Associations between symptoms and all-cause mortality in individuals with serious mental illness

Journal of Psychosomatic Research 72 (2012) 114–119

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Journal of Psychosomatic Research

Associations between symptoms and all-cause mortality in individuals with serious mental illness Richard D. Hayes a,⁎, Chin-Kuo Chang a, Andrea Fernandes a, Aysha Begum a, David To b, Matthew Broadbent c, Matthew Hotopf d, Robert Stewart a a

King's College London, Institute of Psychiatry, Section of Epidemiology, Dept of Health Service and Population Research, London, UK King's College London, Institute of Psychiatry, Biostatistics Dept, London, UK South London and Maudsley NHS Foundation Trust, London, UK d King's College London, Institute of Psychiatry, Academic Dept Psychological Medicine, London, UK b c

a r t i c l e

i n f o

Article history: Received 23 June 2011 received in revised form 27 August 2011 accepted 13 September 2011 Keywords: Bipolar affective disorder Depression Mortality Schizoaffective disorder Schizophrenia Symptoms

a b s t r a c t Objective: To determine if aggression, hallucinations or delusions, and depression contribute to excess mortality risk observed in individuals with serious mental illness (SMI). Methods: We identified SMI cases (schizophrenia, schizoaffective and bipolar disorder) aged ≥ 15 years in a large secondary mental healthcare case register linked to national mortality tracing. We modelled the effect of specific symptoms (HoNOS subscales) on all-cause mortality using Cox regression. Results: We identified 6880 SMI cases (242 deaths) occurring 2007–2010. Bipolar disorder was associated with reduced mortality risk compared to schizophrenia (HR 0.7; 95% CI 0.4–0.96; p = 0.028). Mortality was not significantly associated with hallucinations and delusions or overactive–aggressive behaviour, but was associated with physical illness/disability. There was a positive association between mortality and subclinical depression among individuals with schizophrenia (HR 1.5; 1.1–2.2; p = 0.019) but a negative association with subclinical and more severe depression among those with schizoaffective disorder (HR 0.1; 0.02–0.4; p = 0.001 and 0.3; 0.1–0.8; p = 0.021, respectively). Conclusions: The recognised increased risk of mortality in SMI did not appear to be influenced by severity of hallucinations, delusions, or overactive–aggressive behaviour. Physical illness and lifestyle may need to be addressed and the relationship between depression and mortality requires further investigation. © 2011 Elsevier Inc. All rights reserved.

Introduction Individuals diagnosed with serious mental illness (SMI) including schizophrenia, schizoaffective disorder and bipolar disorder are at higher risk of mortality than the general population [1–4]. The impact of SMI on life expectancy is substantial and generally higher than similarly calculated impacts of well-recognised adverse exposures such as smoking, diabetes and obesity [5]. It has been estimated that individuals with SMI may die between 10 and 15 years earlier than the general population [5] Despite improving healthcare, there continues to be a substantial gap in mortality between people with SMI and the general population. Particular symptoms associated with SMI including depressed mood, auditory or visual hallucinations and delusions, and aggression or violent behaviour [6–8] may play a role in the elevated risk of mortality in this patient group. It is possible that elevated symptoms may ⁎ Corresponding author at: Section of Epidemiology (Box 92), Dept of Health Service and Population Research, Institute of Psychiatry, King's College London, De Crespigny Park, SE5 8AF London, UK. Tel.: + 44 20 3228 8553; fax: + 44 20 3228 8551. E-mail address: [email protected] (R.D. Hayes). 0022-3999/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jpsychores.2011.09.012

increase mortality risk via a variety of mechanisms. For example hallucinations and delusions may distract an individual from real-life dangers or create beliefs of being magically protected [9]; aggression may lead to life threatening conflict (people with SMI are at increased risk mortality from both accidents and homicide [2]); depression may increase the risk of suicide [10]; and these symptoms may interfere with an individual's ability to self-care with potential adverse health consequences [11–12]. Depressed mood, hallucinations, and aggression are not unique to SMI and have been associated with increased risk of mortality in other contexts including community based studies [13–14] and among patients with coronary artery disease [15] and Alzheimer's disease [16]. However research into the impact of individual symptoms and symptom profiles on mortality in individuals with SMI has been very limited. Aggression was associated with increased suicidal behaviour in a retrospective case control study of 149 depressed bipolar patients [17]. Also, in a recent prospective study of 310 patients with schizophrenia (and 31 deaths) Loas et al. [18] reported that high levels of subjective symptoms independently predicted mortality by unnatural causes. Although other symptoms were not associated with mortality in that investigation, the authors acknowledged that

