Adult OCD Research Articles

NEUROIMAGING OF SUBCORTICAL BRAIN VOLUME ALTERATIONS IN PEADIATRIC AND ADULT OBSESSIVE-COMPULSIVE DISORDER: Preliminary findings from the ENIGMA Obsessive-Compulsive Disorder working group

Objective Structural MRI studies investigating the neural correlates of OCD have been numerous. Nevertheless, results of these studies have not always been consistent. Variability in study results may partially be explained by small sample sizes resulting in limited statistical power, clinical heterogeneity between patient samples, and methodological differences between studies. In this context, we initiated the ENIGMA-OCD working group. Our aim is to identify robust imaging markers of OCD using coordinated standardized image processing and statistical analysis protocols. Here, we perform the largest study to date of subcortical brain volumes in OCD patients and healthy controls using an individual participant data (IPD) based meta-analysis approach. Methods Structural T1-weightred MRI scans from 3722 subjects (361 paediatric OCD patients, 1574 adult OCD patients, 314 paediatric controls and 1473 adult controls) from 25 research sites worldwide were analysed using FreeSurfer 5.3. Segmentations of subcortical regions, lateral ventricles and total intracranial volumes (ICV) were visually inspected for accuracy and compared between patients and controls using regression models controlling for age, sex, and ICV. Each site followed standardized protocols designed to facilitate harmonized image analysis across multiple sites. Separate stratified analyses assessing effects of age of onset, disease duration, symptom dimensions, and symptom severity were performed. Results were combined in random-effects meta-analysis models. Meta-regression analyses were used to test whether mean age of each sample and field strength of MR images explained a significant proportion of the variance in effect seizes across sites in the meta-analysis. Results were considered significant if they exceeded a Bonferroni corrected P-value threshold (p=0.05/9 regions = 5.6x10-3). Results Adult patients, compared to adult controls, had significantly smaller hippocampal volumes (Cohen’s d= -0.15, p= 7.4x10-4) and bigger pallidum volumes (d= 0.16, p=1.8x10-3). This effect was notably stronger in medicated patients versus controls (d= -0.29, p=2.8x10-6 and d= 0.24, p=2.5x10-4, respectively). The hippocampus effect seemed to be driven by patients with comorbid depression d= 0.29, p=4.8x10-5). Also, symptom severity was associated with a smaller hippocampus (R= -0.08, p=4.9x10-3). Sample characteristics such as mean age and field strength did not moderate brain volume alterations. None of the subcortical structures, neither ICV nor lateral ventricles were significantly different between paediatric OCD cases and controls after Bonferroni correction. However, unmedicated paediatric patients show bigger thalamus volumes (d= 0.40, p=9.0x10-4) relative to control children. Additionally, longer disease duration and ad trend-significant level, younger age of onset was associated with bigger thalamus volume in paediatric OCD (d= 0.18, p=5.1x10-3 and d= -0.17, p=5.7x10-3, respectively). Conclusion Results of this subcortical meta-analysis indicate a key role of the pallidum in the pathophysiology of OCD. Different ENIGMA disease working groups, such as MDD, schizophrenia, and bipolar disorder also observed hippocampal abnormalities, which suggests that our findings regarding hippocampal abnormalities are aspecific for OCD. In addition, we showed that unmedicated paediatric OCD patients have significantly enlarged thalamus volumes. Moreover, our findings suggest a different pattern of subcortical abnormalities in paediatric OCD patients and adult OCD patients in line with the developmental nature of the disease.

THE ENDOPHENOTYPE OF EMOTIONAL REGULATION IN OBSESSIVE-COMPULSIVE DISORDER (OCD)

