The association between social stress and global cognitive function in a population-based study: the European Prospective Investigation into Cancer (EPIC)-Norfolk study.

BACKGROUND: Stress is thought to exert both positive and negative effects on cognition, but the precise cognitive effects of social stress and individuals' response to stress remain unclear. We aimed to investigate the association between different measures of social stress and cognitive function in a middle- to older-aged population using data from the European Prospective Investigation into Cancer (EPIC)-Norfolk study. METHOD: Participants completed a comprehensive assessment of lifetime social adversity between 1993 and 1997 and the short form of the Mini Mental State Examination (SF-MMSE), an assessment of global cognitive function, during the third health check between 2004 and 2011 (a median of 10.5 years later). A low MMSE score was defined as a score in the bottom quartile (20-26). RESULTS: Completed MMSE scores and stress measures were available for 5129 participants aged 48-90 years. Participants who reported that their lives had been more stressful over the previous 10 years were significantly more likely to have low MMSE scores [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.04-1.24 per unit increase in perceived stress], independently of sociodemographic factors, physical and emotional health. The effects were restricted to the highest level of stress and the association was stronger among participants with a lower educational level. Adaptation following life event experiences also seemed to be associated with MMSE scores after adjusting for sociodemographic factors, but the association was attenuated with further adjustment. CONCLUSIONS: In this generally high-functioning population, individuals' interpretations and responses to stressful events, rather than the events themselves, were associated with cognitive function.

Association between serotonin 5-HT-2C receptor gene (HTR2C) polymorphisms and obesity- and mental health-related phenotypes in a large population-based cohort.

OBJECTIVE: Studies have shown that common single-nucleotide polymorphisms (SNPs) in the serotonin 5-HT-2C receptor (HTR2C) are associated with antipsychotic agent-induced weight gain and the development of behavioural and psychological symptoms. We aimed to analyse whether variation in the HTR2C is associated with obesity- and mental health-related phenotypes in a large population-based cohort. METHOD: Six tagSNPs, which capture all common genetic variation in the HTR2C gene, were genotyped in 4978 men and women from the European Prospective Investigation into Cancer (EPIC)-Norfolk study, an ongoing prospective population-based cohort study in the United Kingdom. To confirm borderline significant associations, the -759C/T SNP (rs3813929) was genotyped in the remaining 16 003 individuals from the EPIC-Norfolk study. We assessed social and psychological circumstances using the Health and Life Experiences Questionnaire. Genmod models were used to test associations between the SNPs and the outcomes. Logistic regression was performed to test for association of SNPs with obesity- and mental health- related phenotypes. RESULTS: Of the six HTR2C SNPs, only the T allele of the -759C/T SNP showed borderline significant associations with higher body mass index (BMI) (0.23 kg m(-2); (95% confidence interval (CI): 0.01-0.44); P=0.051) and increased risk of lifetime major depressive disorder (MDD) (Odds ratio (OR): 1.13 (95% CI: 1.01-1.22), P=0.02). The associations between the -759C/T and BMI and lifetime MDD were independent. As associations only achieved borderline significance, we aimed to validate our findings on the -759C/T SNP in the full EPIC-Norfolk cohort (n=20 981). Although the association with BMI remained borderline significant (beta=0.20 kg m(-2); 95% CI: 0.04-0.44, P=0.09), that with lifetime MDD (OR: 1.01; 95% CI: 0.94-1.09, P=0.73) was not replicated. CONCLUSIONS: Our findings suggest that common HTR2C gene variants are unlikely to have a major role in obesity- and mental health-related traits in the general population.

Prospective association between emotional health and clinical evidence of Parkinson's disease.

