Sensory over-responsivity and orbitofrontal cortex connectivity in obsessive-compulsive disorder.

BACKGROUND: Sensory over-responsivity (SOR) in obsessive-compulsive disorder (OCD) is associated with illness severity and functional impairment. However, the neural substrates of SOR in OCD have not yet been directly probed. METHODS: We examined resting-state global functional connectivity markers of SOR in 119 adults with OCD utilizing the CONN-fMRI Functional Connectivity Toolbox for SPM (v21a). We quantified SOR with the sensory sensitivity and sensory avoiding subscales of the Adult and Adolescent Sensory Profile (AASP). We also measured: OCD severity, with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Obsessive-Compulsive Inventory-Revised (OCI-R); sensory phenomena with the Sensory Phenomena Scale (SPS); general anxiety, with the Beck Anxiety Inventory (BAI); and depressive symptomatology, with Quick Inventory of Depressive Symptoms, Self-Report (QIDS-SR). RESULTS: There was a significant positive relationship of SOR with global connectivity in anterior and medial OFC (Brodmanns area 11, k = 154, x = 14, y = 62, z = -18, whole-brain corrected at FWE p < 0.05). LIMITATIONS: Future investigations should explore neural responses to sensory stimulation tasks in OCD and compare findings with those obtained in other conditions also characterized by high SOR, such as autism spectrum disorder. CONCLUSIONS: This study implicates OFC functional connectivity as a neurobiological mechanism of SOR in OCD and suggests that the substrates of SOR in OCD may be dissociable from both that of other symptoms in OCD, and SOR in other disorders. With replication and extension, the finding may be leveraged to develop and refine treatments for OCD and investigate the pathophysiology of SOR in other conditions.

Associations Between Suicidality and Interoception in Obsessive-Compulsive Disorder.

Background: Individuals with obsessive-compulsive disorder (OCD) are at increased risk for suicide. One potential risk factor is interoceptive sensibility (IS), which is one's subjective experience of bodily sensations. The current study examined the relationship between IS and current suicidal ideation and lifetime history of suicide attempt, controlling for relevant covariates. Methods: Participants (N = 145) were a clinical sample of individuals with OCD from the New York City area. A clinical rater administered a diagnostic interview and an OCD severity assessment, and participants completed questionnaires about demographics, IS, and suicidality. Results: Current suicidal ideation was associated with reduced trusting of the body, and lifetime history of suicide attempt was related to greater general awareness of sensation. These associations remained significant after controlling for covariates. Conclusions: These results suggest that specific facets of IS may be associated with specific domains of suicidality. Decreased body trusting may represent a feeling of disconnection from the body that facilitates desire for death. Increased noticing of bodily sensations may lead to greater mental pain, which could interact with deficits in emotion regulation to increase risk for suicide attempt. Further research on the relationships between IS and suicidality in OCD is warranted.

Failures of Urge Suppression in Obsessive-Compulsive Disorder: Behavioral Modeling Using a Blink Suppression Task.

Many individuals with obsessive-compulsive disorder (OCD) report sensory-based urges (e.g. 'not-just-right experiences') in addition to, or instead of, concrete fear-based obsessions. These sensations may be comparable to normative "urges-for-action" (UFA), such as the urge to blink. While research has identified altered functioning of brain regions related to UFA in OCD, little is known about behavioral patterns of urge suppression in the disorder. Using an urge-to-blink task as a model for sensory-based urges, this study compared failures of urge suppression between OCD patients and controls by measuring eyeblinks during 60-second blocks of instructed blink suppression. Cox shared frailty models estimated the hazard of first blinks during each 60-second block and recurrent blinks following each initial erroneous blink. OCD patients demonstrated a higher hazard of first and recurrent blinks compared to controls, suggesting greater difficulty resisting repetitive sensory-based urges. Within OCD, relationships between task outcomes and symptom severity were inconsistent. Findings provide support for a deficit in delaying initial urge-induced actions and terminating subsequent actions in OCD, which is not clearly related to clinical heterogeneity. Elucidating the nature of behavioral resistance to urges is relevant for informing conceptualizations of obsessive-compulsive psychopathology and optimizing treatment outcomes.

The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

Cognitive Neuroscience of Obsessive-Compulsive Disorder.