R.D. Hayes et al. / Journal of Psychosomatic Research 72 (2012) 114–119

the duration of follow-up and number of deaths may have been insufficient to detect significant effects of other types of symptoms. No previous research has investigated hallucinations and delusions, over-activity and aggression, or depressed mood in relation to mortality in a large sample of individuals with SMI. We reasoned that these symptom profiles may contribute to the elevated risk of mortality reported in this patient group. In this investigation we examine associations between these symptoms and mortality in individuals with SMI known to secondary care services. Methods Setting The South London and Maudsley NHS Foundation Trust (SLaM) is Europe's largest provider of secondary mental healthcare. Under the National Health Service (NHS) system in the UK, there is universal state provision of healthcare, and mental health trusts have a close to 100% monopoly for service provision to defined geographic catchment areas. SLaM provides comprehensive secondary mental healthcare to a population of approximately 1.2 million residents of four London boroughs (Lambeth, Southwark, Lewisham and Croydon), and provision of all aspects of secondary mental healthcare across all age groups including inpatient, community, general hospital liaison and forensic services. From 2006 onwards, electronic clinical records have been used comprehensively across all SLaM services. In 2008 the Case Register Interactive Search (CRIS) system supported by the NIHR Specialist Biomedical Research Centre for Mental Health was developed to enable researchers to efficiently search and retrieve anonymised clinical records. CRIS currently provides anonymised indepth information derived for over 180,000 cases currently represented in the system. The protocol for this case register has been described in detail in an open-access publication [19]. CRIS was approved as a dataset for secondary analysis on this basis by Oxfordshire Research Ethics Committee C (08/H0606/71). Inclusion criteria This dynamic cohort consisted of individuals who were diagnosed with SMI during a specific observation period (from the 1st of January 2007 to the 31st of December 2010, inclusive) and who had been assessed by a clinician using the Health of the Nations Outcome Scale (HoNOS) [20–21] at least once during this observation period. The HoNOS was introduced in 1998 as a standard measure of patient wellbeing that could be applied by clinicians [20]. Approximately three quarters (74.8%) of all SMI patients in SLaM who were diagnosed during the observation period had received at least one HoNOS assessment during that time. Individuals who were under the age of 15 when they received their first HoNOS assessment during the observation period were excluded from this analysis. Diagnoses recorded in the SLaM BRC Case Register were based on the 10th edition of the World Health Organization International Classification of Diseases (ICD-10) [8]. Patients were classified as having an SMI if, while in contact with SLaM services, they had been diagnosed with schizophrenia (ICD-10 code: F20), schizoaffective disorder (F25) or bipolar affective disorder (F31) during the observation period. Main outcome measures The outcome of interest was all-cause mortality that occurred within the 4 years of the observation period (2007–2010, inclusive) in those diagnosed with SMI. Routine mortality tracing allowed us to determine those deaths that occurred during the observation period. Through mortality tracing we were able to detect deaths that occurred while individuals were still SLaM patients and also deaths that occurred after patients had been discharged. The process by which

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SLaM patient deaths are confirmed has been described in detail elsewhere [3]. Briefly, in the UK all death certifications are linked to NHS number, (a unique identifier for UK NHS medical records) and primary and secondary healthcare providers are required by law to keep these records up to date. Each month NHS numbers for all previous and current SLaM contacts are checked against this national mortality database and deaths electronically flagged on the patient record. Explanatory variables In the analysis we used the first HoNOS questionnaire that was completed during the observation period to measure symptoms in each patient. Numerous studies have been conducted to assess the validity and feasibility of applying the HoNOS in a variety of patient groups [20,22–24]. HoNOS consists of 12 items where response options follow the format of 0) not a problem; l) subclinical, minor problem requiring no action; 2) mild problem but definitely present; 3) moderately severe problem; 4) severe to very severe problem, with standard guidance for how and when to apply each level of a given item [21]. Primary exposures of interest for this analysis were HoNOS items 1, 6 and 7 [21]. Item 1 assesses overactive, aggressive, or agitated behaviour regardless of cause; item 6 assesses hallucinations and delusions; and item 7 assesses depressed mood. Three further HoNOS items were included in this analysis as potential confounders. These were the items assessing non-accidental self injury, problem drinking or drug taking, and physical illness or disability problems. These three additional HoNOS items were included in the analysis because self-harm, substance use and physical illness have been associated with mortality and also SMI in previous research and are therefore potential confounders [1,10,25–30]. Due to limited numbers in some categories all HoNOS items were condensed to three response options in the analysis: 0) not a problem, 1) subclinical, minor problem requiring no action, 2–4) mild to very severe problem. Date of birth, ethnicity and gender are routinely recorded on SLaM electronic patient records in designated fields. Age was calculated from the date on which each individual received their first HoNOS assessment during the observation period. Ethnic group classifications were: “White British and other white background”, “East Asian”, “South Asian”, “African, Caribbean and other black background”, and “Mixed, unknown, and others”. Relationship status was classified as being in a current relationship (cohabiting, married or civil partner) and no current relationship (divorced, civil partnership dissolved, separated, single, widowed/surviving civil partner or unknown). Employment status was classified as being in paid employment (part-time or full-time paid employment, self employed), or not in paid employment (unemployed, registered disabled, retired, full-time student including tertiary or school age, government training scheme, volunteer, not known, other). Patients were also grouped into diagnostic categories based on the first SMI diagnosis they had received during the observation period. In order to adjust for the level of patient contact with SLaM services we calculated the number of face to face contacts each patient received in a period of 60 days centred on their first HoNOS assessment in the observation period. The number of contacts was then divided into tertiles for the analysis We linked postcodes from patient addresses to UK Census data for 2007 to provide indices of deprivation for the neighbourhoods in England where patients resided. In this analysis we used an index of multiple deprivation to give a summary of the overall socioeconomic status at the level of lower super output area (LSOA). Each LSOA contains a minimum of 1000 residents and 400 households, but with an average of 1500 residents. The index of multiple deprivation is derived from multiple domains of deprivation including: employment, income, education, health, barriers to housing and services, crime and the living environment. Each domain is given a specific weighting to reflect its overall importance in the calculation of this index.

