Publications by authors named "Catharina A Hartman"

243 Publications

Genetic association study of childhood aggression across raters, instruments, and age.

Transl Psychiatry 2021 07 30;11(1):413. Epub 2021 Jul 30.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGG) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGG. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (r) among rater-specific assessment of AGG ranged from r = 0.46 between self- and teacher-assessment to r = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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http://dx.doi.org/10.1038/s41398-021-01480-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324785PMC
July 2021

Familial resemblance in mental health symptoms, social and cognitive vulnerability, and personality: A study of patients with depressive and anxiety disorders and their siblings.

J Affect Disord 2021 Nov 1;294:420-429. Epub 2021 Jul 1.

Amsterdam UMC, Vrije Universiteit, Psychiatry, Amsterdam Public Health research institute, Amsterdam, The Netherlands.

Background: Investigating siblings of probands with affective disorders enables the identification of psychopathology-related risk features. Leveraging data from an older adult sample, as compared to most previous sibling studies, enabled us to study more definitive clinical profiling across the lifespan. We examined prevalence of depressive/anxiety disorders in siblings, proband-sibling resemblance in psychopathology-related features, and whether unaffected siblings showed higher levels of these features than healthy controls.

Methods: The sample (N=929; M=50.6) consisted of 256 probands with lifetime depressive and/or anxiety disorders, their 380 siblings, and 293 healthy controls without affected relatives. Fifteen psychopathology-related features were investigated across four domains: mental health symptoms, social vulnerabilities, cognitive vulnerabilities, and personality.

Results: Lifetime disorders were present in 50.3% of siblings. Prevalence was 2-3 times higher than Dutch population frequencies. We found small to medium probandsibling resemblance across psychopathology-related features (ρ=0.10-0.32). Unaffected siblings reported poorer interpersonal functioning and more negative life events, childhood trauma, and rumination than healthy controls.

Limitations: Due to the cross-sectional study design, the directionality of effects cannot be determined. No inferences can be made about potential differences in familial resemblance in psychopathology-related features between high- and low-risk families.

Conclusions: Siblings of probands with affective disorders are at higher risk for depressive/anxiety disorders. Even when unaffected, still show higher psychosocial vulnerability than healthy controls. Nevertheless, the only modest proband-sibling resemblance across psychopathology-related features suggests that individual mechanisms differentiate clinical trajectories across the lifespan. Identification of these mechanisms is crucial to improve resilience in subjects with familial risk.
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http://dx.doi.org/10.1016/j.jad.2021.06.072DOI Listing
November 2021

Functional network topology of the right insula affects emotion dysregulation in hyperactive-impulsive attention-deficit/hyperactivity disorder.

Sci Rep 2021 Jul 22;11(1):15045. Epub 2021 Jul 22.

Biological Psychology, Department of Psychology, School of Medicine and Health Sciences, Carl-von-Ossietzky Universität Oldenburg, Postfach 2503, 26111, Oldenburg, Germany.

Emotion dysregulation is common in attention-deficit/hyperactivity disorder (ADHD). It is highly prevalent in young adult ADHD and related to reduced well-being and social impairments. Neuroimaging studies reported neural activity changes in ADHD in brain regions associated with emotion processing and regulation. It is however unknown whether deficits in emotion regulation relate to changes in functional brain network topology in these regions. We used a combination of graph analysis and structural equation modelling (SEM) to analyze resting-state functional connectivity in 147 well-characterized young adults with ADHD and age-matched healthy controls from the NeuroIMAGE database. Emotion dysregulation was gauged with four scales obtained from questionnaires and operationalized through a latent variable derived from SEM. Graph analysis was applied to resting-state data and network topology measures were entered into SEM models to identify brain regions whose local network integration and connectedness differed between subjects and was associated with emotion dysregulation. The latent variable of emotion dysregulation was characterized by scales gauging emotional distress, emotional symptoms, conduct symptoms, and emotional lability. In individuals with ADHD characterized by prominent hyperactivity-impulsivity, the latent emotion dysregulation variable was related to an increased clustering and local efficiency of the right insula. Thus, in the presence of hyperactivity-impulsivity, clustered network formation of the right insula may underpin emotion dysregulation in young adult ADHD.
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http://dx.doi.org/10.1038/s41598-021-94426-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298497PMC
July 2021

Parental rejection in early adolescence predicts a persistent ADHD symptom trajectory across adolescence.

Eur Child Adolesc Psychiatry 2021 Jul 17. Epub 2021 Jul 17.

Department of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Lübeckweg 2, NL-9723 HE, Groningen, The Netherlands.

Despite a general decrease of attention-deficit/hyperactivity disorder (ADHD) symptoms during adolescence, these may persist in some individuals but not in others. Prior cross-sectional studies have shown that parenting style and their interaction with candidate genes are associated with ADHD symptoms. However, there is a lack of longitudinal research examining the independent and interactive effects of parenting and plasticity genes in predicting the course of attention-deficit/hyperactivity disorder (ADHD) symptoms across adolescence. Here, we investigated how children perceived their parents' parenting style (i.e., rejection, overprotection, and emotional warmth) at the age of 11, and their interaction with DRD4, MAOA, and 5-HTTLPR genotypes on parent-reported ADHD symptoms at three time points (mean ages 11.1, 13.4, and 16.2 years) in 1730 adolescents from the TRacking Adolescents' Individual Lives Survey (TRAILS). Growth Mixture Modeling in Mplus identified four ADHD symptom trajectories: low, moderate stable, high decreasing, and high persistent. Perceived parental rejection predicted class membership in the high persistent trajectory compared to the other classes (p < 0.001, odds ratios between 2.14 and 3.74). Gene-environment interactions were not significantly related to class membership. Our results indicate a role of perceived parental rejection in the persistence of ADHD symptoms. Perceived parental rejection should, therefore, be taken into consideration during prevention and treatment of ADHD in young adolescents.
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http://dx.doi.org/10.1007/s00787-021-01844-0DOI Listing
July 2021

Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden: a genetically informed register study.