Cognitive neuroscientific research has the ability to yield important insights into the complex neurobiological processes underlying obsessive-compulsive disorder (OCD). This article provides an updated review of neuroimaging studies in seven neurocognitive domains. Findings from the literature are discussed in the context of obsessive-compulsive phenomenology and treatment. Expanding our knowledge of the neural mechanisms involved in OCD could help optimize treatment outcomes and guide the development of novel interventions.

Relationships between interoceptive sensibility and resting-state functional connectivity of the insula in obsessive-compulsive disorder.

Patients with obsessive-compulsive disorder (OCD) exhibit abnormality in their subjective perception of internal sensation, a process known as interoceptive sensibility (IS), as well as altered functioning of the insula, a key neural structure for interoception. We investigated the multivariate structure of IS in 77 OCD patients and 53 controls and examined associations of IS with resting-state functional connectivity (FC) of the insula within the OCD group. For each group, principal component analysis was performed on 8 subscales of the Multidimensional Assessment of Interoceptive Awareness assessing putatively "adaptive" and "maladaptive" aspects of IS. Associations between IS components and insula FC in the OCD group were evaluated using seed regions placed in each of 3 subdivisions of the insula (posterior, anterior dorsal, and anterior ventral). Behaviorally, controls showed a 2-component solution broadly categorized into "adaptive" and "maladaptive" IS, while OCD patients exhibited a 3-component solution. The general tendency to notice or be aware of sensation loaded onto an "adaptive" IS component in controls but loaded onto both "adaptive" and "maladaptive" IS components in OCD. Within OCD, insula FC was differentially associated with distinct aspects of IS, identifying network connections that could serve as future targets for the modulation of IS in OCD.

The thalamus and its subnuclei-a gateway to obsessive-compulsive disorder.

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered ( https://osf.io/73dvy ) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status.

Imbalance between default mode and sensorimotor connectivity is associated with perseverative thinking in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is highly heterogeneous. Although perseverative negative thinking (PT) is a feature of OCD, little is known about its neural mechanisms or relationship to clinical heterogeneity in the disorder. In a sample of 85 OCD patients, we investigated the relationships between self-reported PT, clinical symptom subtypes, and resting-state functional connectivity measures of local and global connectivity. Results indicated that PT scores were highly variable within the OCD sample, with greater PT relating to higher severity of the "unacceptable thoughts" symptom dimension. PT was positively related to local connectivity in subgenual anterior cingulate cortex (ACC), pregenual ACC, and the temporal poles-areas that are part of, or closely linked to, the default mode network (DMN)-and negatively related to local connectivity in sensorimotor cortex. While the majority of patients showed higher local connectivity strengths in sensorimotor compared to DMN regions, OCD patients with higher PT scores had less of an imbalance between sensorimotor and DMN connectivity than those with lower PT scores, with healthy controls exhibiting an intermediate pattern. Clinically, this imbalance was related to both the "unacceptable thoughts" and "symmetry/not-just-right-experiences" symptom dimensions, but in opposite directions. These effects remained significant after accounting for variance related to psychiatric comorbidity and medication use in the OCD sample, and no significant relationships were found between PT and global connectivity. These data indicate that PT is related to symptom and neural variability in OCD. Future work may wish to target this circuity when developing personalized interventions for patients with these symptoms.

Affective and somatic symptom clusters in depression and their relationship to treatment outcomes in the STAR*D sample.

BACKGROUND: The heterogenous nature of depression continues to stymie efforts to identify biomarkers or predict treatment response. Efforts leveraging large datasets to define more uniform subtypes of depression or subgroups of depressed patients have considered only small subsets of symptoms. We aimed to understand how inclusion of more diverse complaints would impact data-emergent symptom and patient clusters. METHODS: We applied principal components analysis to baselineInventory of Depressive Symptomatology data from 1491 patients with major depressive disorder to derive naturally co-occurring symptom subsets before utilizing k-means clustering to divide patients into groups based on standardized residuals of each symptom subset score. We evaluated the clinical utility of our approach by comparing how cluster membership impacted response to citalopram. RESULTS: Prinicpal components analysis identified nine naturally co-occurring symptom subsets: core affective symptoms, appetite/weight loss, anxiety, somatic symptoms, insomnia, negative intrusive thoughts, leaden paralysis/mood quality, diurnal mood variation, and irritability. Cluster analysis identified two patient groups, differing significantly in 7 of 9 c symptom subsets. Patients distinguished by the prominence of somatic versus core affective symptoms exhibited less reduction in depression severity with citalopram treatment. LIMITATIONS: Results depend not only on raw data, but also parameter selection, and interpretation. Replication is indicated. CONCLUSIONS: Findings are consistent with previous reports linking somatic symptoms to treatment resistance and demonstrating that SSRIs are most effective in treating affective symptoms. A novel distinction between physical somatic symptoms and psychic anxiety highlights the utility of assessing a broad spectrum of symptoms when exploring heterogeneity in depression and the need for treatments targeting physical somatic symptoms specifically.

