David Mataix-Cols

Voxel-wise meta-analysis of grey matter changes in obsessive–compulsive disorder

BACKGROUND Specific cortico-striato-thalamic circuits are hypothesised to mediate the symptoms of obsessive-compulsive disorder (OCD), but structural neuroimaging studies have been inconsistent. AIMS To conduct a meta-analysis of published and unpublished voxel-based morphometry studies in OCD. METHOD Twelve data-sets comprising 401 people with OCD and 376 healthy controls met inclusion criteria. A new improved voxel-based meta-analytic method, signed differential mapping (SDM), was developed to examine regions of increased and decreased grey matter volume in the OCD group v. control group. Results No between-group differences were found in global grey matter volumes. People with OCD had increased regional grey matter volumes in bilateral lenticular nuclei, extending to the caudate nuclei, as well as decreased volumes in bilateral dorsal medial frontal/anterior cingulate gyri. A descriptive analysis of quartiles, a sensitivity analysis as well as analyses of subgroups further confirmed these findings. Meta-regression analyses showed that studies that included individuals with more severe OCD were significantly more likely to report increased grey matter volumes in the basal ganglia. No effect of current antidepressant treatment was observed. Conclusions The results support a dorsal prefrontal-striatal model of the disorder and raise the question of whether functional alterations in other brain regions commonly associated with OCD, such as the orbitofrontal cortex, may reflect secondary compensatory strategies. Whether the reported differences between participants with OCD and controls precede the onset of the symptoms and whether they are specific to OCD remains to be established.

Obsessive-Compulsive Symptom Dimensions as Predictors of Compliance with and Response to Behaviour Therapy: Results from a Controlled Trial

Background: Recent factor-analytic studies in obsessive-compulsive disorder (OCD) identified consistent symptom dimensions. Support for the validity of these dimensions comes from studies of psychiatric comorbidity, functional brain imaging, genetic transmission, and treatment response to medications. This study examined whether previously identified OCD symptom dimensions are associated with treatment compliance and response to behaviour therapy (BT) for OCD. Methods: One hundred and fifty-three OCD outpatients who participated in a multi-centre randomised controlled trial of computer- versus clinician-guided BT for OCD were included in the study. Logistic and multiple regression models tested for significant predictors of compliance with and response to BT and relaxation. Results: The patients studied were phenomenologically comparable (including the presence of ‘pure’ obsessions and mental rituals) to those in previous serotonin reuptake inhibitor (SRI) trials and those in clinical epidemiology studies. High scorers on the ‘hoarding’ dimension were more likely to drop out prematurely from the study and tended to improve less. For those completing treatment, the strongest predictor of outcome was pre-treatment severity. Initial depression scores were unrelated to outcome. After controlling for symptom severity, higher scores on the ‘sexual/religious obsessions’ factor predicted poorer outcome with BT, especially when computer-guided. Conclusions: BT is especially indicated for OCD patients with aggressive/checking, contamination/cleaning and symmetry/ordering symptoms. Previous accounts of unsuccessful BT in patients with hoarding symptoms may be due in part to their propensity to drop out earlier from treatment. Patients with sexual/religious obsessions, but not those with mental rituals, might respond less well to traditional BT techniques. Existing treatments need to be refined and/or new treatments developed to improve these patients’ adherence and response to treatment.

Gray Matter Volume Abnormalities in ADHD: Voxel-Based Meta-Analysis Exploring the Effects of Age and Stimulant Medication

OBJECTIVE Structural neuroimaging studies in attention-deficit hyperactivity disorder (ADHD) have been relatively inconsistent and have mainly been conducted with pediatric samples. Furthermore, there is evidence that stimulant medication may have an effect on brain structure. The authors conducted a meta-analysis of voxel-based morphometry studies in children and adults with ADHD and examined the potential effects of age and stimulant medication on regional gray matter volumes. METHOD The PubMed, ScienceDirect, Web of Knowledge, and Scopus databases were searched for articles published between 2001 and 2011. Manual searches were also conducted, and authors of studies were contacted for additional data. Coordinates were extracted from clusters of significant gray matter difference between ADHD patients and healthy comparison subjects. Metaregression methods were used to explore potential age and stimulant medication effects. RESULTS Fourteen data sets comprising 378 patients with ADHD and 344 healthy subjects met inclusion criteria. The ADHD group had global reductions in gray matter volumes, which were robustly localized in the right lentiform nucleus and extended to the caudate nucleus. Both increasing age and percentage of patients taking stimulant medication were found to be independently associated with more normal values in this region. Patients also had slightly greater gray matter volumes in the left posterior cingulate cortex. CONCLUSIONS These findings confirm that the most prominent and replicable structural abnormalities in ADHD are in the basal ganglia. They furthermore suggest that ADHD patients may progressively catch up with their developmental delay with advancing age and that use of stimulant medication may be associated with normalization of structural abnormalities in ADHD, although longitudinal studies are needed to confirm both observations.

Hoarding disorder: a new diagnosis for DSM-V?