Introduction OCD symptoms have been associated with task-dependent alterations in brain activity implying dysregulation in limbic (e.g. the amygdala) and frontal-striatal circuits. Emerging evidence shows that there are functional neural endophenotypes in executive processing suggesting compensatory hyperactivation of fronto-parietal executive control networks and fronto-limbic dysregulation in OCD patients and first-degree relatives (de Wit et al., 2012; van Velzen et al., 2015). There are however few studies on emotional processing using a family-study design. We recently showed altered frontal-parietal and limbic functioning in OCD patients during emotion processing and emotion regulation (de Wit et al., 2015), but it remains unclear if these changes are also present in first-degree relatives. Method Forty-three unmedicated adult OCD patients, 19 of their unaffected siblings and 38 healthy controls underwent functional magnetic resonance imaging (MRI) during an emotion regulation task including neutral, fear and OCD-related visual stimuli. Stimuli were processed during natural appraisal (‘attend’ instruction) and during cognitive reappraisal (‘regulate’ instruction). Self-report distress ratings were collected from each picture. The neural correlates of emotion regulation were assessed using SPM12. Results Fear and OCD symptom provocation resulted in higher self-report distress ratings in patients compared with both siblings and healthy controls. Functional MRI analyses showed that specifically during OCD-related provocation, compared with controls, BOLD activation amplitude and timing was altered in the left hippocampus, right caudate nucleus and amygdala (for both patients and siblings), and bilateral thalamus (for siblings only). During fear regulation we previously found fronto-parietal hypoactivation in OCD patients, but fronto-parietal activation was not significantly different in siblings from patients or controls. During regulation of OCD-related stimuli siblings were more similar to patients (i.e. showing hyperactivation of the dorsomedial PFC (dmPFC) compared with controls). Compared with both patients and controls, hyperactivation in siblings was more extensive (including the supplementary motor area and parietal regions), and siblings showed increased dmPFC-connectivity with the middle cingulate, superior temporal, and superior frontal cortices during OCD-related emotion regulation. The diminished dmPFC-amygdala connectivity we previously reported in OCD patients during fear-regulation was not present in the sibling group. Discussion Unaffected siblings of OCD patients were similar to controls on the behavioral response to emotional provocation, but showed dissimilar neural responses during OCD-related emotion provocation and regulation compared to healthy controls, while there were fewer differences for general fear stimuli. During OCD-related emotion provocation we observed altered activation in limbic and striatal regions in both OCD patients and siblings. During OCD-related emotion regulation siblings showed few differences compared to patients, but showed increased activation in fronto-parietal and temporal areas compared to controls. Siblings also showed extensive dmPFC hyperconnectivity compared to the patients and controls, which suggests a compensatory response. These results extend previous findings of functional endophenotypes in OCD, and show dissociation between subjective distress and brain activity during emotion processing in unaffected siblings of people with OCD.

Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta-and Mega-Analysis (vol , pg , 2016)

Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta-and Mega-Analysis (vol , pg , 2016)

An investigation into the role of attachment insecurities in obsessive-compulsive symptoms

ABSTRACTThe paper discusses the associations between adult attachment and OCD symptoms in light of current cognitive-behavioural theories of OCD. The role of attachment system in OCD has been increasingly recognised. The aim of this paper was to investigate and evidence for direct and indirect relations between attachment insecurities, obsessional beliefs and OCD symptoms. Data were collected from a sample of university students (N = 334) in a cross-sectional research design. Adjusting for age, sex, income, paternal education and maternal education, attachment anxiety and avoidance in combination with obsessional beliefs (responsibility/threat estimation, perfectionism/certainty and importance/control of thoughts) were regressed onto obssessionality using logistic regression analysis. One-way MANOVA comparisons of obsessionality and obsessive beliefs were run across four attachment styles. Finally, the affect regulation model of attachment theory was refined and tested in relation to OCD symptomatology. Attachment anxiety and attachment avoidance significantly contributed to severity of obsessive-compulsive symptoms. More specifically, respondents with fearful and preoccupied attachment styles reported greater scores on obsessive-compulsive symptomatology and obsessional beliefs. Using a structural modelling approach, we found responsibility/threat estimation significantly contributed to obsessional symptomatology via attachment anxiety and avoidance.

Increased levels of oxytocin in adult OCD patients

Introduction The current model of the pathophysiology of obsessive-compulsive (OCD) is mainly centered on the serotonin (5-HT) system. However, other pharmacological targets have been identified, in particular the dopamine and glutamate systems, and also the neuropeptide oxytocin (OT), both per se and given its interactions with the 5-HT system. Objectives Given the paucity of information, the present study aimed at evaluating plasma OT levels in a group on untreated OCD patients. Aims The study aimed at evaluating plasma OT levels in a group of 44 OCD outpatients, as compared with a similar group of healthy control subjects. On the same time, the relationships between OT and clinical features and romantic attachment characteristics were examined as well. Methods Diagnosis was assessed according to DSM-IV-TR criteria, while the OCD severity was measured by means of the Y-BOCS rating scale. All patients were drug-free and not depressed. The romantic attachment was assessed by means of the Italian version of the Experiences in Close Relationships questionnaire. Plasma OT levels were evaluated by means of a standard RIA kit. Results The main findings of our study showed that OT levels were increased in OCD patients, as compared with healthy subjects, and negatively related to symptom severity. Positive relationships were detected between OT levels and the fearful-avoidant and dismissing styles of romantic attachments, but only in male OCD patients. Conclusions Taken together, these findings suggest that OT may play a role in OCD pathophysiology and also in romantic attachment of patients with gender specificity.

