Examining clinical correlates, treatment outcomes and mediators in young people with comorbid obsessive-compulsive disorder and autism spectrum disorder.

Despite the high comorbidity, surprisingly little is known about the clinical features, treatment prognosis, and treatment mediators for youth with Obsessive-Compulsive Disorder (OCD) and Autism Spectrum Disorder (ASD). This study, the largest to date, compared 172 young people with OCD and ASD (OCD + ASD) to 447 without ASD (OCD) on clinical characteristics, finding those with OCD + ASD were more likely to endorse poorer insight into their OCD, have greater global functional impairment, greater levels of concurrent psychopathology, higher levels of family accommodation and to be on medication. Treatment outcomes following a course of Cognitive Behaviour Therapy with or without medication were explored for a subgroup; 100 young people with OCD + ASD and 223 with OCD. Whilst both groups benefitted from treatment, the OCD + ASD group had significantly poorer treatment outcomes. Greater global functional impairment and being on medication mediated the between-group difference in outcomes. Further research and treatment refinements are needed to improve outcomes for youth with OCD + ASD.

Protocol for the Process Evaluation of the Online Remote Behavioural Intervention for Tics (ORBIT) randomized controlled trial for children and young people.

BACKGROUND: Process evaluations are an important component in the interpretation and understanding of outcomes in trials. The Online Remote Behavioural Intervention for Tics (ORBIT) study is a randomized controlled trial evaluating the effectiveness of an Internet-delivered behavioural intervention (called BIP TIC) compared to an Internet-delivered education programme aimed at children and young people with tics. A process evaluation will be undertaken alongside the main trial to determine precisely how the behavioural intervention works and ascertain whether, and if so, how, the intervention could be successfully implemented in standard clinical practice. This protocol paper describes the rationale, aims, and methodology of the ORBIT trial process evaluation. METHODS: The process evaluation will have a mixed-methods design following the UK Medical Research Council 2015 guidelines, comprising both quantitative and qualitative data collection. This will include analysing data usage of participants in the intervention arm; purposively sampled, semi-structured interviews of parents and children, therapists and supervisors, and referring clinicians of the ORBIT trial, as well as analysis of qualitative comments put into the online therapy platform by participants at the end of treatment. Qualitative data will be analysed thematically. Quantitative and qualitative data will be integrated in a triangulation approach, to provide an understanding of how the intervention works, and what resources are needed for effective implementation, uptake and use in routine clinical care. DISCUSSION: This process evaluation will explore the experiences of participants, therapists and supervisors and referring clinicians of a complex online intervention. By contextualising trial efficacy results, this will help understand how and if the intervention worked and what may be required to sustain the implementation of the treatment long term. The findings will also aid in our understanding of factors that can affect the success of complex interventions. This will enable future researchers developing online behavioural interventions for children and young people with mental health and neurological disorders to gain invaluable information from this process evaluation. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number, ISRCTN70758207. Registered on 20 March 2018. ClinicalTrials.gov, NCT03483493. Registered on 30 March 2018.

Antidepressant prescription patterns and CNS polypharmacy with antidepressants among children, adolescents, and young adults: a population-based study in Sweden.

This study examines trends in antidepressant drug dispensations among young people aged 0-24 years in Sweden during the period 2006-2013, as well as prescription patterns and central nervous system (CNS) polypharmacy with antidepressants. Using linkage of Swedish national registers, we identified all Swedish residents aged 0-24 years that collected at least one antidepressant prescription (here defined as antidepressant users) between 1 January 2006 and 31 December 2013 (n = 174,237), and categorized them as children (0-11 years), adolescents (12-17 years), and young adults (18-24 years). Prevalence of antidepressant dispensation rose from 1.4 to 2.1% between 2006 and 2013, with the greatest relative increase in adolescents [by 97.8% in males (from 0.6 to 1.3%) and by 86.3% in females (from 1.1 to 2.1%)]. Most individuals across age categories were prescribed selective serotonin reuptake inhibitors, received their prescriptions from psychiatric specialist care, and had treatment periods of over 12 months. Prevalence of CNS polypharmacy (dispensation of other CNS drug classes in addition to antidepressants) increased across age categories, with an overall increase in prevalence from 52.4% in 2006 to 62.1% in 2013. Children experienced the largest increase in polypharmacy of three or more psychotropic drug classes (4.4-10.1%). Anxiolytics, hypnotics, and sedatives comprised the most common additional CNS drug class among persons who were prescribed antidepressants. These findings show that the dispensation of antidepressants among the young is prevalent and growing in Sweden. The substantial degree of CNS polypharmacy in young patients receiving antidepressants requires careful monitoring and further research into potential benefits and harms.