Interoception and Obsessive-Compulsive Disorder: A Review of Current Evidence and Future Directions.

Disrupted interoceptive processes are present in a range of psychiatric conditions, and there is a small but growing body of research on the role of interoception in obsessive-compulsive disorder (OCD). In this review, we outline dimensions of interoception and review current literature on the processing of internal bodily sensations within OCD. Investigations in OCD utilizing objective measures of interoception are limited and results mixed, however, the subjective experience of internal bodily sensations appears to be atypical and relate to specific patterns of symptom dimensions. Further, neuroimaging investigations suggest that interoception is related to core features of OCD, particularly sensory phenomena and disgust. Interoception is discussed in the context of treatment by presenting an overview of existing interventions and suggesting how modifications aimed at better targeting interoceptive processes could serve to optimize outcomes. Interoception represents a promising direction for multi-method research in OCD, which we expect, will prove useful for improving current interventions and identifying new treatment targets.

Individual-fMRI-approaches reveal cerebellum and visual communities to be functionally connected in obsessive compulsive disorder.

There is significant interest in understanding the pathophysiology of Obsessive-Compulsive Disorder (OCD) using resting-state fMRI (rsfMRI). Previous studies acknowledge abnormalities within and beyond the fronto-striato-limbic circuit in OCD that require further clarifications. However, limited information could be inferred from the conventional way of investigating the functional connectivity differences between OCD and healthy controls. Here, we identified altered brain organization in patients with OCD by applying individual-based approaches to maximize the identification of underlying network-based features specific to the OCD group. rsfMRI of 20 patients with OCD and 22 controls were preprocessed, and individual-fMRI-subspace was derived for each subject within each group. We evaluated group differences in functional connectivity using individual-fMRI-subspace and established its advantage over conventional-fMRI methodology. We applied prediction-based approaches to highlight the group differences by evaluating the differences in functional connections that predicted the clinical scores (namely, the Obsessive-Compulsive Inventory-Revised (OCI-R) and Hamilton Anxiety Rating Scale). Then, we explored the brain network organization of both groups by estimating the subject-specific communities within each group. Lastly, we evaluated associations between the inter-individual variation of nodes in the communities to clinical measures using linear regression. Functional connectivity analysis using individual-fMRI-subspace detected 83 connections that were different between OCD and control groups, compared to none found using conventional-fMRI methodology. Connectome-based prediction analysis did not show significant overlap between the two groups in the functional connections that predicted the clinical scores. This suggests that the functional architecture in patients with OCD may be different compared to controls. Seven communities were found in both groups. Interestingly, within the OCD group but not controls, we observed functional connectivity between cerebellar and visual regions, and lack of connectivity between striato-limbic and frontal areas. Inter-individual variations in the community-size of these two communities were also associated with the OCI-R score (p < .005). Due to our small sample size, we further validated our results by (i) accounting for head motion, (ii) applying global signal regression (GSR) in data processing, and (iii) using an alternate atlas for parcellation. While the main results were consistently observed with accounting for head motion and using another atlas, the key findings were not reproduced with GSR application. The study demonstrated the existence of disconnectedness in fronto-striato-limbic community and connectedness between cerebellar and visual areas in OCD patients, which was also related to the clinical symptomatology of OCD.

Dimensions of interoception in obsessive-compulsive disorder.

Interoceptive sensibility (IS) refers to the subjective experience of perceiving and being aware of one's internal body sensations, and is typically evaluated using self-report questionnaires or confidence ratings. Here we evaluated IS in 81 patients with OCD and 76 controls using the Multidimensional Scale of Interoceptive Awareness (MAIA), which contains 8 subscales assessing adaptive and maladaptive responses to sensation. Compared to controls, OCD patients showed hyperawareness of body sensations. Patients also demonstrated a more maladaptive profile of IS characterized by greater distraction from and worry about unpleasant sensations, and reduced tendency to experience the body as safe and trustworthy. These findings were independent of medication status and comorbidities in the patient group. Correlational analyses showed that subscales of the MAIA were differentially associated with OCD symptom dimensions. These findings indicate that patients with OCD show abnormality of IS that is independent of confounding factors related to medication and comorbidities and associated with different OCD symptom dimensions. Future work would benefit from examining neural correlates of these effects and evaluating whether dimensions of IS are impacted by treatments for the disorder.

