surveyed between 1937 and 1939. MAIN OUTCOMES: Outcomes included homeostasis model assessment of insulin resistance, total IGF-I and IGF-II, IGF binding protein (IGFBP)-2, and IGFBP-3 in adulthood. RESULTS: Childhood body mass index (BMI) was weakly inversely related to adult IGF-I (coefficient per BMI sd, -3.4 ng/ml; 95% confidence interval, -7.3 to 0.5; P = 0.09). IGF-II (but not IGF-I) increased with higher current fat mass index (coefficient, 26.1 ng/ml; 95% confidence interval, 4.6 to 47.6; P = 0.02) and waist-hip ratio (30.0 ng/ml; 9.4 to 50.5; P = 0.004). IGFBP-2 decreased by 21.2% (17.2 to 24.9; P < 0.001), and homeostasis model assessment of insulin resistance increased by 38.8% (28.9 to 49.6; P < 0.001) per sd higher adult BMI. Among thin adults (BMI tertiles 1 and 2), IGFBP-2 was positively, and insulin resistance was inversely, associated with childhood BMI. CONCLUSION: There was only weak evidence that associations of childhood BMI with chronic disease risk may be mediated by adult IGF-I levels. Circulating IGFBP-2 in adulthood, a marker for insulin sensitivity, was inversely associated with current adiposity, but overweight children who became relatively lean adults were more insulin sensitive than thinner children. The findings may indicate programming of later insulin sensitivity and consequently IGFBP-2 levels in response to childhood adiposity. The role of IGF-II in obesity-related chronic diseases warrants additional investigation.

Adiposity↗
PubMed2006

Insulin-like growth factor-I and growth in height, leg length, and trunk length between ages 5 and 10 years.

OBJECTIVE: IGF-I, a major regulator of childhood growth, is also associated with the risk of several cancers in adult life. Adult height and particularly leg length are also associated with cancer risk. Prepubertal growth is more in leg than trunk length, and it has been suggested that leg length might be a biomarker of childhood IGF-I. However, there is little information on the association between childhood IGF-I and subsequent leg and trunk growth. In this study, we investigated the association of IGF-I measured at 5 and 7-8 yr with growth in height and the components of height (leg and trunk length) from 5 yr to 9-10 yr. PARTICIPANTS: A total of 675 children participated in the Avon Longitudinal Study of Parents and Children. RESULTS: IGF-I was strongly positively associated with growth in height in both sexes. Among boys, IGF-I was strongly associated with subsequent growth in both leg and trunk length, but there was no evidence that IGF-I was more strongly associated with one component of growth than the other. Among girls, IGF-I was strongly positively associated with growth in trunk but not leg length, although there was only weak evidence that these two associations differed in strength (P = 0.058). CONCLUSIONS: These results support the contention that the associations between height and cancer may be mediated by variation in childhood IGF-I. However, they provide no evidence to support the hypothesis that leg length is a better biomarker of childhood IGF-I levels than trunk length.

Anthropometry↗
PubMed2006

Patterns of hospital transfer for self-poisoned patients in rural Sri Lanka: implications for estimating the incidence of self-poisoning in the developing world.

OBJECTIVES: Most data on self-poisoning in rural Asia have come from secondary hospitals. We aimed to: assess how transfers from primary to secondary hospitals affected estimates of case-fatality ratio (CFR); determine whether there was referral bias according to gender or poison; and estimate the annual incidence of all self-poisoning, and of fatal self-poisoning, in a rural developing-world setting. METHODS: Self-poisoning patients admitted to Anuradhapura General Hospital, Sri Lanka, were reviewed on admission from 1 July to 31 December 2002. We audited medical notes of self-poisoning patients admitted to 17 of the 34 surrounding peripheral hospitals for the same period. FINDINGS: A total of 742 patients were admitted with self-poisoning to the secondary hospital; 81 died (CFR 10.9%). 483 patients were admitted to 17 surrounding peripheral hospitals. Six patients (1.2%) died in peripheral hospitals, 249 were discharged home, and 228 were transferred to the secondary hospital. There was no effect of gender or age on likelihood of transfer; however, patients who had ingested oleander or paraquat were more likely to be transferred than were patients who had taken organophosphorus pesticides or other poisons. Estimated annual incidences of self-poisoning and fatal self-poisoning were 363 and 27 per 100,000 population, respectively, with an overall CFR of 7.4% (95% confidence interval 6.0-9.0). CONCLUSION: Fifty per cent of patients admitted to peripheral hospitals were discharged home, showing that CFRs based on secondary hospital data are inflated. However, while incidence of self-poisoning is similar to that in England, fatal self-poisoning is three times more common in Sri Lanka than fatal self-harm by all methods in England. Population based data are essential for making international comparisons of case fatality and incidence, and for assessing public health interventions.