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Moreover, each domain is made up of a number of specific indicators that reflect different aspects of the deprivation they are intended to measure. Increasing scores in the index of multiple deprivation are indicative of more severe deprivation. In this analysis deprivation scores were divided into tertiles. Full details of each domain, the indicators they contain and the domain weightings that were used to derive the index of multiple deprivation are reported elsewhere [31]. In this analysis the address that was recorded closest in time to July 1, 2007 for each patient was used to calculate deprivation scores. If the patient was reported as being homeless in a patient record

Table 1 Cohort characteristics. Variables

Number of individuals (Number of deaths)

Total 6880 Over activity and aggression Not a problem 3857 Subclinical, minor problem requiring no action 1532 Mild to very severe problem 1483 Hallucinations and delusions Not a problem 2839 Subclinical, minor problem requiring no action 1020 Mild to very severe problem 2973 Depressed mood Not a problem 3061 Subclinical, minor problem requiring no action 1993 Mild to very severe problem 1801 Diagnosis Schizophrenia (ICD10 code — F20) 4270 Schizoaffective disorder (ICD 10 code — F25) 771 Bipolar affective disorder (ICD 10 code — F31) 1839 Gender Female 3045 Male 3835 Ethnicity White British or other white background 3103 East Asian 223 South Asian 194 African, Caribbean or other black background 2805 Mixed, unknown others 555 Physical illness or disability problems Not a problem 4313 Subclinical, minor problem requiring no action 1241 Mild to very severe problem 1292 Non-accidental self-injury Not a problem 6020 Subclinical, minor problem requiring no action 475 Mild to very severe problem 364 Problem-drinking or drug taking Not a problem 4975 Subclinical, minor problem requiring no action 738 Mild to very severe problem 1084 Married or cohabiting No 6024 Yes 856 Employment status Not in paid employment 6550 In paid employment 330 Deprivation level in area of residence (in tertiles) Low levels of deprivation 2189 Medium levels of deprivation 2196 High levels of deprivation 2197 Homeless 144 Level of face to face contact with SLaM services (in tertiles) Low level of contact 2013 Medium level of contact 2540 High level of contact 2327 Age group 15 to b 30 years 1460 30 to b 45 years 2855 45 to b 65 years 2175 65 years or older 390

(242) (133) (50) (58) (88) (39) (112)

entry that was closest in time to July 1, 2007 then the patient was assigned to a separate homeless category. All explanatory variables explored in this analysis are listed in Table 1. Statistical analysis We used Cox regression to model the effect of specific symptoms (hallucinations, overactive/aggressive behaviour and depressive symptoms) on all-cause mortality. Cox regression is a statistical modelling technique for use in survival analysis that estimates a hazard ratio (HR), which is a measure of relative risk. For each patient the ‘at-risk’ period commenced from the date of the patient's first HoNOS assessment that occurred during the observation period. The censoring date was the end of the observation period (31st December 2010) for the ones who survived until the end of observation period and the event date was the date of death if it occurred during the observation period. Crude and adjusted associations between mortality and the principal exposures of interest (HoNOS symptoms scores) or potential confounders were examined. Using Cox regression models we tested for interactions by sex and diagnosis, and when observed the data were stratified to determine the direction and extent of the interaction. Results

(218) (24)

