Biomedical subjects

David Mataix-Cols

Publications and source records attributed to David Mataix-Cols.

At least 19 recordsLinked to original sources

PubMed2026

Persistent tic disorders are associated with 17q12 duplications.

Tourette Syndrome (TS) and Persistent Tic Disorder (PTD) are childhood-onset neuropsychiatric conditions with high heritability. Due to current sample size limitations, identifying TS/PTD risk genes has been challenging. This study addressed this issue by conducting a meta-analysis of microarray copy number variant (CNV) studies from three TS/PTD genomics consortia, supplemented with new data from 3291 cases. This approach more than doubled the sample size of previous TS/PTD CNV studies, with CNV calls generated from 5725 TS/PTD cases and 10,982 matched controls. The results confirmed that TS/PTD cases 1) have a higher burden of ultra-rare deletions overlapping loss-of-function intolerant genes (OR = 1.68, P = 9.3×10-5) and 2) are more likely to carry established neurodevelopmental CNVs (OR = 1.42, P = 3.9×10-2) compared to controls. Additionally, a novel, genome-wide significant CNV locus for TS/PTD was discovered, involving duplications at 17q12 (hg19 chr17:34.8 - 36.2 Mb). This locus is associated with a known duplication syndrome associated with variable neuropsychiatric traits, but has not been previously linked to tic disorders. Eight cases and one control carried the canonical ~1.4 Mb duplication at chr17:34.8-36.2 Mb, while one additional case had a smaller 110 kb duplication within this known CNV that included only one gene, ACACA (acetyl-CoA carboxylase, OR = 26.7, P = 5.69×10-7). Overall, this study provides further evidence that rare, genic CNVs play a substantial role in the genetic architecture of TS/PTD and identifies a new genome-wide significant association with this neurodevelopmental disorder.

Journal Article↗

PubMed2006

Neural responses to facial expressions of disgust but not fear are modulated by washing symptoms in OCD.

BACKGROUND: Washing symptoms in Obsessive-Compulsive Disorder (OCD) are associated with increased trait sensitivity to disgust. This study explored neural systems underlying sensitivity to symptom-unrelated disgust and fear in OCD using functional neuroimaging. METHODS: Seventeen OCD subjects and 19 controls viewed facial expressions of disgust and fear (versus neutral) presented just above the level of conscious awareness in a backward masking paradigm. RESULTS: The OCD group showed greater activation than controls in the left ventrolateral prefrontal cortex, but reduced activation in the thalamus, to facial expressions of disgust. There were no between-group differences in response to fear. Further analysis using a median-split to divide OCD subjects into high and low washers suggested that the enhanced ventrolateral prefrontal cortex response was being driven by predominantly female OCD subjects with high washing symptoms. These subjects also reported higher levels of trait sensitivity to disgust. CONCLUSIONS: These findings are consistent with previous reports of increased response to symptom-relevant and generally disgusting stimuli in neural regions associated with disgust and autonomic response processing in OCD patients with prominent washing symptoms. Together, these findings point to increased sensitivity to disgust stimuli as a component of the pathophysiology of the washing/contamination symptom dimension of OCD.

Adult↗

PubMed2006

Probing the working memory system in chronic fatigue syndrome: a functional magnetic resonance imaging study using the n-back task.

OBJECTIVE: Up to 90% of patients with chronic fatigue syndrome (CFS) report substantial cognitive difficulties. However, objective evidence supporting these claims is inconsistent. The present functional magnetic resonance imaging study examined the neural correlates of working memory in patients with CFS compared with controls. METHODS: Seventeen patients with CFS and 12 healthy control subjects were scanned while performing a parametric version of the n-back task (0-, 1-, 2-, and 3-back). RESULTS: Both groups performed comparably well and activated the verbal working memory network during all task levels. However, during the 1-back condition, patients with CFS showed greater activation than control subjects in medial prefrontal regions, including the anterior cingulate gyrus. Conversely, on the more challenging conditions, patients with CFS demonstrated reduced activation in dorsolateral prefrontal and parietal cortices. Furthermore, on the 2- and 3-back conditions, patients but not control subjects significantly activated a large cluster in the right inferior/medial temporal cortex. Trend analyses of task load demonstrated statistically significant differences in brain activation between the two groups as the demands of the task increased. CONCLUSIONS: These results suggest that patients with CFS show both quantitative and qualitative differences in activation of the working memory network compared with healthy control subjects. It remains to be determined whether these findings stay stable after successful treatment.

