The overall and sex- and age-group specific incidence rates of cancer in people with schizophrenia: a population-based cohort study.

AIMS: Decades of research show that people with schizophrenia have an increased risk of death from cancer; however, the relationship between schizophrenia and cancer incidence remains less clear. This population-based study investigates the incidence of seven common types of cancer among people with a hospital diagnosis of schizophrenia and accounting for the effects of age, sex and calendar time. METHODS: This population-based study used 1990-2013 data from three nationwide Swedish registries to calculate the incidence (in total, by age group and by sex) of any cancer and of lung, oesophageal, pancreatic, stomach, colon, (in men) prostate and (in women) breast cancer in 111 306 people with a hospital diagnosis of schizophrenia. The incidence in people with diagnosed schizophrenia was compared with the incidence in the general population. Risk estimates accounted for the effects of calendar time. RESULTS: In 1 424 829 person-years of follow-up, schizophrenia did not confer an overall higher cancer risk (IRR 1.02, 95% CI 0.91-1.13) but was associated with a higher risk for female breast (IRR 1.19, 95% CI 1.12-1.26), lung (IRR 1.42, 95% CI 1.28-1.58), oesophageal (IRR 1.25, 95% CI 1.07-1.46) and pancreatic (IRR 1.10, 95% CI 1.01-1.21) and a lower risk of prostate (IRR 0.66, 95% CI 0.55-0.79) cancer. Some age- and sex-specific differences in risk were observed. CONCLUSIONS: People with schizophrenia do not have a higher overall incidence of cancer than people in the general population. However, there are significant differences in the risk of specific cancer types overall and by sex calling for efforts to develop disease-specific prevention programmes. In people with schizophrenia, higher risk generally occurs in those <75 years.

Increased cardiovascular mortality in people with schizophrenia: a 24-year national register study.

AimsPeople who have schizophrenia die earlier from somatic diseases than do people in the general population, but information about cardiovascular deaths in people who have schizophrenia is limited. We analysed mortality in all age groups of people with schizophrenia by specific cardiovascular diseases (CVDs), focusing on five CVD diagnoses: coronary heart disease, acute myocardial infarction, cerebrovascular disease, heart failure and cardiac arrhythmias. We also compared hospital admissions for CVDs in people who had schizophrenia with hospital admissions for CVDs in the general population. METHODS: This national register study of 10 631 817 people in Sweden included 46 911 people who were admitted to the hospital for schizophrenia between 1 January 1987 and 31 December 2010. Information from national registers was used to identify people who had schizophrenia and obtain data about mortality, causes of death, medical diagnoses and hospitalisations. RESULTS: CVDs were the leading cause of death in people who had schizophrenia (5245 deaths), and CVDs caused more excess deaths than suicide. The mean age of CVD death was 10 years lower for people who had schizophrenia (70.5 years) than the general population (80.7 years). The mortality rate ratio (MRR) for CVDs in all people who had schizophrenia was 2.80 (95% confidence interval (CI) 2.73-2.88). In people aged 15-59 years who had schizophrenia, the MRR for CVDs was 6.16 (95% CI 5.79-6.54). In all people who had schizophrenia, the MRR for coronary heart disease was 2.83 (95% CI 2.73-2.94); acute myocardial infarction, 2.62 (95% CI 2.49-2.75); cerebrovascular disease, 2.4 (95% CI 2.25-2.55); heart failure, 3.25 (95% CI 2.94-3.6); and cardiac arrhythmias, 2.06 (95% CI 1.75-2.43). Hospital admissions for coronary heart disease were less frequent in people who had schizophrenia than in the general population (admission rate ratio, 0.88 (95% CI 0.83-0.94). In all age groups, survival after hospital admission for CVD was lower in people who had schizophrenia than in the general population. CONCLUSIONS: People who had schizophrenia died 10 years earlier from CVDs than did people in the general population. For all five CVD diagnoses, mortality risk was higher for those with schizophrenia than those in the general population. Survival after hospitalisation for CVDs in people who had schizophrenia was comparable with that of people in the general population who were several decades older.

Intensive care admissions due to poisoning.