Lancet Psychiatry 2021 09 6;8(9):774-783. Epub 2021 Jul 6.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden.

Background: Emerging evidence suggests increased risk of several physical health conditions in people with ADHD. Only a few physical conditions have been thoroughly studied in relation to ADHD, and there is little knowledge on associations in older adults in particular. We aimed to investigate the phenotypic and aetiological associations between ADHD and a wide range of physical health conditions across adulthood.

Methods: We did a register study in Sweden and identified full-sibling and maternal half-sibling pairs born between Jan 1, 1932, and Dec 31, 1995, through the Population and Multi-Generation Registers. We excluded individuals who died or emigrated before Jan 1, 2005, and included full-siblings who were not twins and did not have half-siblings. ICD diagnoses were obtained from the National Patient Register. We extracted ICD diagnoses for physical conditions, when participants were aged 18 years or older, from inpatient (recorded 1973-2013) and outpatient (recorded 2001-13) services. Diagnoses were regarded as lifetime presence or absence. Logistic regression models were used to estimate the associations between ADHD (exposure) and 35 physical conditions (outcomes) in individuals and across sibling pairs. Quantitative genetic modelling was used to estimate the extent to which genetic and environmental factors accounted for the associations with ADHD.

Findings: 4 789 799 individuals were identified (2 449 146 [51%] men and 2 340 653 [49%] women), who formed 4 288 451 unique sibling pairs (3 819 207 full-sibling pairs and 469 244 maternal half-sibling pairs) and 1 841 303 family clusters (siblings, parents, cousins, spouses). The mean age at end of follow-up was 47 years (range 18-81; mean birth year 1966); ethnicity data were not available. Adults with ADHD had increased risk for most physical conditions (34 [97%] of 35) compared with adults without ADHD; the strongest associations were with nervous system disorders (eg, sleep disorders, epilepsy, dementia; odds ratios [ORs] 1·50-4·62) and respiratory diseases (eg, asthma, chronic obstructive pulmonary disease; ORs 2·42-3·24). Sex-stratified analyses showed similar patterns of results in men and women. Stronger cross-disorder associations were found between full-siblings than between half-siblings for nervous system, respiratory, musculoskeletal, and metabolic diseases (p<0·007). Quantitative genetic modelling showed that these associations were largely explained by shared genetic factors (60-69% of correlations), except for associations with nervous system disorders, which were mainly explained by non-shared environmental factors.

Interpretation: This mapping of aetiological sources of cross-disorder overlap can guide future research aiming to identify specific mechanisms contributing to risk of physical conditions in people with ADHD, which could ultimately inform preventive and lifestyle intervention efforts. Our findings highlight the importance of assessing the presence of physical conditions in patients with ADHD.

Funding: Swedish Research Council; Swedish Brain Foundation; Swedish Research Council for Health, Working Life, and Welfare; Stockholm County Council; StratNeuro; EU Horizon 2020 research and innovation programme; National Institute of Mental Health.
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http://dx.doi.org/10.1016/S2215-0366(21)00171-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376653PMC
September 2021

Children's Pronoun Interpretation Problems Are Related to Theory of Mind and Inhibition, But Not Working Memory.

Front Psychol 2021 4;12:610401. Epub 2021 Jun 4.

Center for Language and Cognition Groningen, University of Groningen, Groningen, Netherlands.

In several languages, including English and Dutch, children's acquisition of the interpretation of object pronouns (e.g., ) is delayed compared to that of reflexives (e.g., ). 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; = 47), attention-deficit/hyperactivity disorder (ADHD; = 36) or typical development (TD; = 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.
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http://dx.doi.org/10.3389/fpsyg.2021.610401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212991PMC
June 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Investigating whether a combination of higher CRP and depression is differentially associated with worse executive functioning in a cohort of 43,896 adults.

Brain Behav Immun 2021 08 27;96:127-134. Epub 2021 May 27.