The Unlikely Hero of Room 13 B by Teresa Toten (review)

Reviewed by: The Unlikely Hero of Room 13 B by Teresa Toten Karen Coats Toten, Teresa The Unlikely Hero of Room 13 B. Delacorte, 2015 289p Library ed. ISBN 978-0-553-50787-4 $20.99 Trade ed. ISBN 978-0-553-50786-7 $17.99 E-book ed. ISBN 978-0-553-50788-1 $10.99 R Gr. 8-10 When Robyn joins the Young Adult OCD Support Group, fourteen-year-old Adam falls immediately and totally in love. He already plenty on his plate: since his parents’ divorce and his father’s remarriage, his mother has started hoarding, and his new little stepbrother suffers from sadness that only Adam can manage. Meanwhile, Adam seems to have informally taken control of Group as well, introducing them to the comforting space and rituals of his Catholic church. He helps Robyn, too, and they do fall sweetly in love, but as his mother’s hoarding and other symptoms escalate, so do Adam’s compulsions, until finally he is unable to breach the threshold of his own home. Adam is thoroughly likable and thoroughly liked by the other characters, who come to see him as a hero. Readers spend so much time in his head with him that his rituals take on heartbreaking immediacy; his desperation to save his mother, his stepbrother, and his beloved Robyn render the fact that he is losing himself all the more tragic. Toten never plays coy in her depiction of his and others’ illness, but she also shows Adam as someone straining toward normal and sometimes achieving it. While Adam’s altruism never falters, his vulnerability, humor, and thoughtful responses keep him from seeming too good to be true; he’s just a guy who’s chosen compassion over bitterness in the face of his suffering, and his plight is sure to inspire compassion in readers as well. An interview with the author follows the text. Copyright © 2015 The Board of Trustees of the University of Illinois

Fatigue Experiences Among OCD Outpatients.

Patients with OCD are impaired in multiple domains of functioning and quality of life. While associated psychopathology complaints and neuropsychological deficits were reported, the subjective experience of general fatigue and mental fatigue was scarcely investigated. In this single-center case-control study we compared 50 non-depressed OCD outpatients consecutively recruited and 50 panic disorder (PD) outpatients, to determine whether they experienced fatigue differently. Assessment consisted of structured clinical interview for DSM-IV criteria by using the SCID-I and the SCID-II. Symptom severity was assessed using the Yale-Brown Obsessive-Compulsive Scale, the Hamilton Anxiety Rating Scale, the Hamilton Depression Rating Scale, the Clinical Global Impressions Scale, severity and the Global Assessment of Functioning Scale. Fatigue was assessed by using the Multidimensional Fatigue Inventory (MFI). Regarding MFI physical fatigue, an OR of 0.196 (95 % CI 0.080-0.478) was found, suggesting that its presence is associated with lower odds of OCD compared to PD. The same can be said for MFI mental fatigue, as an OR of 0.138 (95 % CI 0.049-0.326) was found, suggesting that its presence is associated with lower odds of OCD. Notably, OCD patients with OCDP co-morbidity reported higher scores of mental fatigue. In this study fatigue, including mental fatigue, seems not to be a prominent experience among adult non-depressed OCD patients.

Impact of age of onset of illness on clinical phenotype in OCD

BackgroundThis study aims to examine the demographic, clinical and comorbid patterns in a large sample of adult OCD subjects at a specialty OCD clinic in India. MethodsConsecutive patients (n=545) who consulted a specialty OCD Clinic over 5 years at a large psychiatric hospital in India were evaluated with the Mini International Neuropsychiatric Interview, the Yale-Brown Obsessive–Compulsive Scale, and the Clinical Global Impression scale. ResultsEarlier age onset of OCD (years) was characterized by male preponderance (19.61±7.98 vs. 25.19±10.39, U=23453.5, p=<0.001), positive family history of OCD (19.60±10.02 vs. 22.27±9.20, U=16590.5, p<0.001) and presence of tic disorder (16.28±8.21 vs. 22.01±9.38, OR=0.86, p=0.001). In addition, early age of onset was associated with presence of sexual obsessions (18.92±7.49 vs. 22.88±9.82, OR=0.96, p=0.02), hoarding (19.61±9.32 vs. 22.21±9.36, OR=0.95, p=0.009), repeating rituals (19.76±8.37 vs. 23.29±9.84, OR=0.95, p=0.006) and need to touch compulsions (16.40±7.19 vs. 22.36±9.43, OR=0.89, p<0.001). ConclusionsOur findings from a large sample not only confirm that early onset OCD could be a valid and distinct subtype of OCD but also support the cross-cultural similarity of early onset phenotype.

