Ellenor Mittendorfer-Rutz

Restricted fetal growth and adverse maternal psychosocial and socioeconomic conditions as risk factors for suicidal behaviour of offspring: a cohort study

BACKGROUND Until now, sparse and contradictory results about an association between adverse neonatal, obstetric, and maternal conditions and heightened suicide risk in adolescents have been reported. The aims of this study were to investigate the relations between fetal growth, obstetric complications, and the mothers psychosocial and socioeconomic situation and the risk in early adulthood of suicide and attempted suicide in the offspring. METHODS Obstetric, neonatal, and maternal risk factors for suicide and attempted suicide in 713370 young adults, born in Sweden between 1973 and 1980, who were followed-up until Dec 31, 1999, were examined by data linkage between Swedish registers. Univariate and multivariate hazard ratios, derived from proportional-hazard models, were estimated. FINDINGS Significantly raised risk of attempted suicide was reported for individuals of short birth length, adjusted for gestational age (hazard ratio 1.29, 95% CI 1.18-1.41, p<0.0001); born fourth or more in birth order (1.79, 1.62-1.97, p<0.0001); born to mothers with a low educational level (1.36, 1.27-1.46, p<0.0001) (attributable proportion 10.3%); and those who, at time of delivery, had mothers aged 19 years or younger (2.09, 1.89-2.32, p<0.0001). Significant predictors of suicide were low birthweight, adjusted for gestational age (2.23, 1.43-3.46, p<0.0001), and teenage motherhood (2.30, 1.64-3.22, p<0.0001). INTERPRETATION Multiparity and low maternal education predicted suicide attempt, whereas restricted fetal growth and teenage motherhood were associated with both suicide completion and attempt in offspring.

Familial clustering of suicidal behaviour and psychopathology in young suicide attempters. A register-based nested case control study.

IntroductionFamilial clustering of suicidal behaviour and psychopathology has been reported in young suicide attempters. Most of these studies were predominantly carried out in clinical treatment settings and lacked statistical power to assess the independent and modifying influences of own and familial psychopathology and suicidal behaviour.MethodsWe carried out a population-based record-linkage study with a nested case control design. The 14,440 individuals hospitalised due to suicide attempt (cases) and 144,400 matched controls were born in Sweden between 1968 and 1980 and followed up till December 31, 1999.ResultsAmong the strongest independent familial risk factors for youth suicide attempt were siblings’ (OR 3.4; 2.8–4.1), maternal (OR 2.7; 2.5–3.1) and paternal (OR 1.9; 1.7–2.1) suicide attempt. Other important risk factors were familial personality and substance abuse disorders, maternal schizophrenia, non-affective psychoses and organic disorders and parental neurotic, stress-related and somatoform disorders (1.9–3.2 fold increase), and paternal (OR 1.9; 1.6–2.3) and maternal (OR 1.8; 1.3–2.4) suicide completion. Mental illnesses in index subjects, particularly substance abuse, affective and personality disorders, were the dominant determinants of suicide attempt. Strong interactions were observed between psychopathology in index subjects and familial suicidality. Familial suicide completion had a stronger effect on suicide attempt of earlier onset and on boys. Nearly half (47%) of all suicide attempts could be attributed to familial psychopathology (13%), family suicide attempt (7%) and suicide completion (1%) and own psychopathology (25%).ConclusionEarly recognition and adequate treatment of individual mental illness contribute to prevent youth suicide attempts. Children of parents with psychopathology and suicidal behaviour should receive early support and attention. Evaluation of familial suicidal behaviour seems to be vital for suicide risk assessment in young psychiatric inpatients. There appears to be an independent effect of familial suicidal behaviour as well as familial psychopathology on youth suicide attempt beyond the transmission of mental illness.