BACKGROUND AND PURPOSE: Whilst disorders of emotion are commonly comorbid with Parkinson's disease (PD), evidence concerning their association with PD risk is limited. We investigate the prospective association between selected measures of emotional health and incident suspected PD. METHODS: 20,855 men and women, considered PD-free at baseline, completed a postal assessment of major depressive disorder (MDD), generalized anxiety disorder (GAD), psychological distress [defined by the five-item Mental Health Inventory (MHI-5)], and neuroticism. PD case ascertainment was based upon PD medication use, self-report questionnaires, hospital record discharge codes, and death certification, subsequently checked against general practitioner, hospital records and neurological service records. RESULTS: 175 suspected cases of incident PD were identified in 160,725 (median 7.9) person-years of follow-up (with 43 recorded in neurological service records). MDD lifetime history, GAD lifetime history, MHI-5 and neuroticism were all significantly associated with suspected PD following adjustment for age, sex, cigarette smoking, alcohol consumption, social class and education. CONCLUSIONS: This study supports an association between measures of emotional health, assessed prior to evidence of motor symptoms, and subsequent suspected PD diagnosis. However, we were unable to determine whether our measures of personality and emotional health represent genuine premorbid risk factors or early stages of PD. Long-term prospective healthy cohort studies are required to investigate the relationship between emotional health history and the evolution of the premotor and motor phases of PD.

Places, people, and their physical and mental functional health.

STUDY OBJECTIVE: To investigate the impact of area of residence on functional health as represented by medical outcomes study SF-36 physical and mental component summary scores. DESIGN: Multilevel analysis of cross sectional data from the European Prospective Investigation into Cancer and Nutrition in Norfolk, UK (EPIC-Norfolk). PARTICIPANTS: A community dwelling cohort of 18399 men and women, aged 41 to 80 and resident in 162 electoral wards in Norfolk, UK. MAIN RESULTS: Significant residual variation in physical functional health was observed at the area level after controlling for important individual level socioeconomic factors (p<0.001). However, the extent of this variation was modest when compared with that at the individual level (representing 0.6% of the total). About half of this variation could be explained by area deprivation. Area deprivation was associated with impaired mental functional health but residual variation at the area level (adjusted for individual level factors) was observed only for men (0.5% of total, p = 0.02). CONCLUSIONS: Area of residence was associated with physical functional health, albeit with modest effect size. Evidence for an association between area of residence and mental functional health was weak.

Psychosocial aetiology of chronic disease: a pragmatic approach to the assessment of lifetime affective morbidity in an EPIC component study.

OBJECTIVES: The Health and Life Experiences Questionnaire (HLEQ) was developed for use in a prospective cohort study of 25,000 men and women living in Norfolk and forms a component study of the European Prospective Investigation into Cancer and Nutrition (EPIC). The HLEQ includes an assessment of mood status over the life course allowing a limited capacity for the imposition of diagnostic criteria to enable eventual evaluation of mental health status for chronic disease outcomes. This paper reports estimates of HLEQ Major Depressive Disorder (MDD) prevalence and compares them with those obtained through interviewer-based methods. In addition evidence for the impact of recall, clustering or cohort effects on these estimates are examined. PARTICIPANTS: 3491 eligible respondents to EPIC in Norfolk, aged 45-74 years, recruited from the first five general practices who completed the HLEQ. MAIN RESULTS: MDD prevalence estimates were found to be closely comparable to those obtained recently (by interview) in the UK and to those lifetime MDD rates determined through international studies. Risk of MDD onset was found to vary with age as expected from earlier studies using interviewer-based assessments. Limited evidence was found to show that the distribution of first onset MDD episodes were compressed during the immediate pre-assessment period. Results were also consistent with previous evidence demonstrating the raised risk of MDD among women and of the decline in gender differences with advancing age. CONCLUSIONS: These results suggest that estimates of putative MDD diagnostic status, derived through the HLEQ, and of associated demographic risk are similar to those derived by more intensive and costly assessment methods. Implications for the future study of MDD both as an outcome and as a risk factor for chronic disease are discussed.

Childhood adversity, gender and depression over the life-course.