Using CRIS, we identified 6880 individuals with a primary diagnosis of schizophrenia, schizoaffective disorder or bipolar disorder who met the inclusion criteria in whom 242 deaths occurred from the beginning of 2007 until the end of 2010. The mean follow-up period was 974.8 days. Table 1 provides numbers of cases and deaths by diagnosis, levels of symptom severity, and other cohort characteristics. Of the 6880 cases included in this investigation 316 (4.6%) had received different SMI diagnosis during the observation period (on different occasions). When examined by diagnosis, the proportion of individuals who received different SMI diagnoses during the observation period was highest among those initially diagnosed with schizoaffective disorder, (75 individuals, 9.7%) and lower among those initially diagnosed with schizophrenia or bipolar disorder (150 individuals, 3.5% and 91 individuals, 5.0%, respectively). The number of face to face contacts in the 60 days centred on the date of the HoNOS ranged from 0 to 139, with a mean of 10.6. Table 2 describes findings from unadjusted and adjusted Cox models of factors potentially associated with all cause mortality in this cohort. Crude and adjusted hazard ratios are presented with the latter models including all variables appearing in Table 2. A likelihood ratio test indicated that it was appropriate to include age as a continuous variable in the analysis. We observed differences in mortality across diagnostic groups with those diagnosed with bipolar disorder being at reduced risk of mortality compared to those diagnosed with schizophrenia (HR 0.7, 95% CI 0.4–0.96, p = 0.028). Also age (HR 1.1 per year increment, 95% CI 1.05–1.1, p b 0.001) and physical illness or disability (subclinical HR 1.9, 95% CI 1.3–2.7, p = 0.001 and mild to very severe HR 3.0, 95% CI 2.1–4.2, p b 0.001) were significantly associated with increased mortality risk. There were no significant associations between mortality and hallucinations and delusions, or overactive/aggressive behaviour in any models. In secondary analyses we investigated if associations between symptoms and mortality varied by sex or diagnosis. The only significant interaction was between diagnosis and depressed mood. Stratifying the data by diagnosis (Table 3) revealed that subclinical depressed mood was associated with increased risk of mortality among individuals with schizophrenia (HR 1.5, 95% CI 1.1–2.2, p = 0.019). Among those with schizoaffective disorder subclinical and more severe depressed mood were associated with reduced risk of mortality (HR 0.1, 95% CI 0.02–0.4, p = 0.001 and HR 0.3, 95% CI 0.1–0.8, p = 0.021, respectively).

(240) (2)

Discussion

(105) (85) (50) (170) (28) (44) (108) (134) (138) (6) (4) (80) (14) (71) (61) (108) (209) (20) (11) (174) (28) (35)

(84) (81) (64) (4) (61) (89) (92) (19) (64) (96) (63)

In this investigation we analysed all-cause mortality data linked to a large secondary mental healthcare case register to test the hypothesis that specific symptoms contribute to the increased risk of mortality among individuals with SMI. We observed differences in mortality across diagnostic groups with those diagnosed with bipolar disorder being at reduced risk of mortality compared to those diagnosed with schizophrenia. Symptoms of over-activity and aggression or hallucinations and delusions were not associated with risk of mortality. However the relationship between depressed mood and mortality was more complex with subclinical depression being associated with

R.D. Hayes et al. / Journal of Psychosomatic Research 72 (2012) 114–119 Table 2 Cox regression analyses of factors associated with all cause mortality in the cohort (individuals with schizophrenia, schizoaffective and bipolar affective disorder). Variablesa

Crude hazard ratio (95% CI)

Overactivity and aggression Not a problem Referent Subclinical, minor problem 1.0 (0.7–1.4) requiring no action Mild to very severe problem 1.2 (0.9–1.6) Hallucinations and delusions Not a problem Referent Subclinical, minor problem 1.2 (0.8–1.8) requiring no action Mild to very severe problem 1.2 (0.9–1.6) Depressed mood Not a problem Referent Subclinical, minor problem 1.2 (0.9–1.6) requiring no action Mild to very severe problem 0.9 (0.6–1.2) Diagnosis Schizophrenia (ICD10 Referent code — F20) Schizoaffective disorder 0.9 (0.6–1.3) (ICD 10 code — F25) Bipolar affective disorder 0.6 (0.5–0.9) (ICD 10 code — F31) Gender Female Referent Male 1.0 (0.7–1.2) Ethnicity White British or other white Referent background East Asian 0.6 (0.3–1.3) South Asian 0.4 (0.2–1.2) African, Caribbean or other 0.6 (0.4–0.8) black background Mixed, unknown others 0.6 (0.3–1.0) Physical illness or disability Not a problem Referent Subclinical, minor problem 2.9 (2.1–4.1) requiring no action Mild to very severe problem 5.3 (3.9–7.1) Non-accidental self-injury Not a problem Referent Subclinical, minor problem 1.3 (0.8–2.1) requiring no action Mild to very severe problem 1.0 (0.5–1.8) Problem-drinking or drug taking Not a problem Referent Subclinical, minor problem 1.0 (0.7–1.6) requiring no action Mild to very severe problem 0.9 (0.6–1.3) Married or cohabiting No Referent Yes 0.8 (0.5–1.3) Employment status Not in paid employment Referent or student In paid employment 0.2 (0.04–0.7) Deprivation in area of residence (in tertiles) Low levels of deprivation Referent Medium levels of deprivation 0.9 (0.7–1.2) High levels of deprivation 0.7 (0.5–1.0) Homeless 0.7 (0.3–1.9) Level of face to face contact with SLaM services (in Low level of contact Referent Medium level of contact 1.0 (0.7–1.4) High level of contact 1.1 (0.8–1.5) Age 1.1 (1.1–1.1)