Adult↗

PubMed2006

Effect of referral source on outcome with cognitive-behavior therapy self-help.

Little is known about how psychiatric patients' source of referral relates to treatment outcome. This study examines the effect of referral source on clinical outcome with computer-aided cognitive-behavior therapy (CCBT) for anxiety and depressive disorders. Three hundred fifty-five referrals to a clinic that offered CCBT with brief backup from a clinician were classified into general practitioner (GP) referrals (34%), mental health (MH) professional referrals (42%), and self-referrals (SR, 24%), and compared on sociodemographic and clinical features and treatment outcome. At intake, referrals from all 3 sources had similar sociodemographic features and problem duration, but GP referrals had less comorbidity, whereas MH professional referrals were being treated for their problem more often and were less motivated to change than were SR. Among treatment completers, SRs had the least and MH professional referrals had the most impaired work/social adjustment. Each referral group improved on generic and syndrome-specific measures; however, GP referrals improved the most and MH professional referrals the least. The 3 groups received similar therapist support and were equally satisfied after treatment. We conclude that GP referrals had the best outcome with CCBT for anxiety/depressive disorders. Referral source can be important in psychotherapy research because it may affect the type of patient seen and may predict treatment outcome.

Adult↗

PubMed2006

Applications of functional magnetic resonance imaging in psychiatry.

While the use of MRI techniques has become a cornerstone of the neurology clinic, the application of such methods in psychiatry was rather limited until the advent of functional magnetic resonance imaging (fMRI). Over the past decade fMRI has superseded radionuclide-imaging techniques and blossomed into a widely used psychiatric research tool. This review focuses on the neurobiological findings from fMRI research in three less well-documented psychiatric disorders: attention deficit hyperactivity disorder (ADHD), depression, and obsessive-compulsive disorder (OCD). Although there was some disparity in early findings, greater standardization of image acquisition, analysis, and paradigms, and improved clinical classification are leading to a greater convergence of observations from different laboratories. fMRI is also beginning to realize its potential as an important mediator between genes and phenotypes, and may thus contribute to a better understanding of the pathophysiology of major neuropsychiatric diseases. The role of fMRI in the objective assessment of therapeutic intervention and early prediction of response to treatment is also discussed.

Brain↗

PubMed2006

Common and distinct neural correlates of obsessive-compulsive and related disorders.

Obsessive-compulsive disorder (OCD) often co-occurs with other anxiety disorders and a number of other disorders of similar phenomenology known as the "OCD spectrum" disorders. Neurobiologically, it is unclear how all these disorders relate to each other. The picture is further complicated by the clinical heterogeneity of OCD itself. This article reviews the literature on the common and distinct neural correlates of OCD, its symptom dimensions, and other anxiety and OCD spectrum disorders with the hope of providing a conceptual and heuristic framework to help understand the relationship between these phenomena.

Anxiety Disorders↗

PubMed2006

Decision making and set shifting impairments are associated with distinct symptom dimensions in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is clinically heterogeneous. The authors examined how specific OCD symptom dimensions were related to neuropsychological functions using multiple regression analyses. A total of 39 OCD patients and 40 controls completed the Iowa Gambling Task (IGT; A. Bechara, A. R. Damasio, H. Damasio, & S. W. Anderson, 1994), which is a test of decision making, and the Wisconsin Card Sorting Test (R. K. Heaton, 1981), which is a test of set shifting. OCD patients and controls showed comparable decision making. However, patients with prominent hoarding symptoms showed impaired decision making on the IGT as well as reduced skin conductance responses. OCD patients had poorer set shifting abilities than controls, and symmetry/ordering symptoms were negatively associated with set shifting. These results help explain previous inconsistent findings in neuropsychological research in OCD and support recent neuroimaging data showing dissociable neural mechanisms involved in mediating the different OCD symptom dimensions.