Faculty of Medical Sciences, University of Groningen, the Netherlands. Electronic address:

Many depressed individuals experience difficulties in executive functioning that contribute substantially to functional impairment. It is unknown whether a subtype of depression characterized by chronic inflammation is differentially associated with worse executive functioning. This study examined whether the combination of depression and higher C reactive protein (CRP) is differentially associated with worse executive functioning and whether this association is stronger in older adults. This cross-sectional study analyzed data collected from a population-representative sample of 43,896 adults aged 44.13 years (SD = 13.52) who participated in the baseline assessment of the Lifelines cohort study. Multivariate regression models tested whether depressed individuals (established via structured interview) exhibiting higher levels of inflammation (indexed via high-sensitivity CRP assay following an overnight fast) performed worse on a behavioral test of executive functioning. Depression (B = -3.66, 95% CI: -4.82, -2.49, p < .001) and higher log-transformed CRP (B = -0.67, 95% CI: -0.87,-0.47, p < .001) were associated with worse executive functioning, after adjustment for age, sex, educational attainment, body mass index, smoking status, exposure to stressful life events and chronic stressors, sedentary behavior, and number of chronic medical conditions. Depressed individuals with higher log-transformed CRP exhibited differentially poorer executive functioning (B = -1.09, 95% CI: -2.07,-0.11, p < .001). This association did not differ based on age (B = 0.01, 95% CI: -0.08, 0.10, p = .82). Executive functioning is poorer in depressed individuals with higher CRP, even in early adulthood. Interventions that reduce inflammation may improve cognitive functioning in depression.
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http://dx.doi.org/10.1016/j.bbi.2021.05.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319077PMC
August 2021

Longitudinal Associations Between Symptoms of ADHD and BMI From Late Childhood to Early Adulthood.

Pediatrics 2021 Jun;147(6)

Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation, University Medical Center Groningen, University of Groningen, Groningen, Netherlands;

Background And Objectives: Attention-deficit/hyperactivity disorder (ADHD) and obesity are 2 frequent conditions that co-occur, which has implications for the management of both conditions. We hypothesized that ADHD symptoms predict BMI and vice versa from late childhood (10-12 years) up to early adulthood (20-22 years).

Methods: Participants were adolescents in the Netherlands ( = 2773, 52.5% male, mean age = 11 years at baseline, 5 waves up to mean age 22) from the Tracking Adolescents' Individual Lives Survey cohort. We examined bidirectional relationship between ADHD symptoms (hyperactivity/impulsivity and inattention) and BMI using the random intercept cross-lagged panel model. Time-varying covariates were pubertal status, stimulant use, depressive symptoms, and family functioning, and socioeconomic status was a time-invariant covariate.

Results: We found a time-invariant association of BMI with hyperactivity and impulsivity, but not with inattention, which was slightly stronger in female adolescents (female: = 0.102; male: = 0.086, < .05). No longitudinal direct effects were found between ADHD symptoms and BMI during this period.

Conclusions: Over the course of adolescence, the link between ADHD and BMI is stable and is predominantly with hyperactive and impulsive symptoms rather than inattention. There was no direct effect of ADHD symptoms on BMI increase nor of BMI on enhanced ADHD symptoms during this developmental period. The findings point to a shared genetic or familial background and/or potential causal effects established already earlier in childhood, thus suggesting that intervention and prevention programs targeting overweight and obesity in children with ADHD should be implemented in early childhood.
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http://dx.doi.org/10.1542/peds.2020-036657DOI Listing
June 2021

Maternal serotonin transporter genotype and offsprings' clinical and cognitive measures of ADHD and ASD.

Prog Neuropsychopharmacol Biol Psychiatry 2021 Aug 15;110:110354. Epub 2021 May 15.

Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Center, Kapittelweg 29, 6525 EN Nijmegen, the Netherlands; Karakter Child and Adolescent Psychiatry University Center, Reinier Postlaan 12, 6525 GC Nijmegen, the Netherlands. Electronic address:

Serotonin (5-HT) is an important factor for prenatal neurodevelopment whereby its neurotrophic actions can be regulated through maternal-fetal interactions. We explored if maternal 5-HTTLPR genotype is associated with clinical and cognitive measures of attention-deficit/hyperactivity disorder (ADHD) and comorbid autism spectrum disorder (ASD) in typically-developing and ADHD-diagnosed offspring, beyond classical inheritance and environmental- and comorbidity-mediators/confounders. Family-based variance decomposition analyses were performed incorporating 6-31 year-old offsprings' as well as parental genotypes of 462 ADHD and control families from the NeuroIMAGE cohort. Dependent measures were offsprings' ADHD symptom- and ASD trait-scores and cognitive measures including executive functioning (including response inhibition and cognitive flexibility), sustained attention, reward processing, motor control, and emotion recognition. Offsprings' stereotyped behavior was predicted by an interaction between maternal 5-HTTLPR genotype and offsprings' sex. Furthermore, offspring of mothers with low-expressing genotypes demonstrated larger reward-related reductions in reaction time. While specifically adult male offspring of these mothers reported a faster reversal learning with less errors, specifically young female offspring of these mothers were more accurate in identifying happy faces. Adult offspring from the mothers with low-expressing 5-HTTLPR genotypes were also slower in identifying happy faces. However, this association seemed to be mediated by offsprings' high anxiety levels. In sum, we found some support for a role of the maternal 5-HT system in modulating fetal brain development and behavior. Offsprings' cognitive measures might be more sensitive to small alterations within the maternal 5-HT system than their ADHD and ASD clinical phenotypes. Further studies are needed to specify the association between maternal genotype and risk for neurodevelopmental disorders.
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http://dx.doi.org/10.1016/j.pnpbp.2021.110354DOI Listing
August 2021

Characterizing the heterogeneous course of inattention and hyperactivity-impulsivity from childhood to young adulthood.

Eur Child Adolesc Psychiatry 2021 Apr 3. Epub 2021 Apr 3.

Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

To advance understanding of the heterogeneity in the course of ADHD, joint symptom trajectories of inattention and hyperactivity-impulsivity from childhood to young adulthood were modelled and associated with genetic, demographic, and clinical characteristics. Data were obtained from the NeuroIMAGE cohort which includes 485 individuals with ADHD, their 665 siblings, and 399 typically developing children. Trajectories were based on scores of the Conners Parent Rating Scale Revised and estimated over seven homogeneous age bins (from 5 to 28 years) using parallel process latent class growth analysis on data collected across 2-4 time points. Multilevel multinomial logistic regression was used to identify characteristics that differentiated between the derived classes. A seven-class solution revealed "severe combined stable" (4.8%), "severe combined decreasing" (13%), "severe inattentive stable" (4.8%), "moderate combined increasing" (7.5%), "moderate combined decreasing" (12.7%), "stable mild" (12.9%), and "stable low" (44.3%) classes. Polygenic risk for depression, ADHD diagnosis, ADHD medication use, IQ, comorbid symptom levels (foremost oppositional behaviour), and functional impairment levels differentiated classes with similar ADHD symptom levels in childhood but a diverging course thereafter. The course of ADHD is highly heterogeneous, with stable, decreasing, and increasing trajectories. Overall, severe symptom levels in childhood are associated with elevated-to-severe symptom levels in adolescence and young adulthood, despite substantial symptom reductions. Beyond symptom severity in childhood, genetic, demographic, and clinical characteristics distinguish the heterogeneous course.
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http://dx.doi.org/10.1007/s00787-021-01764-zDOI Listing
April 2021

Discrepancies of polygenic effects on symptom dimensions between adolescents and adults with ADHD.

Psychiatry Res Neuroimaging 2021 05 20;311:111282. Epub 2021 Mar 20.

Department of Psychology, Georgia State University, United States; Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology and Emory University, USA; Neuroscience Institute, Georgia State University, USA.

A significant proportion of individuals with attention-deficit/hyperactivity disorder (ADHD) show persistence into adulthood. The genetic and neural correlates of ADHD in adolescents versus adults remain poorly characterized. We investigated ADHD polygenic risk score (PRS) in relation to previously identified gray matter (GM) patterns, neurocognitive, and symptom findings in the same ADHD sample (462 adolescents & 422 adults from the NeuroIMAGE and IMpACT cohorts). Significant effects of ADHD PRS were found on hyperactivity and impulsivity symptoms in adolescents, hyperactivity symptom in adults, but not GM volume components. A distinct PRS effect between adolescents and adults on individual ADHD symptoms is suggested.
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http://dx.doi.org/10.1016/j.pscychresns.2021.111282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058322PMC
May 2021

Gray matter networks associated with attention and working memory deficit in ADHD across adolescence and adulthood.

Transl Psychiatry 2021 03 25;11(1):184. Epub 2021 Mar 25.

Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University Georgia Institute of Technology and Emory University, Atlanta, GA, USA.

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neuropsychiatric disorder and may persist into adulthood. Working memory and attention deficits have been reported to persist from childhood to adulthood. How neuronal underpinnings of deficits differ across adolescence and adulthood is not clear. In this study, we investigated gray matter of two cohorts, 486 adults and 508 adolescents, each including participants from ADHD and healthy controls families. Two cohorts both presented significant attention and working memory deficits in individuals with ADHD. Independent component analysis was applied to the gray matter of each cohort, separately, to extract cohort-inherent networks. Then, we identified gray matter networks associated with inattention or working memory in each cohort, and projected them onto the other cohort for comparison. Two components in the inferior, middle/superior frontal regions identified in adults and one component in the insula and inferior frontal region identified in adolescents were significantly associated with working memory in both cohorts. One component in bilateral cerebellar tonsil and culmen identified in adults and one component in left cerebellar region identified in adolescents were significantly associated with inattention in both cohorts. All these components presented a significant or nominal level of gray matter reduction for ADHD participants in adolescents, but only one showed nominal reduction in adults. Our findings suggest although the gray matter reduction of these regions may not be indicative of persistency of ADHD, their persistent associations with inattention or working memory indicate an important role of these regions in the mechanism of persistence or remission of the disorder.
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http://dx.doi.org/10.1038/s41398-021-01301-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994833PMC
March 2021

Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets.

J Child Psychol Psychiatry 2021 Mar 22. Epub 2021 Mar 22.

Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.

Objective: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.

Methods: We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.

Results: There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.

Conclusion: Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.
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http://dx.doi.org/10.1111/jcpp.13396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455726PMC
March 2021

The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder.

Neurosci Biobehav Rev 2021 09 4;128:789-818. Epub 2021 Feb 4.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Wuerzburg, Germany. Electronic address:

Background: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base.

Methods: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder.

Results: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents.

Conclusions: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.
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http://dx.doi.org/10.1016/j.neubiorev.2021.01.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328933PMC
September 2021

The important gain is that we are lumpers and splitters now; it is the splitting that needs our hard work.

World Psychiatry 2021 Feb;20(1):72-73

Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

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http://dx.doi.org/10.1002/wps.20816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801837PMC
February 2021

Prevention programmes for children of parents with a mood/anxiety disorder: Systematic review of existing programmes and meta-analysis of their efficacy.

Br J Clin Psychol 2021 Jun 6;60(2):212-251. Epub 2021 Jan 6.

Department of Psychiatry and Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.