BACKGROUND: Poisoning represents a significant part of admissions to intensive care units. The aim of this nationwide study was to describe recent national quality register data of demographics and mortality for these patients. METHOD: A retrospective national observational study including all patients over 19 years admitted to an ICU in Sweden, between 1 January 2010 and 31 December 2011, with an ICD-10 code for poisoning. The data were collected from three national registers (The Swedish Intensive Care Register, The National Patient Register, and The Cause of Death Register). RESULTS: The incidence of ICU-treated poisonings was 43/100,000. Twenty-one per cent (n = 8155) of all poisoned patients seeking medical care were admitted to the ICU. Their median age was 38 years (q1-q3: 26-51), as many men as women and 46.5% (n = 3790) had a previous registered poisoning. A mix of different substances was the most common type of suspected poisoning (29.7%, n = 2424). The in-hospital mortality was 1.9% and was correlated to invasive mechanical ventilation (OR 6.91 CI 95% 4.59-10.42), age > 40 (OR 4.54 CI 95% 2.86-7.21) and no previous hospitalisation for poisoning (OR 3.23 CI 95% 2.06-5.07). For 78.3% (n = 119) of the deceased patients, the fatal poisoning was their first diagnosed poisoning. The 30-day mortality was 2.7%, a majority died from poisoning (P < 0.01). CONCLUSION: In Sweden, patients treated in the ICU due to poisoning represent a fifth of all poisoned patients seeking medical care. Older men with no previous poisoning were considered a high-risk group.

Mortality and life expectancy of people with alcohol use disorder in Denmark, Finland and Sweden.

OBJECTIVE: To analyse mortality and life expectancy in people with alcohol use disorder in Denmark, Finland and Sweden. METHOD: A population-based register study including all patients admitted to hospital diagnosed with alcohol use disorder (1,158,486 person-years) from 1987 to 2006 in Denmark, Finland and Sweden. RESULTS: Life expectancy was 24-28 years shorter in people with alcohol use disorder than in the general population. From 1987 to 2006, the difference in life expectancy between patients with alcohol use disorder and the general population increased in men (Denmark, 1.8 years; Finland, 2.6 years; Sweden, 1.0 years); in women, the difference in life expectancy increased in Denmark (0.3 years) but decreased in Finland (-0.8 years) and Sweden (-1.8 years). People with alcohol use disorder had higher mortality from all causes of death (mortality rate ratio, 3.0-5.2), all diseases and medical conditions (2.3-4.8), and suicide (9.3-35.9). CONCLUSION: People hospitalized with alcohol use disorder have an average life expectancy of 47-53 years (men) and 50-58 years (women) and die 24-28 years earlier than people in the general population.

The KMO allele encoding Arg452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression.

The kynurenine pathway metabolite kynurenic acid (KYNA), modulating glutamatergic and cholinergic neurotransmission, is increased in cerebrospinal fluid (CSF) of patients with schizophrenia or bipolar disorder type 1 with psychotic features. KYNA production is critically dependent on kynurenine 3-monooxygenase (KMO). KMO mRNA levels and activity in prefrontal cortex (PFC) are reduced in schizophrenia. We hypothesized that KMO expression in PFC would be reduced in bipolar disorder with psychotic features and that a functional genetic variant of KMO would associate with this disease, CSF KYNA level and KMO expression. KMO mRNA levels were reduced in PFC of bipolar disorder patients with lifetime psychotic features (P=0.005, n=19) or schizophrenia (P=0.02, n=36) compared with nonpsychotic patients and controls. KMO genetic association to psychotic features in bipolar disorder type 1 was studied in 493 patients and 1044 controls from Sweden. The KMO Arg(452) allele was associated with psychotic features during manic episodes (P=0.003). KMO Arg(452) was studied for association to CSF KYNA levels in an independent sample of 55 Swedish patients, and to KMO expression in 717 lymphoblastoid cell lines and 138 hippocampal biopsies. KMO Arg(452) associated with increased levels of CSF KYNA (P=0.03) and reduced lymphoblastoid and hippocampal KMO expression (P≤0.05). Thus, findings from five independent cohorts suggest that genetic variation in KMO influences the risk for psychotic features in mania of bipolar disorder patients. This provides a possible mechanism for the previous findings of elevated CSF KYNA levels in those bipolar patients with lifetime psychotic features and positive association between KYNA levels and number of manic episodes.

Suicide seasonality and antidepressants: a register-based study in Sweden.