Adolescent↗

PubMed2006

Deconstructing obsessive-compulsive disorder: a multidimensional perspective.

PURPOSE OF REVIEW: The aim of this article is to critically summarize the most promising attempts to split obsessive-compulsive disorder into subgroups based on clinical characteristics (i.e. age of onset, presence of comorbid tics, positive family history) and symptom theme, with particular emphasis on the latter. RECENT FINDINGS: Attempts to split obsessive-compulsive disorder into mutually exclusive sub-groups based on clinical characteristics have been useful but not exempt of problems. The complex clinical presentation of the condition can be reduced to a few consistent, temporally stable symptom dimensions that can coexist in any given individual. Researchers have begun to investigate the genetics and neural mechanisms of these symptom dimensions and to develop specific assessment and treatment protocols for each particular problem. SUMMARY: The multidimensional model of obsessive-compulsive disorder proposes a middle ground between the 'lumping' and 'splitting' perspectives. The disorder can be better understood as a spectrum of multiple potentially overlapping syndromes. The most fruitful research strategy will be to examine the common and specific etiological factors implicated in each symptom dimension.

Brain↗

PubMed2006

Spanish version of the savings inventory-revised: adaptation, psychometric properties, and relationship to personality variables.

The factor structure, psychometric properties, and relationship with personality variables of a Spanish version of the Savings Inventory-Revised (SI-R) are investigated in a sample of 381 undergraduate students. A maximum likelihood factor analysis suggests a three-factor structure, which is similar but not identical to that of the original English version. The three factors mirror the three hypothesized domains of compulsive hoarding: acquisition, difficulty discarding, and clutter. The Spanish SI-R demonstrates acceptable high internal consistency and test-retest reliability, but its divergent validity is weaker than expected because of a significant overlap with depressive symptoms. Different SI-R factors are associated with different personality traits: Whereas the difficulty discarding dimension is predominantly associated with susceptibility to punishment, the acquisition dimension is predominantly associated with susceptibility to reward. The authors conclude that the Spanish SI-R is a promising instrument to measure hoarding symptoms.

Depression↗

PubMed2006

Are there sex differences in neuropsychological functions among patients with obsessive-compulsive disorder?

The purpose of this study was to examine whether men and women with obsessive-compulsive disorder (OCD) demonstrate differences in neuropsychological functioning compared to healthy men and women. Participants were 56 consecutive patients (33 male, 23 female) and 40 healthy control participants (20 male, 20 female) of comparable characteristics. Male and female patients had comparable symptom severity, illness duration, comorbidity, in- or out-patient status, and medication usage. An extensive neuropsychological test battery was administered including tests of general nonverbal intelligence, attention, verbal and nonverbal memory, and executive functions. Male and female OCD patients showed comparable neuropsychological performances on most cognitive domains. However, we found some evidence for cross-sex shifts in verbal fluency tasks (FAS and Category Alternation Test [CAT]), the reading component of the Stroop test, and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Span-Forward test. Post hoc analyses revealed that female patients showed reduced performance on these tests compared to healthy women, in the male-typical direction. Among OCD women only, there were significant negative correlations between OCD symptom severity and performance on the CAT and the reading Stroop. We conclude that sex does not seem to be a major determinant of neuropsychological function in OCD, but the observed cross-sex shifts on some tasks deserve further examination.

Adult↗

PubMed2005

Self-help with minimal therapist contact for obsessive-compulsive disorder: a review.

Though there are effective psychological and drug treatments for obsessive-compulsive disorder (OCD), many patients remain inadequately treated or untreated. Making effective self-treatment guidance available may increase the number of patients being helped. In this review, database and manual literature searches were performed of case studies, open and randomised controlled trials (RCTs) of bibliotherapy, self-help groups, telecare and computer-aided self-help for OCD. We found no RCTs of bibliotherapy or self-help groups for OCD. Three open studies showed the efficacy of brief exposure and ritual prevention (ERP) instructions delivered by a live therapist by phone. A vicarious ERP computer program was effective in a small open study. Fully interactive computer-aided self-help by ERP for OCD was efficacious in two open studies and a large multicentre RCT, and in a small RCT compliance and outcome with that program was enhanced by brief scheduled support from a clinician. Although more research is needed, self-help approaches have the potential to help many more patients who would otherwise remain inadequately treated or untreated. Their dissemination could save resources used by health care providers. We propose a stepped care model for the treatment of OCD.