Treatment outcome in adult OCD: Predictors and processes of change

The current study investigates predictors of treatment response in 41 treatment-seeking adults with OCD. Further, this study examines the relationship between OCD symptom change following CBT, and change in OCD-related cognitive variables. It was hypothesised that higher OCD severity, the presence of hoarding, sexual obsessions and religious obsessions, and elevated anxiety and depression would be associated with a poorer response to CBT. It was also hypothesised that symptom change would be associated with change in OCD-related cognitive biases. Results found that only severity of OCD and the presence of sexual obsessions predicted poorer treatment response. Furthermore, whilst treatment resulted in significant reductions in cognitive biases argued to be associated with OCD, these changes were not correlated with OCD symptomatic change. Implications of this research are discussed in light of future treatment considerations.

Refining clinical judgment of treatment outcome in obsessive–compulsive disorder

This research aimed to provide clinicians and investigators with optimal treatment outcome criteria for accurately predicting response and remission in both research studies and clinical practice. Data from 153 adult OCD outpatients (ages 18–79) who had participated in a treatment outcome study were examined. Signal detection analysis was conducted to compare levels of Yale–Brown Obsessive Compulsive Scale (Y-BOCS) symptom percent reductions and post treatment absolute scores with Clinical Global Impression (CGI) ratings of symptom improvement and severity. Optimal cutoff criteria were based on sensitivity, specificity and efficiency and were assessed via the Quality Receiver Operating Characteristic curve. A Y-BOCS reduction of 45% was observed to be the most efficient for predicting response in research trials, whereas a reduction of 35% may be optimal for clinical use. A 55% Y-BOCS reduction was determined to be the optimal cutoff for predicting remission in both clinical and research settings. A Y-BOCS absolute raw score of 12 or less was optimal for predicting remission in a clinical setting and a raw score of 14 or below was most favorable in research trials. This research provides the first empirical contrast of optimal outcome criteria in OCD based on differing ideals of both research and practice.

The Rationale and Some Features of the Nordic Long-Term OCD Treatment Study (NordLOTS) in Childhood and Adolescence

OCD is a more prevalent disorder than was once thought at a point prevalence from 0.6–1.5% in older children and young adolescents (Heyman et al. 2001) often running a chronic course as found in a meta-analysis of available outcome studies (Stewart et al. 2004). While a third of those who still were ill did fairly well, the other 2/3 had significant impairment and suffering. However, the patients had received very different therapies ranging from those known to be ineffective, such as psychodynamic psychotherapy, ‘‘classical’’ family therapy or drugs as benzodiazepines to therapies that had included CBT and/or serotonine active drugs at some point. The range of outcome did not differ as much as one would have hoped, given the range of treatments (see also Nissen and Thomsen 2008). Those who had had an inadequate first treatment tended to do worse. More than 50% of adults with OCD report onset in childhood/adolescence (Rasmussen and Eisen 1992), and we really do not know to what extent adults with OCD had been in treatment as children, nor if they had, to what extent it helped. The question of chronic pediatric OCD is not a trivial one, children with OCD grow up and many adults with OCD had childhood onset (Rasmussen and Eisen 1992). Adult OCD is the 10:th most common cause of disability from illness, including somatic illness (Lopez 1996, cited in Haynes et al. 2006).

Childhood neuropsychological deficits and adult OCD

We read Grisham et al ’s paper[1][1] with some concerns. Without doubt, the study – using longitudinal data instead of cross-sectional designs as in previous studies – adds positively to the subject area, which has not been well researched and the results of which are far from conclusive.

Neurocognitive correlates of child obsessive compulsive disorder and Tourette syndrome

This study investigated the neurocognitive correlates of childhood OCD and TS, which are purported to share frontal–striatal dysfunction. Neurocognitive measures tapping frontal–striatal functions such as executive, attention/memory, and visuomotor abilities were administered to three groups of participants, OCD without comorbid TS (OCD), TS without comorbid OCD (TS), and normal controls. Results suggested that OCD group demonstrated deficits in the area of spatial attention relative to healthy controls. The OCD participants demonstrated no cognitive deficits compared to the TS group. TS participants showed trends towards impairments in the areas of response inhibition, divided attention, and cognitive flexibility relative to the OCD and normal control groups. Spatial attention deficits for the OCD group are partially consistent with adult OCD studies indicating deficits in spatial memory. TS findings were less robust and may be construed tentatively as suggestive of executive function deficits. Future research is needed to delineate the influence of development on neurocognitive deficits associated with OCD and TS.

