Developing and testing a case-management intervention to support the return to work of health care workers with common mental health disorders.

BACKGROUND: To assess the feasibility and acceptability of conducting a trial of the clinical effectiveness and cost-effectiveness of a new case-management intervention to facilitate the return to work of health care workers, on sick leave, having a common mental disorder (CMD). METHODS: A mixed methods feasibility study. RESULTS: Systematic review examined 40 articles and 2 guidelines. Forty-nine National Health Service Occupational Health (OH) providers completed a usual care survey. We trained six OH nurses as case managers and established six recruitment sites. Forty-two out of 1938 staff on sick leave with a CMD were screened for eligibility, and 24 participants were recruited. Out of them, 94% were female. Eleven participants received the intervention and 13 received usual care. Engagement with most intervention components was excellent. Return-to-work self-efficacy improved more in the intervention group than in the usual care group. Qualitative feedback showed the intervention was acceptable. CONCLUSIONS: The intervention was acceptable, feasible and low cost to deliver, but it was not considered feasible to recommend a large-scale effectiveness trial unless an effective method could be devised to improve the early OH referral of staff sick with CMD. Alternatively, the intervention could be trialled as a new stand-alone OH intervention initiated at the time of usual OH referral.

Variation in rates of self-harm hospital admission and re-admission by ethnicity in London: a population cohort study.

PURPOSE: To compare sex-specific rates of hospital admission and repeat admission following self-harm between ethnic groups in London and test whether differences persist after adjustment for socio-economic deprivation. METHODS: A population-based cohort of all individuals aged over 11 admitted to a general hospital for physical health treatment following self-harm between 2008 and 2018, using administrative Hospital Episode Statistics for all people living in Greater London. RESULTS: There were 59,510 individuals admitted to the hospital following self-harm in the 10 year study period, ethnicity data were available for 94% of individuals. The highest rates of self-harm admission and readmission were found in the White Irish group. Rates of admission and readmission were lower in Black and Asian people compared to White people for both sexes at all ages and in all more specific Black and Asian ethnic groups compared to White British. These differences increased with adjustment for socio-economic deprivation. People of Mixed ethnicity had higher rates of readmission. Rates were highest in the 25-49 age group for Black and Mixed ethnicity men, but in under-25 s for all other groups. There were substantial differences in rates within the broader ethnic categories, especially for the Black and White groups. CONCLUSION: In contrast to earlier UK studies, self-harm rates were not higher in Black or South Asian women, with lower self-harm admission rates seen in almost all ethnic minority groups. Differences in rates by ethnicity were not explained by socio-economic deprivation. Aggregating ethnicity into broad categories masks important differences in self-harm rates between groups.

Longitudinal patterns of mental health service utilisation by those with mental-physical comorbidity in the community.

OBJECTIVE: Successful healthcare integration demands an understanding of current service utilisation by people with comorbidity. Physical illness may impact on mental health service use (MHSU), but longitudinal studies of comorbidity and MHSU are rare. This study 1) estimated associations between mental-physical comorbidity and longitudinal MHSU patterns; 2) tested whether associations between comorbidity and continuous MHSU are driven by "need". METHODS: Survey data from a South East London community cohort were used (N = 1052). Common mental disorder symptoms (CMDS) were measured using the Clinical Interview Schedule Revised and self-report of long-standing disorders. A checklist of common conditions measured chronic physical conditions. MHSU captured self-reported use of mental health services in the past year at two time points. "Need" indicators included CMDS at follow-up, suicidal ideation, somatic symptom severity, self-rated health, daily functioning problems and perceived functioning limitations due to emotional health. Analyses used logistic and multinomial regression. RESULTS: Continuous MHSU (at both time-points) was twice as commonly reported by those with comorbidity than those without physical comorbidity (30.9% vs 12.3%). CMDS at follow-up, suicidal ideation, and perceived functioning limitations due to emotional health only partially explained the association between CMDS-physical comorbidity and continuous MHSU. In the adjusted model, comorbidity remained associated with continuous MHSU (RRR = 3.23, 95% CI: 1.39-7.51; p = .002), while the association for non-comorbid CMDS was fully attenuated (RRR = 1.08, 95% CI: 0.40-2.93; p = .85). CONCLUSION: CMDS-physical comorbidity was strongly associated with continuous MHSU, and "need" did not account for this association, suggesting that comorbidity itself represents a "need" indicator.