Bibliotherapy↗

PubMed2005

Brief scheduled phone support from a clinician to enhance computer-aided self-help for obsessive-compulsive disorder: randomized controlled trial.

Treatment-resistant obsessive-compulsive disorder (OCD) patients from around the United Kingdom who employed computer-guided self-help by using BTSteps over 17 weeks were randomized to have brief live phone support from a clinician either (1) in nine Scheduled clinician-initiated calls or (2) only in calls Requested by the patient (n=22 per condition). Call content and mean duration were similar across conditions. Scheduled-support patients dropped out significantly less often, did more homework of self-exposure and self-imposed ritual prevention (95% vs. 57%), and showed more improvement in OCD symptoms and disability. Mean total support time per patient over 17 weeks was 76 minutes for Scheduled and 16 minutes for Requested patients. Giving brief support proactively by phone enhanced OCD patients' completion of and improvement with computer-aided self-help.

Humans↗

PubMed2005

Screening people with anxiety/depression for suitability for guided self-help.

The aim of this study was to test a questionnaire for screening people with anxiety/ depression for their suitability for certain forms of computer-guided self-help. A total of 196 referrals completed the screening questionnaire. Three clinicians each independently judged the referrals' broad problem type and suitability. Referrals were randomized to 1 of 3 clinicians for a screening interview. The results show that inter-clinician agreement was good for questionnaire-based problem type and suitability, and excellent for screening interview-based problem type and suitability. Agreement between the questionnaire and interview was good on problem type but poor on suitability. Compared with the screening interview, the questionnaire detected suitable patients well but unsuitable patients less well. In conclusion, by quickly scanning the completed questionnaire, clinicians were able sensitively to detect patients' problem types that were suitable for certain forms of self-help. Some unsuitability items need refining.

Adolescent↗

PubMed2005

Internet-guided self-help with or without exposure therapy for phobic and panic disorders.

BACKGROUND: As many sufferers from phobic and panic (phobia/panic) disorders cannot get to suitable therapists, routine aspects of therapy were delegated to internet-accessed computer-aided self-help with or without exposure instructions. METHODS: Phobia/panic referrals were randomised to computer-aided self-help via the internet at home in a 2:1 ratio either by self-exposure cognitive behaviour therapy (CBT) [FearFighter (FF), n = 45] or by minimal CBT without exposure [Managing Anxiety (MA), n = 23]. All had brief backup phone advice from a clinician concerning their computer guidance. RESULTS: On self-ratings and blinded assessor ratings, patients improved equally with each form of self-help over 10 treatment weeks but significantly more on 5 out of 10 measures by week 14 (1-month follow-up) when the self-help included self-exposure instructions than when it did not. In accord with this, standardised effect sizes (Cohen's d) indicated superiority of FF over MA on 5 measures by week 14. Satisfaction with treatment in all patients pooled correlated positively with improvement after treatment and at 1-month follow-up. CONCLUSIONS: At the end of treatment, computer-aided CBT self-help at home via the internet plus brief live helpline support was effective with or without exposure instructions, and at 1-month follow-up it was more effective on some measures if exposure instructions had been included. Analysis is needed of how non-exposure CBT produced its shorter-term effect.

