Brain Structural Correlates of Subclinical Obsessive-Compulsive Symptoms in Healthy Children

doi:10.1016/j.jaac.2017.10.016

Journal of the American Academy of Child & Adolescent Psychiatry

Volume 57, Issue 1, January 2018, Pages 41-47

https://doi.org/10.1016/j.jaac.2017.10.016 Get rights and content

Objective

Subclinical obsessive-compulsive (OC) symptoms are frequently observed in children and have been reported to predict a subsequent diagnosis of OC disorder (OCD). Therefore, identifying the putative neurobiological signatures of such risk is crucial, because it would allow for the characterization of the underpinnings of OCD without the interfering effects of chronicity, medication, or comorbidities, especially when interpreted within the context of OCD clinical heterogeneity and taking into account normal neurodevelopmental changes. The present study aimed to identify the brain volumetric features associated with subclinical OC symptoms and the potential modulatory effects of sex and age in a large sample of healthy children.

Method

Two hundred fifty-five healthy children were assessed using the Obsessive-Compulsive Inventory–Child Version and underwent a brain structural magnetic resonance examination. The relation between total and symptom-specific scores and regional gray and white matter (GM and WM) volumes was evaluated. Participants were grouped according to sex and age (younger versus older) to assess the effect of these factors on symptom–brain morphometry associations.

Results

Ordering symptoms were negatively related to GM volumes in the ventral caudate. Hoarding symptoms were positively associated with GM and WM volumes in the left inferior frontal gyrus, and obsessing symptoms correlated negatively with GM and WM volumes in the right temporal pole. Doubt-checking symptoms correlated positively with WM volumes in the right inferior fronto-occipital fasciculus and the corpus callosum. Sex and age modulated some of these associations.

Conclusion

Subclinical OC symptoms are associated with specific brain volumetric features, which could be considered potential neural signatures of increased risk for OCD.

Section snippets

Participants

The sample consisted of 255 healthy school children from the BREATHE project (European Commission: FP7-ERC-2010-AdG, ID 268479). The general project design is described elsewhere.²⁰ In brief, 1,564 families from 39 schools in the city of Barcelona, Spain were invited to participate in a study to assess the effects of environmental pollutants on normal neurodevelopment, although we did not use these data in the present study (see21, 22, 23, 24, 25). Children with special needs or mental health

Descriptive Variables

Table 1 presents information on demographics, total GM and WM volumes, and SDQ and OCI-CV scores of participants. OCI-CV mean values of our sample were similar to those obtained in the Spanish validation of the questionnaire²⁸ (Table S1, available online). Clinical interviews detected no cases susceptible to receiving a diagnosis of a psychiatric disorder (including OCD), although 25 children (9.8%) had symptoms of ADHD (6 were taking methylphenidate hydrochloride or atomoxetine hydrochloride).

Discussion

This is the first study to identify associations between subclinical OC symptoms and specific brain volumetric features in healthy children. We found associations between ordering, hoarding, obsessing, and doubt-checking symptoms and different GM and WM clusters. In addition, some GM findings were found to be moderated by the sex and/or age of the participants.

The negative association between ordering traits and GM volumes at the bilateral ventral caudate region resonates with previous clinical

References (57)

L.A. Valleni-Basile et al.
Incidence of obsessive-compulsive disorder in a community sample of young adolescents
J Am Acad Child Adolesc Psychiatry
(1996)
P.G. Alvarenga et al.
Obsessive-compulsive symptom dimensions correlate to specific gray matter volumes in treatment-naïve patients
J Psychiatr Res
(2012)
R.K. Lenroot et al.
Sexual dimorphism of brain developmental trajectories during childhood and adolescence
Neuroimage
(2007)
E.E. Nelson et al.
The development of the ventral prefrontal cortex and social flexibility
Dev Cogn Neurosci
(2011)
C.G. Last et al.
Obsessive-compulsive disorder in childhood
J Anxiety Disord
(1989)
M. Mortamais et al.
Effect of exposure to polycyclic aromatic hydrocarbons on basal ganglia and attention-deficit hyperactivity disorder symptoms in primary school children
Environ Int
(2017)
J. Pujol et al.
Traffic pollution exposure is associated with altered brain connectivity in school children
Neuroimage
(2016)
E.B. Foa et al.
Development and validation of a child version of the Obsessive Compulsive Inventory
Behav Ther
(2010)
J.C. Britton et al.
Cognitive inflexibility and frontal-cortical activation in pediatric obsessive-compulsive disorder
J Am Acad Child Adolesc Psychiatry
(2010)
R. Marsh et al.
Altered activation in fronto-striatal circuits during sequential processing of conflict in unmedicated adults with obsessive-compulsive disorder
Biol Psychiatry
(2014)

R.M. Roth et al.