Childhood abuse and psychotic experiences - evidence for mediation by adulthood adverse life events.

AIMS: We have previously reported an association between childhood abuse and psychotic experiences (PEs) in survey data from South East London. Childhood abuse is related to subsequent adulthood adversity, which could form one pathway to PEs. We aimed to investigate evidence of mediation of the association between childhood abuse and PEs by adverse life events. METHODS: Data were analysed from the South East London Community Health Study (SELCoH, n = 1698). Estimates of the total effects on PEs of any physical or sexual abuse while growing up were partitioned into direct (i.e. unmediated) and indirect (total and specific) effects, mediated via violent and non-violent life events. RESULTS: There was strong statistical evidence for direct (OR 1.58, 95% CI: 1.19-2.1) and indirect (OR 1.51, 95% CI: 1.32-1.72) effects of childhood abuse on PEs after adjustment for potential confounders, indicating partial mediation of this effect via violent and non-violent life events. An estimated 47% of the total effect of abuse on PEs was mediated via adulthood adverse life events, of which violent life events made up 33% and non-violent life events the remaining 14%. CONCLUSIONS: The association between childhood abuse and PEs is partly mediated through the experience of adverse life events in adulthood. There is some evidence that a larger proportion of this effect was mediated through violent life events than non-violent life events.

Psychiatric symptoms and risk of victimisation: a population-based study from Southeast London.

AimsAlthough violence is a vital public health problem, no prospective studies have tested for subsequent vulnerability to violence, as a victim or witness, in members of the general population with a range of psychiatric symptoms, or evaluated the importance of higher symptom burden on this vulnerability. METHODS: We used successive waves of a household survey of Southeast London, taken 2 years apart, to test if association exists between psychiatric symptoms (symptoms of psychosis, common mental disorders, post-traumatic stress disorder and personality disorder) and later victimisation, in the form of either witnessing violence or being physically victimised, in weighted logistic regression models. Statistical adjustment was made for prior violence exposure, sociodemographic confounders, substance/alcohol use and violence perpetration. Sensitivity analyses were stratified by violence perpetration, sex and history of mental health service use. RESULTS: After adjustments, psychiatric symptoms were prospectively associated with reporting any subsequent victimisation (odds ratio (OR) 1.88, 95% confidence interval (CI) 1.25-2.83), a two times greater odds of reporting witnessed violence (OR 2.24, 95% CI 1.33-3.76) and reporting physical victimisation (OR 1.76, 95% CI 1.01-3.06). One more symptom endorsed was accompanied by 47% greater odds of subsequent victimisation (OR 1.47, 95% CI 1.16-1.86). In stratified analyses, statistical associations remained evident in non-perpetrators, and among those without a history of using mental health services, and were similar in magnitude in both men and women. CONCLUSIONS: Psychiatric symptoms increase liability to victimisation compared with those without psychiatric symptoms, independently of a prior history of violence exposure and irrespective of whether they themselves are perpetrators of violence. Clinicians should be mindful of the impact of psychiatric symptoms on vulnerability to victimisation, including among those with common psychiatric symptoms and among those who are not considered at risk of perpetrating violence.

Taking an intersectional approach to define latent classes of socioeconomic status, ethnicity and migration status for psychiatric epidemiological research.

