Roger Webb

Higher risk of offspring schizophrenia following antenatal maternal exposure to severe adverse life events.

CONTEXT Most societies believe that a mothers psychological state can influence her unborn baby. Severe adverse life events during pregnancy have been consistently associated with an elevated risk of low birth weight and prematurity. Such events during the first trimester have also been associated with risk of congenital malformations. OBJECTIVE To assess the effect in offspring of antenatal maternal exposure to an objective measure of stress on risk of adverse neurodevelopment, specifically schizophrenia. We hypothesized that the strongest relationship would be to maternal exposures during the first trimester. DESIGN Population-based study. SETTING Denmark. PARTICIPANTS In a cohort of 1.38 million Danish births from 1973 to 1995, mothers were considered exposed if 1 (or more) of their close relatives died or was diagnosed with cancer, acute myocardial infarction, or stroke syndrome up to 6 months before conception or during pregnancy. Offspring were followed up from their 10th birthday until their death, migration, onset of schizophrenia, or June 30, 2005; admissions were identified by linkage to the Central Psychiatric Register. Main Outcome Measure Schizophrenia. RESULTS The risk of schizophrenia and related disorders was raised in offspring whose mothers were exposed to death of a relative during the first trimester (adjusted relative risk, 1.67 [95% confidence interval, 1.02-2.73]). Death of a relative during other trimesters or up to 6 months before pregnancy were not linked with a higher risk of schizophrenia. CONCLUSIONS Our population-based study suggests that severe stress to a mother during the first trimester may alter the risk of schizophrenia in offspring. This finding is consistent with ecological evidence from whole populations exposed to severe stressors and suggests that environment may influence neurodevelopment at the feto-placental-maternal interface.

Prevalence and predictors of intense, chronic, and disabling neck and back pain in the UK general population.

Study Design. Multiphase cross-sectional survey of musculoskeletal pain. Objectives. To estimate the prevalence of all reported and clinically significant spinal pain. To identify independent predictors of spinal pain. Methods. A total of 5752 adults sampled from three general practice registers were mailed a screening questionnaire. Subjects who reported the spine as a predominant site of pain were sent a site-specific questionnaire (i.e., back or neck) that asked about severity. Prevalence estimates were calculated and extrapolated to the general population. Predictors of spinal pain were identified using logistic regression with comprehensive adjustment for confounders (including pain at other anatomic sites). Results. The 1-month–period prevalence of all reported spinal pain was 29% (95% confidence interval 27–31%), of which about half was intense, half was chronic, 40% was disabling, and 20% was intense, disabling, and chronic. Most people with back (75%) or neck (89%) pain also reported pain at other sites. Age, female gender (neck pain only), high body mass index, living in an area of raised material deprivation, and south Asian ethnicity were significant predictors of spinal pain with disability. The association between body mass index and deprivation and neck pain was lost after adjustment for pain at other sites. However, even after full adjustment, obesity (OR, 1.7; 95% confidence interval, 1.1–2.5) and high deprivation (OR, 1.7; 95% confidence interval, 1.1–2.7) were predictors of back pain with disability. Conclusions. Adjustment for pain at other sites enabled assessment of whether observed associations were with spinal pain itself or with the other sites of pain. Obesity is an important independent predictor of back pain and its severity. This has implications for primary prevention. The prevalence of spinal pain with disability continues to rise into old age. This has implications for healthcare planning.

Suicide in recently released prisoners: a population-based cohort study.

BACKGROUND Several studies have been undertaken on suicide in custody, but few on suicide after the release from prison. We undertook a population-based cohort study to investigate suicide rates in recently released prisoners in England and Wales. METHODS We used the database of the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness for England and Wales to identify all individuals who died by suicide or who received an open verdict at the coroners inquest between 2000 and 2002. These records were linked to a Home Office register to identify all such deaths in people within 1 year of release from prison in England and Wales. We compared suicide rates per 100,000 person-years in these released prisoners with rates in the general population by using the indirectly age-standardised mortality ratio. FINDINGS We identified 382 suicides occurring in 244 988 individuals within 1 year of release from prison; a suicide rate of 156 per 100 000 person-years. 79 (21%) suicides occurred within the first 28 days after release. In all age groups, suicide rates were higher in recently released prisoners than in the general population. The overall age-standardised mortality ratio for recently released prisoners was 8.3 (95% CI 7.5-9.3) for men and 35.8 (25.4-50.2) for women. INTERPRETATION Recently released prisoners are at a much greater risk of suicide than the general population, especially in the first few weeks after release. The risk of suicide in recently released prisoners is approaching that seen in discharged psychiatric patients. A shared responsibility lies with the prison, probation, health, and social services to develop more collaborative practices in providing services for this high-risk group.

Birth weight, schizophrenia, and adult mental disorder: is risk confined to the smallest babies?