New-onset obsessive-compulsive disorder following neurosurgery for medication-refractory seizure disorder

Epilepsy Behav

(2009)

P. Alonso et al.

Neural correlates of obsessive-compulsive related dysfunctional beliefs

Prog Neuropsychopharmacol Biol Psychiatry

(2013)

F. Piras et al.

Widespread structural brain changes in OCD: a systematic review of voxel-based morphometry studies

Cortex

(2015)

M.M. Vaghi et al.

Specific fronto-striatal circuits for impaired cognitive flexibility and goal-directed planning in obsessive-compulsive disorder: evidence from resting-state functional connectivity

Biol Psychiatry

(2017)

R. Leopold et al.

Neuropsychological differences between obsessive-compulsive washers and checkers: a systematic review and meta-analysis

J Anxiety Disord

(2015)

I. Snorrason et al.

Are nonclinical obsessive-compulsive symptoms associated with bias toward habits?

Psychiatry Res

(2016)

M. Zarei et al.

Changes in gray matter volume and white matter microstructure in adolescents with obsessive-compulsive disorder

Biol Psychiatry

(2011)

V. Garibotto et al.

Disorganization of anatomical connectivity in obsessive compulsive disorder: a multi-parameter diffusion tensor imaging study in a subpopulation of patients

Neurobiol Dis

(2010)

K. Koch et al.

Diffusion tensor imaging (DTI) studies in patients with obsessive-compulsive disorder (OCD): a review

J Psychiatr Res

(2014)

M.A. Fullana et al.

Obsessions and compulsions in the community: prevalence, interference, help-seeking, developmental stability, and co-occurring psychiatric conditions

Am J Psychiatry

(2009)

A.M. Ruscio et al.

The epidemiology of obsessive-compulsive disorder in the national comorbidity survey replication

Mol Psychiatry

(2010)

D.W. Black et al.

Subclinical obsessive-compulsive disorder in children and adolescents: additional results from a “high-risk” study

CNS Spectr

(2008)

G. Nestadt et al.

A family study of obsessive-compulsive disorder

Arch Gen Psychiatry

(2000)

P.R. Szeszko et al.

Gray matter structural alterations in psychotropic drug-naive pediatric obsessive-compulsive disorder: an optimized voxel-based morphometry study

Am J Psychiatry

(2008)

L.J. Norman et al.

Structural and functional brain abnormalities in attention-deficit/hyperactivity disorder and obsessive-compulsive disorder

JAMA Psychiatry

(2016)

D. Mataix-Cols et al.

A multidimensional model of obsessive-compulsive disorder

Am J Psychiatry

(2005)

J.F. Leckman et al.

Symptom dimensions and subtypes of obsessive-compulsive disorder: a developmental perspective

Dialogues Clin Neurosci

(2009)

E. Foa et al.

The validation of a new obsessive-compulsive disorder scale: the Obsessive-Compulsive Inventory

Psychol Assess

(1998)

Cited by (22)

