Phenotypic differences in early- and late-onset obsessive-compulsive disorder☆
Abstract
Early-onset forms of many medical diseases have been associated with specific genetic anomalies. To assess the potential marker value of onset age in obsessive-compulsive disorder (OCD), we examined and compared the phenotypic characteristics of patients with early and later onset. The study sample included 38 children with DSM-IV OCD and 129 adults 19 years of age or older, 77 of whom reported OCD onset prior to age 18 and 52 of whom reported OCD onset at 18 years of age or older. DSM-IV diagnoses were ascertained for all subjects using an amended version of the Diagnostic Interview for Genetic Studies (DIGS). An initial comparison of children and adults with childhood onset revealed several differences, including an earlier onset of clinically significant symptoms without impairment and earlier onset of DSM-IV OCD, a higher frequency of learning disabilities, and fewer obsessions and compulsions among our child patients. For this reason, subsequent analyses included only adult patients with early and later OCD onset. Nonimpairing symptom onset prior to puberty, a relatively aggressive course, and a greater number of obsessions and compulsions unrelated to the amount of time in illness characterized early-onset OCD. Later-onset OCD was characterized by non-impairing symptom onset during puberty, a static course, and relatively few obsessions and compulsions that were variably related to the amount of time in illness. We conclude that children with OCD and adults with childhood onset differ in their report of clinical characteristics and should be analyzed separately in studies concerning the phenotypic characteristics of OCD. Early- and late-onset forms of OCD appear to be characterized by phenotypic features that have important neurobiologic and perhaps genetic implications.
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Associations between somatomotor-putamen resting state connectivity and obsessive-compulsive symptoms vary as a function of stress during early adolescence: Data from the ABCD study
2024, Brain Research BulletinObsessive-compulsive symptoms (OCS) are relatively common during adolescence although most individuals do not meet diagnostic criteria for obsessive-compulsive disorder (OCD). Nonetheless, OCS during adolescence are associated with comorbid psychopathologies and behavioral problems. Heightened levels of environmental stress and greater functional connectivity between the somatomotor network and putamen have been previously associated with elevated OCS in OCD patients relative to healthy controls. However, the interaction of these factors within the same sample of individuals has been understudied. This study examined somatomotor-putamen resting state connectivity, stress, and their interaction on OCS in adolescents from 9–12 years of age. Participants (n = 6386) were drawn from the ABCD Study 4.0 release. Multilevel modeling was used to account for nesting in the data and to assess changes in OCS in this age range. Stress moderated the association between somatomotor-putamen connectivity and OCS (β = 0.35, S.E. = 0.13, p = 0.006). Participants who reported more stress than their average and had greater somatomotor-left putamen connectivity reported more OCS, whereas participants who reported less stress than their average and had greater somatomotor-left putamen connectivity reported less OCS. These data suggest that stress differentially affects the direction of association between somatomotor-putamen connectivity and OCS. Individual differences in the experience or perception of stress may contribute to more OCS in adolescents with greater somatomotor-putamen connectivity.
Early-onset obsessive-compulsive disorder: Sociodemographic and clinical characterization of a large outpatient cohort
2024, Journal of Psychiatric ResearchObsessive-compulsive disorder (OCD) is a prevalent and disabling condition characterized by a wide variety of phenotypic expressions. Several studies have reinforced the hypothesis of OCD heterogeneity by proposing subtypes based on predominant symptomatology, course, and comorbidities. Early-onset OCD (EO) could be considered a neurodevelopmental subtype of OCD, with evidence of distinct neurocircuits supporting disease progression. To deepen the heterogeneous nature of the disorder, we analyzed sociodemographic and clinical differences between the EO and late-onset (LO) subtypes in a large outpatient cohort.
Two hundred and eighty-four patients diagnosed with OCD were consecutively recruited from the OCD Tertiary Clinic at Luigi Sacco University Hospital in Milan. Sociodemographic and clinical variables were analyzed for the entire sample and compared between the two subgroups (EO, age <18 years [n = 117,41.2 %]; LO: late-onset, age ≥18 years [n = 167, 58.8 %]).
The EO group showed a higher frequency of male gender (65 % vs 42.5 %, p < .001), and a higher prevalence of Tic and Tourette disorders (9.4 % vs 0 %, p < .001) compared to the LO group. Additionally, in the EO subgroup, a longer duration of untreated illness was observed (9.01 ± 9.88 vs 4.81 ± 7.12; p < .001), along with a lower presence of insight (13.8 % vs. 7.5 %, p < .05).
The early-onset OCD subtype highlights a more severe clinical profile compared to the LO group. Exploring distinct manifestations and developmental trajectories of OCD can contribute to a better definition of homogeneous subtypes, useful for defining targeted therapeutic strategies for treatment.
Distinct alterations of amygdala subregional functional connectivity in early- and late-onset obsessive-compulsive disorder
2022, Journal of Affective DisordersAge of onset may be an important feature associated with distinct subtypes of obsessive-compulsive disorder (OCD). The amygdala joined neurocircuitry models of OCD for its role in mediating fear and regulating anxiety. The present study aims to identify the underlying pathophysiological specifics in OCD with different onset times by assessing amygdala subregional functional connectivity (FC) alterations in early-onset OCD (EO-OCD) and late-onset OCD (LO-OCD).