AIMS: Inequalities in mental health are well documented using individual social statuses such as socioeconomic status (SES), ethnicity and migration status. However, few studies have taken an intersectional approach to investigate inequalities in mental health using latent class analysis (LCA). This study will examine the association between multiple indicator classes of social identity with common mental disorder (CMD). METHODS: Data on CMD symptoms were assessed in a diverse inner London sample of 1052 participants in the second wave of the South East London Community Health study. LCA was used to define classes of social identity using multiple indicators of SES, ethnicity and migration status. Adjusted associations between CMD and both individual indicators and multiple indicators of social identity are presented. RESULTS: LCA identified six groups that were differentiated by varying levels of privilege and disadvantage based on multiple SES indicators. This intersectional approach highlighted nuanced differences in odds of CMD, with the economically inactive group with multiple levels of disadvantage most likely to have a CMD. Adding ethnicity and migration status further differentiated between groups. The migrant, economically inactive and White British, economically inactive classes both had increased odds of CMD. CONCLUSIONS: This is the first study to examine the intersections of SES, ethnicity and migration status with CMD using LCA. Results showed that both the migrant, economically inactive and the White British, economically inactive classes had a similarly high prevalence of CMD. Findings suggest that LCA is a useful methodology for investigating health inequalities by intersectional identities.

Tobacco smoking is associated with psychotic experiences in the general population of South London.

BACKGROUND: The association between cigarette smoking and psychosis remains unexplained, but could relate to causal effects in both directions, confounding by socioeconomic factors, such as ethnicity, or use of other substances, including cannabis. Few studies have evaluated the association between cigarettes and psychotic experiences (PEs) in diverse, inner-city populations, or relationships with number of cigarettes consumed. METHODS: We assessed associations and dose-response relationships between cigarette smoking and PEs in a cross-sectional survey of household residents (n = 1680) in South East London, using logistic regression to adjust for cannabis use, other illicit substances, and socioeconomic factors, including ethnicity. RESULTS: We found association between any PEs and daily cigarette smoking, which remained following adjustment for age, gender, ethnicity, cannabis and use of illicit stimulant drugs (fully adjusted odds ratio 1.47, 95% confidence interval 1.01-2.15). Fully adjusted estimates for the association, and with number of PEs, increased with number of cigarettes smoked daily, implying a dose-response effect (p = 0.001 and <0.001, respectively). Odds of reporting any PEs in ex-smokers were similar to never-smokers. CONCLUSIONS: In this diverse epidemiological sample, association between smoking and PEs was not explained by confounders such as cannabis or illicit drugs. Daily cigarette consumption showed a dose-response relationship with the odds of reporting PEs, and of reporting a greater number of PEs. There was no difference in odds of reporting PEs between ex-smokers and never-smokers, raising the possibility that the increase in PEs associated with smoking may be reversible.

Stigma-related barriers and facilitators to help seeking for mental health issues in the armed forces: a systematic review and thematic synthesis of qualitative literature.

A recent quantitative review in the area of stigma and help seeking in the armed forces has questioned the association between these factors (Sharp et al. 2015). To date, the contribution of qualitative literature in this area has largely been ignored, despite the value this research brings to the understanding of complex social constructs such as stigma. The aim of the current systematic review of qualitative studies was to identify appropriate literature, assess the quality and synthesize findings across studies regarding evidence of stigma-related barriers and facilitators to help seeking for mental health issues within the armed forces. A multi-database text word search incorporating searches of PsycINFO, MEDLINE, Social Policy and Practice, Social Work Abstracts, EMBASE, ERIC and EBM Review databases between 1980 and April 2015 was conducted. Literature was quality assessed using the Critical Appraisal Skills Programme tool. Thematic synthesis was conducted across the literature. The review identified eight studies with 1012 participants meeting the inclusion criteria. Five overarching themes were identified across the literature: (1) non-disclosure; (2) individual beliefs about mental health; (3) anticipated and personal experience of stigma; (4) career concerns; and (5) factors influencing stigma. The findings from the current systematic review found that unlike inconsistent findings in the quantitative literature, there was substantial evidence of a negative relationship between stigma and help seeking for mental health difficulties within the armed forces. The study advocates for refinement of measures to accurately capture the complexity of stigma and help seeking in future quantitative studies.