Neurogenetics of Dynamic Connectivity Patterns Associated With Obsessive-Compulsive Symptoms in Healthy Children
2022, Biological Psychiatry Global Open Science
Obsessive-compulsive symptoms (OCSs) during childhood predispose to obsessive-compulsive disorder and have been associated with changes in brain circuits altered in obsessive-compulsive disorder samples. OCSs may arise from disturbed glutamatergic neurotransmission, impairing cognitive oscillations and promoting overstable functional states.
A total of 227 healthy children completed the Obsessive Compulsive Inventory–Child Version and underwent a resting-state functional magnetic resonance imaging examination. Genome-wide data were obtained from 149 of them. We used a graph theory–based approach and characterized associations between OCSs and dynamic functional connectivity (dFC). dFC evaluates fluctuations over time in FC between brain regions, which allows characterizing regions with stable connectivity patterns (attractors). We then compared the spatial similarity between OCS-dFC correlation maps and mappings of genetic expression across brain regions to identify genes potentially associated with connectivity changes. In post hoc analyses, we investigated which specific single nucleotide polymorphisms of these genes moderated the association between OCSs and patterns of dFC.
OCSs correlated with decreased attractor properties in the left ventral putamen and increased attractor properties in (pre)motor areas and the left hippocampus. At the specific symptom level, increased attractor properties in the right superior parietal cortex correlated with ordering symptoms. In the hippocampus, we identified two single nucleotide polymorphisms in glutamatergic neurotransmission genes (GRM7, GNAQ) that moderated the association between OCSs and attractor features.
We provide evidence that in healthy children, the association between dFC changes and OCSs may be mapped onto brain circuits predicted by prevailing neurobiological models of obsessive-compulsive disorder. Moreover, our findings support the involvement of glutamatergic neurotransmission in such brain network changes.
Thalamic Subregions and Obsessive-Compulsive Symptoms in 2,500 Children From the General Population
2022, Journal of the American Academy of Child and Adolescent Psychiatry
Pediatric obsessive-compulsive disorder (OCD) and clinically relevant obsessive-compulsive symptoms in the general population are associated with increased thalamic volume. It is unknown whether this enlargement is explained by specific thalamic subregions. The relation between obsessive-compulsive symptoms and volume of thalamic subregions was investigated in a population-based sample of children.
Obsessive-compulsive symptoms were measured in children (9-12 years of age) from the Generation R Study using the Short Obsessive-Compulsive Disorder Screener (SOCS). Thalamic nuclei volumes were extracted from structural 3T magnetic resonance imaging scans using the ThalamicNuclei pipeline and regrouped into anterior, ventral, intralaminar/medial, lateral, and pulvinar subregions. Volumes were compared between children with symptoms above clinical cutoff (probable OCD cases, SOCS ≥ 6, n = 156) and matched children without symptoms (n = 156). Linear regression models were fitted to investigate the association between continuous SOCS score and subregional volume in the whole sample (N = 2500).
Children with probable OCD had larger ventral nuclei compared with children without symptoms (d = 0.25, p = .025, false discovery rate adjusted p = .126). SOCS score showed a negative association with pulvinar volume when accounting for overall thalamic volume (β = −0.057, p = .009, false discovery rate adjusted p = .09). However, these associations did not survive multiple testing correction.
The results suggest that individual nuclei groups contribute in varying degrees to overall thalamic volume in children with probable OCD, although this did not survive multiple comparisons correction. Understanding the role of thalamic nuclei and their associated circuits in pediatric OCD could lead toward treatment strategies targeting these circuits.
Editorial: Thalamic Subregions Are Differentially Associated With Obsessive-Compulsive Symptoms in Children
2022, Journal of the American Academy of Child and Adolescent Psychiatry
Brain Functional Connectivity Correlates of Subclinical Obsessive-Compulsive Symptoms in Healthy Children
2021, Journal of the American Academy of Child and Adolescent Psychiatry
Citation Excerpt :
Of these, 491 families were successfully contacted by phone, and from this pool 263 children completed the imaging protocol. Ten children were excluded based on image quality criteria, and 1 child was excluded because of incomplete Obsessive-Compulsive Inventory–Child Version (OCI-CV) data, leaving a sample of 252 children, which was the sample used to assess the brain structural correlates of subclinical OC symptoms in a previous study.5 In the present study, however, we excluded from the main analyses 25 children with attention-deficit/hyperactivity disorder (ADHD) symptoms, as detailed below, leaving a final sample size of 227 participants.
Commonly observed subclinical obsessive-compulsive symptoms in healthy children may predispose to obsessive-compulsive disorder (OCD). Therefore, investigating the underlying neurobiology may be relevant to identify alterations in specific brain circuits potentially accounting for clinical heterogeneity in OCD without the confounding effects of clinical samples. We analyzed the brain correlates of different obsessive-compulsive symptoms in a large group of healthy children using functional connectivity measures.