Adult↗
PubMed2006

Suicide rates, life satisfaction and happiness as markers for population mental health.

OBJECTIVE: To examine the association of variables from survey data on well-being with suicide rates and other markers of population mental health in Europe. DESIGN: Ecological study correlating (Spearman's rank correlation) life satisfaction and happiness (European Values Survey 1999/2000) in 32 countries with suicide rates (WHO Mortality Database), rates of hospital discharge for mental and behavioural disorders and prevalence of mental disorders based on registered mental patients (WHO Regional Office for Europe) and Mental Health Index (MHI)-5 survey data (European Opinion Research Group). RESULTS: An inverse association exists between suicide rates and life satisfaction (r=-0.44; 95% CI: -0.68, -0.11) and happiness (r=-0.42; 95% CI: -0.67, -0.08). Similar though weaker associations were seen with hospital discharge data and MHI-5 data but not with the prevalence of mental disorders. The association between suicide rates and life satisfaction was weaker amongst 15-44 year olds (r=-0.31; 95% CI: -0.59, 0.04) than amongst 45-64 year olds (r=-0.47; 95% CI: -0.70, -0.14). It was strongest in the 65+ age group (r=-0.54; 95% CI: -0.75, -0.23). A similar pattern was observed for the association with happiness. In a subgroup analysis, the association between suicide and life satisfaction in Eastern Europe was similar to that in the whole dataset (r=-0.35) but a positive association was seen in Western Europe (r=0.47). CONCLUSIONS: Life satisfaction and happiness were modestly associated with other indicators of population mental health. Since all such markers have their limitations, surveys of well-being may be useful indicators of population mental health.

Adolescent↗
PubMed2006

Fetal growth and childhood behavioral problems: results from the ALSPAC cohort.

Using data on 4,813 children from the ALSPAC cohort in Bristol, United Kingdom, recontacted in 1998-1999, the authors investigated whether intrauterine growth restriction (indexed by birth weight and length) was associated with behavioral problems at age 7 years. Childhood behavioral problems were measured by using a brief behavioral screening questionnaire (the Strengths and Difficulties Questionnaire (parental completion)). For term singleton infants, a one standard deviation increase in birth weight was associated with an 11% reduction in the odds of behavioral problems at age 81 months. After adjustment for confounders and birth length, this association was no longer seen. The association with birth length remained after adjustment for confounders. A one standard deviation increase in birth length was associated with a 14% decrease in the odds of being in the top tertile of total behavioral difficulties at age 81 months (odds ratio = 0.86, 95% confidence interval: 0.79, 0.95) and was similarly associated with hyperactivity and conduct problems. Evidence was weak for an association between birth length and behavioral problems earlier in childhood. In summary, there was a weak association between intrauterine growth restriction, indexed by birth length (rather than weight), and childhood behavioral problems. Future work should focus on elucidating the biologic mechanisms that lead to variations in birth length and underlie this association.

Birth Weight↗
PubMed2006

Associations of childhood and adulthood height and the components of height with insulin-like growth factor levels in adulthood: a 65-year follow-up of the Boyd Orr cohort.