BACKGROUND: Full investigation of hypotheses concerning early risk factors and episodes of depression in adult life requires consideration of the separate risks of first onset and of recurrent episodes. This paper is based upon such an investigation. METHODS: A sample of participants in a large-scale population study (n=3491) provided information through retrospective assessment of lifetime history of (putative) major depressive disorder and of their adverse experiences in childhood. A statistical model based on Poisson regression, that combined both the (survival) distribution of first onset times with the subsequent rate of episode recurrence was specified to permit investigation of the gender difference in lifetime depression and the influence of childhood adversities on adult depression. RESULTS: A gender difference (with women at increased risk) was revealed for first onsets of depression only and was found to decrease with increasing age, being no longer apparent in those aged over 50. Experience either of a frightening event or of physical abuse in childhood was associated with an increased risk of first onset in younger adults (those aged < or =30). LIMITATIONS: The method of data collection used in this study warrants some caution in the interpretation of substantive findings. CONCLUSIONS: The relationships revealed concerning the risk for early and for late first onset and the risk of recurrence suggest different causal pathways underlying the associations between risk factors experienced early in life and depression in adulthood. Analyses that take full account of episode history can aid understanding of the origins of depression in adulthood.

Sense of coherence, lifestyle choices and mortality.

BACKGROUND: Based on data from the European Prospective Investigation into Cancer, Norfolk (EPIC-Norfolk) study, we have previously shown a strong sense of coherence (SOC) to be associated with a reduced rate of all-cause mortality. OBJECTIVES: To investigate the extent to which the SOC mortality association can be explained by socioeconomic status and lifestyle choices. DESIGN AND SETTING: Prospective population-based cohort study. PARTICIPANTS: 18 287 study participants aged 41-80 years who reported no pre-existing chronic disease at baseline and who completed an assessment of SOC. RESULTS: Based on 1599 deaths during a mean follow-up of 8.3 years, a strong SOC was associated with a 20% reduced risk of all-cause mortality. Measures of lifestyle choice (cigarette smoking, physical activity, dietary intakes of fruit, vegetables and fibre) and socioeconomic status (social class and education) explained 23% of this association. CONCLUSIONS: The SOC concept embraces multiple sets of chronic disease risk factors that include lifestyle choices and those associated with socioeconomic status, and is a potential aid in understanding differences in health outcomes in similar individuals.

Psychological distress, major depressive disorder, and risk of stroke.

BACKGROUND: Studies have suggested that mood status is associated with an increased risk of stroke, though mostly based on measures of depression defined by symptoms alone rather than diagnostic criteria representative of clinically important distress and impairment. We investigated this association based upon a large population-based prospective cohort study. METHODS: Baseline assessment of major depressive disorder (MDD) and of mental health well-being (defined by the Mental Health Inventory, MHI-5) was completed by 20,627 stroke-free participants, aged 41 to 80 years, in the United Kingdom European Prospective Investigation into Cancer-Norfolk study. RESULTS: During 8.5 years of follow-up, 595 incident (fatal and nonfatal) stroke endpoints were recorded. Neither past year nor lifetime MDD was associated with stroke. A one SD decrease in MHI-5 scale score (representing greater emotional distress) was associated with an 11% increased risk of stroke after adjustment for age, sex, cigarette smoking, systolic blood pressure, cholesterol, obesity, preexisting myocardial infarction, diabetes, social class, education, hypertension treatment, family history of stroke, and antidepressant medication use (hazard ratio 1.11, 95% CI 1.00 to 1.22). This association was consistent for men and for women, for fatal and nonfatal stroke, and conformed to a dose-response relationship. CONCLUSIONS: Findings from this large prospective cohort study suggest that increased psychological distress is associated with elevated stroke risk. Episodic major depressive disorder was not associated with incident stroke in this study.

Psychosocial factors and incident asthma hospital admissions in the EPIC-Norfolk cohort study.