OBJECTIVE: Seasonality of completed suicides with a peak in spring and early summer is a well-documented finding. The circannual serotonergic functioning is hypothesized to be central in this phenomenon. Antidepressant medications exert their pharmacological action mainly by regulating serotonin. Our aim is to study the amplitude of the seasonal effect among suicide victims positive for different classes of antidepressants or without any antidepressants at the time of death. METHOD: By using Swedish Registers, 12 448 suicides with forensic data for antidepressive medication and information on in-patient-treated mental disorder were identified during 1992-2003. Seasonality was estimated with a Poisson regression variant of the circular normal distribution of completed suicides. RESULTS: Higher suicide seasonality was found for individuals treated with selective serotonin reuptake inhibitor (SSRIs) compared to those with other antidepressant treatment or without any antidepressant treatment. The finding is more evident for men and violent suicide methods and those without history of in-patient treatment. CONCLUSION: Our results provide preliminary support for the serotonergic hypothesis of suicide seasonality and raise the question of a possible accentuation of the natural suicide seasonality in patients treated with SSRIs, a hypothesis that warrants further investigation.

Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder.

Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable psychiatric disorders with overlapping susceptibility loci and symptomatology. We conducted a genome-wide association study (GWAS) of these disorders in a large Swedish sample. We report a new and independent case-control analysis of 1507 SCZ cases, 836 BD cases and 2093 controls. No single-nucleotide polymorphisms (SNPs) achieved significance in these new samples; however, combining new and previously reported SCZ samples (2111 SCZ and 2535 controls) revealed a genome-wide significant association in the major histocompatibility complex (MHC) region (rs886424, P=4.54 × 10(-8)). Imputation using multiple reference panels and meta-analysis with the Psychiatric Genomics Consortium SCZ results underscored the broad, significant association in the MHC region in the full SCZ sample. We evaluated the role of copy number variants (CNVs) in these subjects. As in prior reports, deletions were enriched in SCZ, but not BD cases compared with controls. Singleton deletions were more frequent in both case groups compared with controls (SCZ: P=0.003, BD: P=0.013), whereas the largest CNVs (>500 kb) were significantly enriched only in SCZ cases (P=0.0035). Two CNVs with previously reported SCZ associations were also overrepresented in this SCZ sample: 16p11.2 duplications (P=0.0035) and 22q11 deletions (P=0.03). These results reinforce prior reports of significant MHC and CNV associations in SCZ, but not BD.

Genes and alcohol.

The negative effects of excessive alcohol use include dependence, psychiatric co-morbidity and increased risk for suicide. A dominating risk factor is heritage. A large number of studies have addressed the genetic basis, either "candidate genes" in the brain reward system, or searched for unknown genes in family studies by linkage analysis. It is clear that no single gene polymorphism is of use in preventive medicine. A consistent finding, however, is that polymorphism in the alcohol dehydrogenase cluster and other metabolic pathways are of some relevance on a population basis, suggesting a link between alcohol toxicity in general and dependence. An emerging concern is potential gender differences as women, who are generally more sensitive, acquire male drinking habits.

Antidepressant medication prevents suicide in depression.

OBJECTIVE: Ecological studies have demonstrated a substantial decrease in suicide in parallel with an increasing use of antidepressants. To investigate on the individual level the hypothesis that antidepressant medication was a causal factor. METHOD: Data on the toxicological detection of antidepressants in 18 922 suicides in Sweden 1992-2003 were linked to registers of psychiatric hospitalization as well as registers with sociodemographic data. RESULTS: The probability for the toxicological detection of an antidepressant was lowest in the non-suicide controls, higher in suicides, and even higher in suicides that had been psychiatric in-patients but excluding those who had been in-patients for the treatment of depression. CONCLUSION: The finding that in-patient care for depression did not increase the probability of the detection of antidepressants in suicides is difficult to explain other than by the assumption that a substantial number of depressed individuals were saved from suicide by postdischarge treatment with antidepressant medication.

Decrease in suicide among the individuals treated with antidepressants: a controlled study of antidepressants in suicide, Sweden 1995-2005.