Subcortical functioning in obsessive-compulsive disorder: An exploratory EEG coherence study

Background. Given the paucity of quantitative EEG studies using coherence measures to understand the electrophysiological functional integrity of sub-cortical structures in obsessive-compulsive disorder, the current study was carried out. Methods. We obtained EEG coherence values for 20 adult OCD patients (10 males; 10 females) and 19 appropriately matched healthy controls across delta (0.5–3.5 Hz), theta (4–7.5 Hz), alpha (8–12 Hz), beta1 (12.5–20 Hz) and beta2 (20.5–30 Hz) bands. As coherence between distant brain regions reflects physiological activities at sub-cortical neural networks, we chose EEG channels at four distant brain regions – anterior interhemispheric, posterior interhemispheric, fronto-temporal and fronto-occipital. Results. In comparison to controls we found significant increase of theta band EEG coherence in the fronto-occipital region in OCD patients (P = 0.045) which did not correlate significantly with either medication status or disease severity. Conclusion. This EEG coherence study that suggests hyperactivity at subcortical circuitry in OCD patients is in agreement with existing neuro-imaging findings. Furthermore, this finding provides external validity for sub-cortical dysfunction hypothesis of OCD.

Cognitive–behavioural theory and therapy for obsessive–compulsive disorder in children and adolescents: Current status and future directions

Obsessive–compulsive disorder is recognised to be much more common than once thought, and increased awareness of prevalence has been associated with an increase in clinical and research attention. However, while the cognitive behavioural model of OCD has received considerable empirical support from adult studies, there has been relatively little investigation of this model in childhood populations. Although this literature is beginning to emerge, initial evaluations suggest there may be important differences between childhood and adult OCD with regard to the cognitive, behavioural, and family factors implicated in the etiology and maintenance of the disorder. Despite this, cognitive–behavioural interventions have been largely modelled on their adult counterparts, and there has been little evaluation of the effectiveness of various treatment components. This paper therefore seeks to critically review the current status of CBT for children and adolescents with OCD, addressing both cognitive behavioural theory and therapy. Current issues in clinical practice will be identified, gaps in the knowledge base will be highlighted, and the paper will conclude by making specific recommendations regarding the integration of research and practice.

Subtyping obsessive-compulsive disorder: Clinical and immunological findings in child and adult onset

It has been suggested that certain kinds of childhood OCD with specific clinical, biological and immunological characteristics may form a subgroup of OCD. We study the presence of these characteristics in child onset OCD and propose that the disorder be considered as a subtype of adult OCD. Forty adult patients with OCD were divided in two groups according to time of disease onset: 18 early onset and 21 late. Both sets were compared with a control group of 14 psychiatric patients. Child onset OCD was associated with higher mean ASLO titers, higher frequencies of history of tic disorders and tonsillitis in childhood and compulsive symptoms. No differences were found in D8/17 antibody titers or in other autoimmune parameters. The findings suggest that child onset OCD can be considered as a subgroup of adult OCD, although more specific biological markers are needed to identify it.

Glutamatergic Dysfunction in OCD

The role of glutamatergic dysfunction in the pathophysiology of OCD has hardly been explored despite recent reports implicating glutamatergic dysfunction in OCD. We decided to investigate CSF glutamate levels in adult OCD probands compared to psychiatrically normal controls. In total, 21 consenting psychotropic drug-naïve adult OCD patients, diagnosed using SCID-IV-CV, and 18 consenting psychiatrically normal controls with age within 10 years of age of the patients, who did not have any history of head injury or neurological illness, were included into the study. Aseptically collected and stored CSF samples obtained from the patients and control subjects were used for glutamate estimation, which was carried out by a modification of the procedure described by Lund (1986). CSF glutamate (micromol/l) level was found to be significantly higher [F(1,31)=6.846, p=0.014] in OCD patients (47.12+/-4.25) compared to control subjects (41.36+/-3.63) on analysis of covariance. There was no effect of gender, age, duration of illness, Y-BOCS score, or CGI-S score on CSF glutamate levels. Our study provides preliminary evidence implicating glutamatergic excess in the pathophysiology of OCD, which needs to be further explored by studies from other centers involving larger sample sets from different age groups.