CONTEXT Studies linking birth weight and mental illness onset are inconclusive. They have primarily focused on the World Health Organization low birth weight threshold (2500 g) and schizophrenia. To our knowledge, low birth weight per se has not been conclusively linked with schizophrenia risk and specificity of the effect to birth weight below the standard threshold or to particular psychiatric diagnoses has not been demonstrated. OBJECTIVES To examine whether (1) low birth weight (<2500 g) is associated with increased risk for adult schizophrenia; (2) risk extends into the normal weight range; and (3) risk is confined to schizophrenia or linked to other adult mental illnesses. DESIGN Population-based cohort study. SETTING Sweden and Denmark. PARTICIPANTS Singleton live births in Sweden (1973-1984) and Denmark (1979-1986) (N = 1.49 million). Births were linked to comprehensive national registers of psychiatric treatment, with follow-up to December 31, 2002 (Sweden), or to June 30, 2005 (Denmark). There were 5445 cases of schizophrenia and 57 455 cases of any adult psychiatric disorder. MAIN OUTCOME MEASURE Crude and adjusted odds ratios for birth weight less than or more than 3500 to 3999 g in consecutive 500-g strata (from 500-1499 g to > or =4500 g) for schizophrenia, any psychiatric diagnoses, and specified psychiatric diagnoses. RESULTS Schizophrenia was associated with birth weight less than 2500 g. The association was not restricted to birth weight less than 2500 g and there was a significant linear trend of increasing odds ratios with decreasing birth weight across the birth weight range. This was mirrored for any psychiatric diagnosis and for each of the categories of psychiatric disorder. CONCLUSIONS Findings suggest there is an association between birth weight and adult mental disorder, but there is no indication this effect is specific to birth weight less than 2500 g or to schizophrenia. Future research should explore common disorder-specific mechanisms that may link birth weight to development of psychiatric disorder in adulthood.

Suicide in recently discharged psychiatric patients: A case-control study

BACKGROUND Few controlled studies have specifically investigated aspects of mental health care in relation to suicide risk among recently discharged psychiatric patients. We aimed to identify risk factors, including variation in healthcare received, for suicide within 3 months of discharge. METHOD We conducted a national population-based case-control study of 238 psychiatric patients dying by suicide within 3 months of hospital discharge, matched on date of discharge to 238 living controls. RESULTS Forty-three per cent of suicides occurred within a month of discharge, 47% of whom died before their first follow-up appointment. The first week and the first day after discharge were particular high-risk periods. Risk factors for suicide included a history of self-harm, a primary diagnosis of affective disorder, recent last contact with services and expressing clinical symptoms at last contact with staff. Suicide cases were more likely to have initiated their own discharge and to have missed their last appointment with services. Patients who were detained for compulsory treatment at last admission, or who were subject to enhanced levels of aftercare, were less likely to die by suicide. CONCLUSIONS The weeks after discharge from psychiatric care represent a critical period for suicide risk. Measures that could reduce risk include intensive and early community follow-up. Assessment of risk should include established risk factors as well as current mental state and there should be clear follow-up procedures for those who have self-discharged. Recent detention under the Mental Health Act and current use of enhanced levels of aftercare may be protective.

Reduced infant birthweight consequent upon maternal exposure to severe life events.

Objective: To investigate the association between maternal exposure to severe life events and fetal growth (birthweight and small for gestational age). Stress has been associated with adverse pregnancy outcome. Methods: Mothers of 1.38 million singleton live births in Denmark between January 1, 1979 and December 31, 2002 were linked to information on their spouses, parents, siblings, and older children. Exposure was defined as death or serious illness in a relative during pregnancy or in the 6 months before conception. Linear regression was used to examine the effect of exposure on birthweight. Log-linear binomial regression was used to assess the effect of exposure on small for gestational age. Results: Death of a relative during pregnancy or in the 6 months before conception reduced birthweight by 27 g (adjusted estimate −27 g, 95% Confidence Interval (CI) = −33, −22). There was a significant association between maternal exposure to death of a relative and risk of a baby weighing below the 10th percentile (adjusted relative risk (RR) = 1.17, 95% CI = 1.13, 1.22) and 5th percentile (adjusted RR = 1.22, 95% CI = 1.15, 1.29). Conclusions: Mothers exposed to severe life events before conception or during pregnancy have babies with significantly lower birthweight. If this association is causal, the potential mechanisms of stress-related effects on birthweight include changes in lifestyle due to the exposure and stress-related dysregulation of the hypothalamic-pituitary-adrenal axis during pregnancy. IUGR = intrauterine growth restriction; CVA = cerebrovascular accident; AMI = acute myocardial infarction; SGA = small for gestational age; VSGA = very small for gestational age; GHQ = general health questionnaire; SES = socioeconomic status.