Moderators and predictors of outcomes in telephone delivered compared to face-to-face cognitive behaviour therapy for paediatric obsessive-compulsive disorder: preliminary evidence from a non-inferiority RCT.

This study provides a preliminary exploration of factors which differentially predict treatment response to telephone-delivered cognitive behavioural therapy (TCBT) compared to face-to-face CBT (CBT) in a randomised non-inferiority controlled trial of 72 children (aged 11-18 years) with obsessive-compulsive disorder (OCD). Potential moderator variables, their interaction with treatment group (CBT, TCBT) and baseline levels of OCD severity were entered into separate regression models where the primary outcome measure was the post-intervention Children's Yale-Brown Obsessive-Compulsive Scale total score (CYBOCS). Separate regressions were also used to test associations between predictors and outcome controlling for pretreatment CYBOCS. Only pretreatment level of parent-rated child peer problems moderated the effects of the two interventions on CYBOCS severity at post-treatment. After controlling for baseline CYBOCS, only family accommodation rated by mothers predicted poorer outcomes in both groups. While CBT and TCBT may be equally effective for adolescents with OCD, the current results tentatively suggest that higher baseline level of peer problems strengthened the response to therapy for youth receiving TCBT and the predictor analyses reinforce the importance of directly addressing family accommodation during CBT for paediatric OCD regardless of delivery mode. Limitations of the current findings and directions for future work are discussed.

Perinatal risk factors in Tourette's and chronic tic disorders: a total population sibling comparison study.

Adverse perinatal events may increase the risk of Tourette's and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973-2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose-response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose-response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33-1.50) for one event to 2.42 (95% CI: 1.65-3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.

A total-population multigenerational family clustering study of autoimmune diseases in obsessive-compulsive disorder and Tourette's/chronic tic disorders.

The association between obsessive-compulsive disorder (OCD) and Tourette's/chronic tic disorders (TD/CTD) with autoimmune diseases (ADs) is uncertain. In this nationwide study, we sought to clarify the patterns of comorbidity and familial clustering of a broad range of ADs in individuals with OCD, individuals with TD/CTD and their biological relatives. From a birth cohort of 7 465 455 individuals born in Sweden between 1940 and 2007, we identified 30 082 OCD and 7279 TD/CTD cases in the National Patient Register and followed them up to 31 December 2013. The risk of 40 ADs was evaluated in individuals with OCD, individuals with TD/CTD and their first- (siblings, mothers, fathers), second- (half siblings) and third-degree (cousins) relatives, compared with population controls. Individuals with OCD and TD/CTD had increased comorbidity with any AD (43% and 36%, respectively) and many individual ADs. The risk of any AD and several individual ADs was consistently higher among first-degree relatives than among second- and third-degree relatives of OCD and TD/CTD probands. The risk of ADs was very similar in mothers, fathers and siblings of OCD probands, whereas it tended to be higher in mothers and fathers of TD/CTD probands (compared with siblings). The results suggest a familial link between ADs in general (that is, not limited to Streptococcus-related conditions) and both OCD and TD/CTD. Additional mother-specific factors, such as the placental transmission of antibodies, cannot be fully ruled out, particularly in TD/CTD.

Comparison of neural substrates of temporal discounting between youth with autism spectrum disorder and with obsessive-compulsive disorder.