CONTEXT: Taller individuals with longer legs have a higher risk of cancer but a lower risk of coronary heart disease. OBJECTIVE: We investigated whether childhood height and its components are associated with the IGF system in adulthood. DESIGN AND PARTICIPANTS: We analyzed data from 429 participants of the Boyd Orr cohort, for whom height measured in childhood (mean age, 7.4 yr) in 1937-1939 could be related to levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-2, and IGFBP-3 in adulthood (mean age, 71.1 yr). In 385 participants, measured height in adulthood could be related to IGF levels. RESULTS: In fully adjusted models (controlling for age, sex, socioeconomic factors, lifestyle, and body mass index), childhood height and its components were not associated with adult circulating IGF-I, IGF-II, or IGFBP-2 levels. IGFBP-3 was 85.5 ng/ml higher (95% confidence interval, -11.6 to 182.5; P = 0.08) per sd increase in childhood trunk length and 83.6 ng/ml lower (95% confidence interval, -10.3 to 177.5; P = 0.08) per sd increase in childhood leg/trunk ratio. Height in adulthood was not associated with IGF-I, IGF-II, or IGFBP-3 and was inversely associated with IGFBP-2 (P = 0.05) after additionally controlling for childhood height. CONCLUSION: There was no evidence that associations of childhood height with cancer and coronary heart disease risk are mediated by IGF-I in adulthood. The anthropometric associations with IGFBP-2 and IGFBP-3 could be chance findings but warrant additional investigation. IGF levels in childhood may be more important determinants of long-term disease risk than adult levels.

Adolescent↗
PubMed2006

Continuing controversy over monitoring men with localized prostate cancer: a systematic review of programs in the prostate specific antigen era.

PURPOSE: There is continuing controversy over the most appropriate treatment for screen detected and clinically localized prostate cancer, and increasing interest in monitoring such men initially with radical treatment targeted at cancers showing signs of progressive potential but while they are still curable. Current evidence on monitoring protocols and biomarkers used to predict disease progression was systematically reviewed. MATERIALS AND METHODS: The MEDLINE and Excerpta Medica (EMBASE) bibliographic databases were searched from 1988 to October 2004, supplemented by manual searches of reference lists, focusing on studies reporting monitoring of men with localized prostate cancer. RESULTS: A total of 48 potentially eligible articles were found but only 5 studies, in which there was a total of 451 participants, restricted entry criteria to men with clinically localized (T1-T2) prostate cancer. Monitoring protocols varied with little consensus, although the majority used prostate specific antigen and digital rectal examination, while some added re-biopsy to assess progression. Actuarial probabilities of freedom from disease progression at 4 to 5 years of followup were 67% to 72%. However, up to 50% of men abandoned monitoring within 2 years, largely because of anxiety related to increasing prostate specific antigen rather than objective evidence of disease progression. There was no robust evidence to support prostate specific antigen doubling times or velocity to identify men in whom disease may progress. Studies were characterized by small sample size, short-term followup, observer bias and uncertain validity around variable definitions of progression. CONCLUSIONS: Current evidence suggests that some form of monitoring would be a suitable treatment option in men with localized prostate cancer but there is little consensus over what markers should be used in such a program or how progression should be properly defined. The search for a method that safely identifies men with prostate cancer who could avoid radical intervention must continue.

Disease Progression↗
PubMed2006

Milk as a food for growth? The insulin-like growth factors link.

OBJECTIVE: The mechanisms underlying the association of insulin-like growth factor-I (IGF-I) and leg length (a marker of prepubertal growth) with cancer risk are uncertain. One hypothesis is that diet in early childhood might provide the link. The aim of the present study was to examine the association between early diet - in particular, the intakes of cows' milk and dairy products - and height, leg length and IGF-I levels at age 7-8 years. SUBJECTS: Children participating in the Avon Longitudinal Study of Parents and Children. DESIGN: Diet was assessed using a 3-day unweighed food record. Anthropometry, IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) were measured by standard methods. RESULTS: Data on both diet and height were available for 744 children (404 boys) and on diet and IGF for 538 (295 boys). After adjusting for energy, both cows' milk and dairy product intakes were positively associated with IGF-I (P=0.040 and 0.027, respectively) and IGFBP-3 levels (P=0.082 and 0.067, respectively). These associations persisted on adjustment for potential confounders, but were abolished on controlling for protein intake. In energy-adjusted models there was only weak evidence of associations of milk and dairy product intakes with anthropometry. In boys only, dairy product intake was positively associated with leg length (equivalent to a 0.058 (0.002, 0.114) standard deviation score increase in leg length per 100 g increase in daily intake). CONCLUSIONS: These data provide some evidence that variation in childhood milk and dairy product intakes underlies associations of leg length, IGF-I and cancer risk. The association appears to be due to the protein content of milk.

Animals↗
PubMed2006

Choice of poison for intentional self-poisoning in rural Sri Lanka.

