Association of pre-existing maternal cardiovascular diseases with neurodevelopmental disorders in offspring: a cohort study in Sweden and British Columbia, Canada.

BACKGROUND: We aimed to investigate the associations of pre-existing maternal cardiovascular disease (CVD) with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID) in offspring. METHODS: This population-based cohort study included singletons live-born without major malformations in Sweden (n = 2 699 675) and British Columbia (BC), Canada (n = 887 582) during 1990-2019, with follow-up from age 1 year until the outcome, death, emigration or December 2020, whichever came first. The primary exposure was defined as a composite CVD diagnosed prior to conception: cerebrovascular disease, arrhythmia, heart failure, valvular and congenital heart diseases. The incidences of ADHD, ASD and ID, comparing offspring of mothers with versus without CVD, were calculated as adjusted hazard ratios (aHRs). These results were compared with models using paternal CVD as negative control exposure. RESULTS: Compared with offspring of mothers without CVD, offspring of mothers with CVD had 1.15-fold higher aHRs of ADHD [95% confidence interval (CI): 1.10-1.20] and ASD (95% CI 1.07-1.22). No association was found between maternal CVD and ID. Stratification by maternal CVD subtypes showed increased hazards of ADHD for maternal heart failure (HR 1.31, 95% CI 1.02-1.61), cerebrovascular disease (HR 1.20, 95% CI 1.08-1.32), congenital heart disease (HR 1.18, 95% CI 1.08-1.27), arrhythmia (HR 1.13, 95% CI 1.08-1.19) and valvular heart disease (HR 1.12, 95% CI 1.00-1.24). Increased hazards of ASD were observed for maternal cerebrovascular disease (HR 1.25, 95% CI 1.04-1.46), congenital heart disease (HR 1.17, 95% CI 1.01-1.33) and arrythmia (HR 1.12, 95% CI 1.01-1.21). Paternal CVD did not show associations with ADHD, ASD or ID, except for cerebrovascular disease which showed associations with ADHD and ASD. CONCLUSIONS: In this large cohort study, pre-existing maternal CVD was associated with increased risk of ADHD and ASD in offspring.

In search of environmental risk factors for obsessive-compulsive disorder: Study protocol for the OCDTWIN project.

Background The causes of obsessive-compulsive disorder (OCD) remain unknown. Gene-searching efforts are well underway, but the identification of environmental risk factors is at least as important and should be a priority because some of them may be amenable to prevention or early intervention strategies. Genetically informative studies, particularly those employing the discordant monozygotic (MZ) twin design, are ideally suited to study environmental risk factors. This protocol paper describes the study rationale, aims, and methods of OCDTWIN, an open cohort of MZ twin pairs who are discordant for the diagnosis of OCD. Methods OCDTWIN has two broad aims. In Aim 1, we are recruiting MZ twin pairs from across Sweden, conducting thorough clinical assessments, and building a biobank of biological specimens, including blood, saliva, urine, stool, hair, nails, and multimodal brain imaging. A wealth of early life exposures (e.g., perinatal variables, health-related information, psychosocial stressors) are available through linkage with the nationwide registers and the Swedish Twin Registry. Blood spots stored in the Swedish phenylketonuria (PKU) biobank will be available to extract DNA, proteins, and metabolites, providing an invaluable source of biomaterial taken at birth. In Aim 2, we will perform within-pair comparisons of discordant MZ twins, which will allow us to isolate unique environmental risk factors that are in the causal pathway to OCD, while strictly controlling for genetic and early shared environmental influences. To date (May 2023), 43 pairs of twins (21 discordant for OCD) have been recruited. Discussion OCDTWIN hopes to generate unique insights into environmental risk factors that are in the causal pathway to OCD, some of which have the potential of being actionable targets.

Association of anxiety or depression with risk of recurrent cardiovascular events and death after myocardial infarction: A nationwide registry study.