Objectives: To systematically describe the characteristics and techniques of prevention programmes for children of parents with mood/anxiety disorders. In addition, recruitment approaches and difficulties were identified and a meta-analysis was conducted to examine the efficacy of these prevention programmes.

Methods: Randomized controlled trials assessing the efficacy of a prevention programme for children (6-25 years) of parents with mood and/or anxiety disorders were included. A systematic literature search was conducted in PubMed, PsychINFO, and CENTRAL from the earliest record to March 2019. In addition, programme manuals of identified prevention programmes were requested for a content analysis.

Results: Twenty-two articles containing eight unique prevention programmes involving 1,325 subjects were identified. Programmes varied in the number and types of techniques, but all provided psychoeducation. Results suggested that recruitment via clinicians was more successful than recruitment via health maintenance organization databases. In a meta-analysis, a significant risk difference was found in favour of prevention programmes on the risk of developing a depressive/anxiety disorder in offspring at short-term (9-18 months follow-up; RR = 0.37, 95% CI [0.21; 0.66]) and long-term follow-up (24 months or longer follow-up; RR = 0.71, 95% CI [0.57; 0.87] and on symptom levels in offspring at post-intervention (SMD = -0.19, 95% CI [-0.36; -0.02]) and at 12-months follow-up (SMD = -0.31, 95% CI [-0.57; -0.06]).

Conclusions: The prevention programmes combined psychoeducational elements with skills training and/or cognitive-behavioural therapy elements. The recruitment process and the content of these programmes are sometimes insufficiently described. Nevertheless, they appear to be effective, indicating a need to further examine how these programmes exactly work and for whom.

Practitioner Points: Preventive interventions for children of parents with mood/anxiety disorders appear to be effective in preventing these disorders in offspring. Available preventive intervention programmes focus mostly on psychoeducation, cognitive-behavioural therapy, and family processes. More effort should be made into describing preventive interventions so that they can be easily implemented by practitioners. Studies should further examine why and for whom preventive interventions for children of parents with mood/anxiety disorders are effective.
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http://dx.doi.org/10.1111/bjc.12277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248072PMC
June 2021

Why some siblings thrive whereas others struggle: A within-family study on recollections of childhood parental bonding and current adult depressive and anxiety symptoms.

J Affect Disord 2021 02 16;281:413-421. Epub 2020 Dec 16.

Institute of Clinical Psychology, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden University Medical Center, Leiden, the Netherlands.

Background: Brothers and sisters growing up together share a large proportion of their genes and rearing environment. However, some siblings thrive whereas others struggle. This study investigated family-wide childhood bonding experiences with mother and father, in addition to individual-specific recollections, in relation to current depressive and anxiety symptom levels in adulthood. We examined whether extraversion and internal locus of control (iLoC) had a protective effect in this.

Methods: The sample consisted of 256 families with at least one lifetime depressed or anxious person (N = 596; ages 20-78). Multilevel modeling with cross-level interactions was used.

Results: Adult siblings showed moderate to high agreement in their childhood parental bonding (PB) recollections. Over-and-above the association between individual-specific recollections of PB and adult internalizing symptoms, family-wide poor PB was additionally linked to elevated symptom levels. Within families characterized by poor maternal bonding persons with an iLoC were relatively less anxious (but not less depressed), whereas extraversion was not protective in this context.

Limitation: Although evidence exists that poor childhood PB has an impact on (adult) psychopathology, causality cannot be determined and possible recall bias of PB should be noted. Moreover, next to their moderating effects, extraversion and LoC may also act as mediators.

Conclusions: Our findings extend prior work by demonstrating the importance of siblings' childhood PB experiences next to a person's own recollections when investigating adult internalizing symptoms, while also elucidating individual differences within families.
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http://dx.doi.org/10.1016/j.jad.2020.12.045DOI Listing
February 2021

Cognitive mechanisms underlying depressive disorders in ADHD: A systematic review.

Neurosci Biobehav Rev 2021 02 7;121:307-345. Epub 2021 Jan 7.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Goethe University, Deutschordenstraße 50, 60528 Frankfurt am Main, Germany.

The risk for major depressive disorder (MDD) is considerably increased in young adults with attention-deficit/hyperactivity disorder (ADHD) but underlying mechanisms are poorly understood. This review explores ADHD-specific neurocognitive impairments as possible underlying mechanisms for ADHD-depression comorbidity. Two systematic literature searches were conducted in EBSCOhost, PubMED, and Cochrane Reviews databases according to PRISMA guidelines. The first search identified 18 meta-analyses of cross-sectional and longitudinal studies on cognitive dysfunctions in MDD across the lifespan. The second search identified six original studies on reaction time variability in MDD. During acute depression, children and adults showed cognitive deficits that overlapped with some of the ADHD-related impairments. Findings from remitted patients, high-risk individuals, and few prospective studies suggest that a subset of these shared impairments, specifically executive dysfunctions (selective attention, verbal fluency, working memory) and long-term memory problems, are candidate pre-existing risk markers of depression. We discuss if and how these specific neurocognitive mechanisms may mediate developmental pathways from ADHD to depression. If replicated by longitudinal studies, these findings may guide future prevention strategies.
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http://dx.doi.org/10.1016/j.neubiorev.2020.12.018DOI Listing
February 2021

Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis.

Nat Hum Behav 2021 01 16;5(1):113-122. Epub 2020 Nov 16.