Adjustedb hazard ratio (95% CI)

Adjustedb P value

Referent 0.8 (0.6–1.2)

0.333

1.1 (0.8–1.6)

0.604

Referent 1.1 (0.7–1.6)

0.773

1.0 (0.7–1.4)

0.990

Referent 1.2 (0.9–1.7)

0.174

0.9 (0.6–1.3)

0.534

Referent 1.0 (0.6–1.5)

0.927

0.7 (0.4–0.96)

0.028

Referent 1.2 (0.9–1.6)

0.141

Referent 0.8 (0.3–1.8) 0.5 (0.2–1.5) 0.8 (0.6–1.0)

0.561 0.218 0.075

1.0 (0.5–1.8)

0.918

Referent 1.9 (1.3–2.7)

0.001

3.0 (2.1–4.1)

b0.001

Referent 1.4 (0.8–2.2)

0.227

1.0 (0.5–2.0)

0.969

Referent 1.5 (1.0–2.3)

0.066

1.2 (0.8–1.8)

0.444

Referent 0.7 (0.5–1.2)

0.195

Referent 0.2 (0.02–1.3)

0.084

Referent 1.0(0.8–1.4) 0.8 (0.5–1.1) 0.7 (0.3–2.0) tertiles)

0.842 0.106 0.507 0.040⁎

1.0 (0.7–1.5) 1.5 (1.01–2.1) 1.1 (1.05–1.1)

0.831 0.043 b0.001

a

Numbers of individuals and number of deaths in each category are given in Table 1. Adjusted for all other variables that appear in this table. ⁎ P for trend. P values b 0.05 are in bold. b

increased risk of mortality among individuals with schizophrenia but depression being associated with reduced risk in those with schizoaffective disorder.

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Despite the well-recognised association between SMI and substantially reduced life expectancy, there has been limited research into subgroups at particular risk — in particular in relation to symptom profiles. Our results are consistent with a previous small study (n = 310) where no association was found between mortality and positive, negative, hostile or anxious–depressive symptoms [18]. Some previous studies have reported associations between mortality and hallucinations or hostility, but in other disorders [15–16]. Nonaccidental self injury was not associated with increased risk of mortality although it is important to bear in mind that our analyses did not attempt to differentiate specific causes of death and previous research has suggested that individuals with SMI may be at higher risk of suicide than the general population [2,27,32]. There are a range of potential mechanisms by which SMI may have a negative impact on survival. Adverse lifestyle choices such as smoking, poor diet, use of illicit drugs and physical inactivity, may contribute [26,33–35]. In our cohort, general illness or disability was strongly associated with mortality, although the recorded presence of problem drinking or drug taking was not a significant risk factor. However a previous investigation, also based on SLaM patient records, indicated that those with a substance use disorder diagnosis were at increased risk of mortality [30]. In the present investigation the cohort was restricted to those with an SMI as their primary diagnosis. It is possible that the worst cases of substance use may have received substance use disorder rather than SMI as their primary diagnosis and hence these individuals would have been missed from our cohort. This may explain why we did not detect an association between mortality and problem drinking and drug taking. A sizable proportion of the cohort (37.0%) had some degree of illness or disability. Interestingly, even those assessed as having subclinical illness or disability that required no action were at a significantly elevated risk of mortality with almost twice the adjusted risk compared to those with no illness nor disability problems. A particular strength of the study was the size and comprehensiveness of the sample. SLaM is the largest unit provider of secondary mental healthcare in Europe and is a single near-monopoly provider of secondary mental healthcare for its geographic catchment. We were able to draw on complete electronic clinical records of more than six thousand SMI cases providing the statistical power to simultaneously control for a range of potential confounders in a detailed longitudinal analysis. SLaM patient death tracing is updated monthly and is based on death certificates issued across the UK. Moreover, there is a legal requirement for primary and secondary healthcare providers to keep these records up to date. Consequently current patient deaths and those occurring after discharge are recorded and only deaths occurring outside the UK are likely to be missed. Certain limitations however need to be considered. Although we adjusted for a broad range of factors, there may still be residual confounding. In particular medication use was not included in this analysis which may have had an impact on results. Medications may reduce symptoms obscuring any relationship between underlying disease severity and mortality. In addition there may be deleterious physical consequences of long-term antipsychotic use [26] which we were not able to take into account in this analysis. Also a reliable assessment of duration of illness was not available for this cohort. It was not possible to manually code free text fields in patient records due to the large sample size and numerous records per patient. Consequently, symptom assessment was restricted to HoNOS items. A previous investigation of individuals with Alzheimer's disease reported that hallucinations but not delusions were associated with mortality [16]. However, in the HoNOS instrument, hallucinations and delusions are combined as one item making it impossible to analyse these domains separately. In addition there has been some criticism of HoNOS in the literature, including its assessment of symptoms [36–37]. Due to small numbers in some response categories, it was necessary to group together people who had mild through to very