BACKGROUND: Depression and anxiety are risk factors for patients with myocardial infarction (MI). However, the association of a previous psychiatric diagnosis of anxiety or depression, or only such self-reported symptoms, with cardiovascular outcomes and mortality post-MI has not been previously examined in the same nationwide cohort. METHODS: We linked demographic, socioeconomic and clinical data from four nationwide Swedish registries for patients enrolled in cardiac rehabilitation (CR) after first-time MI (2006-2015, N = 45,096). After multiple imputation, we applied Cox regression to estimate the post-MI outcome risk for patients with a previous psychiatric diagnosis of anxiety/depression (Diagnosis), patients with no formal diagnosis but self-reported symptoms of anxiety/depression (Symptoms), versus patients with neither Diagnosis nor Symptoms (Reference). RESULTS: During one-year follow-up, fully adjusted models showed that patients with Diagnosis had a higher risk (hazard ratio [95%CI]) of all-cause mortality (1.86 [1.36, 2.53]), reinfarction (1.14 [1.06, 1.22]), their composite (1.15 [1.07, 1.23]), and an extended cardiovascular composite (1.19 [1.12, 1.26]), versus Reference, even though 77% reported no symptoms at the time of MI. In patients with Symptoms, estimates were also elevated yet somewhat attenuated compared to Reference. Findings were overall robust across multiple sensitivity analyses. CONCLUSIONS: Both a previous diagnosis, and present self-reported symptoms of anxiety or depression are associated with an increased risk of death and recurrent cardiovascular events in adults with first-time MI. Only screening for present symptoms is inadequate for assessing this excessive risk. Assessment of both psychiatric history and self-reported symptoms seems warranted for these patients.

Association and Familial Coaggregation of Idiopathic Dystonia With Psychiatric Outcomes.

BACKGROUND: Psychiatric comorbidities are common and major determinants of quality of life in idiopathic dystonia. Their prevalence estimates from service-based studies are heterogeneous. OBJECTIVE: We explored the association between idiopathic dystonia and depressive disorders, anxiety disorders, suicide attempts, and death by suicide using Swedish population-based registers. METHODS: Diagnoses of idiopathic dystonia and psychiatric outcomes from inpatient and outpatient specialist services (1997-2013) were collected from the National Patient Register and the Cause of Death Register. Familial associations were explored using the Multi-Generation Register. Adjusted logistic regression analyses measured associations with psychiatric disorders in individuals with dystonia compared with general population individuals and their unaffected siblings, as well as in full siblings of individuals with dystonia compared with full siblings of unaffected individuals. RESULTS: Individuals with dystonia were more likely than those without to have a diagnosis of depressive disorder (adjusted odds ratio = 2.00, 95% confidence interval: 1.77-2.26), anxiety disorder (adjusted odds ratio = 2.13, 95% confidence interval: 1.90-2.39), and suicide attempts/death by suicide combined (adjusted odds ratio = 1.80, 95% confidence interval: 1.50-2.17), with odds higher in most idiopathic dystonia forms. In the full sibling comparison, estimates followed the same pattern, with overall attenuated magnitude. Full siblings of individuals with dystonia had higher likelihood of depressive or anxiety disorders and suicide attempts/death by suicide combined compared with siblings of individuals without dystonia. CONCLUSIONS: Different forms of idiopathic dystonia confirm its association with increased risk for depressive and anxiety disorders and suicide attempts. Familial coaggregation of dystonia and these psychiatric comorbidities supports shared genetic and extragenetic factors. © 2020 International Parkinson and Movement Disorder Society.

Changes in Dosing and Dose Timing of D-Cycloserine Explain Its Apparent Declining Efficacy for Augmenting Exposure Therapy for Anxiety-related Disorders: An Individual Participant-data Meta-analysis.

The apparent efficacy of d-cycloserine (DCS) for enhancing exposure treatment for anxiety disorders appears to have declined over the past 14 years. We examined whether variations in how DCS has been administered can account for this "declining effect". We also investigated the association between DCS administration characteristics and treatment outcome to find optimal dosing parameters. We conducted a secondary analysis of individual participant data obtained from 1047 participants in 21 studies testing the efficacy of DCS-augmented exposure treatments. Different outcome measures in different studies were harmonized to a 0-100 scale. Intent-to-treat analyses showed that, in participants randomized to DCS augmentation (n = 523), fewer DCS doses, later timing of DCS dose, and lower baseline severity appear to account for this decline effect. More DCS doses were related to better outcomes, but this advantage leveled-off at nine doses. Administering DCS more than 60 minutes before exposures was also related to better outcomes. These predictors were not significant in the placebo arm (n = 521). Results suggested that optimal DCS administration could increase pre-to-follow-up DCS effect size by 50%. In conclusion, the apparent declining effectiveness of DCS over time may be accounted for by how it has been administered. Optimal DCS administration may substantially improve outcomes. Registration: The analysis plan for this manuscript was registered on Open Science Framework (https://osf.io/c39p8/).