Premature mortality in autism spectrum disorder

BACKGROUND Mortality has been suggested to be increased in autism spectrum disorder (ASD). AIMS To examine both all-cause and cause-specific mortality in ASD, as well as investigate moderating role of gender and intellectual ability. METHOD Odds ratios (ORs) were calculated for a population-based cohort of ASD probands (n = 27,122, diagnosed between 1987 and 2009) compared with gender-, age- and county of residence-matched controls (n = 2,672,185). RESULTS During the observed period, 24,358 (0.91%) individuals in the general population died, whereas the corresponding figure for individuals with ASD was 706 (2.60%; OR = 2.56; 95% CI 2.38-2.76). Cause-specific analyses showed elevated mortality in ASD for almost all analysed diagnostic categories. Mortality and patterns for cause-specific mortality were partly moderated by gender and general intellectual ability. CONCLUSIONS Premature mortality was markedly increased in ASD owing to a multitude of medical conditions.

Antipsychotic Treatment and Mortality in Schizophrenia

BACKGROUND It is generally believed that long-term use of antipsychotics increases mortality and, especially, the risk of cardiovascular death. However, there are no solid data to substantiate this view. METHODS We identified all individuals in Sweden with schizophrenia diagnoses before year 2006 (N = 21 492), aged 17-65 years, and persons with first-episode schizophrenia during the follow-up 2006-2010 (N = 1230). Patient information was prospectively collected through nationwide registers. Total and cause-specific mortalities were calculated as a function of cumulative antipsychotic exposure from January 2006 to December 2010. RESULTS Compared with age- and gender-matched controls from the general population (N = 214920), the highest overall mortality was observed among patients with no antipsychotic exposure (hazard ratio [HR] = 6.3, 95% CI: 5.5-7.3), ie, 0.0 defined daily dose (DDD)/day, followed by high exposure (>1.5 DDD/day) group (HR = 5.7, 5.2-6.2), low exposure (<0.5 DDD/day) group (HR = 4.1, 3.6-4.6), and moderate exposure (0.5-1.5 DDD/day) group (HR = 4.0, 3.7-4.4). High exposure (HR = 8.5, 7.3-9.8) and no exposure (HR = 7.6, 5.8-9.9) were associated with higher cardiovascular mortality than either low exposure (HR = 4.7, 3.7-6.0) or moderate exposure (HR = 5.6, 4.8-6.6). The highest excess overall mortality was observed among first-episode patients with no antipsychotic use (HR = 9.9, 5.9-16.6). CONCLUSIONS Among patients with schizophrenia, the cumulative antipsychotic exposure displays a U-shaped curve for overall mortality, revealing the highest risk of death among those patients with no antipsychotic use. These results indicate that both excess overall and cardiovascular mortality in schizophrenia is attributable to other factors than antipsychotic treatment when used in adequate dosages.

Exposure to parental mortality and markers of morbidity, and the risks of attempted and completed suicide in offspring: an analysis of sensitive life periods

Background There is evidence of parental risk factors for suicidal behaviour in offspring, but research on variations in their effects with offsprings age at first exposure is sparse. Aims To explore the effects of age at exposure to parental mortality and markers of morbidity on the risks of suicide and attempted suicide in offspring. Methods This was a case–control study effected through record linkage between Swedish registers. Individuals born 1973–83 who committed suicide (n=1407) or were hospitalised due to an attempted suicide (n=17 159) were matched to ≤10 controls by sex, month and county of birth. ORs were measured in time windows representing age at first exposure. Results A general pattern of increasing risks of suicide and attempted suicide in offspring with decreasing age at exposure to parental risk factors emerged. Adjusted suicide risk (OR (95% CI)) was most pronounced in the youngest exposure window for parental psychiatric disability pension (3.1 (1.6 to 5.8)), somatic disability pension (1.9 (1.0 to 3.4)), psychiatric inpatient care (2.5 (2.0 to 3.1)), parental attempted suicide (2.9 (2.0 to 4.1)) and suicide (2.9 (1.7 to 5.2)). For parental non-suicidal deaths, the general pattern was the opposite. Patterns in offspring attempted suicide were similar to completed suicide for parental disability pension, psychiatric inpatient care and non-suicidal death. Attempted suicide risk after parental suicide showed an increasing trend with increasing age at exposure. Conclusion Parental morbidity and parental suicidal behaviour show the most detrimental effects on completed suicide among offspring when they appear early in life. Early interventions in families at risk are necessary to prevent suicide in offspring.