Minority status and mental distress: a comparison of group density effects.

BACKGROUND: It has been observed that mental disorders, such as psychosis, are more common for people in some ethnic groups in areas where their ethnic group is less common. We set out to test whether this ethnic density effect reflects minority status in general, by looking at three situations where individual characteristics differ from what is usual in a locality. METHOD: Using data from the South East London Community Health study (n = 1698) we investigated associations between minority status (defined by: ethnicity, household status and occupational social class) and risk of psychotic experiences, common mental disorders and parasuicide. We used a multilevel logistic model to examine cross-level interactions between minority status at individual and neighbourhood levels. RESULTS: Being Black in an area where this was less common (10%) was associated with higher odds of psychotic experiences [odds ratio (OR) 1.34 95% confidence interval (CI) 1.07-1.67], and attempted suicide (OR 1.84 95% CI 1.19-2.85). Living alone where this was less usual (10% less) was associated with increased odds of psychotic experiences (OR 2.18 95% CI 0.91-5.26), while being in a disadvantaged social class where this was less usual (10% less) was associated with increased odds of attempted suicide (OR 1.33 95% CI 1.03-1.71). We found no evidence for an association with common mental disorders. CONCLUSIONS: The relationship between minority status and mental distress was most apparent when defined in terms of broad ethnic group but was also observed for individual household status and occupational social class.

Discrimination and common mental disorder among migrant and ethnic groups: findings from a South East London Community sample.

PURPOSE: Few studies have examined discrimination and mental health in the UK, particularly by migrant status and in urban contexts with greater demographic diversity. This study aims to (1) describe the prevalence of discrimination experiences across multiple life domains; (2) to describe associations between discrimination experiences and common mental disorder (CMD); (3) to determine whether or not the relationship between discrimination and CMD varies by migrant status and ethnicity. METHODS: Data on major, anticipated and everyday discrimination and CMD symptoms were collected from an ethnically diverse prospective sample of 1052 participants followed up from 2008 to 2013 in the South East London Community Health study, a population-based household survey. RESULTS: With few exceptions, discrimination was most prevalent among those in the Black Caribbean group. However, those in the White Other ethnic group had similar or greater reporting major and anticipated discrimination to Black or mixed ethnic minority groups. The effects of discrimination on CMD were most pronounced for individuals who had recently migrated to the UK, an ethnically heterogeneous group, and for Black and Mixed ethnic minority groups in partially adjusted models. Prior CMD accounted for differences between the Mixed and White British ethnic groups, but the strength of the association for the most recent migrant group and the Black ethnic groups remained two or more times greater than the reference groups. CONCLUSIONS: The strength of the relationship suggests a need for more consideration of migration status along with ethnicity in examining the impact of discrimination on mental disorder in community and clinical samples.

Eating disorders in a multi-ethnic inner-city UK sample: prevalence, comorbidity and service use.

PURPOSE: No studies have investigated the prevalence of eating disorders (ED) according to DSM-5 criteria and few have explored their comorbidity and service use in the general population in the UK. We aimed to estimate the prevalence, comorbidity, and service use in individuals with ED in a multi-ethnic inner city sample. METHODS: A total of 1698 individuals (age 16/90) were screened for ED in the first phase of the South East London Community Health Study and 145 were followed up with a diagnostic interview. Data was weighed for survey design and Chi Square tests were used to investigate socio-demographic distribution, comorbidity and service use in participants with ED. RESULTS: The point prevalence of ED was 4.4 % (Binge Eating Disorder (BED) 3.6 %; Bulimia Nervosa (BN) 0.8 %) and 7.4 % when including sub-threshold diagnoses (Purging Disorder (PD) 0.6 %; Other Specified Feeding and Eating Disorders (OSFED) 2.4 %). No cases of AN were identified. Purging Disorder was the ED with the highest proportion of comorbid disorders. A minority of participants with ED had accessed specialist care services. CONCLUSIONS: ED are common, the comorbidity of ED was in line with previous studies and no ethnic differences were identified. Although PD is not a full diagnosis in DSM-5, we found some evidence of high comorbidity with other disorders, that needs to be replicated using larger samples. Service use was low across ED diagnoses, despite high levels of comorbidity.

