Attention-deficit/hyperactivity disorder (ADHD) is often comorbid with other psychiatric conditions in adults. Yet, less is known about its relationship with common metabolic disorders and how sex ...and ageing affect the overall comorbidity patterns of adult ADHD. We aimed to examine associations of adult ADHD with several common psychiatric and metabolic conditions. Through the linkage of multiple Swedish national registers, 5,551,807 adults aged 18 to 64 years and living in Sweden on December 31, 2013 were identified and assessed for clinical diagnoses of adult ADHD, substance use disorder (SUD), depression, bipolar disorder, anxiety, type 2 diabetes mellitus (T2DM), and hypertension. Logistic regression models and regression standardization method were employed to obtain estimates of prevalence, prevalence difference (PD), and prevalence ratio (PR). All comorbid conditions of interest were more prevalent in adults with ADHD (3.90% to 44.65%) than in those without (0.72% to 4.89%), with the estimated PRs being over nine for psychiatric conditions (p < 0.001) and around two for metabolic conditions (p < 0.001). Sex differences in the prevalence of comorbidities were observed among adults with ADHD. Effect modification by sex was detected on the additive scale and/or multiplicative scale for the associations of adult ADHD with all comorbidities. ADHD remained associated with all comorbidities in older adults aged 50 to 64 when all conditions were assessed from age 50 onwards. The comorbidity patterns of adult ADHD underscore the severity and clinical complexity of the disorder. Clinicians should remain vigilant for a wide range of psychiatric and metabolic problems in ADHD affected adults of all ages and both sexes.
•Low socioeconomic status was consistently associated with worse executive functioning, episodic memory and verbal fluency.•Low socioeconomic status was associated with worse executive functioning ...via C-reactive protein, stress, and sedentary behaviors.•Sedentary behavior consistently linked low socioeconomic status with worse executive functioning, episodic memory and verbal fluency.
Higher C-reactive protein (CRP) is associated with cognitive difficulties. The nature of this association remains unclear given that multiple other variables are linked with both CRP and cognitive difficulties, which may confound the association. The goal of the current study is to determine whether low socioeconomic status (SES) is associated with worse cognitive functioning via higher CRP and whether this association is independent of known associations with other health, stress and lifestyle factors (e.g., depression, physical activity, body mass). Assessments in a longitudinal study of 1,029 Dutch adolescents were based on a combination of self-report and parent-report questionnaires, diagnostic assessment, behavioral testing, and blood assay. We estimated latent variables for cognitive functioning (executive functioning, verbal fluency, episodic memory) and used structural equation analysis to test whether SES (wave 1: 11.08 years (SD=0.55); 55% female was associated with worse cognitive outcomes (wave 4: aged 18.97 years; SD=0.55) via increased CRP, depression, stress, body mass, substance use or physical inactivity (wave 3: aged 16.17 years; SD=0.61). Low SES was associated with worse cognitive functioning via increased CRP. Additionally, low SES was associated with (i) worse executive functioning via higher body mass, higher levels of sedentary behavior, and higher stress, (ii) worse verbal fluency via higher levels of sedentary behavior and (iii) worse episodic memory via sedentary behaviors, body mass, and substance use. These results confirm the link between SES, CRP and cognitive functioning and additionally identify four modifiable lifestyle factors that may be implicated in the link between low SES and worse performance on tests of cognitive functioning.