Establishing the Brief Assessment of Cognition - Short form.

The study aims to identify and validate a parsimonious subset of tests in the commonly used Brief Assessment of Cognition in Schizophrenia (BACS) that allows the evaluation of global cognitive ability. Several permutations of subtests from the BACS were examined to identify the best subset of tests to compose the short form measure. The Brief Assessment of Cognition-Short Form (BAC-SF) was evaluated for convergent validity in healthy and psychiatric samples (N = 3718). Verbal Memory, Digit Sequencing, and Symbol Coding subtests were found to best summarize the variance of composite scores in both Asian and US Norming samples (r = 0.91) indicating that BAC-SF is an appropriate approximation of cognitive deficits. Test re-test reliability of the BAC-SF was adequate (Intraclass Correlation Coefficient (ICC) = 0.73) and showed sufficient separation between healthy controls and schizophrenia (Average Predictive Accuracy = 79.9%; replication = 76.5%). Findings indicate that the BAC-SF an could be used as a cognitive screener for large-scale clinical and epidemiological studies. The short form does not replace the need for comprehensive neuropsychological batteries purposed for detailed neuropsychological and clinical investigation of cognitive function. Further replication of the construct might be necessary in other clinical populations.

Screening for Drinking Problems in the Elderly in Singapore Using the CAGE Questionnaire.

INTRODUCTION: Given that past research on drinking problems has focused primarily on younger samples, the present study sought to examine the prevalence and correlates of alcohol use among the elderly in Singapore. MATERIALS AND METHODS: Data were extracted from the Well-being of the Singapore Elderly (WiSE) study, a cross-sectional, epidemiological survey conducted among a nationally representative sample of Singapore residents (n = 2565) aged 60 years and above. Variables assessed include drinking problems, depression and anxiety symptoms, obesity, smoking status, chronic physical disorders and disability. RESULTS: The weighted prevalence of drinking problems (CAGE score ≥2) in our sample was 4.2%. Male sex, Indian ethnicity, and being divorced or separated were associated with a significantly higher likelihood of drinking problems. Participants with drinking problems were also more likely to have subthreshold depression. There were no significant differences in disability among those with drinking problems, those without drinking problems and non-drinkers, after adjusting for demographic variables. CONCLUSION: Our findings contribute to the body of research that indicates an association between drinking problems and depressive symptoms among the elderly. Thus, screening for depressive symptoms in the elderly with drinking problems may be useful in identifying such comorbidities in order to aid treatment planning.

Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: an integrative review.

Obsessive-compulsive disorder (OCD) is a debilitating disorder. However, existing neuroimaging findings involving executive function and structural abnormalities in OCD have been mixed. Here we conducted meta-analyses to investigate differences in OCD samples and controls in: Study 1 - grey matter structure; Study 2 - executive function task-related activations during (i) response inhibition, (ii) interference, and (iii) switching tasks; and Study 3 - white matter diffusivity. Results showed grey matter differences in the frontal, striatal, thalamus, parietal and cerebellar regions; task domain-specific neural differences in similar regions; and abnormal diffusivity in major white matter regions in OCD samples compared to controls. Our results reported concurrence of abnormal white matter diffusivity with corresponding abnormalities in grey matter and task-related functional activations. Our findings suggested the involvement of other brain regions not included in the cortico-striato-thalamo-cortical network, such as the cerebellum and parietal cortex, and questioned the involvement of the orbitofrontal region in OCD pathophysiology. Future research is needed to clarify the roles of these brain regions in the disorder.

Prevalence of Dementia in People Aged 60 Years and Above: Results from the WiSE Study.