We evaluated 227 healthy children (52% girls; mean [SD] age 9.71 [0.86] years; range, 8–12.1 years). Participants underwent clinical assessment with the Obsessive-Compulsive Inventory–Child Version and a resting-state functional magnetic resonance imaging examination. Total and symptom-specific severity were correlated with voxelwise global functional connectivity degree values. Significant clusters were then used as seeds of interest in seed-to-voxel analyses. Modulating effects of age and sex were also assessed.
Global functional connectivity of the left ventral putamen and medial dorsal thalamus correlated negatively with total obsessive-compulsive symptom severity. Seed-to-voxel analyses revealed specific negative correlations from these clusters with limbic, sensorimotor, and insular regions in association with obsessing, ordering, and doubt-checking symptoms, respectively. Hoarding symptoms were associated with negative correlations between the left medial dorsal thalamus and a widespread pattern of regions, with such associations modulated by sex and age.
Our findings concur with prevailing neurobiological models of OCD on the importance of cortico-striato-thalamo-cortical dysfunction to account for symptom severity. Notably, we showed that changes in cortico-striato-thalamo-cortical connectivity are present at subclinical stages, which may result in an increased vulnerability for OCD. Moreover, we mapped different symptom dimensions onto specific cortico-striato-thalamo-cortical circuit attributes.
The temporal pole: From anatomy to function—A literature appraisal
2021, Journal of Chemical Neuroanatomy
Citation Excerpt :
There was a significant negative correlation between temporal pole thickness and normalized medication dose, symptom severity, and duration of illness, and a positive correlation with age at onset, confirming previous studies suggesting a smaller cortical surface of the temporal pole in subjects with schizophrenia (Rais et al., 2012; Horn et al., 2010; Tomelleri et al., 2009; Crespo-Facorro et al., 2004; Kasai et al., 2003; Xu et al., 2015; Lee et al., 2016). Reduced temporal pole volume was also found in several other psychiatric disease : obsessive-compulsive syndrome (with a correlation between obsessing symptoms and right temporal pole volume, Suñol et al., 2018), panic disorders (Kang et al., 2017), post-traumatic stress disorder (Kühn and Gallinat, 2013), social anxiety disorder (Talati et al., 2013), bipolar disorder type I (Neves et al., 2015), mild depressive symptoms (Webb et al., 2014), major depressive disorder (Peng et al., 2011) and ADHD (Fernández-Jaén et al., 2014). Some patients with personality disorder, mostly patients with social cognition deficiency, also had reduced temporal pole volume, such as cocaine-dependent patients with personality disorders (Albein-Urios et al., 2013) or offending pedophiles (Schiffer et al., 2017)
Historically, the anterior part of the temporal lobe was labelled as a unique structure named Brain Area 38 by Brodmann or Temporopolar Area TG by Von Economo, but its functions were unknown at that time. Later on, a few studies proposed to divide the temporal pole in several different subparts, based on distinct cytoarchitectural structure or connectivity patterns, while a still growing number of studies have associated the temporal pole with many cognitive functions. In this review, we provide an overview of the temporal pole anatomical and histological structure and its various functions. We performed a literature review of articles published prior to September 30, 2020 that included 112 articles. The temporal pole has thereby been associated with several high-level cognitive processes: visual processing for complex objects and face recognition, autobiographic memory, naming and word-object labelling, semantic processing in all modalities, and socio-emotional processing, as demonstrated in healthy subjects and in patients with neurological or psychiatric diseases, especially in the field of neurodegenerative disorders. A good knowledge of those functions and the symptoms associated with temporal pole lesions or dysfunctions is helpful to identify these diseases, whose diagnosis may otherwise be difficult.
Brain Morphology Associated With Obsessive-Compulsive Symptoms in 2,551 Children From the General Population
2021, Journal of the American Academy of Child and Adolescent Psychiatry
Obsessive-compulsive (OC) symptoms are common in the general population, but it is unclear whether subclinical OC symptoms and obsessive-compulsive disorder (OCD) are part of a neuroanatomical continuum. The goal of this study was to investigate the relation between OC symptoms and subcortical and cortical morphology in a population-based sample of children.
The study included 2,551 participants, aged 9–12 years, from the population-based Generation R Study. OC symptoms were measured using the 7-item caregiver-rated Short Obsessive-Compulsive Disorder Screener (SOCS). Structural (3T) magnetic resonance imaging scans were processed using FreeSurfer to study the thalamus and other subcortical volumes, intracranial volume, vertexwise cortical thickness, and surface area. We used linear regression models to investigate the association between OC symptoms and brain morphology. Emulating case-control studies from the literature, we compared children scoring above the clinical cutoff of the SOCS (probable OCD cases, n = 164) with matched children without symptoms.
Children with probable OCD had larger thalami compared with the control group (d 0.16, p = .044). Vertexwise analysis showed a positive association between OC symptoms and thickness of the right inferior parietal cortex, which disappeared after adjusting for total behavioral problems. SOCS scores correlated negatively with intracranial volume (B = −2444, p = .038).
Children with probable OCD showed thalamus alterations similar to those previously reported in unmedicated children with OCD. OC symptoms showed a stronger association with total intracranial volume than regional brain measures. Longitudinal studies are needed to further elucidate similarities and distinctions between neural correlates of subclinical and clinical OC symptoms.