BACKGROUND: Case series and case-control studies have shown high rates of psychosocial and behavioural risk factors amongst patients admitted to hospital with severe asthma. General population studies have shown associations between psychosocial factors and prevalent asthma but few have investigated incident asthma outcomes. METHODS: Data on psychosocial factors and asthma hospital admissions were available for 20 854 participants, aged 41-80 years, in the Norfolk cohort of the European Prospective Investigation into Cancer study. Postal assessments included details of physical functioning, mood disorder history, social adversity and social support. RESULTS: A total of 686 asthma hospital admissions were recorded. Psychosocial factors present at baseline, including current mood disorders, adverse circumstances in childhood, the impact of life events experienced during adulthood and negative perceived support from a close confidant, were associated with increased rates of hospital admission independent of age, sex, indicators of socio-economic status, physical functional health, and obesity. Restricted to those participants who reported lifetime doctor-diagnosed asthma at baseline, the reported impact of adverse life events experienced in adulthood, and both confiding and negative aspects of support quality, were associated with asthma hospital admission. The magnitude of these associations was comparable to those involving indicators of socio-economic status and physical health. CONCLUSIONS: These results show that psychosocial factors are associated with incident asthma hospital admissions and highlight the potential importance of taking account of psychosocial factors, including availability and quality of support networks, in guiding long-term asthma management.

Physical health-related quality of life predicts stroke in the EPIC-Norfolk.

OBJECTIVE: To examine the relationship between Short Form (SF)-36 physical functional health-related quality of life and incident stroke. METHODS: A total of 13,615 men and women participating in the European Prospective Investigation into Cancer-Norfolk who were free of stroke, myocardial infarction, and cancer at baseline were included in the study. Participants completed a health and lifestyle questionnaire and attended a health examination during 1993 to 1997. Self-reported physical functional health was assessed using physical component summary scores of SF-36 18 months later. Stroke incidence was ascertained by death certification and hospital record linkage up to 2005. RESULTS: There were 244 incident strokes (total person years = 99,191). People who reported better physical functional health had significantly lower risk of incident stroke. Using Cox proportional hazard models adjusting for age, sex, body mass index, systolic blood pressure, cholesterol, smoking, diabetes, physical activity, social class, alcohol consumption, and respiratory function, men and women who were in the top quartile of SF-36 physical component summary scores had half the risk of stroke (RR = 0.50 [0.31, 0.78]) compared to the people in the bottom quartile. The relationships remained unchanged after excluding strokes occurring within the first 2 years of follow-up. CONCLUSIONS: Physical functional health-related quality of life measured as Short Form-36 predicts subsequent stroke risk independently of known risk factors in a general population. Poor physical functional health may indicate a high-risk population for stroke who may benefit most from targeted preventive interventions such as management of known risk factors.

Respiratory function and self-reported functional health: EPIC-Norfolk population study.

Respiratory function is known to be associated with mortality. However, its association with health related quality of life (HRQoL) has not yet been examined. A population-based cross sectional study was conducted in 16,738 subjects aged 40-79 yrs and resident in Norfolk, to examine the association between forced expiratory volume in one second (FEV1) and HRQoL measured by the 36-item short form questionnaire. Individuals who were in the highest quintiles of FEV1 were more likely to report good physical functional health (odds ratio (OR) 1.60; 95% confidence interval (CI) 1.28-2.01 and OR 1.71; 95% CI 1.40-2.10 for males and females, respectively) controlling for age, height, weight or body mass index, smoking, physical activity, prevalent illness and social class. Being in the highest quintile for FEV1 was associated with significantly lower likelihood of poor self-reported mental functional health status in males (OR 0.78; 95% CI 0.61-0.99), but not in females (OR 1.00; 95% CI 0.82-1.22). In conclusion, forced expiratory volume in one second independently predicts self perceived physical well being in a general population across the whole normal distribution of respiratory function.

Fragile states of mind: neuroticism, vulnerability and the long-term outcome of depression.