BACKGROUND: Although intentional self-poisoning is a major public health problem in rural parts of the Asia-Pacific region, relatively little is known of its epidemiology. We aimed to determine why Sri Lankan self-poisoning patients choose particular poisons, and whether acts of self-harm with highly dangerous poisons were associated with more premeditation and effort. METHODS: We interviewed 268 self-poisoning patients presenting to two district general hospitals in rural Sri Lanka. RESULTS: Eighty-five percent of patients cited easy availability as the basis for their choice of poison. There was little premeditation: more than 50% ingested the poison less than 30 minutes after deciding to self-harm. Patients had little knowledge about treatment options or lethality of the poison chosen. We found no difference in reasons for choice of poison between people ingesting different poisons, despite marked differences in toxicity, and between people who died and those who survived. CONCLUSIONS: Poisons were chosen on the basis of availability, often at short notice. There was no evidence that people using highly toxic poisons made a more serious or premeditated attempt. Restrictions on availability of highly toxic poisons in rural communities must be considered in strategies to reduce the number of intentional self-poisoning deaths in the Asia Pacific region.

Adolescent↗
PubMed2006

Association of body mass index measured in childhood, adolescence, and young adulthood with risk of ischemic heart disease and stroke: findings from 3 historical cohort studies.

BACKGROUND: It is unclear whether early life body mass index (BMI; in kg/m(2)) is associated with adult cardiovascular disease. OBJECTIVE: The objective was to assess the association of early life BMI with the risk of ischemic heart disease (IHD) and stroke. DESIGN: The association between early life BMI and risk of adult mortality from IHD and stroke was assessed in 3 historical cohort studies in which height and weight had been assessed by using standard procedures. Participants were traced and linked to national mortality data. Participants in the 3 cohorts were born between 1922 and 1937, 1927 and 1956, and 1928 and 1950 and were aged 2-15, 9-18, and 16-22 y, respectively, at the time of assessment of their height and weight. RESULTS: Participants in all 3 cohorts had mean BMIs similar to those reported for contemporary children and young adults, but fewer of the cohort participants were overweight or obese. BMI was not associated with future risk of IHD or stroke in any cohort. The pooled (all 3 cohorts) adjusted hazard ratio per SD of early life BMI was 1.09 (95% CI: 1.01, 1.19) for IHD and 0.94 (95% CI: 0.82, 1.08) for stroke. The pooled hazard ratio of IHD when participants who were overweight or obese for their age were compared with all other participants was 1.34 (95% CI: 0.95, 1.91), and no association was found between overweight or obesity and stroke risk. The effects of BMI did not vary by cohort or by age. CONCLUSION: These results do not provide strong evidence that being overweight or obese in childhood is associated with future cardiovascular disease risk.

Adolescent↗
PubMed2006

Effects of n-3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials.

BACKGROUND: Greater dietary intakes of n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) may be beneficial for depressed mood. OBJECTIVE: This study aimed to systematically review all published randomized controlled trials investigating the effects of n-3 PUFAs on depressed mood. DESIGN: Eight medical and health databases were searched over all years of records until June 2006 for trials that exposed participants to n-3 PUFAs or fish, measured depressed mood, were conducted on human participants, and included a comparison group. RESULTS: Eighteen randomized controlled trials were identified; 12 were included in a meta-analysis. The pooled standardized difference in mean outcome (fixed-effects model) was 0.13 SDs (95% CI: 0.01, 0.25) in those receiving n-3 PUFAs compared with placebo, with strong evidence of heterogeneity (I2 = 79%, P < 0.001). The presence of funnel plot asymmetry suggested that publication bias was the likely source of heterogeneity. Sensitivity analyses that excluded one large trial increased the effect size estimates but did not reduce heterogeneity. Meta-regression provided some evidence that the effect was stronger in trials involving populations with major depression-the difference in the effect size estimates was 0.73 (95% CI: 0.05, 1.41; P = 0.04), but there was still considerable heterogeneity when trials that involved populations with major depression were pooled separately (I2 = 72%, P < 0.001). CONCLUSIONS: Trial evidence that examines the effects of n-3 PUFAs on depressed mood is limited and is difficult to summarize and evaluate because of considerable heterogeneity. The evidence available provides little support for the use of n-3 PUFAs to improve depressed mood. Larger trials with adequate power to detect clinically important benefits are required.

Adult↗