Research Institute of Child Development and Education, University of Amsterdam, Amsterdam, the Netherlands.

We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending <6 h in bed. TST was similar across countries, but insomnia symptoms were 1.5-2.9 times higher in the United States. Women (≥41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.
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http://dx.doi.org/10.1038/s41562-020-00965-xDOI Listing
January 2021

The combined self- and parent-rated SDQ score profile predicts care use and psychiatric diagnoses.

Eur Child Adolesc Psychiatry 2020 Oct 30. Epub 2020 Oct 30.

Heymans Institute for Psychological Research, University of Groningen, Groningen, The Netherlands.

The Strengths and Difficulties Questionnaire (SDQ) is widely used, based on evidence of its value for screening. This evidence primarily regards the single informant total difficulties scale and separate difficulties subscales. We assessed to what degree adolescents' SDQ profiles that combined all self- and parent-rated subscales were associated with use of care and psychiatric diagnoses, and examined the added value thereof over using only a single informant and the total scale. Cluster analysis was used to identify common SDQ profiles based on self- and parent-reports among adolescents aged 12-17 in mental healthcare (n = 4282), social care (n = 124), and the general population (n = 1293). We investigated associations of the profiles with 'care use' and 'DSM-IV diagnoses', depending on gender. We identified six common SDQ profiles: five profiles with varying types and severities of reported difficulties, pertaining to 95% of adolescents in care, and one without difficulties, pertaining to 55% of adolescents not in care. The types of reported difficulties in the profiles matched DSM-IV diagnoses for 88% of the diagnosed adolescents. The SDQ profiles were found to be more useful for predicting care use and diagnoses than SDQ scores reported by the adolescent as single informant and the total difficulties scale. The latter indicated the presence of problems among 42-63% of the adolescents in care, missing a substantial number of adolescents with reported emotional difficulties and borderline problem severity. These findings advocate the use of combined self- and parent-rated SDQ score profiles for screening.
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http://dx.doi.org/10.1007/s00787-020-01667-5DOI Listing
October 2020

Neurocognitive markers of late-onset ADHD: a 6-year longitudinal study.

J Child Psychol Psychiatry 2021 02 12;62(2):244-252. Epub 2020 Jul 12.

Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, The Netherlands.

Background: There is an increased interest in 'late-onset' attention-deficit/hyperactivity disorder (ADHD), referring to the onset of clinically significant ADHD symptoms after the age of 12 years. This study aimed to examine whether unaffected siblings with late-onset ADHD could be differentiated from stable unaffected siblings by their neurocognitive functioning in childhood.

Methods: We report findings from a 6-year prospective, longitudinal study of the Dutch part of the International Multicenter ADHD Genetics (IMAGE) study, including individuals with childhood-onset (persistent) ADHD (n = 193), their siblings with late-onset ADHD (n = 34), their stable unaffected siblings (n = 111) and healthy controls (n = 186). At study entry (mean age: 11.3) and follow-up (mean age: 17.01), participants were assessed for ADHD by structured psychiatric interviews and multi-informant questionnaires. Several neurocognitive functions were assessed at baseline and after 6 years, including time reproduction, timing variability (reaction time variability and time production variability), reaction time speed, motor control and working memory; intelligence was taken as a measure of overall neurocognitive functioning.

Results: Siblings with late-onset ADHD were similar to individuals with childhood-onset ADHD in showing longer reaction times and/or higher error rates on all neurocognitive measures at baseline and follow-up, when compared to healthy controls. They differed from stable unaffected siblings (who were similar to healthy controls) by greater reaction time variability and timing production variability at baseline. No significant group by time interaction was found for any of the tasks.

Conclusions: For unaffected siblings of individuals with ADHD, reaction time variability and timing production variability may serve as neurocognitive marker for late-onset ADHD.
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http://dx.doi.org/10.1111/jcpp.13272DOI Listing
February 2021

White Matter Microstructure in Attention-Deficit/Hyperactivity Disorder: A Systematic Tractography Study in 654 Individuals.

Biol Psychiatry Cogn Neurosci Neuroimaging 2020 Aug 1. Epub 2020 Aug 1.

Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands; Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by age-inappropriate levels of inattention and/or hyperactivity-impulsivity. ADHD has been related to differences in white matter (WM) microstructure. However, much remains unclear regarding the nature of these WM differences and which clinical aspects of ADHD they reflect. We systematically investigated whether fractional anisotropy (FA) is associated with current and/or lifetime categorical diagnosis, impairment in daily life, and continuous ADHD symptom measures.

Methods: Diffusion-weighted imaging data were obtained from 654 participants (322 unaffected, 258 affected, 74 subthreshold; 7-29 years of age). We applied automated global probabilistic tractography on 18 major WM pathways. Linear mixed-effects regression models were used to examine associations of clinical measures with overall brain and tract-specific FA.

Results: There were significant interactions of tract with all ADHD variables on FA. There were no significant associations of FA with current or lifetime diagnosis, nor with impairment. Lower FA in the right cingulum angular bundle was associated with higher hyperactivity-impulsivity symptom severity (p = .045). There were no significant effects for other tracts.

