Depression, anxiety, obesity and substance use are heritable and often co-occur. However, the mechanisms underlying this co-occurrence are not fully understood. We estimated their familial ...aggregation and co-aggregation as well as heritabilities and genetic correlations to improve etiological understanding. Data came from the multi-generational population-based Lifelines Cohort Study (n = 162,439). Current depression and anxiety were determined using the MINI International Neuropsychiatric Interview. Smoking, alcohol and drug use were assessed by self-report questionnaires. Body mass index (BMI) and obesity were calculated by measured height and weight. Modified Cox proportional hazards models estimated recurrence risk ratios (λ
), and restricted maximum likelihood variance decomposition methods estimated heritabilities (h
) and genetic correlations (r
). All analyses were adjusted for age, age
, and sex. Depression, anxiety, obesity and substance use aggregated within families (λ
= 1.08-2.74) as well as between spouses (λ
= 1.11-6.60). All phenotypes were moderately heritable (from h
= 0.25 to h
= 0.53). Depression, anxiety, obesity and smoking showed positive familial co-aggregation. That is, each of these traits confers increased risk on the other ones within families, consistent with the positive genetic correlations between these phenotypes (r
= 0.16-0.94). The exception was obesity, which showed a negative co-aggregation with alcohol and drug use and vice versa, consistent with the negative genetic correlations of BMI with alcohol (r
= -0.14) and soft drug use (r
= -0.10). Patterns of cross-phenotype recurrence risk highlight the co-occurrence among depression, anxiety, obesity and substance use within families. Patterns of genetic overlap between these phenotypes provide clues to uncovering the mechanisms underlying familial co-aggregation.
Attention-deficit/hyperactivity disorder (ADHD) is associated with functional impairments in different areas of daily life. One such area is social functioning. The purpose of this paper is to ...critically review research on social dysfunctioning in children with ADHD. Children with ADHD often have conflicts with adults and peers, and suffer from unpopularity, rejection by peers, and a lack of friendships, in part as a consequence of their ADHD symptoms. Comorbid oppositional defiant or conduct disorder aggravates these impairments. In some cases the inadequate social behavior of children with ADHD may be phenomenologically and etiologically related to pervasive developmental disorders (PDD). However, the causes and consequences of PDD symptoms in ADHD are understudied. Also, the relative contributions of ADHD, on the one hand, and comorbid disorders, on the other, to the course of social impairments are unknown. Social dysfunctioning in children with ADHD appears to increase their risk of later psychopathology other than ADHD. Thus far effective treatment for social dysfunctioning is lacking. Future research should address the exact nature and long-term consequences of social dysfunctioning in children with ADHD, and focus on development of effective treatment strategies.
We propose to bring together the hitherto rather separate research fields of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), and argue that by contrasting and ...combining findings of the endophenotypes of ASD and ADHD new insights can be gained into the etiology and pathophysiology of these two disorders. Given the highly heritable nature of both disorders, studies of the genes explaining the shared origins of the two neurodevelopmental disorders seem particularly called for. Instead of the clinical diagnosis, using neurocognitive measures as (endo)phenotypes that index genetic liability appears a powerful tool in gene finding. We, therefore, extensively reviewed the literature and not only included research wherein ASD and ADHD were compared within a single study, but extended our search also to the separate lines of cognitive neuroscience research. We discuss which cognitive and brain measures will be useful in future genetic studies targeting pleiotropic genes for ASD and ADHD. By specifying the most promising endophenotypic measures we chart the future course for endophenotypic research in ASD and ADHD. We also discuss the various models that may explain the frequent co-occurrence of ASD and ADHD.