Suicide risk in primary care patients with major physical diseases: a case-control study

CONTEXT Most previous studies have examined suicide risk in relation to a single physical disease. OBJECTIVES To estimate relative risk across a range of physical diseases, to assess the confounding effect of clinical depression and effect modification by sex and age, and to examine physical illness multimorbidity. DESIGN Nested case-control study. SETTING Family practices in England (n = 224) [corrected] registered with the General Practice Research Database from January 1, 2001, through December 31, 2008. The case-control data were drawn from approximately 4.7 [corrected] million complete patient records, with complete linkage to national mortality records. PARTICIPANTS A total of 873 adult suicide cases and 17 460 living controls matched on age and sex were studied. The reference group for relative risk estimation consisted of people without any of the specific physical illnesses examined. MAIN OUTCOME MEASURES Suicide and open verdicts. RESULTS Among all patients, coronary heart disease, stroke, chronic obstructive pulmonary disease, and osteoporosis were linked with elevated suicide risk, and, with the exception of osteoporosis, the increase was explained by clinical depression. The only significantly elevated risk in men was with osteoporosis. Female effect sizes were greater, with 2- or 3-fold higher risk found among women diagnosed as having cancer, coronary heart disease, stroke, chronic obstructive pulmonary disease, and osteoporosis. In women with cancer and coronary heart disease, a significant elevation persisted after adjustment for depression. Overall, heightened risk was confined to physically ill women younger than 50 years and to older women with multiple physical diseases. CONCLUSIONS Our findings indicate that clinical depression is a strong confounder of increased suicide risk among physically ill people. They also demonstrate an independent elevation in risk linked with certain diagnoses, particularly among women. Health care professionals working across all medical specialties should be vigilant for signs of undetected psychological symptoms.

Musculoskeletal pain is associated with a long-term increased risk of cancer and cardiovascular-related mortality

Objectives. To test the hypothesis that individuals with regional and widespread pain disorders have an increased risk of mortality. Methods. We conducted a prospective cohort study of 4515 adults. Subjects were an age- and sex-stratified sample who had participated in a population study of pain occurrence during 1996. Based on those reports subjects were classified as having no pain, regional pain or widespread pain. All subjects were identified on the National Health Service Central Register and followed up until April 2005, a total of 8.2 yrs, at which time information was obtained on vital status, and if applicable, date and cause of death. The relationship between pain status and subsequent death is expressed as mortality rate ratios with 95% CIs, adjusted for age, gender, ethnicity and practice. Results. A total of 35.2% reported regional pain and 16.9% satisfied criteria for widespread pain. In comparison with those without pain, there was a 20% and 30% increased risk of dying over the follow-up period among subjects with regional and widespread pain, respectively. The specific causes of death in excess were cancer and cardiovascular disease. In addition, the mortality risk from both cancer and cardiovascular deaths was found to increase as the number of pain sites that subjects reported increased. Conclusions. This study supports a previous observation that persons with regional and widespread pain are at an increased risk of cancer death. Possible mechanisms should be explored.

Rates of preterm birth following antenatal maternal exposure to severe life events: a population-based cohort study

BACKGROUND Preterm birth and other pregnancy complications have been linked to maternal stress during pregnancy. We investigated the association between maternal exposure to severe life events and risk of preterm birth. METHODS Mothers of all singleton live births (n = 1.35 million births) in Denmark between 1 January 1979 and 31 December 2002 were linked to data on their children, parents, siblings and partners. We defined exposure as death or serious illness in close relatives in the first or second trimesters or in the 6 months before conception. Log-linear binomial regression was used to estimate the effect of exposure on preterm birth, very preterm birth and extremely preterm birth. RESULTS There were 58 626 (4.34%) preterm births (<37 weeks), 11 732 (0.87%) very preterm births and 3288 (0.24%) extremely preterm births in the study cohort. Severe life events in close relatives in the 6 months before conception increased the risk of preterm birth by 16% (relative risk, RR = 1.16, [95% CI: 1.08-1.23]). Severe life events in older children in the 6 months before conception increased the risk of preterm birth by 23% (RR = 1.23, [95% CI: 1.02-1.49]) and the risk of very preterm birth by 59% (RR = 1.59, [95% CI: 1.08-2.35]). CONCLUSIONS Our population-based cohort study suggests that maternal exposure to severe life events, particularly in the 6 months before pregnancy, may increase the risk of preterm and very preterm birth.

Suicide in current psychiatric in-patients: a case-control study The National Confidential Inquiry into Suicide and Homicide.

BACKGROUND Few controlled studies have investigated factors associated with suicide in current in-patients. We aimed to identify psychosocial, behavioural and clinical risk factors, including variations in care, for in-patient suicide. METHOD We conducted a national population-based case-control study of people who died by suicide between 1 April 1999 and 31 December 2000 while in psychiatric in-patient care in England. Cases were 222 adult mental health in-patients who died by suicide matched on date of death with 222 living controls. RESULTS Nearly a quarter of suicides took place within the first week of admission; most of these died on the ward or after absconding. After the first week, however, most suicides occurred away from the ward, the majority of patients having left the ward with staff agreement. Previous deliberate self-harm, recent adverse life events, symptoms of mental illness at last contact with staff and a co-morbid psychiatric disorder were associated with increased risk for suicide. Being off the ward without staff agreement was a particularly strong predictor. Those patients who were detained for compulsory treatment were less likely to die by suicide. Independent predictors of in-patient suicide were male sex, a primary diagnosis of affective disorder and a history of self-harm. Being unemployed or on long-term sick leave appeared to be independently protective. CONCLUSION Prevention of in-patient suicide should emphasize adequate treatment of affective disorder, vigilance in the first week of admission and regular risk assessments during recovery and prior to granting leave. Use of compulsory treatment may reduce risk.