Conclusions: This is the first time global probabilistic tractography has been applied to an ADHD dataset of this size. We found no evidence for altered FA in association with ADHD diagnosis. Our findings indicate that associations of FA with ADHD are not uniformly distributed across WM tracts. Continuous symptom measures of ADHD may be more sensitive to FA than diagnostic categories. The right cingulum angular bundle in particular may play a role in symptoms of hyperactivity and impulsivity.
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http://dx.doi.org/10.1016/j.bpsc.2020.07.015DOI Listing
August 2020

Early warning signals in psychopathology: what do they tell?

BMC Med 2020 10 14;18(1):269. Epub 2020 Oct 14.

Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion regulation (ICPE), University of Groningen, University Medical Center Groningen, Internal Postal Code: CC72, Triade Building Entrance 24, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.

Background: Despite the increasing understanding of factors that might underlie psychiatric disorders, prospectively detecting shifts from a healthy towards a symptomatic state has remained unattainable. A complex systems perspective on psychopathology implies that such symptom shifts may be foreseen by generic indicators of instability, or early warning signals (EWS). EWS include, for instance, increasing variability, covariance, and autocorrelation in momentary affective states-of which the latter was studied. The present study investigated if EWS predict (i) future worsening of symptoms as well as (ii) the type of symptoms that will develop, meaning that the association between EWS and future symptom shifts would be most pronounced for congruent affective states and psychopathological domains (e.g., feeling down and depression).

Methods: A registered general population cohort of adolescents (mean age 18 years, 36% male) provided ten daily ratings of their affective states for 6 consecutive days. The resulting time series were used to compute EWS in feeling down, listless, anxious, not relaxed, insecure, suspicious, and unwell. At baseline and 1-year follow-up, symptom severity was assessed by the Symptom Checklist-90 (SCL-90). We selected four subsamples of participants who reported an increase in one of the following SCL-90 domains: depression (N = 180), anxiety (N = 192), interpersonal sensitivity (N = 184), or somatic complaints (N = 166).

Results: Multilevel models showed that EWS in feeling suspicious anticipated increases in interpersonal sensitivity, as hypothesized. EWS were absent for other domains. While the association between EWS and symptom increases was restricted to the interpersonal sensitivity domain, post hoc analyses showed that symptom severity at baseline was related to heightened autocorrelations in congruent affective states for interpersonal sensitivity, depression, and anxiety. This pattern replicated in a second, independent dataset.

Conclusions: The presence of EWS prior to symptom shifts may depend on the dynamics of the psychopathological domain under consideration: for depression, EWS may manifest only several weeks prior to a shift, while for interpersonal sensitivity, EWS may already occur 1 year in advance. Intensive longitudinal designs where EWS and symptoms are assessed in real-time are required in order to determine at what timescale and for what type of domain EWS are most informative of future psychopathology.
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http://dx.doi.org/10.1186/s12916-020-01742-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557008PMC
October 2020

Greater male than female variability in regional brain structure across the lifespan.

Hum Brain Mapp 2020 Oct 12. Epub 2020 Oct 12.

FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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http://dx.doi.org/10.1002/hbm.25204DOI Listing
October 2020

Attention-deficit/hyperactivity disorder symptoms and dietary habits in adulthood: A large population-based twin study in Sweden.

Am J Med Genet B Neuropsychiatr Genet 2020 12 7;183(8):475-485. Epub 2020 Oct 7.

School of Medical Sciences, Örebro University, Örebro, Sweden.

Associations between adult attention-deficit/hyperactivity disorder (ADHD) symptoms and dietary habits have not been well established and the underlying mechanisms remain unclear. We explored these associations using a Swedish population-based twin study with 17,999 individuals aged 20-47 years. We estimated correlations between inattention and hyperactivity/impulsivity with dietary habits and fitted twin models to determine the genetic and environmental contributions. Dietary habits were defined as (a) consumption of food groups, (b) consumption of food items rich in particular macronutrients, and (c) healthy and unhealthy dietary patterns. At the phenotypic level, inattention was positively correlated with seafood, high-fat, high-sugar, high-protein food consumptions, and unhealthy dietary pattern, with correlation coefficients ranging from 0.03 (95%CI: 0.01, 0.05) to 0.13 (95% CI: 0.11, 0.15). Inattention was negatively correlated with fruits, vegetables consumptions and healthy dietary pattern, with correlation coefficients ranging from -0.06 (95%CI: -0.08, -0.04) to -0.07 (95%CI: -0.09, -0.05). Hyperactivity/impulsivity and dietary habits showed similar but weaker patterns compared to inattention. All associations remained stable across age, sex and socioeconomic status. Nonshared environmental effects contributed substantially to the correlations of inattention (56-60%) and hyperactivity/impulsivity (63-80%) with dietary habits. The highest and lowest genetic correlations were between inattention and high-sugar food (r = .16, 95% CI: 0.07, 0.25), and between hyperactivity/impulsivity and unhealthy dietary pattern (r = .05, 95% CI: -0.05, 0.14), respectively. We found phenotypic and etiological overlap between ADHD and dietary habits, although these associations were weak. Our findings contribute to a better understanding of common etiological pathways between ADHD symptoms and various dietary habits.
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http://dx.doi.org/10.1002/ajmg.b.32825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702140PMC
December 2020

Disease burden and direct medical costs of incident adult ADHD: A retrospective longitudinal analysis based on German statutory health insurance claims data.

Eur Psychiatry 2020 10 1;63(1):e86. Epub 2020 Oct 1.

Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany.