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Table 3 Cox regression analyses of symptoms and all cause mortality stratifying the cohort by diagnosis. Schizophrenia Variables

Total Overactivity and aggression Not a problem Subclinical, minor problem requiring no action Mild to very severe problem Hallucinations and delusions Not a problem Subclinical, minor problem requiring no action Mild to very severe problem Depressed mood Not a problem Subclinical, minor problem requiring no action Mild to very severe problem

Schizoaffective disorder

Bipolar affective disorder

Na

Adjustedb

Adjustedb

Na

Adjustedb

Adjustedb

Na

Adjustedb

Adjustedb

Individuals (deaths)

Hazard ratio (95% CI)

P value

Individuals (deaths)

Hazard ratio (95% CI)

P value

Individuals (deaths)

Hazard ratio (95% CI)

P value

4064 (156)

745 (27)

1770 (41)

2400 (93) 898 (33)

Referent 0.7 (0.5–1.1)

0.147

392 (13) 165 (8)

Referent 2.2 (0.8–5.6)

0.115

944 (22) 403 (6)

Referent 0.6 (0.2–1.6)

0.294

766 (30)

1.0 (0.6–1.5)

0.931

188 (6)

0.8 (0.3–2.3)

0.640

423 (13)

1.4 (0.6–3.3)

0.455

1322 (47) 662 (29)

Referent 1.2 (0.7–1.9)

0.507

264 (9) 121 (4)

Referent 1.0 (0.3–3.4)

0.992

1176 (28) 207 (4)

Referent 0.7 (0.2–2.2)

0.561

2080 (80)

1.0 (0.7–1.5)

0.947

360 (14)

1.2 (0.5–3.2)

0.666

387 (9)

0.7 (0.3–1.6)

0.362

1963 (67) 1284 (61)

Referent 1.5 (1.1–2.2)

0.019

309 (17) 220 (2)

Referent 0.1 (0.02–0.4)

0.001

684 (16) 414 (16)

Referent 1.9 (0.9–3.8)

0.091

817 (28)

1.2 (0.8–1.9)

0.443

216 (8)

0.3 (0.1–0.8)

0.021

672 (9)

0.7 (0.3–1.6)

0.380

a

Numbers exclude those dropped from the multivariate analysis due to missing values. b Adjusted for all variables that were described in Table 2. P values b 0.05 are in bold.

severe problems. It is possible that this grouping might have obscured associations. Moreover, in this analysis symptom assessment was based on the first HoNOS measurement in the observation period. Patients may experience fluctuations in their symptoms over time which would not be well captured by a single HoNOS assessment. However in a previous investigation where Cox proportional hazards models were used to investigate mortality in schizophrenia, researchers did detect a significant association between mortality and symptoms scores measured at a single time point [18]. We only examined selected symptoms associated with SMI. It is possible that mortality risk is mediated by a different set of symptoms than those examined in this investigation. Under the UK National Health Service (NHS), all secondary mental healthcare within the four boroughs that form the SLaM catchment is provided at no cost to consumers by SLaM, the only exception being people seeking exclusively private healthcare [38]. However, levels of disadvantage or referral bias may still influence the characteristics of the cohort who present to secondary care. The generalisability of these findings is therefore principally to secondary care rather than primary care populations. Finally, cause of death was not analysed as these data are not yet available, although we hope to investigate this specifically in the future. The finding that subclinical depression is a risk factor in those with schizophrenia but depression is protective in those with schizoaffective disorder is difficult to interpret. Among individuals with schizophrenia, subclinical depression may be a marker for more serious underlying depression that has remained untreated. However, in those with schizoaffective disorder it is possible that the presence of depressed mood identifies individuals who are more prone to depressive rather than manic episodes and it may be that fewer manic episodes is protective. Also it is noteworthy that almost 10% of those initially diagnosed with schizoaffective disorder were later diagnosed with a different SMI. The relationship between subclinical depressed mood and mortality appears to be complex and requires further investigation. In addition, in may be useful to incorporate fluctuations in patient's symptoms over time into the measure of exposure in future research. These results have implications for clinical practice. Our findings suggest that reducing the severity of hallucinations and delusions or overactive–aggressive behaviour is unlikely to have a major impact on reducing the risk of mortality in patients with SMI. Other factors

