Association Between Prepartum Maternal Iron Deficiency and Offspring Risk of Schizophrenia: Population-Based Cohort Study With Linkage of Danish National Registers

Recent findings suggest that maternal iron deficiency may increase the risk of schizophrenia-spectrum disorder in offspring. We initiated this study to determine whether maternal prepartum anemia influences offspring risk of schizophrenia. We conducted a population-based study with individual record linkage of the Danish Civil Registration System, the Danish Psychiatric Central Register, and the Danish National Hospital Register. In a cohort of 1 115 752 Danish singleton births from 1978 to 1998, cohort members were considered as having a maternal history of anemia if the mother had received a diagnosis of anemia at any time during the pregnancy. Cohort members were followed from their 10th birthday until onset of schizophrenia, death, or December 31, 2008, whichever came first. Adjusted for relevant confounders, cohort members whose mothers had received a diagnosis of anemia during pregnancy had a 1.60-fold (95% confidence interval = 1.16–2.15) increased risk of schizophrenia. Although the underlying mechanisms are unknown and independent replication is needed, our findings suggest that maternal iron deficiency increases offspring risk of schizophrenia.     

Risk of Subsequent Asthma in Children With Febrile Seizures: A Nationwide Population-Based Retrospective Cohort Study

BackgroundNo study has reported a relationship between febrile seizures and asthma; thus, we examined the association between these two disorders.MethodsWe identified 991 cases of children with febrile seizures as the case cohort, and the control group was matched according to age, sex, urbanization level, and their parents' occupation at a 1:4 ratio. We applied the Cox proportional hazards regression model to estimate the hazard ratios and 95% confidence intervals for asthma among the children with febrile seizures.ResultsAfter 11 years of follow-up, the asthma incidence in the febrile seizure group was approximately 5% higher than that in the control group (log-rank test, P < 0.0001). The risk of asthma in the febrile seizure group was 1.41 times higher than that in the control group (95% confidence interval, 1.21-1.65; P < 0.001). Furthermore, the risk of asthma development increased (0.96 vs 3.62) in conjunction with the frequency of febrile seizure-related medical visits (one to two visits vs more than four visits; P < 0.0001).ConclusionFebrile seizures may be associated with an increase in the risk of future asthma occurrence in children. We observed a significantly higher cumulative incidence of asthma occurrence in children with more febrile seizure-related medical visits.     

Outpatient Follow-Up Visit after Hospital Discharge Lowers Risk of Rehospitalization in Patients with Schizophrenia: A Nationwide Population-Based Study

Objective

Non-adherence to medication is a recognized problem in psychiatric patients and may be one of the most challenging aspects of treatment for patients with schizophrenia. Failure of follow-up care after discharge greatly increases non-adherence to prescribed medications, relapse and rehospitalization. However, it is still unknown whether and how much outpatient follow-up visits can mitigate the risk of rehospitalization. Therefore we sought to investigate the continuity and effectiveness of outpatient care after inpatient discharge and its effect on rehospitalization of patients with schizophrenia.

Methods

Data were extracted from National Health Insurance Claim Database covering the period from 2007 through 2010. We identified 10,246 patients aged 18 years or older who were admitted in psychiatric facilities with the diagnosis of schizophrenia between January 1 and December 31 in 2007. The number of outpatient visits within 60 days after discharge from index admission was defined as the indicator for the continuous care and rehospitalization was inspected during the following 36-month period. Cox''s proportional hazard model was used to examine the factors affecting the risk of rehospitalization including the number of outpatient visits, age, sex, comorbidities, antipsychotics, and characteristics of medical institution.

Results

We found that 12.7% (n=1,327) of the patients visited psychiatric outpatient department once within 60 days after hospital discharge, 34.8% (n=3,626) twice, and 27.8% (n=2,900) more than three times. Patients taking atypical antipsychotics showed higher proportion in 2 or more outpatient visits, whereas patients taking typical antipsychotics showed higher proportion in one or no outpatient visits. Cox hazard ratios of rehospitalization for the factor of 3 or more outpatient visits referenced to that of no follow-up visit were 0.567 (0.428-0.750, 95% confidence interval) within 90 days, 0.673 (0.574-0.789) within 180 days, 0.800 (0.713-0.898) within a year, 0.906 (0.824-0.997) within 2 years, and 0.993 (0.910-1.084) within 3 years.