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: This research received funding from the European Research Council under ERC Grant Agreement number 268479; the BREATHE project; the Instituto de Salud Carlos III (ISCIII; PI13/01958, PI16/00889); FEDER funds/European Regional Development Fund (ERDF); A Way to Build Europe; and AGAUR (2014 SGR 1672). CIBERSAM and CIBERESP are initiatives of the Carlos III Health Institute. Ms. Suñol was supported by a CIBERSAM PhD grant (CNV665/914). Dr. Contreras-Rodríguez was supported by a Sara Borrell contract (CD14/00246), Dr. Subirà was supported by a Rio Hortega contract (CM15/00189), and Dr. Soriano-Mas was supported by a Miguel Servet contract (CPII16/00048) from the ISCIII.

: Ms. Suñol and Dr. Contreras-Rodríguez contributed equally to this article.

: Disclosure: Drs. Contreras-Rodríguez, Subirà, Pujol, Sunyer, Soriano-Mas, Ms. Suñol, Mr. Macià, Mr. Martínez-Vilavella, and Mr. Martínez-Zalacaín report no biomedical financial interests or potential conflicts of interest.

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New researchBrain Structural Correlates of Subclinical Obsessive-Compulsive Symptoms in Healthy Children

Objective

Method

Results

Conclusion

Section snippets

Participants

Descriptive Variables

Discussion

J Am Acad Child Adolesc Psychiatry

J Psychiatr Res

Neuroimage

Dev Cogn Neurosci

J Anxiety Disord

Environ Int

Neuroimage

Behav Ther

J Am Acad Child Adolesc Psychiatry

Biol Psychiatry

Epilepsy Behav

Prog Neuropsychopharmacol Biol Psychiatry

Cortex

Biol Psychiatry

J Anxiety Disord

Psychiatry Res

Biol Psychiatry

Neurobiol Dis

J Psychiatr Res

Obsessions and compulsions in the community: prevalence, interference, help-seeking, developmental stability, and co-occurring psychiatric conditions

Am J Psychiatry

The epidemiology of obsessive-compulsive disorder in the national comorbidity survey replication

Mol Psychiatry

Subclinical obsessive-compulsive disorder in children and adolescents: additional results from a “high-risk” study

CNS Spectr

A family study of obsessive-compulsive disorder

Arch Gen Psychiatry

Gray matter structural alterations in psychotropic drug-naive pediatric obsessive-compulsive disorder: an optimized voxel-based morphometry study

Am J Psychiatry

Structural and functional brain abnormalities in attention-deficit/hyperactivity disorder and obsessive-compulsive disorder

JAMA Psychiatry

A multidimensional model of obsessive-compulsive disorder

Am J Psychiatry

Symptom dimensions and subtypes of obsessive-compulsive disorder: a developmental perspective

Dialogues Clin Neurosci

The validation of a new obsessive-compulsive disorder scale: the Obsessive-Compulsive Inventory

Psychol Assess

New research
Brain Structural Correlates of Subclinical Obsessive-Compulsive Symptoms in Healthy Children