need to be considered. Poor general health may make a major contribution to mortality among individuals with SMI [26,33–35]. Our results indicate that even individuals with subclinical illness or disability have an almost two-fold increased risk of mortality. This level of physical illness was assessed as requiring no action despite the elevated mortality risk. It is possible that low level physical illness among individuals with SMI is currently being undertreated. In future, health management of individuals with SMI may need to more effectively target the general health of these patients if we are to substantially reduce the excess mortality risk among those with SMI. Author contributions All the authors listed contributed to the process of hypothesis generation, data collection, statistical analyses, or manuscript preparation, and fulfilled the criteria for authorship. Conflict of interest None. Acknowledgements The development of the SLaM BRC Case Register has been funded by two Capital Awards from the UK National Institute for Health Research and is further supported through the BRC Nucleus funded jointly by the Guy's and St Thomas' Charity and South London and Maudsley Special Trustees. RH, CKC, AF, AB, DT, MB, MH and RS are funded by the National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London. The sponsors had no further role in the study design; in the collection, analysis or interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. References [1] Harris EC, Barraclough B. Excess mortality of mental disorder. Br J Psychiatry 1998;173:11–53.

R.D. Hayes et al. / Journal of Psychosomatic Research 72 (2012) 114–119 [2] Hiroeh U, Appleby L, Mortensen PB, Dunn G. Death by homicide, suicide, and other unnatural causes in people with mental illness: a population-based study. Lancet 2001;358(9299):2110–2. [3] Chang CK, Hayes RD, Broadbent M, Fernandes A, Lee W, Hotopf M, et al. All-cause mortality among people with serious mental illness (SMI), substance use disorders, and depressive disorders in Southeast London: a cohort study. BMC Psychiatry 2010;10:77. [4] Capasso RM, Lineberry TW, Bostwick JM, Decker PA, St. Sauver J. Mortality in schizophrenia and schizoaffective disorder: an Olmsted County, Minnesota cohort: 1950–2005. Schizophr Res 2008;98(1–3):287–94. [5] Chang CK, Hayes RD, Perera G, Broadbent MTM, Fernandes AC, Lee WE, et al. Life expectancy at birth for people with serious mental illness from a secondary mental health care case register in London, UK. PLoS One 2011;6(5). [6] Breier A, Schreiber JL, Dyer J, Pickar D. National Institute of Mental Health longitudinal study of chronic schizophrenia. Prognosis and predictors of outcome. Arch Gen Psychiatry 1991;48(3):239–46. [7] Latalova K. Bipolar disorder and aggression. Int J Clin Pract 2009;63(6):889–99. [8] World Health Organisation. Manual of the international statistical classification of diseases and realted health problems 10 revision (ICD-10); 2000. [9] Siris SG. Suicide and schizophrenia. J Psychopharmacol 2001;15(2):127–35. [10] Large M, Sharma S, Cannon E, Ryan C, Nielssen O. Risk factors for suicide within a year of discharge from psychiatric hospital: a systematic meta-analysis. Aust N Z J Psychiatry 2011;45(8):619–28. [11] Kilbourne AM, Rofey DL, McCarthy JF, Post EP, Welsh D, Blow FC. Nutrition and exercise behavior among patients with bipolar disorder. Bipolar Disord 2007;9(5): 443–52. [12] Semkovska M, Bedard MA, Godbout L, Limoge F, Stip E. Assessment of executive dysfunction during activities of daily living in schizophrenia. Schizophr Res 2004;69(2–3):289–300. [13] Mykletun A, Bjerkeset O, Dewey M, Prince M, Overland S, Stewart R. Anxiety, depression, and cause-specific mortality: the HUNT study. Psychosom Med 2007;69(4):323–31. [14] Mykletun A, Bjerkeset O, Overland S, Prince M, Dewey M, Stewart R. Levels of anxiety and depression as predictors of mortality: the HUNT study. Br J Psychiatry 2009;195(2):118–25. [15] Boyle SH, Williams RB, Mark DB, Brummett BH, Siegler IC, Helms MJ, et al. Hostility as a predictor of survival in patients with coronary artery disease. Psychosom Med 2004;66(5):629–32. [16] Wilson RS, Krueger KR, Kamenetsky JM, Tang Y, Gilley DW, Bennett DA, et al. Hallucinations and mortality in Alzheimer disease. Am J Geriatr Psychiatry 2005;13(11):984–90. [17] Dervic K, Carballo JJ, Baca-Garcia E, Galfalvy HC, Mann JJ, Brent DA, et al. Moral or religious objections to suicide may protect against suicidal behavior in bipolar disorder. J Clin Psychiatry 2011 [Epub ahead of print]. [18] Loas G, Yon V, Marechal V, Decle P. Relationships between subjective or objective symptoms and mortality in schizophrenia: a prospective study on 310 schizophrenic patients with a median follow-up of 8.4 years. Psychiatry Res 2011;185(1–2):49–53. [19] Stewart R, Soremekun M, Perera G, Broadbent M, Callard F, Denis M, et al. The South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLAM BRC) case register: development and descriptive data. BMC Psychiatry 2009;9:51.