BACKGROUND: This paper considers the extent to which vulnerability to the outcome of major affective disorder is conferred through personality deviance. Results are based upon a 12 year longitudinal follow-up study of 80 patients with a primary depressive disorder, originally selected from a consecutive series seeking care at a hospital in Scotland. METHODS: The study included detailed clinical course assessments in association with the formal application of diagnostic criteria. Assessments on recovery from the index episode included measures of self-confidence and of neuroticism. Experience of selected severe loss events over the study period was also determined. RESULTS: Limited self-confidence was strongly related, unlike neuroticism, to the subsequent first recurrence of affective disorder. Relationships between psychosocial, clinical and demographic factors and long-term outcome revealed psychosocial factors, in particular neuroticism and a lack of self-confidence, to have the greatest prognostic significance. CONCLUSIONS: These results reveal the heightened risk over the long-term of a poor outcome for depressive disorder consequent upon measures of personality deviance and of exposure to adversity. While giving only limited support to narrowly defined psychosocial models of depression, they clarify the risk gradients involved and through this may provide a firmer basis than hitherto for relapse prevention.

Surviving adversity: event decay, vulnerability and the onset of anxiety and depressive disorder.

Knowledge concerning the temporal relationship between adverse experiences and the onset of anxiety and depressive disorders remains sparse despite life stress forming a pivotal component to social, neurological and cognitive science models of their aetiology. In this study two groups of married women were selected through their shared adverse experiences; for one group, the marital partner had recently died, and in the second group, the marital partner had recently experienced a myocardial infarction. These groups were assessed in close proximity to their event experiences and again approximately 3 months later. Adaptations of both the Longitudinal Interval Follow-up Evaluation and the Life Event and Difficulty Schedule were used to provide a detailed clinical and event history both preceding and following their experiences. Analysis showed clear evidence for the progressive decay in the adverse effects of life events over time; an attribute thus far largely neglected in work seeking to clarify event-illness relationships. Comparisons between fixed and time-varying effects, representative of precisely formulated models of vulnerability/resilience, confirmed the role both of previous psychiatric consultation history and of limited individual coping skills as risk factors for the onset of diagnosable disorder. Improvements in the specification of stress modelling procedures should facilitate the integration of ideas from competing aetiological models of the onset and subsequent course of anxiety and depressive disorder.

Diagnostic boundaries, reasoning and depressive disorder, I. Development of a probabilistic morbidity model for public health psychiatry.

BACKGROUND: In recent years diagnostic practice in psychiatry has become increasingly structured in an attempt to standardize definitions of disorders and improve reliability. At the same time there has been an increasing recognition of the need to take account of uncertainty in the process of diagnostic decision making. For the most part, diagnosis is still represented by a binary outcome while this is known to entail a substantial loss of information. Many diagnostic schemes involve, in part, taking thresholds on the numbers of symptoms required from symptom lists. METHODS: A model is proposed here, using ideas derived from latent class analysis to permit generalization from these schemes through moving from a binary to a probabilistic measure of psychiatric case status and replacing thresholds with smoothed transitions. RESULTS: An outcome measure is produced where disorder status is expressed in terms of probabilities without changing the meaning of the original measure. Prevalence estimates (using ICD-10 Depressive Episode criteria) are more stable and can be given with increased precision. CONCLUSIONS: Disorder status when expressed in this way retains more diagnostic information and provides a useful extension to traditional binary analyses when looking at prevalence and risk factor estimation.

Obesity, confidant support and functional health: cross-sectional evidence from the EPIC-Norfolk cohort.

OBJECTIVE: To investigate the association between body mass index (BMI) and functional health according to age and the support available from a close confidant. DESIGN: A cross-sectional population-based study. PARTICIPANTS: A total of 20 921 participants in the European Prospective Investigation into Cancer and Nutrition, aged 41-80 y resident in Norfolk, England. MEASUREMENTS: Standardised clinic-based assessment of BMI, self-reported functional health status assessment (according to the anglicised Short Form 36 (SF-36) Health Survey questionnaire) and the availability (and quality) of a close confiding relationship. RESULTS: Self-reported physical functioning declined steadily with increasing age. Obesity (BMI >/=30) was strongly associated with self-reported physical functional health, equivalent to being 11 y older for men and 16 y older for women (after adjustment that included prevalent chronic physical conditions and cigarette smoking). This adverse effect of obesity on physical functional health was found to increase with age for both men and women. Perceived inadequacy of a confiding relationship was associated with reduced physical functional capacity, equivalent to being 4 y older for men and 5 y older for women. For those with markedly inadequate confidant relationships, the impact of obesity on physical functional capacity was approximately constant by age. For those not critical of the adequacy of their confiding relationships, the impact of obesity was least for those younger but rose to equivalent levels as those with markedly inadequate confidant relationships among older participants. CONCLUSIONS: The availability of a close confidant relationship (perceived as uncritical and characterised by the absence of shared negative interactions) may delay the impact of obesity in reducing physical functional capacity.