Background: Adult attention-deficit/hyperactivity disorder (aADHD) is still a largely unrecognized psychiatric condition despite its strong impact on individuals' well-being. Here, we describe the healthcare situation of individuals with incident aADHD over 4 years before and 4 years after initial administrative diagnosis.

Methods: A retrospective, longitudinal cohort analysis was conducted using German claims data. The InGef database contained approximately 5 million member-records from over 60 nationwide statutory health insurances (SHI). Individuals were indexed upon initial diagnosis of aADHD.

Results: Average age at diagnosis of aADHD was 35 years, and 60% of individuals were male. Comorbidities, resource use, and healthcare costs were substantial before initial diagnosis and decreased within the 4 years thereafter. Only 32% of individuals received initial ADHD medication and adherence was low. The majority received psychotherapy. Individuals with initial ADHD medication showed the highest share in comorbidities, physician visits, medication use for comorbidities, psychotherapy, and costs. Overall, healthcare costs were at over €4,000 per individual within the year of aADHD diagnosis.

Conclusions: We conclude that earlier recognition of aADHD could prevent the development and aggravation of comorbid mental illnesses. At the same time, comorbid conditions may have masked ("over-shadowed") aADHD and delayed diagnosis. The burden of disease in aADHD is high, which was noticeable especially among individuals who received initial ADHD-medication, suggesting that psychopharmacological treatment was mainly considered for the most severely ill. We conclude that measures to facilitate access of aADHD patients to clinical experts are required to improve reality of care in the outpatient setting.
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http://dx.doi.org/10.1192/j.eurpsy.2020.84DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576526PMC
October 2020

Comorbidity between depression and anxiety: assessing the role of bridge mental states in dynamic psychological networks.

BMC Med 2020 09 29;18(1):308. Epub 2020 Sep 29.

Department of Psychiatry, Interdisciplinary Center for Psychopathology and Emotion regulation (ICPE), University Medical Center Groningen (UMCG), University of Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1186/s12916-020-01738-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523307PMC
September 2020

Reduced fronto-striatal volume in attention-deficit/hyperactivity disorder in two cohorts across the lifespan.

Neuroimage Clin 2020 28;28:102403. Epub 2020 Aug 28.

Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Radboud University Medical Center, Nijmegen, The Netherlands; Centre for Cognitive Neuroimaging, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address:

Attention-Deficit/Hyperactivity Disorder (ADHD) has been associated with altered brain anatomy in neuroimaging studies. However, small and heterogeneous study samples, and the use of region-of-interest and tissue-specific analyses have limited the consistency and replicability of these effects. We used a data-driven multivariate approach to investigate neuroanatomical features associated with ADHD in two independent cohorts: the Dutch NeuroIMAGE cohort (n = 890, 17.2 years) and the Brazilian IMpACT cohort (n = 180, 44.2 years). Using independent component analysis of whole-brain morphometry images, 375 neuroanatomical components were assessed for association with ADHD. In both discovery (corrected-p = 0.0085) and replication (p = 0.032) cohorts, ADHD was associated with reduced volume in frontal lobes, striatum, and their interconnecting white-matter. Current results provide further evidence for the role of the fronto-striatal circuit in ADHD in children, and for the first time show its relevance to ADHD in adults. The fact that the cohorts are from different continents and comprise different age ranges highlights the robustness of the findings.
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http://dx.doi.org/10.1016/j.nicl.2020.102403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502360PMC
June 2021

Investigating whether depressed youth exhibiting elevated C reactive protein perform worse on measures of executive functioning, verbal fluency and episodic memory in a large, population based sample of Dutch adolescents.

Brain Behav Immun 2021 05 2;94:369-380. Epub 2020 Sep 2.

Faculty of Medical Sciences, University of Groningen, The Netherlands.

Cognitive functioning is disrupted during a depressive episode and cognitive dysfunction persists when depression is in remission. A subtype of depressed individuals who exhibit elevated inflammatory biomarkers may be at particular risk for cognitive dysfunction. We examined whether an elevated inflammatory biomarker (C-reactive protein: CRP) in acute and/or remitted depression was associated with specific deficits in executive functioning, episodic memory, and verbal fluency. Data were drawn from a population-based sample of Dutch adolescents (N = 1066; 46% male) recruited at the age of 11 and followed over the course of eight years. We tested whether adolescents with either, (i) a history of depression (Wave 1-3) or (ii) current depression (Wave 4), and elevated levels of C-reactive protein measured in blood at Wave 3 performed worse on cognitive assessments at Wave 4. Eight measures of cognitive functioning were hypothesized to load on to one of three dimensions of cognitive functioning (executive functioning, episodic memory, and verbal fluency) within a structural equation model framework. Higher levels of CRP were associated with worse future executive functioning in adolescents with and without current/prior depression. A current depression diagnosis also was associated with worse executive functioning. There was consistent evidence linking low socioeconomic status and health-related covariates (high body mass index/sedentary behavior) with worse performance across multiple measures of cognitive functioning and, importantly, the association of depression/CRP and executive functioning was no longer significant when controlling for these covariates. Future studies may benefit from investigating whether specific depressogenic behaviors (e.g., sedentary behavior/substance use) mediate a relationship between depression and worse executive functioning, potentially via a prospective pathway through elevated inflammation.
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http://dx.doi.org/10.1016/j.bbi.2020.08.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921209PMC
May 2021
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