Resting-state functional magnetic resonance imaging data were acquired from 88 medication-free OCD patients (including 30 EO-OCD and 58 LO-OCD) and age- and sex-matched healthy controls (HC) for each patient group. Onset-by-diagnosis interactions were examined and comparisons between each OCD group and the corresponding HC group were performed regarding the FC of amygdala subregions including the basolateral amygdala (BLA), centromedial amygdala (CMA), superficial amygdala (SFA) and amygdalostriatal transition area (Astr).
Significant onset-by-diagnosis interactions were found in FC between bilateral SFA, right CMA, left Astr and the cerebellum. EO-OCD patients showed abnormally increased BLA/SFA-cerebellum, BLA-precuneus and BLA/SFA-fusiform connectivity in addition to decreased BLA/SFA-orbitofrontal cortex connectivity. In contrast, LO-OCD patients exhibited increased CMA/Astr-precentral/postcentral gyrus and CMA-cuneus connectivity as well as decreased CMA/Astr-cerebellum and BLA-striatum connectivity.
The exclusion of comorbidity may reduce the generalizability of our results.
These findings emphasized the different patterns of amygdala subregional connectivity alterations associated with EO-OCD and LO-OCD patients. These results provide unique insights into constructing evidence-based distinct OCD subtypes based on brain intrinsic connectivity and point to the need of specified management for EO-OCD and LO-OCD in clinical setting.
Differences in OCD symptom presentations across age, culture, and gender: A quantitative review of studies using the Y-BOCS symptom checklist
2020, Journal of Obsessive-Compulsive and Related DisordersPresentations of obsessive-compulsive disorder (OCD) have been found to differ between patients of different ages, cultures, and genders, but inconsistent findings have limited our understanding of how these demographic factors influence the expression of OCD. To address this gap, the present review utilized data from 51 studies (N = 9404 OCD patients) to determine how the frequencies of OCD presentations from the Yale-Brown Obsessive-Compulsive Scale Symptom Checklist differed across patient samples from different age groups (adults versus children), cultural regions (United States/Europe, South America, South Africa, Asia, and the Middle East) and gender compositions (proportions of males and females in the sample). For age-group comparisons, virtually all presentations were more common in child relative to adult OCD patients, but most differences disappeared when controlling for the total number of presentations endorsed in each sample. Similarly, while all presentation varied significantly across cultural regions, differences were again more modest when controlling for total OCD presentations, which also revealed symmetry obsessions and ordering compulsions to be the only presentations with frequencies that did not significantly differ across cultures. Finally, no symptom presentation covaried with sample gender composition except for sexual obsessions, which were more commonly endorsed in samples with more male patients. Collectively, these results indicate that OCD’s major subtypes are fairly universal across different age groups, cultures, and genders and suggest that presentational differences across these demographics in previous OCD studies may have derived partly from disparities in nonspecific factors that altered the frequency of multiple OCD presentations.
Obsessive–compulsive and related disorders
2020, Handbook of Clinical NeurologyObsessive–compulsive and related disorders (OCRDs), sometimes referred to as obsessive–compulsive spectrum disorders, cause significant impairment and share similar features across several domains, including clinical course, risk factors, and response to treatment. Generally, individuals meeting criteria for one or more OCRDs present with symptoms focused on preoccupations and repetitive behaviors. Sex differences emerge in the clinical presentation of OCRDs, and the associated. Literature emphasizes the importance of considering sex when investigating causal factors, prognosis, and outcomes of OCRDs. Understanding sex-specific phenotypes can help clinicians and healthcare providers to screen for and recognize relevant symptoms, and to create a more tailored approach for care of males and females. In this chapter, we review sex differences in obsessive–compulsive disorder (OCD), body dysmorphic disorder (BDD), hoarding disorder, trichotillomania (hair-pulling disorder), and excoriation (skin-picking) disorder. Here, we provide an updated review on the sex differences in the prevalence, symptomatology, illness course and prognosis, comorbidity, risk factors, and treatment outcomes associated with OCRDs, and highlight gaps in the current literature on sex differences in these disorders.
Are candidate neurocognitive endophenotypes of OCD present in paediatric patients? A systematic review
2020, Neuroscience and Biobehavioral ReviewsTo-date it has been difficult to ascertain the exact cognitive profile of childhood OCD as studies report variable results. Adult OCD research lately utilises the endophenotype approach; studying cognitive traits that are present in both patients and their unaffected first-degree relatives, and are thought to lie closer to the genotype than the full-blown disorder. By observing whether candidate endopenotypes of adult OCD are present in child patients, we can determine whether the two subtypes show cognitive overlap. We conducted a systematic review of the paediatric OCD literature focussing on proposed neurocognitive endophenotypes of OCD: cognitive flexibility, response inhibition, memory, planning, decision-making, action monitoring, and reversal learning. We found that paediatric patients present robust increases in brain error related negativity associated with abnormal action monitoring, impaired decision-making under uncertainty, planning, and visual working memory, but there is less evidence for deficits in other cognitive domains. This implies that children with OCD show some cognitive similarities with adult patients, but other dysfunctions may only manifest later in the disorder trajectory.
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Supported by The Rockefeller University and The G. and F. Armour Foundation, and in part by a Lucille P. Markey Clinical Scholarship (C.S.) and an Irma T. Hirschl Career Scientist Award (M.K.). Clinical work at the Rockefeller University Hospital was supported by Grant No. MO1RRO102