In several languages, including English and Dutch, children’s acquisition of the interpretation of object pronouns (e.g.,
him
) is delayed compared to that of reflexives (e.g.,
himself
). Various ...syntactic and pragmatic explanations have been proposed to account for this delay in children’s acquisition of pronoun interpretation. This study aims to provide more insight into this delay by investigating potential cognitive mechanisms underlying this delay. Dutch-speaking children between 6 and 12 years old with autism spectrum disorder (ASD;
n
= 47), attention-deficit/hyperactivity disorder (ADHD;
n
= 36) or typical development (TD;
n
= 38) were tested on their interpretation and production of object pronouns and reflexives and on theory of mind, working memory, and response inhibition. It was found that all three groups of children had difficulty with pronoun interpretation and that their performance on pronoun interpretation was associated with theory of mind and inhibition. These findings support an explanation of object pronoun interpretation in terms of perspective taking, according to which listeners need to consider the speaker’s perspective in order to block coreference between the object pronoun and the subject of the same sentence. Unlike what is predicted by alternative theoretical accounts, performance on pronoun interpretation was not associated with working memory, and the children made virtually no errors in their production of object pronouns. As the difficulties with pronoun interpretation were similar for children with ASD, children with ADHD and typically developing children, this suggests that certain types of perspective taking are unaffected in children with ASD and ADHD.
One neurodevelopmental theory hypothesizes remission of attention-deficit/hyperactivity disorder (ADHD) to result from improved prefrontal top-down control, while ADHD, independent of the current ...diagnosis, is characterized by stable non-cortical deficits (Halperin & Schulz, 2006). We tested this theory using resting state functional MRI (fMRI) data in a large sample of adolescents with remitting ADHD, persistent ADHD, and healthy controls.
Participants in this follow-up study were 100 healthy controls and 129 adolescents with ADHD combined type at baseline (mean age at baseline 11.8 years; at follow-up 17.5 years). Diagnostic information was collected twice and augmented with magnetic resonance imaging (MRI) scanning at follow-up. We used resting state functional connectivity (RSFC) of the executive control network to investigate whether improved prefrontal top-down control was related to a developmental decrease in ADHD symptoms. In addition, we tested whether non-cortical RSFC, i.e., cerebellar and striatal RSFC, was aberrant in persistent and/or remittent ADHD compared to controls.
Higher connectivity within frontal regions (anterior cingulate cortex) of the executive control network was related to decreases in ADHD symptoms. This association was driven by change in hyperactive/impulsive symptoms and not by change in inattention. Participants with remitting ADHD showed stronger RSFC than controls within this network, while persistent ADHD cases exhibited RSFC strengths intermediate to remittent ADHD cases and controls. Cerebellar and subcortical RSFC did not differ between participants with ADHD and controls.
In line with the neurodevelopmental theory, symptom recovery in ADHD was related to stronger integration of prefrontal regions in the executive control network. The pattern of RSFC strength across remittent ADHD, persistent ADHD, and healthy controls potentially reflects the presence of compensatory neural mechanisms that aid symptomatic remission.
Although a genetic basis of depression has been well established in twin studies, identification of genome-wide significant loci has been difficult. We hypothesized that bivariate analyses of ...findings from a meta-analysis of genome-wide association studies (meta-GWASs) of the broad depression phenotype with those from meta-GWASs of self-reported and recurrent major depressive disorder (MDD), bipolar disorder and schizophrenia would enhance statistical power to identify novel genetic loci for depression. LD score regression analyses were first used to estimate the genetic correlations of broad depression with self-reported MDD, recurrent MDD, bipolar disorder and schizophrenia. Then, we performed four bivariate GWAS analyses. The genetic correlations (r
± SE) of broad depression with self-reported MDD, recurrent MDD, bipolar disorder and schizophrenia were 0.79 ± 0.07, 0.24 ± 0.08, 0.53 ± 0.09 and 0.57 ± 0.05, respectively. From a total of 20 independent genome-wide significant loci, 13 loci replicated of which 8 were novel for depression. These were MUC21 for the broad depression phenotype with self-reported MDD and ZNF804A, MIR3143, PSORS1C2, STK19, SPATA31D1, RTN1 and TCF4 for the broad depression phenotype with schizophrenia. Post-GWAS functional analyses of these loci revealed their potential biological involvement in psychiatric disorders. Our results emphasize the genetic similarities among different psychiatric disorders and indicate that cross-disorder analyses may be the best way forward to accelerate gene finding for depression, or psychiatric disorders in general.
