Jilly Naaijen

YNICL Journal 2023 Journal Article

Different whole-brain functional connectivity correlates of reactive-proactive aggression and callous-unemotional traits in children and adolescents with disruptive behaviors

• Julia E. Werhahn
• Lukasz Smigielski
• Seda Sacu
• Susanna Mohl
• David Willinger
• Jilly Naaijen
• Leandra M. Mulder
• Jeffrey C. Glennon

BACKGROUND: Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationship between resting state functional connectivity (rsFC) and aggression subtypes considering comorbidities. METHODS: The large sample of children and adolescents aged 8-18 years (n = 207; mean age = 13.30±2.60 years, 150 males) included 118 cases with disruptive behavior (80 with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptom scores were analyzed as covariates when assessing group differences and dimensional aggression effects on hypothesis-free global and local voxel-to-voxel whole-brain rsFC based on functional magnetic resonance imaging at 3 Tesla. RESULTS: Compared to controls, the cases demonstrated altered rsFC in frontal areas, when anxiety but not ADHD symptoms were controlled for. For cases, reactive and proactive aggression scores were related to global and local rsFC in the central gyrus and precuneus, regions linked to aggression-related impairments. Callous-unemotional trait severity was correlated with ICC in the inferior and middle temporal regions implicated in empathy, emotion, and reward processing. Most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety were controlled for. CONCLUSIONS: This study clarifies that hypothesis-free brain connectivity measures can disentangle distinct though overlapping dimensions of aggression in youths. Moreover, our results highlight the importance of considering comorbid symptoms to detect aggression-related rsFC alterations in youths.

YNICL Journal 2022 Journal Article

Longitudinal changes of ADHD symptoms in association with white matter microstructure: A tract-specific fixel-based analysis

• Christienne G. Damatac
• Sourena Soheili-Nezhad
• Guilherme Blazquez Freches
• Marcel P. Zwiers
• Sanne de Bruijn
• Seyma Ikde
• Christel M. Portengen
• Amy C. Abelmann

BACKGROUND: Variation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18 - 34 years), and using the more physiologically informative fixel-based analysis (FBA). METHODS: Data were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined ADHD and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up. RESULTS: = 0.019). CONCLUSIONS: Aberrant white matter development involves both lCST micro- and macrostructural alterations, and its path may be moderated by preceding symptom trajectory.

YNICL Journal 2021 Journal Article

Developmental changes in fronto-striatal glutamate and their association with functioning during inhibitory control in autism spectrum disorder and obsessive compulsive disorder

• Viola Hollestein
• Jan K. Buitelaar
• Daniel Brandeis
• Tobias Banaschewski
• Anna Kaiser
• Sarah Hohmann
• Bob Oranje
• Bram Gooskens

H-MRS data and fMRI data separately as well as integrated in a multimodal analysis using linear models focusing on diagnosis and continuous measures of overlapping compulsivity symptoms. ACC glutamate was reduced over time in the ASD group compared with controls, while striatal glutamate decreased over time independent of diagnosis. Increased compulsive behavior seemed to be associated with increased striatal activity during failed inhibitory control. The integrated analyses showed differential involvement of increased striatal glutamate during failed but decreased striatal glutamate during successful inhibitory control in the OCD group compared to controls and ASD, suggesting different underlying mechanisms for OCD compared to ASD.

YNIMG Journal 2021 Journal Article

Emotion dysregulation and integration of emotion-related brain networks affect intraindividual change in ADHD severity throughout late adolescence

• Tammo Viering
• Pieter J. Hoekstra
• Alexandra Philipsen
• Jilly Naaijen
• Andrea Dietrich
• Catharina A. Hartman
• Barbara Franke
• Jan K. Buitelaar

YNICL Journal 2020 Journal Article

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

• Renata Basso Cupertino
• Sourena Soheili-Nezhad
• Eugenio Horacio Grevet
• Cibele Edom Bandeira
• Felipe Almeida Picon
• Maria Eduarda de Araujo Tavares
• Jilly Naaijen
• Daan van Rooij

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.

YNICL Journal 2020 Journal Article

Specific cortical and subcortical alterations for reactive and proactive aggression in children and adolescents with disruptive behavior

• Jilly Naaijen
• Leandra M Mulder
• Shahrzad Ilbegi
• Sanne de Bruijn
• Renee Kleine-Deters
• Andrea Dietrich
• Pieter J Hoekstra
• Jan-Bernard C Marsman

Maladaptive aggression, as present in conduct disorder (CD) and, to a lesser extent, oppositional defiant disorder (ODD), has been associated with structural alterations in various brain regions, such as ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), amygdala, insula and ventral striatum. Although aggression can be subdivided into reactive and proactive subtypes, no neuroimaging studies have yet investigated if any structural brain alterations are associated with either of the subtypes specifically. Here we investigated associations between aggression subtypes, CU traits and ADHD symptoms in predefined regions of interest. T1-weighted magnetic resonance images were acquired from 158 children and adolescents with disruptive behavior (ODD/CD) and 96 controls in a multi-center study (aged 8-18). Aggression subtypes were assessed by questionnaires filled in by participants and their parents. Cortical volume and subcortical volumes and shape were determined using Freesurfer and the FMRIB integrated registration and segmentation tool. Associations between volumes and continuous measures of aggression were established using multilevel linear mixed effects models. Proactive aggression was negatively associated with amygdala volume (b = -10.7, p = 0.02), while reactive aggression was negatively associated with insula volume (b = -21.7, p = 0.01). No associations were found with CU traits or ADHD symptomatology. Classical group comparison showed that children and adolescents with disruptive behavior had smaller volumes than controls in (bilateral) vmPFC (p = 0.003) with modest effect size and a reduced shape in the anterior part of the left ventral striatum (p = 0.005). Our study showed negative associations between reactive aggression and volumes in a region involved in threat responsivity and between proactive aggression and a region linked to empathy. This provides evidence for aggression subtype-specific alterations in brain structure which may provide useful insights for clinical practice.

YNICL Journal 2017 Journal Article

Fronto-striatal glutamate in children with Tourette's disorder and attention-deficit/hyperactivity disorder

• Jilly Naaijen
• Natalie J. Forde
• David J. Lythgoe
• Sophie E.A. Akkermans
• Thaira J.C. Openneer
• Andrea Dietrich
• Marcel P. Zwiers
• Pieter J. Hoekstra

OBJECTIVE: Both Tourette's disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) have been related to abnormalities in glutamatergic neurochemistry in the fronto-striatal circuitry. TD and ADHD often co-occur and the neural underpinnings of this co-occurrence have been insufficiently investigated in prior studies. METHOD: = 53) as an in vivo method of evaluating glutamate concentrations in the fronto-striatal circuit. Spectra were collected on a 3 Tesla Siemens scanner from two voxels in each participant: the anterior cingulate cortex (ACC) and the left dorsal striatum. LC-model was used to process spectra and generate glutamate concentrations in institutional units. A one-way analysis of variance was performed to determine significant effects of diagnostic group on glutamate concentrations. RESULTS: = 0.02). CONCLUSION: We found no evidence for glutamatergic neuropathology in TD or ADHD within the fronto-striatal circuits. However, the correlation of OC-symptoms with ACC glutamate concentrations suggests that altered glutamatergic transmission is involved in OC-symptoms within TD, but this needs further investigation.