Mental health among UK inner city non-heterosexuals: the role of risk factors, protective factors and place.

BACKGROUND: Sexual minorities experience excess psychological ill health globally, yet the UK data exploring reasons for poor mental health among sexual minorities is lacking. This study compares the prevalence of a measure of well-being, symptoms of common mental disorder (CMD), lifetime suicidal ideation, harmful alcohol and drug use among inner city non-heterosexual and heterosexual individuals. It is the first UK study which aims to quantify how much major, everyday and anticipated discrimination; lifetime and childhood trauma; and coping strategies for dealing with unfair treatment, predict excess mental ill health among non-heterosexuals. Further, inner city and national outcomes are compared. METHODS: Self-report survey data came from the South East London Community Health study (N = 1052) and the Adult Psychiatric Morbidity Survey (N = 7403). RESULTS: Adjustments for greater exposure to measured experiences of discrimination and lifetime and childhood trauma had a small to moderate impact on effect sizes for adverse health outcomes though in fully adjusted models, non-heterosexual orientation remained strongly associated with CMD, lifetime suicidal ideation, harmful alcohol and drug use. There was limited support for the hypothesis that measured coping strategies might mediate some of these associations. The inner city sample had poorer mental health overall compared with the national sample and the discrepancy was larger for non-heterosexuals than heterosexuals. CONCLUSIONS: Childhood and adult adversity substantially influence but do not account for sexual orientation-related mental health disparities. Longitudinal work taking a life course approach with more specific measures of discrimination and coping is required to further understand these associations. Sexual minorities should be considered as a priority in the design and delivery of health and social services.

How equitable are psychological therapy services in South East London now? A comparison of referrals to a new psychological therapy service with participants in a psychiatric morbidity survey in the same London borough.

PURPOSE: Psychological therapy services are sometimes characterised as being small and inequitable, with an over-representation of white middle class women. The 'Improving Access to Psychological Therapies (IAPT)' initiative is a programme in England that attempts to make evidence-based therapies accessible to more people more equitably. The aim of this study is to assess whether an IAPT service is delivering an equitable service a London borough. Patients using services at the Southwark IAPT service (n = 4,781) were compared with a sub-group of participants in the South East London Community Health study (SELCOH) with diagnosable mental health problems and who were also resident in Southwark (n = 196). METHODS: We compared Southwark IAPT patients and SELCOH participants on equity criteria of age, gender, ethnicity, occupational status and benefits status. To investigate if referral pathways influenced equity, patients referred by their general practitioner (GP pathway) (n = 3,738) or who self-referred (self-referral pathway) (n = 482) were compared with SELCOH participants. RESULTS: Southwark IAPT patients significantly differed from SELCOH participants on all our equity criteria and similar differences were found with GP pathway patients. However, self-referrals did not differ from the SELCOH group on age, gender, ethnicity and benefit status. CONCLUSIONS: When compared to a community sample with diagnosable mental disorders, health disparities were found with the overall Southwark IAPT service and with GP pathway patients. Although unemployed people did access IAPT, fewer disparities were found with the self-referral pathway patients, suggesting that the IAPT self-referral pathway may be important in reducing inequitable access to services.

Influence of perceived and actual neighbourhood disorder on common mental illness.