This article provides a focused review of the literature on compulsive hoarding and presents a number of options and preliminary recommendations to be considered for DSM‐V. In DSM‐IV‐TR, hoarding is listed as one of the diagnostic criteria for obsessive–compulsive personality disorder (OCPD). According to DSM‐IV‐TR, when hoarding is extreme, clinicians should consider a diagnosis of obsessive–compulsive disorder (OCD) and may diagnose both OCPD and OCD if the criteria for both are met. However, compulsive hoarding seems to frequently be independent from other neurological and psychiatric disorders, including OCD and OCPD. In this review, we first address whether hoarding should be considered a symptom of OCD and/or a criterion of OCPD. Second, we address whether compulsive hoarding should be classified as a separate disorder in DSM‐V, weighing the advantages and disadvantages of doing so. Finally, we discuss where compulsive hoarding should be classified in DSM‐V if included as a separate disorder. We conclude that there is sufficient evidence to recommend the creation of a new disorder, provisionally called hoarding disorder. Given the historical link between hoarding and OCD/OCPD, and the conservative approach adopted by DSM‐V, it may make sense to provisionally list it as an obsessive–compulsive spectrum disorder. An alternative to our recommendation would be to include it in an Appendix of Criteria Sets Provided for Further Study. The creation of a new diagnosis in DSM‐V would likely increase public awareness, improve identification of cases, and stimulate both research and the development of specific treatments for hoarding disorder. Depression and Anxiety, 2010.© 2010 Wiley‐Liss, Inc.

Meta-analysis of Functional Magnetic Resonance Imaging Studies of Inhibition and Attention in Attention-deficit/Hyperactivity Disorder: Exploring Task-Specific, Stimulant Medication, and Age Effects

CONTEXT Functional magnetic resonance imaging studies in attention-deficit/hyperactivity disorder (ADHD) revealed fronto-striato-parietal dysfunctions during tasks of inhibition and attention. However, it is unclear whether task-dissociated dysfunctions exist and to what extent they may be influenced by age and by long-term stimulant medication use. OBJECTIVE To conduct a meta-analysis of functional magnetic resonance imaging studies in ADHD during inhibition and attention tasks, exploring age and long-term stimulant medication use effects. DATA SOURCES PubMed, ScienceDirect, Web of Knowledge, Google Scholar, and Scopus databases were searched up to May 2012 for meta-analyses. Meta-regression methods explored age and long-term stimulant medication use effects. STUDY SELECTION Twenty-one data sets were included for inhibition (287 patients with ADHD and 320 control subjects), and 13 data sets were included for attention (171 patients with ADHD and 178 control subjects). DATA EXTRACTION Peak coordinates of clusters of significant group differences, as well as demographic, clinical, and methodological variables, were extracted for each study or were obtained from the authors. DATA SYNTHESIS Patients with ADHD relative to controls showed reduced activation for inhibition in the right inferior frontal cortex, supplementary motor area, and anterior cingulate cortex, as well as striato-thalamic areas, and showed reduced activation for attention in the right dorsolateral prefrontal cortex, posterior basal ganglia, and thalamic and parietal regions. Furthermore, the meta-regression analysis for the attention domain showed that long-term stimulant medication use was associated with more similar right caudate activation relative to controls. Age effects could be analyzed only for the inhibition meta-analysis, showing that the supplementary motor area and basal ganglia were underactivated solely in children with ADHD relative to controls, while the inferior frontal cortex and thalamus were underactivated solely in adults with ADHD relative to controls. CONCLUSIONS Patients with ADHD have consistent functional abnormalities in 2 distinct domain-dissociated right hemispheric fronto-basal ganglia networks, including the inferior frontal cortex, supplementary motor area, and anterior cingulate cortex for inhibition and dorsolateral prefrontal cortex, parietal, and cerebellar areas for attention. Furthermore, preliminary evidence suggests that long-term stimulant medication use may be associated with more normal activation in right caudate during the attention domain.

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.

Meta-analytical Comparison of Voxel-Based Morphometry Studies in Obsessive-Compulsive Disorder vs Other Anxiety Disorders

CONTEXT Whether obsessive-compulsive disorder (OCD) is adequately classified as an anxiety disorder is a matter of considerable debate. OBJECTIVES To quantitatively compare structural brain changes in OCD and other anxiety disorders using novel voxel-based meta-analytical methods and to generate an online database to facilitate replication and further analyses by other researchers. DATA SOURCES The PubMed, ScienceDirect, and Scopus databases were searched between 2001 (the date of the first voxel-based morphometry study in any anxiety disorder) and 2009. All voxel-based morphometry studies comparing patients with any anxiety disorder and healthy controls were retrieved. Manual searches were also conducted. Authors were contacted soliciting additional data. STUDY SELECTION Thirty-seven data sets were identified, of which 26 (including 639 patients with anxiety disorders and 737 healthy controls) met inclusion criteria. DATA EXTRACTION Coordinates were extracted from clusters of significant gray matter difference between patients and controls. Demographic, clinical, and methodological variables were extracted from each study or obtained from the authors. DATA SYNTHESIS Patients with anxiety disorders (including OCD) showed decreased bilateral gray matter volumes in the dorsomedial frontal/anterior cingulate gyri. Individuals with OCD had increased bilateral gray matter volumes (vs healthy controls and vs individuals with other anxiety disorders) in the lenticular/caudate nuclei, while patients with other anxiety disorders (mainly panic and posttraumatic stress disorders) had decreased gray matter volumes in the left lenticular nucleus. The findings remained largely unchanged in quartile and jackknife sensitivity analyses. Controlling for potential confounders such as age or antidepressant medication had little impact on the results. CONCLUSIONS The meta-analysis consistently revealed common as well as distinct neural substrates in OCD and other anxiety disorders. These results have implications for the current debate surrounding the classification of OCD in the DSM-V.