The recent successful genome-wide association studies (GWASs) for depression have yielded more than 80 replicated loci and brought back the excitement that had evaporated during the years of negative ...GWAS findings. The identified loci provide anchors to explore their relevance for depression, but this comes with new challenges. Using the watershed model of genotype-phenotype relationships as a conceptual aid and recent genetic findings on other complex phenotypes, we discuss why it took so long and identify seven future challenges. The biggest challenge involves the identification of causal mechanisms since GWAS associations merely flag genomic regions without a direct link to underlying biological function. Furthermore, the genetic association with the index phenotype may also be part of a more extensive causal pathway (e.g., from variant to comorbid condition) or be due to indirect influences via intermediate traits located in the causal pathways to the final outcome. This challenge is highly relevant for depression because even its narrow definition of major depressive disorder captures a heterogeneous set of phenotypes which are often measured by even more broadly defined operational definitions consisting of a few questions (minimal phenotyping). Here, Mendelian randomization and future discovery of additional genetic variants for depression and related phenotypes will be of great help. In addition, reduction of phenotypic heterogeneity may also be worthwhile. Other challenges include detecting rare variants, determining the genetic architecture of depression, closing the "heritability gap", and realizing the potential for personalized treatment. Along the way, we identify pertinent open questions that, when addressed, will advance the field.
Introduction
Attention deficit hyperactivity disorder (ADHD) is associated with risk‐taking behavior, leading to accidents and unintentional injuries (summarized here as incidents). Main aim of this ...study is to determine if men and women with and without ADHD differ in the risk of mild (treated outpatient) and severe (treated inpatient) incidents across the adult lifespan (age groups: 18–29; 30–59, and ≥60 years). Secondary aim: investigate the role of comorbid mental disorders and drugs for the treatment of these comorbidities, and ADHD‐medication.
Methods
Using anonymized German claims data (N = 4,575,027), adults with ADHD diagnosis during 2016–2019 (N = 17,041) were compared with a 1:4 age and sex‐matched group without ADHD diagnosis. Regression analyses statistically tested group differences.
Results
Incidents occur in a U‐shaped form across the adult lifespan. Individuals with ADHD show the same pattern but at a substantially increased risk of both mild and severe incidents throughout the lifespan. Women without ADHD are at lower risk in young adulthood than men but at higher risk in older adulthood. Women with ADHD show the same pattern for severe incidents, but for mild incidents they have the highest risk throughout the lifespan. Co‐occurring anxiety disorder and the use of psycholeptics and ADHD‐medication decreased the incident risk.
Conclusion
We extend available knowledge which has hitherto focused on young adult males and traffic accidents. ADHD is associated with increased incidents across the adult lifespan, with distinct patterns regarding age, sex, and incident severity. An accurate diagnosis of ADHD in adulthood provides the first step towards prevention of accidents and unintentional injuries.
Comorbidity between depressive and anxiety disorders is common. A hypothesis of the network perspective on psychopathology is that comorbidity arises due to the interplay of symptoms shared by both ...disorders, with overlapping symptoms acting as so-called bridges, funneling symptom activation between symptom clusters of each disorder. This study investigated this hypothesis by testing whether (i) two overlapping mental states "worrying" and "feeling irritated" functioned as bridges in dynamic mental state networks of individuals with both depression and anxiety as compared to individuals with either disorder alone, and (ii) overlapping or non-overlapping mental states functioned as stronger bridges.
Data come from the Netherlands Study of Depression and Anxiety (NESDA). A total of 143 participants met criteria for comorbid depression and anxiety (65%), 40 participants for depression-only (18.2%), and 37 for anxiety-only (16.8%) during any NESDA wave. Participants completed momentary assessments of symptoms (i.e., mental states) of depression and anxiety, five times a day, for 2 weeks (14,185 assessments). First, dynamics between mental states were modeled with a multilevel vector autoregressive model, using Bayesian estimation. Summed average lagged indirect effects through the hypothesized bridge mental states were compared between groups. Second, we evaluated the role of all mental states as potential bridge mental states.
While the summed indirect effect for the bridge mental state "worrying" was larger in the comorbid group compared to the single disorder groups, differences between groups were not statistically significant. The difference between groups became more pronounced when only examining individuals with recent diagnoses (< 6 months). However, the credible intervals of the difference scores remained wide. In the second analysis, a non-overlapping item ("feeling down") acted as the strongest bridge mental state in both the comorbid and anxiety-only groups.