Diagnostic boundaries, reasoning and depressive disorder, II. Application of a probabilistic model to the OPCS general population survey of psychiatric morbidity in Great Britain.

BACKGROUND: Reliable prevalence and risk estimation of psychiatric disorder is a cornerstone to achieving objectives in public health psychiatry. Research strategies have increasingly depended, therefore, upon the progressive evolution and refinement of diagnostic approaches designed to reflect better current knowledge concerning prognosis, course and outcome but essentially the need to improve agreement between users of the various schemes. METHODS: This paper contrasts a conventional with a probabilistic approach to the diagnosis of depression based upon the OPCS United Kingdom National survey of psychiatric morbidity. The probabilistic approach, while designed to mimic current diagnostic practice in relation to the depressive disorders, naturally includes provision for the allocation of respondents on a scale of diagnostic uncertainty according to the severity of their presenting condition. RESULTS: Findings are reported arising from the application of the probabilistic method to three areas of research interest in public health psychiatry, namely; an evaluation of additivity of event exposure and depressive morbidity, secondly use of the approach for investigating psychosocial models of depressive disorder and thirdly for assessing the agreement between depressive disorder when classified according to competing diagnostic schemes. CONCLUSIONS: The results show application of the probabilistic approach to provide a firm basis for achieving gains in both the stability and precision of risk profile estimation for depressive conditions.

The role of life events and childhood experiences in the development of rheumatoid arthritis.

OBJECTIVE: To evaluate the role of stressful life events, including negative childhood experiences on the development of rheumatoid arthritis (RA). METHODS: Retrospective, community based, case-control study founded upon 116 cases, aged 45 to 74 years, registered with the Norfolk Arthritis Register (NOAR), who were also participants in the Norfolk European Prospective Investigation of Cancer study (EPIC). Three controls, matched for age and sex, were selected for each of the cases from among EPIC participants not suffering from arthritis. Data on adverse experiences during childhood and adulthood were available from a self-report questionnaire. The 1987 American Rheumatism Association (ARA) criteria for RA were met by 55 NOAR cases and this subset provided the primary focus for analysis. RESULTS: The number and timing of occurrence of stressful life events, as well as their subjective immediate impact, did not differ between participants who developed RA and their matched controls. Termination of pregnancy was the only specific event individually associated with a higher risk of developing RA (OR 3.74; 95% CI 1.4-9.9). Negative childhood experiences were not associated with the risk of RA. However, RA cases reported significantly slower adaptation to the effects of adverse events than controls. CONCLUSION: The results of this study do not support the hypothesis that the rate of exposure or reported impact of stressful life events and of adverse childhood experiences play an etiologic role in the development of RA.

Determinants of general practitioner recognition of psychological problems in a multi-ethnic inner-city health district.

BACKGROUND: With few exceptions, evaluation of the capacity of general practitioners (GPs) to recognise psychiatric disorder in their patients has failed to consider the role of ethnic diversity in the consultation process and whether such knowledge can improve understanding of the degree to which psychiatric morbidity is recognised within GP settings. METHODS: This research was completed in five general practices representative of all those within an inner-city health district. Psychiatric morbidity in patients consecutively attending the practices was then assessed using the General Health Questionnaire; in addition, GPs were asked to complete a checklist of current problems identified during each consultation. RESULTS: Analysis suggested that Asian and Black patients were less likely than White patients to have psychological problems identified; that social problems and a psychiatric history facilitated recognition; and that current physical illness hindered recognition. CONCLUSIONS: GP recognition of psychological problems varies according to patient ethnicity but can be substantially masked by both the physical and social circumstances of patients at consultation.