PURPOSE: Fear of crime and perceived neighbourhood disorder have been linked to common mental illness (CMI). However, few UK studies have also considered the experience of crime at the individual and neighbourhood level. This study aims to identify individual and local area factors associated with increased perceived neighbourhood disorder and test associations between CMI and individuals' perceptions of disorder in their neighbourhoods, personal experiences of crime and neighbourhood crime rates. METHODS: A cross-sectional survey was conducted of 1,698 adults living in 1,075 households in Lambeth and Southwark, London. CMI was assessed using the Revised Clinical Interview Schedule. Data were analysed using multilevel logistic regression with neighbourhood defined as lower super output area. RESULTS: Individuals who reported neighbourhood disorder were more likely to suffer CMI (OR 2.12) as were those with individual experience of crime. These effects remained significant when individual characteristics were controlled for. While 14 % of the variance in perceived neighbourhood disorder occurred at the neighbourhood level, there was no significant variance at this level for CMI. CONCLUSIONS: Perceived neighbourhood disorder is more common in income-deprived areas and individuals who are unemployed. Worry about one's local area and individual experience of crime are strongly and independently associated with CMI, but neighbourhood crime rates do not appear to impact on mental health.

Prevalence and correlates of disordered eating in a general population sample: the South East London Community Health (SELCoH) study.

PURPOSE: Disordered eating has been shown to be more prevalent than full eating disorders diagnoses. However, research on its prevalence, socio-demographic, psychological correlates, and patterns of service use in multi-ethnic samples is still limited. This paper explores these associations in a South London-based (UK) sample. METHODS: The South East London Community Health (SELCoH) study is a general population survey (N = 1,698) of individuals aged 16+. Disordered eating was defined as ≥2 positive answers at the SCOFF questionnaire. Crude and adjusted logistic and multinomial logistic regression models were fit to investigate associations between socio-demographic characteristics, disordered eating, psychiatric comorbidity, and service use. RESULTS: A total of 164 (10 %) participants reported disordered eating and the majority were from ethnic minorities. In adjusted models, Asian ethnicity was associated with purging, loss of control eating and preoccupation with food. Individuals with disordered eating had higher odds of screening positive for post-traumatic stress disorder and personality disorders and of having anxiety/mood disorders, suicidal ideation/attempts, hazardous levels of drinking, and used drugs in the previous year. Only 36 % of individuals with disordered eating had sought professional help in the previous 12 months mostly through their general practitioner (27.4 %), followed by psychotherapists (12.8 %) and mental health specialists (5.5 %). CONCLUSION: This study found a high prevalence of disordered eating, especially amongst ethnic minorities, and associations with a number of psychiatric conditions. Overall few participants accessed specialist services. These findings suggest that both disordered eating manifestations amongst ethnic minorities and access to care need better investigation.

Suicidal behaviours in South East London: prevalence, risk factors and the role of socio-economic status.

BACKGROUND: Low socio-economic status (SES) is an established risk factor of suicidal behaviours, but it is unknown to what extent its association is direct, indirect or confounded, given its strong association to mental health. We aimed to (I) estimate the prevalence of suicidal behaviours; (II) describe relevant risk factors; and (III) investigate direct and indirect effects of SES on suicidal behaviours. METHODS: We used cross-sectional community survey data of adults from randomly selected South East London households (SELCoH). Suicidal outcome measures replicated the 2007 Adult Psychiatric Morbidity Survey in England (APMS). Lifetime prevalence was described by socio-demographics, SES, mental health indicators, and life events. Structured symptom screens and a drug use questionnaire measured mental health. Structural equation models estimated direct and indirect effects of a latent SES variable on suicidal ideation and suicide attempts, adjusting for covariates. RESULTS: 20.5% (95% CI: 18.4-22.7) reported suicidal ideation and 8.1% (95% CI: 6.8-9.7) reported suicide attempts (higher than APMS estimates: 13.7%, 4.8%, respectively). Unadjusted risk factors included poor mental health, low SES, and non-married/non-cohabitating relationship status. Black African ethnicity was protective, and women reported more suicide attempts. SES was directly associated to suicide attempts, but not suicidal ideation. SES had indirect effects on suicidal outcomes via mental health and life events. LIMITATIONS: The cross-sectional design and application of measures for different time periods did not allow for causal inferences. CONCLUSIONS: Suicidal behaviours were more prevalent than in the general UK population. Interventions targeting low SES individuals may prove effective in preventing suicide attempts.