•Emotion dysregulation predicts change in ADHD severity.•Nodal efficiency in emotion-related brain networks impacts change in ADHD severity.•Strongest link between change in ADHD severity and nodal ...efficiency in OFC.
The course of attention deficit hyperactivity disorder (ADHD) from adolescence into adulthood shows large variations between individuals; nonetheless determinants of interindividual differences in the course are not well understood. A frequent problem in ADHD, associated with worse outcomes, is emotion dysregulation. We investigated whether emotion dysregulation and integration of emotion-related functional brain networks affect interindividual differences in ADHD severity change. ADHD severity and resting state neuroimaging data were measured in ADHD and unaffected individuals at two points during adolescence and young adulthood. Bivariate latent change score models were applied to investigate whether emotion dysregulation and network integration affect ADHD severity changes. Emotion dysregulation was gauged from questionnaire subscales for conduct problems, emotional problems and emotional lability. Better emotion regulation was associated with a better course of ADHD (104 participants, 44 females, age range: 12–27). Using graph analysis, we determined network integration of emotion-related functional brain networks. Network integration was measured by nodal efficiency, i.e., the average inverse path distance from one node to all other nodes. A pattern of low nodal efficiency of cortical regions associated with emotion processing and high nodal efficiency in subcortical areas and cortical areas involved in implicit emotion regulation predicted a better ADHD course. Larger nodal efficiency of the right orbitofrontal cortex was related to a better course of ADHD (99 participants, 42 females, age range: 10–29). We demonstrated that neural and behavioral covariates associated with emotion regulation affect the course of ADHD severity throughout adolescence and early adulthood beyond baseline effects of ADHD severity.
ADHD is a highly prevalent disease in childhood which often persists into adulthood, then co-occurring with common adult conditions. Especially for adult ADHD, little is known about the costs of ADHD ...and the additional costs of comorbid conditions.
To determine medical costs of ADHD and costs of comorbidities (mood, anxiety and substance use disorders, obesity), including their co-occurrence rates, stratified by age and gender.
Claims data from a German Statutory Health Insurance database with approximately four million member-records per year were analysed. A total of 25,300 prevalent ADHD patients were identified by means of an ICD-10 GM diagnosis of ADHD. A 1:1 age and gender adjusted reference group without ADHD diagnosis was randomly selected. Total health claims and health care costs related to ADHD were analysed, in addition to more targeted analyses of the occurrence and costs of pre-defined common comorbidities of, in particular, adult ADHD (SUD, mood and anxiety disorders, obesity). Outcomes were mean costs per patient and occurrence rates of comorbid conditions. Surplus costs of a comorbid condition in persons with ADHD relative to costs of this condition in persons without ADHD were calculated. Subgroup analyses were conducted based on age (0-12 years, 13-17 years, 18-30years, 30+ years) and gender.
Patients with ADHD were €1500 more expensive annually than individuals without ADHD (p < 0.001). Main cost drivers were inpatient care, psychiatrists and psychotherapists. Mood, anxiety, substance use disorders and obesity were significantly more frequent in ADHD patients and additional costs resulting from the comorbid conditions amounted up to €2800. Costs were slightly higher in women than men and increased with age for both genders. In young adults (18-30 years) health care costs dropped notably, especially costs for the medical treatment of ADHD with stimulants and costs for psychiatrists, before rising again in the group of patients over 30 years who had higher comorbidity rates.
Medical costs for ADHD are substantial, in part through frequently occurring comorbid conditions, and particularly in adulthood, and are likely to further accelerate in the coming years. A gap of care was found, starting with the transition age group of patients over 17 years, as indicated by reduced costs per person during young adulthood, as well as an overall strong drop in administrative prevalence. In the future, approaches to improve the situation of care and reduce costs at the same time, i.e. through managed care programmes, should be implemented and benefit from detailed knowledge on age and gender-specific cost-drivers.
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