Cognitive Behavioral Therapy↗

PubMed2005

A multidimensional model of obsessive-compulsive disorder.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition. This heterogeneity can reduce the power and obscure the findings from natural history studies to genome scans, neuroimaging, and clinical trials. The authors review the evidence supporting a multidimensional model of OCD. METHOD: Computerized and manual literature searches were performed to identify factor-analytic studies of obsessive-compulsive symptoms before data from disciplines that bear on the potential usefulness of these dimensions were considered. Selection criteria included the novelty and importance of studies and their relevance to outcomes of interest to well-informed mental health professionals. RESULTS: Twelve factor-analytic studies involving more than 2,000 patients were identified that consistently extracted at least four symptom dimensions: symmetry/ordering, hoarding, contamination/cleaning, and obsessions/checking. These dimensions were associated with distinct patterns of comorbidity, genetic transmission, neural substrates, and treatment response. The evidence supporting the hoarding dimension is particularly robust. CONCLUSIONS: The complex clinical presentation of OCD can be summarized with a few consistent, temporally stable symptom dimensions. These can be understood as a spectrum of potentially overlapping syndromes that may 1) coexist in any patient, 2) be continuous with normal obsessive-compulsive phenomena, and 3) extend beyond the traditional nosological boundaries of OCD. Although the dimensional structure of obsessive-compulsive symptoms is imperfect, this quantitative approach to phenotypic traits has the potential to advance our understanding of OCD and may aid in the identification of more robust endophenotypes. The need for a dimensional rating scale and suggestions for future research aimed at reducing the burden of this disorder are discussed.

Brain↗

PubMed2005

Obsessions and compulsions in Asperger syndrome and high-functioning autism.

BACKGROUND: Obsessive-compulsive behaviours are common and disabling in autistic-spectrum disorders (ASD) but little is known about how they compare with those experienced by people with obsessive-compulsive disorder (OCD). AIM: To make such a comparison. METHOD: A group of adults with high-functioning ASD (n=40) were administered the Yale-Brown Obsessive-Compulsive Scale and Symptom Checklist and their symptoms compared with a gender-matched group of adults with a primary diagnosis of OCD (n=45). OCD symptoms were carefully distinguished from stereotypic behaviours and interests usually displayed by those with ASD. RESULTS: The two groups had similar frequencies of obsessive-compulsive symptoms, with only somatic obsessions and repeating rituals being more common in the OCD group. The OCD group had higher obsessive-compulsive symptom severity ratings but up to 50% of the ASD group reported at least moderate levels of interference from their symptoms. CONCLUSIONS: Obsessions and compulsions are both common in adults with high-functioning ASD and are associated with significant levels of distress.

Adult↗

PubMed2004

Psychometric properties of the Spanish version of the Obsessive-Compulsive Inventory--revised in a non-clinical sample.

The psychometric properties of a Spanish version of the Obsessive-Compulsive Inventory-Revised (OCI-R) were examined in a non-clinical student sample (n=381). A confirmatory factor analysis replicated the original six-factor structure. The total and each of the subscales of the Spanish OCI-R demonstrated moderate to good internal consistency and test-retest reliability, moderate convergent validity and good divergent validity. The Spanish version of the OCI-R retains the sound psychometric properties of the original version.

Adult↗

PubMed2004

High sensitivity to punishment and low impulsivity in obsessive-compulsive patients with hoarding symptoms.

Recent factor-analytic studies involving over 2000 patients have reduced the symptoms of obsessive-compulsive disorder (OCD) into a few dimensions or potentially overlapping syndromes. Hoarding consistently emerged as a separate factor in all these studies. This study investigated the relationship between OCD symptom dimensions and normal personality traits in a sample of 56 OCD patients. They were administered the Sensitivity to Punishment and Sensitivity to Reward Questionnaire and the Eysenck Personality Questionnaire, derived from Gray's and Eysenck's personality models, respectively. The personality scores were correlated with previously identified symptom dimensions from the Yale-Brown Obsessive-Compulsive Scale Symptom Checklist (Y-BOCS-SC), controlling for overall illness severity. High scores on the hoarding dimension of the Y-BOCS-SC were positively correlated with scores on the Sensitivity to Punishment scale and negatively with Eysenck's Psychoticism scale. While high sensitivity to punishment is a personality feature common to many OCD patients, it is more strongly pronounced in patients with hoarding symptoms. These patients also appear to be less impulsive or novelty seeking as reflected by low scores on Eysenck's Psychoticism scale. High sensitivity to punishment and low novelty seeking in OCD hoarders might explain their poor compliance and response to conventional treatments, but this question needs to be explored further in a prospective treatment study.

Adult↗