Mortality and Cumulative Exposure to Antipsychotics, Antidepressants, and Benzodiazepines in Patients With Schizophrenia: An Observational Follow-Up Study

OBJECTIVE Although mortality related to psychotropic medications has received much attention in recent years, little is known about the relationship between risk of death and cumulative antipsychotic load, and even less about the relationship between mortality and cumulative exposure to antidepressants or benzodiazepines. The authors examined these relationships using nationwide databases. METHOD The authors used prospectively collected nationwide databases to identify all individuals 16-65 years of age with a schizophrenia diagnosis (N=21,492) in Sweden. All-cause and cause-specific mortality rates were calculated as a function of cumulative low, moderate, and high exposure to antipsychotics, antidepressants, and benzodiazepines from 2006 through 2010. RESULTS Compared with no exposure, both moderate (adjusted hazard ratio=0.59, 95% CI=0.49-0.70) and high (adjusted hazard ratio=0.75, 95% CI=0.63-0.89) antipsychotic exposures were associated with substantially lower overall mortality. Moderate antidepressant exposure was associated with a lower mortality (adjusted hazard ratio=0.85, 95% CI=0.73-0.98), and high exposure, even lower (adjusted hazard ratio=0.71, 95% CI=0.59-0.86). Exposure to benzodiazepines showed a dose-response relationship with mortality (hazard ratios up to 1.74 [95% CI=1.50-2.03]). CONCLUSIONS Moderate and high-dose antipsychotic and antidepressant use were associated with 15%-40% lower overall mortality, whereas chronic high-dose use of benzodiazepines was associated with up to a 70% higher risk of death compared with no exposure. Since patients with anxiety and depressive symptoms may have a higher intrinsic risk of death, the finding for benzodiazepines may be attributable to some extent to residual confounding.

Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia

Importance It has remained unclear whether there are clinically meaningful differences between antipsychotic treatments with regard to preventing relapse of schizophrenia, owing to the impossibility of including large unselected patient populations in randomized clinical trials, as well as residual confounding from selection biases in observational studies. Objective To study the comparative real-world effectiveness of antipsychotic treatments for patients with schizophrenia. Design, Setting, and Participants Prospectively gathered nationwide databases were linked to study the risk of rehospitalization and treatment failure from July 1, 2006, to December 31, 2013, among all patients in Sweden with a schizophrenia diagnosis who were 16 to 64 years of age in 2006 (29 823 patients in the total prevalent cohort; 4603 in the incident cohort of newly diagnosed patients). Within-individual analyses were used for primary analyses, in which each individual was used as his or her own control to eliminate selection bias. Traditional Cox proportional hazards multivariate regression was used for secondary analyses. Main Outcomes and Measures Risk of rehospitalization and treatment failure (defined as psychiatric rehospitalization, suicide attempt, discontinuation or switch to other medication, or death). Results There were 29 823 patients (12 822 women and 17 001 men; mean [SD] age, 44.9 [12.0] years). During follow-up, 13 042 of 29 823 patients (43.7%) were rehospitalized, and 20 225 of 28 189 patients (71.7%) experienced treatment failure. The risk of psychiatric rehospitalization was the lowest during monotherapy with once-monthly long-acting injectable paliperidone (hazard ratio [HR], 0.51; 95% CI, 0.41-0.64), long-acting injectable zuclopenthixol (HR, 0.53; 95% CI, 0.48-0.57), clozapine (HR, 0.53; 95% CI, 0.48-0.58), long-acting injectable perphenazine (HR, 0.58; 95% CI, 0.52-0.65), and long-acting injectable olanzapine (HR, 0.58; 95% CI, 0.44-0.77) compared with no use of antipsychotic medication. Oral flupentixol (HR, 0.92; 95% CI, 0.74-1.14), quetiapine (HR, 0.91; 95% CI, 0.83-1.00), and oral perphenazine (HR, 0.86; 95% CI, 0.77-0.97) were associated with the highest risk of rehospitalization. Long-acting injectable antipsychotic medications were associated with substantially lower risk of rehospitalization compared with equivalent oral formulations (HR, 0.78; 95% CI, 0.72-0.84 in the total cohort; HR, 0.68; 95% CI, 0.53-0.86 in the incident cohort). Clozapine (HR, 0.58; 95% CI, 0.53-0.63) and all long-acting injectable antipsychotic medications (HRs 0.65-0.80) were associated with the lowest rates of treatment failure compared with the most widely used medication, oral olanzapine. The results of several sensitivity analyses were consistent with those of the primary analyses. Conclusions and Relevance Clozapine and long-acting injectable antipsychotic medications were the pharmacologic treatments with the highest rates of prevention of relapse in schizophrenia. The risk of rehospitalization is about 20% to 30% lower during long-acting injectable treatments compared with equivalent oral formulations.