OBJECTIVE: Ecological studies have demonstrated a substantial decrease in suicide in parallel with an increase in the use of antidepressants. Causality cannot, however, be inferred from such studies. The aim of this study was to test on the individual level the hypothesis that treatment with antidepressant medication has been a substantially contributing cause of the decrease in suicide. METHOD: Time trends in the detection of antidepressants and five 'control medications' in the forensic toxicological screening of 16 937 suicides and 33 426 controls in Sweden 1995-2005. RESULTS: The expected number of antidepressant-positive suicides in 2005 was 409 if the hypothesis was true and 603 if it was false. The observed number in 2005 was 420. The control medications were detected to the extent that was expected if not preventing suicide. CONCLUSION: The observed trend in the number of suicides with antidepressants was well predicted by the hypothesis that the increased use of antidepressants has been a substantially contributing cause of the decrease in suicide.

Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2.

We and others have previously reported linkage to schizophrenia on chromosome 10q25-q26 but, to date, a susceptibility gene in the region has not been identified. We examined data from 3606 single-nucleotide polymorphisms (SNPs) mapping to 10q25-q26 that had been typed in a genome-wide association study (GWAS) of schizophrenia (479 UK cases/2937 controls). SNPs with P<0.01 (n=40) were genotyped in an additional 163 UK cases and those markers that remained nominally significant at P<0.01 (n=22) were genotyped in replication samples from Ireland, Germany and Bulgaria consisting of a total of 1664 cases with schizophrenia and 3541 controls. Only one SNP, rs17101921, was nominally significant after meta-analyses across the replication samples and this was genotyped in an additional six samples from the United States/Australia, Germany, China, Japan, Israel and Sweden (n=5142 cases/6561 controls). Across all replication samples, the allele at rs17101921 that was associated in the GWAS showed evidence for association independent of the original data (OR 1.17 (95% CI 1.06-1.29), P=0.0009). The SNP maps 85 kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene for schizophrenia.

A systematic genomewide linkage study in 353 sib pairs with schizophrenia.

We undertook a genomewide linkage study in a total of 353 affected sib pairs (ASPs) with schizophrenia. Our sample consisted of 179 ASPs from the United Kingdom, 134 from Sweden, and 40 from the United States. We typed 372 microsatellite markers at approximately 10-cM intervals. Our strongest finding was a LOD score of 3.87 on chromosome 10q25.3-q26.3, with positive results being contributed by all three samples and a LOD-1 interval of 15 cM. This finding achieved genomewide significance (P<.05), on the basis of simulation studies. We also found two regions, 17p11.2-q25.1 (maximum LOD score [MLS] = 3.35) and 22q11 (MLS = 2.29), in which the evidence for linkage was highly suggestive. Linkage to all of these regions has been supported by other studies. Moreover, we found strong evidence for linkage (genomewide P<.02) to 17p11.2-q25.1 in a single pedigree with schizophrenia. In our view, the evidence is now sufficiently compelling to undertake detailed mapping studies of these three regions.

Excess mortality in bipolar and unipolar disorder in Sweden.

BACKGROUND: Selected groups of patients with bipolar and unipolar disorder have an increased mortality rate from suicide and natural causes of death. However, there has been no population-based study of mortality of patients followed up from the onset of the illness. METHODS: All patients with a hospital diagnosis of bipolar (n = 15 386) or unipolar (n = 39 182) disorder in Sweden from 1973 to 1995 were identified from the inpatient register and linked with the national cause-of-death register to determine the date and cause of death. Overall and cause-specific standardized mortality ratios (SMRs) and numbers of excess deaths were calculated by 5-year age classes and 5-year calendar periods. RESULTS: The SMRs for suicide were 15.0 for males and 22.4 for females with bipolar disorder, and 20.9 and 27.0, respectively, for unipolar disorder. For all natural causes of death, SMRs were 1.9 for males and 2.1 for females with bipolar disorder, and 1.5 and 1.6, respectively, for unipolar disorder. For bipolar disorder, most excess deaths were from natural causes, whereas for unipolar disorder, most excess deaths were from unnatural causes. The SMR for suicide was especially high for younger patients during the first years after the first diagnosis. Increasing SMR for suicide during the period of study was found for female patients with unipolar disorder. CONCLUSIONS: This population-based study of patients treated in the hospital documented increased SMRs for suicide in patients with bipolar and unipolar disorder. The SMR for all natural causes of death was also increased, causing about half the excess deaths.

Time trends in first admissions for schizophrenia and paranoid psychosis in Stockholm County, Sweden.