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[20] Wing JK, Beevor AS, Curtis RH, Park SB, Hadden S, Burns A. Health of the Nation Outcome Scales (HoNOS). Research and development. Br J Psychiatry 1998;172:11–8. [21] Wing J, Curtis RH, Beevor A. Health of the Nation Outcome Scales (HoNOS). Glossary for HoNOS score sheet. Br J Psychiatry 1999;174:432–4. [22] Orrell M, Yard P, Handysides J, Schapira R. Validity and reliability of the Health of the Nation Outcome Scales in psychiatric patients in the community. Br J Psychiatry 1999;174:409–12. [23] Pirkis JE, Burgess PM, Kirk PK, Dodson S, Coombs TJ, Williamson MK. A review of the psychometric properties of the Health of the Nation Outcome Scales (HoNOS) family of measures. Health Qual Life Outcomes 2005;3:76. [24] Hunter R, Cameron R, Norrie J. Using patient-reported outcomes in schizophrenia: the Scottish Schizophrenia Outcomes Study. Psychiatr Serv 2009;60(2):240–5. [25] Politi P, Piccinelli M, Klersy C, Madini S, Segagni LG, Fratti C, et al. Mortality in psychiatric patients 5 to 21 years after hospital admission in Italy. Psychol Med 2002;32(2):227–37. [26] Auquier P, Lancon C, Rouillon F, Lader M, Holmes C. Mortality in schizophrenia. Pharmacoepidemiol Drug Saf 2006;15(12):873–9. [27] Brown S. Excess mortality of schizophrenia. A meta-analysis. Br J Psychiatry 1997;171:502–8. [28] Osborn DP, Levy G, Nazareth I, Petersen I, Islam A, King MB. Relative risk of cardiovascular and cancer mortality in people with severe mental illness from the United Kingdom's General Practice Rsearch Database. Arch Gen Psychiatry 2007;64(2):242–9. [29] Roshanaei-Moghaddam B, Katon W. Premature mortality from general medical illnesses among persons with bipolar disorder: a review. Psychiatr Serv 2009;60(2):147–56. [30] Hayes RD, Chang CK, Fernandes A, Broadbent M, Lee W, Hotopf M, et al. Associations between substance use disorder sub-groups, life expectancy and all-cause mortality in a large British specialist mental healthcare service. Drug Alcohol Depend 2011;118:56–61. [31] Noble M, mcLennan D, Wilkinson K, Whitworth A, Barnes H, Dibben C. The English indices of deprivation 2007. London: Communities and Local Government; 2008. [32] Dutta R, Murray RM, Hotopf M, Allardyce J, Jones PB, Boydell J. Reassessing the long term risk of suicide following a first episode of psychosis. Arch Gen Psychiatry 2010;67(12):1230–7. [33] Robson D, Gray R. Serious mental illness and physical health problems: a discussion paper. Int J Nurs Stud 2007;44(3):457–66. [34] Fagiolini A, Goracci A. The effects of undertreated chronic medical illnesses in patients with severe mental disorders. J Clin Psychiatry 2009;70(Suppl. 3):22–9. [35] Brown S, Birtwistle J, Roe L, Thompson C. The unhealthy lifestyle of people with schizophrenia. Psychol Med 1999;29(3):697–701. [36] Stein GS. Usefulness of the Health of the Nation Outcome Scales. Br J Psychiatry 1999;174:375–7. [37] Bebbington P, Brugha T, Hill T, Marsden L, Window S. Validation of the Health of the Nation Outcome Scales. Br J Psychiatry 1999;174:389–94. [38] Keown P, Mercer G, Scott J. Retrospective analysis of hospital episode statistics, involuntary admissions under the Mental Health Act 1983, and number of psychiatric beds in England 1996–2006. BMJ 2008;337:a1837.