Refining the diagnostic boundaries of compulsive hoarding: a critical review.

Like most human behaviors, saving and collecting possessions can range from totally normal and adaptive to excessive or pathological. Hoarding, or compulsive hoarding, are some of the more commonly used terms to refer to this excessive form of collectionism. Hoarding is highly prevalent and, when severe, it is associated with substantial functional disability and represents a great burden for the sufferers, their families, and society in general. It is generally considered difficult to treat. Hoarding can occur in the context of a variety of neurological and psychiatric conditions. Although it has frequently been considered a symptom (or symptom dimension) of obsessive-compulsive disorder, and is listed as one of the diagnostic criteria for obsessive-compulsive personality disorder, its diagnostic boundaries are still a matter of debate. Recent data suggest that compulsive hoarding can also be a standalone problem. Growing evidence from epidemiological, phenomenological, neurobiological, and treatment studies suggests that compulsive hoarding may be best classified as a discrete disorder with its own diagnostic criteria.

Compulsive Hoarding: OCD Symptom, Distinct Clinical Syndrome, or Both?

OBJECTIVE Compulsive hoarding is a debilitating problem that is often associated with obsessive-compulsive disorder (OCD) and obsessive-compulsive personality disorder. However, the precise nosology of compulsive hoarding has yet to be determined. METHOD Participants were 25 patients with severe compulsive hoarding with OCD and 27 patients with severe compulsive hoarding without OCD. Both groups were carefully characterized and compared on the following sociodemographic and clinical variables: precise phenomenology of hoarding behavior, severity of other OCD symptoms, axis I and axis II psychopathology, and adaptive functioning. For comparison purposes, the following individuals were also recruited: 71 patients with OCD without hoarding, 19 patients with anxiety disorder, and 21 community participants. RESULTS Overall, the phenomenology of hoarding behavior was similar in the two hoarding groups. The majority of participants in both groups reported hoarding common items as a result of their emotional and/or intrinsic value. However, approximately one-fourth of participants in the compulsive hoarding with OCD group showed a different psychopathological profile, which was characterized by the hoarding of bizarre items and the presence of other obsessions and compulsions related to their hoarding, such as fear of catastrophic consequences, the need to perform checking rituals, and the need to perform mental compulsions before discarding any item. These patients had a more severe and disabling form of the disorder. The strong relationship between compulsive hoarding and obsessive-compulsive personality disorder was explained entirely by the overlapping item content. CONCLUSIONS In most individuals, compulsive hoarding appears to be a syndrome separate from OCD, which is associated with substantial levels of disability and social isolation. However, in other individuals, compulsive hoarding may be considered a symptom of OCD and has unique clinical features. These findings have implications for the classification of OCD and compulsive hoarding in the next edition of DSM.

OBSESSIVE-COMPULSIVE DISORDER: A REVIEW OF THE DIAGNOSTIC CRITERIA AND POSSIBLE SUBTYPES AND DIMENSIONAL SPECIFIERS FOR DSM-V

Background: Since the publication of the DSM‐IV in 1994, research on obsessive–compulsive disorder (OCD) has continued to expand. It is timely to reconsider the nosology of this disorder, assessing whether changes to diagnostic criteria as well as subtypes and specifiers may improve diagnostic validity and clinical utility. Methods: The existing criteria were evaluated. Key issues were identified. Electronic databases of PubMed, ScienceDirect, and PsycINFO were searched for relevant studies. Results: This review presents a number of options and preliminary recommendations to be considered for DSM‐V. These include: (1) clarifying and simplifying the definition of obsessions and compulsions (criterion A); (2) possibly deleting the requirement that people recognize that their obsessions or compulsions are excessive or unreasonable (criterion B); (3) rethinking the clinical significance criterion (criterion C) and, in the interim, possibly adjusting what is considered “time‐consuming” for OCD; (4) listing additional disorders to help with the differential diagnosis (criterion D); (5) rethinking the medical exclusion criterion (criterion E) and clarifying what is meant by a “general medical condition”; (6) revising the specifiers (i.e., clarifying that OCD can involve a range of insight, in addition to “poor insight,” and adding “tic‐related OCD”); and (7) highlighting in the DSM‐V text important clinical features of OCD that are not currently mentioned in the criteria (e.g., the major symptom dimensions). Conclusions: A number of changes to the existing diagnostic criteria for OCD are proposed. These proposed criteria may change as the DSM‐V process progresses. Depression and Anxiety, 2010.