BACKGROUND: The challenge of an aging population with its expected attendant problem of an increase in the number of people with dementia is a growing concern across the world. OBJECTIVE: The aims of this study were to establish the prevalence and risk factors of dementia in Singapore among the elderly resident population (aged 60 years and above). METHODS: The WiSE study was a comprehensive single phase, cross-sectional, epidemiological survey that adapted the 10/66 protocol to establish the 10/66 and the Diagnostic and Statistical Manual of mental disorders -fourth edition (DSM-IV) diagnosis of dementia. 10/66 and DSM-IV dementia diagnosis as established by the survey questionnaires was validated by comparing against a gold standard of clinical assessment. RESULTS: A total of 2,565 respondents completed the study giving a response rate of 65.6%. The validity of 10/66 dementia was higher (sensitivity = 95.6%, specificity = 81.8%) than that of DSM-IV dementia (sensitivity = 75.6%, specificity = 88.6%) when compared against the clinical gold standard. The study found that the prevalence of 10/66 dementia was 10% in the older adult population while the prevalence of DSM-IV dementia was 4.6%. Older age (75 years and above); no formal education, or completed primary education (versus higher education); homemaker and retired status (versus employed); and a history of stroke were associated with a higher risk of 10/66 dementia. CONCLUSION: The establishment of accurate data on the number of people with dementia is essential in the planning of services and initiatives.

The continuous performance test, identical pairs: norms, reliability and performance in healthy controls and patients with schizophrenia in Singapore.

AIM: To provide normative values for the healthy ethnic Chinese Singaporean population and a large sample of patients with schizophrenia for the Continuous Performance Task-Identical Pairs (CPT-IP). Participants Data were collected on 1011 healthy ethnic Chinese and 654 patients diagnosed with schizophrenia, all between 21 and 55 years of age. METHODS: Data were stratified by age and gender. The effects of age, gender and education were explored in patients and controls. Performance indices were assessed in their ability to predict group inclusion. Controls' performance was compared with that reported in a US sample. RESULTS: Performance was affected by age, sex, and education, with youth, male sex and higher education providing a performance advantage. Patients' performance was lower than controls' by more than 1 standard deviation, with the 3-digit d' score most significantly discriminating between controls and patients. The effects of socio-demographic factors on performance were in line with those conducted in the US and previously reported in the literature. CONCLUSIONS: This is the largest norming study ever conducted on the CPT-IP. It will enable investigators and clinicians to select appropriate indices to assess severity of cognitive decline and/or evaluate cognitive remediation therapy outcomes after taking into account age, gender and education factors.

Development, validity and reliability of the short multidimensional positive mental health instrument.

PURPOSE: The 47-item positive mental health (PMH) instrument measures the level of PMH in multiethnic adult Asian populations. This study aimed to (1) develop a short PMH instrument and (2) establish its validity and reliability among the adult Singapore population. METHODS: Two separate studies were conducted among adult community-dwelling Singapore residents of Chinese, Malay or Indian ethnicity where participants completed self-administered questionnaires. In the first study, secondary data analysis was conducted using confirmatory factor analysis (CFA) to shorten the PMH instrument. In the second study, the newly developed short PMH instrument and other scales were administered to 201 residents to establish its factor structure, validity and reliability. RESULTS: A 20-item short PMH instrument fulfilling a higher-order six-factor structure was developed following secondary analysis. The mean age of the participants in the second study was 41 years and about 53% were women. One item with poor factor loading was further removed to generate a 19-item version of the PMH instrument. CFA demonstrated a first-order six-factor model of the short PMH instrument. The PMH-19 instrument and its subscales fulfilled criterion validity hypotheses. Internal consistency and test-retest reliability of the PMH-19 instrument were high (Cronbach's α coefficient = 0.87; intraclass correlation coefficient = 0.93, respectively). CONCLUSIONS: The 19-item PMH instrument is multidimensional, valid and reliable, and most importantly, with its reduced administration time, the short PMH instrument can be used to measure and evaluate PMH in Asian communities.

Brief assessment of cognition in schizophrenia: normative data in an English-speaking ethnic Chinese sample.

There is a dearth of non-Western normative data for neuropsychological batteries designed to measure cognitive deficits in schizophrenia. Here, we provide normative data for English-speaking ethnic Chinese on the widely used Brief Assessment of Cognition in Schizophrenia acquired from 595 healthy community participants between ages 14 and 55. Means and standard deviations of subtests and composite scores were stratified by age group and sex. We also explored linear regression approaches to generate continuous norms adjusted for age, sex, and education. Notable differences in subtest performances were found against a Western comparison sample. Normative data established in the current sample are essential for clinical and research purposes as it serves as a reference source of cognition for ethnic Chinese.