Conclusion

Although continuous outpatient treatment is important for relapse prevention, patients with schizophrenia showed a low rate of outpatient visit as 62.6% of total patients in 2 or more visits within 60 days after discharge. Lack of follow-up treatment might lead to increase psychotic symptoms and raised risk of relapse and rehospitalization. Our data suggest that the number of outpatient visits within 60 days after discharge in patients with schizophrenia is an important indicator of rehospitalization within a year. Therefore, further efforts to examine factors affecting failure of outpatient follow-up after discharge are warranted.     

Excess Mortality and Life-Years Lost in People With Schizophrenia and Other Non-affective Psychoses: An 11-Year Population-Based Cohort Study

Psychotic disorders are associated with premature mortality, but research was primarily based on Western countries and rarely examined non-affective psychoses other than schizophrenia (ONAP). This population-based cohort study investigated excess mortality in 46 896 schizophrenia and 20 651 ONAP patients between January 2006 and December 2016 in Hong Kong (HK), by estimating all-cause and cause-specific standardized mortality ratios (SMRs), and life-years lost (LYLs), a recently developed, more precise reduced life expectancy measure taking into account the illness onset (age at first-recorded diagnosis). Changes in mortality metrics over the study period were assessed. Study data were retrieved from a territory-wide medical-record database of public healthcare services to 7.5 million HK residents. Results showed that schizophrenia and ONAP patients had higher all-cause (schizophrenia: SMR: 2.49 [95% CI: 2.43–2.55]; ONAP: 2.00 [1.92–2.09]), natural-cause (1.80 [1.74–1.85]; 1.47 [1.40–1.54]), and unnatural-cause (6.97 [6.47–7.49]; 8.53 [7.61–9.52]) mortality rates than general population. Respiratory diseases, cardiovascular diseases, and cancers accounted for the majority of deaths in patient cohorts. Men and women with schizophrenia had 9.53 years and 8.07 years of excess LYLs, respectively. For ONAP, excess LYLs was 8.18 years for men and 5.44 years for women. The overall mortality gap remained similar for both patient groups over time despite their improved longevity and declined unnatural-cause mortality rates. Taken together, schizophrenia and ONAP are associated with increased premature mortality and substantially reduced lifespan in a predominantly Chinese population, with excess deaths mainly attributed to a natural cause. Persistent mortality gap highlights an urgent need for targeted interventions to improve the physical health of patients with psychotic disorders.     

Catatonic Schizophrenia: A Cohort Prospective Study

Background:

In the 20th century, catatonia was usually deemed a subtype of schizophrenia. Recently, the nature and classification of catatonia are being reconsidered. This study is the first to describe catatonia using prospectively collected data and to examine how catatonic schizophrenia differs from, or resembles, other types of schizophrenia.

Methods:

Data were analyzed in a cohort of 90 079 offspring followed from birth till ages 29–41 years. Proportional hazards models were used, calculating time to first psychiatric hospital admission, to compare risk factors for catatonic schizophrenia vs “other schizophrenia.”

Results:

Of 568 cases of schizophrenia, 43 (7.6%) had catatonic schizophrenia. The sexes were equally at risk for catatonic schizophrenia in contrast to other schizophrenia, for which the incidence was higher in males (1.70, 1.42–2.03, P < .0001). Advancing paternal age had no influence on the risk of catatonic schizophrenia in contrast to other schizophrenia, in which the risk to offspring of fathers age 35+ was 1.27 (1.03–1.57, P = .03) compared with those of younger fathers. Those with catatonic schizophrenia were somewhat more likely to have older mothers (aged 35+) (relative risk = 2.14, 0.85–5.54) while maternal age was not related to other schizophrenia. Both were equally affected by parental history of schizophrenia. Patients with catatonia were significantly more likely to attempt suicide (P = .006).

Conclusion:

Patients with catatonic schizophrenia show a somewhat different profile of risk factors from those with other types of schizophrenia in this cohort and are more likely to attempt suicide. This lends some support to the hypothesis that catatonic schizophrenia may have a distinct etiology.     