Impact of exposure to combat during deployment to Iraq and Afghanistan on mental health by gender.

BACKGROUND: Interest in the mental health of women deployed to modern military campaigns is increasing, although research examining gender differences is limited. Little is known about experiences women have had on these deployments, or whether men and women respond differently to combat exposure. METHOD: The current study used data from a representative sample of UK Armed Forces personnel to examine gender differences among those deployed to Iraq and Afghanistan (n=432 women, n=4554 men) in three measures of experience: 'risk to self', 'trauma to others' and 'appraisal of deployment'. We examined the impact of such experiences on post-deployment symptoms of post-traumatic stress disorder (PTSD), symptoms of common mental disorder (CMD) and hazardous alcohol use. RESULTS: After adjustment, men reported more exposure to 'risk to self' and 'trauma to others' events and more negative appraisals of their deployment. Among both genders, all measures of combat experience were associated with symptoms of PTSD and CMD (except 'risk to self' events on symptoms of CMD among women) but not with alcohol misuse. Women reported higher scores on the PTSD Checklist--Civilian Version (PCL-C) among those exposed to lower levels of each experience type but this did not hold in the higher levels. Women reported greater symptoms of CMD and men reported greater hazardous alcohol use across both levels of each experience type. Examining men and women separately suggested similar responses to exposure to adverse combat experiences. CONCLUSIONS: The current findings suggest that, although gender differences in mental health exist, the impact of deployment on mental health is similar among men and women.

Associations between IQ and common mental disorders: the 2000 British National Survey of Psychiatric Morbidity.

BACKGROUND: Associations have been described between lower IQ and serious mental illness. Associations between common mental disorders (CMDs) and IQ have received little research. The objective of this study was to investigate the association between verbal IQ and CMD symptoms and diagnoses, and to investigate the role of potential mediating and confounding factors. METHOD: Data were analysed from a British national survey with an analysed sample of 8054 people aged 16-74 years. Associations between verbal IQ (NART) and mental symptoms/disorders (CIS-R) were analysed with covariates including education, social class, income, debt, problem drinking, life events, physical health and relationship quality. RESULTS: CMD was associated with lower IQ. This association was stronger for depressive disorder/symptoms than for generalised anxiety disorder/symptoms. The most important covariates were education, social class, income and relationship quality. CONCLUSION: The association between lower IQ and CMD is partly accounted for by adverse social/socioeconomic conditions. Stronger associations for depression than anxiety may indicate an effect of IQ on the way mental distress is communicated.

Regulated basal, inducible, and tissue-specific human erythropoietin gene expression in transgenic mice requires multiple cis DNA sequences.

Erythropoietin (Epo) gene expression in kidney and liver is inducible by anemia. To localize the sequences necessary for regulated expression of the Epo gene, we constructed transgenic mice containing five human Epo gene constructs and examined Epo expression under basal conditions and with anemia. Mice containing the Epo gene with 0.3 kb of 5' flanking sequence, 0.7 kb of 3' flanking sequence, and either all introns or only intron I alone were polycythemic, had Epo expression in various tissues (including non-Epo-producing tissues), and induction only in liver. In contrast, mice containing the Epo gene with 8.5 kb of 3' flanking sequence and either 9.5 or 22 kb of 5' flanking sequence had basal expression at low levels in appropriate tissues and were less likely to be markedly polycythemic. Mice with the smaller of these two constructs had induction only in the liver, whereas those with the larger construct had induction in the kidney and liver. These studies indicate that sequences sufficient for induction in the liver are located in close proximity to the Epo gene, including the immediate 5' and 3' flanking sequence and the first intron. They also indicate that sequences required for induction in the kidney are located more than 9.5 kb 5' to the gene. Furthermore, comparison of these and prior transgenic studies suggest that sequences that limit the basal expression of the Epo gene are located downstream of the gene. We conclude that multiple cis DNA sequences are required for regulated Epo gene expression.