BACKGROUND: Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) share abnormalities in hot executive functions such as reward-based decision-making, as measured in the temporal discounting task (TD). No studies, however, have directly compared these disorders to investigate common/distinct neural profiles underlying such abnormalities. We wanted to test whether reward-based decision-making is a shared transdiagnostic feature of both disorders with similar neurofunctional substrates or whether it is a shared phenotype with disorder-differential neurofunctional underpinnings. METHODS: Age and IQ-matched boys with ASD (N = 20), with OCD (N = 20) and 20 healthy controls, performed an individually-adjusted functional magnetic resonance imaging (fMRI) TD task. Brain activation and performance were compared between groups. RESULTS: Boys with ASD showed greater choice-impulsivity than OCD and control boys. Whole-brain between-group comparison revealed shared reductions in ASD and OCD relative to control boys for delayed-immediate choices in right ventromedial/lateral orbitofrontal cortex extending into medial/inferior prefrontal cortex, and in cerebellum, posterior cingulate and precuneus. For immediate-delayed choices, patients relative to controls showed reduced activation in anterior cingulate/ventromedial prefrontal cortex reaching into left caudate, which, at a trend level, was more decreased in ASD than OCD patients, and in bilateral temporal and inferior parietal regions. CONCLUSIONS: This first fMRI comparison between youth with ASD and with OCD, using a reward-based decision-making task, shows predominantly shared neurofunctional abnormalities during TD in key ventromedial, orbital- and inferior fronto-striatal, temporo-parietal and cerebellar regions of temporal foresight and reward processing, suggesting trans-diagnostic neurofunctional deficits.

Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis.

Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

Suicide in obsessive-compulsive disorder: a population-based study of 36 788 Swedish patients.

The risk of death by suicide in individuals with obsessive-compulsive disorder (OCD) is largely unknown. Previous studies have been small and methodologically flawed. We analyzed data from the Swedish national registers to estimate the risk of suicide in OCD and identify the risk and protective factors associated with suicidal behavior in this group. We used a matched case-cohort design to estimate the risk of deaths by suicide and attempted suicide in individuals diagnosed with OCD, compared with matched general population controls (1:10). Cox regression models were used to study predictors of suicidal behavior. We identified 36 788 OCD patients in the Swedish National Patient Register between 1969 and 2013. Of these, 545 had died by suicide and 4297 had attempted suicide. In unadjusted models, individuals with OCD had an increased risk of both dying by suicide (odds ratio (OR)=9.83 (95% confidence interval (CI), 8.72-11.08)) and attempting suicide (OR=5.45 (95% CI, 5.24-5.67)), compared with matched controls. After adjusting for psychiatric comorbidities, the risk was reduced but remained substantial for both death by suicide and attempted suicide. Within the OCD cohort, a previous suicide attempt was the strongest predictor of death by suicide. Having a comorbid personality or substance use disorder also increased the risk of suicide. Being a woman, higher parental education and having a comorbid anxiety disorder were protective factors. We conclude that patients with OCD are at a substantial risk of suicide. Importantly, this risk remains substantial after adjusting for psychiatric comorbidities. Suicide risk should be carefully monitored in patients with OCD.

Emotion regulation before and after transcranial magnetic stimulation in obsessive compulsive disorder.

BACKGROUND: Impaired emotion regulation may underlie exaggerated emotional reactivity in patients with obsessive compulsive disorder (OCD), yet instructed emotion regulation has never been studied in the disorder. METHOD: This study aimed to assess the neural correlates of emotion processing and regulation in 43 medication-free OCD patients and 38 matched healthy controls, and additionally test if these can be modulated by stimulatory (patients) and inhibitory (controls) repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (dlPFC). Participants performed an emotion regulation task during functional magnetic resonance imaging before and after a single session of randomly assigned real or sham rTMS. Effect of group and rTMS were assessed on self-reported distress ratings and brain activity in frontal-limbic regions of interest. RESULTS: Patients had higher distress ratings than controls during emotion provocation, but similar rates of distress reduction after voluntary emotion regulation. OCD patients compared with controls showed altered amygdala responsiveness during symptom provocation and diminished left dlPFC activity and frontal-amygdala connectivity during emotion regulation. Real v. sham dlPFC stimulation differentially modulated frontal-amygdala connectivity during emotion regulation in OCD patients. CONCLUSIONS: We propose that the increased emotional reactivity in OCD may be due to a deficit in emotion regulation caused by a failure of cognitive control exerted by the dorsal frontal cortex. Modulatory rTMS over the left dlPFC may influence automatic emotion regulation capabilities by influencing frontal-limbic connectivity.