Risk of Mortality Associated With Atypical Antipsychotic use: A National Cohort Study of Older Adults With Depression and Parkinson's Disease

ObjectivesThis study examined the risk of all-cause-mortality in patients with Parkinson's Disease (PD) and comorbid depression using inappropriate atypical antipsychotics (AAPs), based on the 2015 American Geriatrics Society Beers criteria.MethodsA retrospective analysis of 2007–2010 Minimum Data Set linked Medicare data was conducted using a propensity-matched approach. The cohort included PD patients aged 65 years or older without schizophrenia or bipolar disorder who started AAPs. All patients had a diagnosis of comorbid depression. Risk of 6-month all-cause-mortality was compared across appropriate AAPs (aripiprazole, clozapine, or quetiapine) and inappropriate AAPs (olanzapine, asenapine, brexpiprazole, iloperidone, lurasidone, paliperidone, risperidone, or ziprasidone) using robust Cox regression models involving the matched cohort.ResultsAll-cause mortality rate was 15.65% in appropriate AAP group (n = 6,038) and 16.91% in inappropriate AAP group (n = 6,038) over 6-month follow-up in the matched cohort. The robust Cox proportional hazards models revealed increased risk of all-cause mortality (hazard ratio [HR] 1.13 [95% confidence interval {CI}: 1.01–1.28)] for patients who used inappropriate compared to appropriate AAPs. Risk of death was also higher for risperidone compared to quetiapine (HR: 1.20 [95% CI: 1.03–1.40]) in sensitivity analysis. However, there was a significant relationship between pneumonia and death in all analyses. The impact of inappropriate AAP use on mortality was not significant when pneumonia was modeled as a mediator.ConclusionsInappropriate AAP use is associated with a higher risk of all-cause-mortality in older patients with PD which is mainly mediated by pneumonia. Therefore, inappropriate AAP use should be avoided to improve quality of care in PD.     

Risk Factors for Full- and Partial-Syndrome Early Adolescent Eating Disorders: A Population-Based Pregnancy Cohort Study

ObjectiveTo identify prospective predictors of eating disorders in a population-based sample of 14-year-old boys and girls, using previously collected antenatal, biomedical, familial, demographic, and psychosocial data.MethodParticipants (N = 1,597) were drawn from the Western Australian Pregnancy Cohort (Raine) Study. Data were collected during pregnancy, at birth, and when children were aged 1, 2, 5, 8, 10, and 14 years. An adapted version of the Eating Disorder Examination Questionnaire was used to assess eating disorder symptoms at age 14 years. Logistic regression was used to identify prospective predictors of eating disorder caseness, relative to general control and psychiatric control groups.ResultsAt age 14 years, 6% of the sample met full or partial criteria for a DSM-IV eating disorder. Being female and being perceived as overweight by one's parent were the strongest predictors of eating disorder caseness in the final multivariate models, relative to both control groups. Maternal body mass index, social problems, low social-related self-efficacy, and neurocognitive difficulties were also predictive of eating disorder caseness relative to the general control group only.ConclusionsThe results suggest that parent's perceptions of their child's weight are more powerful than objective child body weight in predicting the development of eating disorders. Parent-perceived child overweight was also a specific risk factor for eating disorders, whereas elevated maternal weight and childhood psychosocial difficulties seem to be associated with increased risk for psychiatric disturbance more generally. These results have implications for the prevention of eating disorders, particularly in light of recent increases in the prevalence of childhood obesity.     

Increased Risk for Substance Use-Related Problems in Autism Spectrum Disorders: A Population-Based Cohort Study

Despite limited and ambiguous empirical data, substance use-related problems have been assumed to be rare among patients with autism spectrum disorders (ASD). Using Swedish population-based registers we identified 26,986 individuals diagnosed with ASD during 1973–2009, and their 96,557 non-ASD relatives. ASD, without diagnosed comorbidity of attention deficit hyperactivity disorder (ADHD) or intellectual disability, was related to a doubled risk of substance use-related problems. The risk of substance use-related problems was the highest among individuals with ASD and ADHD. Further, risks of substance use-related problems were increased among full siblings of ASD probands, half-siblings and parents. We conclude that ASD is a risk factor for substance use-related problems. The elevated risks among relatives of probands with ASD suggest shared familial (genetic and/or shared environmental) liability.     

Prevalence,Employment Rate,and Cost of Schizophrenia in a High-Income Welfare Society: A Population-Based Study Using Comprehensive Health and Welfare Registers

Schizophrenia is associated with recurrent hospitalizations, need for long-term community support, poor social functioning, and low employment rates. Despite the wide- ranging financial and social burdens associated with the illness, there is great uncertainty regarding prevalence, employment rates, and the societal costs of schizophrenia. The current study investigates 12-month prevalence of patients treated for schizophrenia, employment rates, and cost of schizophrenia using a population-based top-down approach. Data were obtained from comprehensive and mandatory health and welfare registers in Norway. We identified a 12-month prevalence of 0.17% for the entire population. The employment rate among working-age individuals was 10.24%. The societal costs for the 12-month period were USD 890 million. The average cost per individual with schizophrenia was USD 106 thousand. Inpatient care and lost productivity due to high unemployment represented 33% and 29%, respectively, of the total costs. The use of mandatory health and welfare registers enabled a unique and informative analysis on true population-based datasets.Key words: schizophrenia, prevalence, employment, cost-of-illness     

Statin Use and the Risk of Dementia in Patients with Stroke: A Nationwide Population-Based Cohort Study

Background: Patients with stroke have an increased risk of dementia. Some studies have found that statin use might lower the risk of incident dementia; however, there is still a lack of data from patients with stroke. Therefore, the aim of our study was to investigate the impact of statin use on the risk of dementia in patients with stroke.