Sickness Absence Due to Specific Mental Diagnoses and All-Cause and Cause-Specific Mortality: A Cohort Study of 4.9 Million Inhabitants of Sweden

Background Despite the magnitude and increase of sickness absence due to mental diagnoses, little is known regarding long-term health outcomes. The aim of this nationwide population-based, prospective cohort study was to investigate the association between sickness absence due to specific mental diagnoses and the risk of all-cause and cause-specific mortality. Methods A cohort of all 4 857 943 individuals living in Sweden on 31.12.2004 (aged 16–64 years, not sickness absent, or on retirement or disability pension), was followed from 01.01.2005 through 31.12.2008 for all-cause and cause-specific mortality (suicide, cancer, circulatory disease) through linkage of individual register data. Individuals with at least one new sick-leave spell with a mental diagnosis in 2005 were compared to individuals with no sickness absence. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regression, adjusting for age, sex, education, country of birth, family situation, area of residence, and pre-existing morbidity (diagnosis-specific hospital inpatient (2000–2005) and outpatient (2001–2005) care). Results In the multivariate analyses, mental sickness absence in 2005 was associated with an increased risk for all-cause mortality: HR: 1.65, 95% CI: 1.47–1.86 in women and in men: 1.73, 1.57–1.91; for suicide, cancer (both smoking and non-smoking related) as well as mortality due to circulatory disease only in men. Estimates for cause-specific mortality ranged from 1.48 to 3.37. Associations with all-cause mortality were found for all mental sickness absence diagnostic groups studied. Conclusions Knowledge about the prognosis of patients sickness absent with specific mental diagnoses is of crucial clinical importance in health care. Sickness absence due to specific mental diagnoses may here be used as a risk indictor for subsequent mortality.

Quality of medical care and excess mortality in psychiatric patients—a nationwide register-based study in Sweden

Objective To assess overall and cause-specific mortality and the quality of somatic care among psychiatric patients. Design A register-based cohort study. Setting All individuals aged 20–79 years in Sweden in 2005. Participants In total 6 294 339 individuals. Primary outcome measure The individuals were followed for mortality in 2006 and 2007, generating 72 187 deaths. Psychiatric patients were grouped according to their diagnosis in the National Patient Register. Mortality risk of psychiatric patients was compared with that of non-psychiatric patients. Estimates of RR of mortality were calculated as incidence rate ratios (IRRs) with 95% CIs using Poisson regression analysis. Psychiatric patients were compared with non-psychiatric patients for three healthcare quality indicators: the proportion of avoidable hospitalisations, case death rate after myocardial infarction and statin use among diabetic patients. Results Compared with individuals with no episodes of treatment for mental disorder, psychiatric patients had a substantially increased risk of all studied causes of death as well as death from conditions considered amenable to intervention by the health service, that is, avoidable mortality. The highest mortality was found among those with another mental disorder, predominantly substance abuse (for women, an IRR of 4.7 (95% CI 4.3 to 5.0) and for men, an IRR of 4.8 (95% CI 4.6 to 5.0)). The analysis of quality of somatic care revealed lower levels of healthcare quality for psychiatric patients, signalling failures in public health and medical care. Conclusion This study shows a marked increase in excess mortality, suggesting a lower quality of somatic healthcare in psychiatric patients.

Recent time trends in levels of self‐reported anxiety, mental health service use and suicidal behaviour in Stockholm

Kosidou K, Magnusson C, Mittendorfer‐Rutz E, Hallqvist J, Gumpert CH, Idrizbegovic S, Dal H, Dalman C. Recent time trends in levels of self‐reported anxiety, mental health service use and suicidal behaviour in Stockholm.