This study empirically examined a prominent network-approach hypothesis for the first time using longitudinal data. No support was found for overlapping mental states "worrying" and "feeling irritable" functioning as bridge mental states in individuals vulnerable for comorbid depression and anxiety. Potentially, bridge mental state activity can only be observed during acute symptomatology. If so, these may present as interesting targets in treatment, but not prevention. This requires further investigation.
Objective
A thorough and comprehensive knowledge base on the extent of comorbidity of attention‐deficit/hyperactivity disorder (ADHD) and somatic conditions is needed.
Method
We compared the ...prevalence of a wide range of somatic conditions in individuals with and without ADHD and described sex and lifecourse differences. Individuals with an ADHD diagnosis (N = 87,394) and age and sex‐matched individuals without an ADHD diagnosis were identified from a large health claims dataset representative of the general German population, including both primary and specialized care (N = 4.874,754). Results were provided for the full sample as well as stratified for sex and age (<12 years, 13–17 years, 18–29 years, 30–59 years, ≥60 years).
Results
The results showed that ADHD is associated with a wide variety of somatic conditions across the entire lifecourse. Specifically neurological disorders such as Parkison's disease (odds ratio OR: 5.21) and dementia (OR: 2.23), sleep‐related disorders (OR: 2.38) and autoimmune disorders affecting the musculoskeletal, digestive, and endocrine system (fibromyalgia OR: 3.33; lupus OR: 2.17) are strongly and significantly associated with ADHD. Additionally, ADHD is associated with higher occurrence of common acute diseases typically treated by the general practitioner, hinting at an overall general lower health status. Sex differences in somatic comorbidity were not prominent. Age differences, in contrast, stood out: in particular endocrine, cardiovascular, and neurological disorders had an early onset in individuals with compared to individuals without ADHD.
Conclusion
This research underlines the high burden of disease due to somatic conditions among individuals with ADHD. The findings indicate the need for preventive measures to reduce comorbidity.
Autism spectrum disorder (ASD) and Attention-deficit/hyperactivity disorder (ADHD) are often comorbid. The purpose of this study is to explore the relationships between ASD and ADHD symptoms by ...applying causal modeling. We used a large phenotypic data set of 417 children with ASD and/or ADHD, 562 affected and unaffected siblings, and 414 controls, to infer a structural equation model using a causal discovery algorithm. Three distinct pathways between ASD and ADHD were identified: (1) from impulsivity to difficulties with understanding social information, (2) from hyperactivity to stereotypic, repetitive behavior, (3) a pairwise pathway between inattention, difficulties with understanding social information, and verbal IQ. These findings may inform future studies on understanding the pathophysiological mechanisms behind the overlap between ASD and ADHD.
It is unclear whether and to what extent stress-related exposures moderate the effects of polygenic risk scores (PRSs) on depression and anxiety. We aimed to examine such moderation effects for a ...variety of stress-related exposures on depression and anxiety. We included 41,810 participants with both genome-wide genetic data and measurements of depression and anxiety in the Lifelines Cohort Study. Current depression and anxiety were measured by the MINI International Neuropsychiatric Interview. Stress-related exposures included long-term difficulties, stressful life events, reduced social support, childhood trauma, and loneliness, which were measured by self-report questionnaires. PRSs were calculated based on recent large genome-wide association studies for depression and anxiety. We used linear mixed models adjusting for family relationships to estimate the interactions between PRSs and stress-related exposures. Nine of the ten investigated interactions between the five stress-related exposures and the two PRSs for depression and anxiety were significant (Ps < 0.001). Reduced social support, and higher exposure to long-term difficulties, stressful life events, and loneliness amplified the genetic effects on both depression and anxiety. As for childhood trauma exposure, its interaction with the PRS was significant for depression (P = 1.78 × 10
) but not for anxiety (P = 0.32). Higher levels of stress-related exposures significantly amplify the effects of genetic susceptibility on depression and anxiety. With a large sample size and a comprehensive set of stress-related exposures, our study provides powerful evidence on the presence of polygenic risk-by-environment interactions in relation to depression and anxiety.
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