Early Signs of Autism in Toddlers: A Follow-Up Study in the Danish National Birth Cohort

To identify possible early signs of autism spectrum disorder (ASD) within the Danish National Birth Cohort, we studied prospectively collected interviews from 76,441 mothers about their children’s development and behaviour at 6 and 18 months. In Danish national registries, 720 children with ASD and 231 children with intellectual disability (ID) were identified. At 6 months, associations between early signs and ASD or ID were found only in few areas. At 18 months social, language, and motor skills were delayed, and suspicion of vision and hearing problems were increased for both groups. Signs distinguishing ASD from ID were unclear, and the positive predictive values regarding ASD were below 10 % for individual predictors and aggregated risk scores.     

Childhood Bullying Behaviors as a Risk for Suicide Attempts and Completed Suicides: A Population-Based Birth Cohort Study

ObjectiveThere are no previous studies about the association of childhood bullying behavior with later suicide attempts and completed suicides among both sexes. The aim was to study associations between childhood bullying behaviors at age 8 years and suicide attempts and completed suicides up to age 25 years in a large representative population-based birth cohort.MethodThe sample includes 5,302 Finnish children born in 1981. Information about bullying was gathered at age 8 years from self-report, as well as parent and teacher reports. Information about suicide attempts requiring hospital admission and completed suicides was gathered from three different Finnish registries until the study participants were 25 years old. Regression analyses were conducted to determine whether children who experience childhood bullying behaviors are at risk for later suicide attempts and completed suicides after controlling for baseline conduct and depression symptoms.ResultsThe association between bullying behavior at age 8 years and later suicide attempts and completed suicides varies by sex. Among boys, frequent bullying and victimization are associated with later suicide attempts and completed suicides but not after controlling for conduct and depression symptoms; frequent victimization among girls is associated with later suicide attempts and completed suicides, even after controlling for conduct and depression symptoms.ConclusionsWhen examining childhood bullying behavior as a risk factor for later suicide attempts and completed suicides, each sex has a different risk profile.     

Treatment Capacity and Clinical Outcomes for Patients With Schizophrenia Who Were Treated With Electroconvulsive Therapy: A Retrospective Cohort Study

BackgroundPatients with schizophrenia are often found incapable to consent to psychiatric treatment. We evaluated clinical outcomes for incapable and capable patients with schizophrenia treated with electroconvulsive therapy (ECT). MethodsWe conducted a chart review of all inpatients treated with an acute course of ECT between 2010 and 2018 at the Centre for Addiction and Mental Health, Toronto, Canada. Short-term outcomes included treatment response and cognitive impairment. We assessed whether incapable patients regained the capacity to consent to treatment. Long-term outcomes included readmissions and subsequent courses of acute or maintenance ECT. ResultsA total of 159 (67%) incapable and 79 (33%) capable patients were included. Patients experienced treatment response (incapable, n = 108, 67.9%; capable, n = 52, 65.8%; P = .771) and few experienced cognitive impairment (incapable, n = 21, 13.2%; capable, n = 19, 24.1%; P = .043). A minority of patients were treated with a subsequent course of acute ECT (incapable, n = 46, 28.9%; capable, n = 16, 20.3%; P = .162). Incapable patients were more likely to be treated with maintenance ECT for at least 6 months (incapable, n = 46, 28.9%; capable, n = 13, 16.5%; P = .039). Both groups had similar readmission rates (incapable, n = 70, 44.0%; capable, n = 35, 44.3%; P = 1.000). Eight (5.0%) incapable patients regained capacity and 7 consented to further treatment. ConclusionsIrrespective of treatment capacity, the majority of patients demonstrated clinical improvement. Incapable patients experienced less cognitive side effects when compared with capable patients, though they had fewer treatments overall. This study informs clinicians, patients, and substitute decision-makers about the outcomes and challenges of ECT in patients with schizophrenia.