Several studies have reported decreasing time trends in first diagnosed schizophrenia patients. The aim of this study was to analyze time trends for first admissions with a diagnosis of schizophrenia or a diagnosis of either schizophrenia or paranoid psychosis during 1978-1994 in Stockholm County, Sweden, with a population of around 1.8million. Information about first psychiatric admission with the diagnosis schizophrenia or paranoid psychosis for residents of Stockholm County was obtained from the Swedish population-based psychiatric inpatient register. Age-adjusted average yearly changes in first hospitalization rates were estimated in a Poisson regression model. Time trends in first admission rates were calculated from 1978 to 1994, while admissions during 1971 to 1977 were observed only to eliminate later re-admissions. First admissions for schizophrenia declined by 1.9% annually for females and by 1.3% for males, while first admissions for schizophrenia and paranoid psychosis together were unchanged over the study period for both genders. Our results indicate that the incidence of schizophrenia and paranoid psychosis taken together was essentially the same over the studied time period in Stockholm County, and that the apparent decline in first admission rates for schizophrenia may be an effect of changes in clinical diagnosis over time.

Mortality and causes of death in schizophrenia in Stockholm county, Sweden.

A study of mortality for all patients with a first hospital diagnosis of schizophrenia in Stockholm County, Sweden, during 1973 to 1995 was performed, by linking the in-patient register with the national cause-of-death register. Overall and cause-specific standardized mortality ratios (SMR) were calculated by 5-year age classes and 5-year calendar time periods. The number of excess deaths was calculated by reducing the observed number of deaths by those expected. Our results confirmed a marked increase in mortality in schizophrenia both in males and females. Natural (somatic) causes of death was the main cause of excess deaths, with more than half of the excess deaths in females, and almost half of the excess deaths in males. Suicide was the specific cause of the largest number of excess deaths in males, while in females it was cardiovascular disease. SMRs were increased in both natural and unnatural causes of death, with 2.8 for males and 2.4 for females for all deaths, but were highest in suicide with 15.7 for males and 19.7 for females, and in unspecified violence with 11.7 for males and 9.9 for females. SMRs in suicide were especially high in young patients in the first year after the first diagnosis.

Stability of performance on neuropsychological tests in patients with schizophrenia.

This study evaluated the stability of performance on neuropsychological tests in a group of 14 schizophrenic patients. These patients were first tested as inpatients and later on as outpatients. The patients' results are also compared with matched normal controls and with standardized norms. The patients' test results were stable over time and no change in performance was found for the patients as a group, suggesting that these aspects of the patients' functioning were of a trait quality. The patient group had significantly poorer results on a majority of the tests compared with the controls. The variation of the level of cognitive functioning among the patients, however, was great. In clinical practice today, neuropsychological examinations are often included in the diagnostic procedure, and their results also have impact on treatment planning. However, the possibility to generalize the findings is reduced as a consequence of the low number of patients in the study.

[Important current genetic findings in schizophrenia]. / Nya genetiska fynd av betydelse vid schizofreni.

Twin and adoption studies have yielded convincing evidence of the involvement of genetic factors in the aetiology of schizophrenia. A genetic link with chromosome 6 reported just over a year ago has since been confirmed by other research groups. There is reason to hope that one or more schizophrenia genes will be identified in the next few years.

Two-year outcome of team-based intensive case management for patients with schizophrenia.

OBJECTIVES: Two-year outcomes of patients with schizophrenic disorders who were assigned to an intensive, team-based case management program and patients who received standard psychiatric services were assessed. The case management model featured increased staff contact time with patients, rehabilitation plans based on patients' expressed needs, and patients' attendance at team meetings where their rehabilitation plan was discussed. METHODS: Forty patients were randomly assigned to either the case management group or the control group that received standard services. Patients' use of emergency and inpatient services, their quality of life, the size of their social networks, and their relatives' burden of care were assessed at assignment to the study groups and at two-year follow-up. RESULTS: Patients in the case management group had significantly fewer emergency visits compared with the two years before the study, and their relatives reported significantly reduced burden of care associated with relationships with psychiatric services over the two-year period. The size of patients' social networks increased for the case management group and decreased for the control group. CONCLUSIONS: A team-based intensive case management model is an effective intervention in the rehabilitation of patients with chronic schizophrenia.