Population-based, multi-generational family clustering study of social anxiety disorder and avoidant personality disorder.

BACKGROUND: We aimed to provide unbiased estimates of familial risk and heritability of social anxiety disorder (SAD) and avoidant personality disorder (AVPD). METHOD: We identified 18 399 individuals diagnosed with SAD and 2673 with AVPD in the Swedish National Patient Register between 1997 and 2009. Risks (odds ratios; OR) for SAD in all biological and non-biological relatives of probands, compared to relatives of unaffected individuals were calculated. We also estimated the risks for AVPD in relatives of probands with SAD. RESULTS: The risk for SAD among relatives of SAD probands increased proportionally to the degree of genetic relatedness. The risks for first-degree relatives [OR 4.74, 95% confidence interval (CI) 4.28-5.25] were significantly higher than for second-degree and third-degree relatives. Second-degree relatives (OR 2.30, 95% CI 2.01-2.63) had significantly higher risk than third-degree relatives (OR 1.72, 95% CI 1.52-1.94). Relatives at similar genetic distances had similar risks for SAD, despite different degrees of shared environment. Heritability was estimated to be approximately 56%. There were no significant sex differences in the familial patterns. The risk of AVPD in relatives of SAD probands was significantly elevated, even after excluding individuals with both diagnoses (first-degree OR 3.54, second-degree OR 2.20, third-degree OR 1.62). Non-biological relatives (spouses/partners) also had elevated risks for both SAD (OR 4.01) and AVPD (OR 3.85). CONCLUSIONS: SAD clusters in families primarily due to genetic factors. SAD and AVPD are aetiologically related and may represent different expressions of the same vulnerability. The strong marital concordance observed in SAD/AVPD may indicate assortative mating but the exact mechanisms and implications require further investigation.

Are stressful life events causally related to the severity of obsessive-compulsive symptoms? A monozygotic twin difference study.

Traumatic or stressful life events have long been hypothesized to play a role in causing or precipitating obsessive-compulsive symptoms but the impact of these environmental factors has rarely been investigated using genetically informative designs. We tested whether a wide range of retrospectively-reported stressful life events (SLEs) influence the lifetime presence and severity of obsessive-compulsive symptoms (OCS) in a large Swedish population-based cohort of 22,084 twins. Multiple regression models examined whether differences in SLEs within twin pairs were significantly associated with differences in OCS. In the entire sample (i.e., both monozygotic [MZ] and dizygotic twin pairs), two SLEs factors, "abuse and family disruption" and "sexual abuse", were significantly associated with the severity of OCS even after controlling for depressive symptoms. Other SLEs factors were either not associated with OCS ("loss", "non-sexual assault") or were no longer associated with OCS after controlling for depression ("illness/injury"). Within MZ pair analyses, which effectively control for genetic and shared environmental effects, showed that only the "abuse and family disruption" factor remained independently related to within-pair differences in OCS severity, even after controlling for depressive symptoms. Despite being statistically significant, the magnitude of the associations was small; "abuse and family disruption" explained approximately 3% of the variance in OCS severity. We conclude that OCS are selectively associated with certain types of stressful life events. In particular, a history of interpersonal abuse, neglect and family disruption may make a modest but significant contribution to the severity of OCS. Further replication in longitudinal cohorts is essential before causality can be firmly established.

Predicting response to cognitive behavioral therapy in contamination-based obsessive-compulsive disorder from functional magnetic resonance imaging.

BACKGROUND: Although cognitive behavioral therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD), few reliable predictors of treatment outcome have been identified. The present study examined the neural correlates of symptom improvement with CBT among OCD patients with predominantly contamination obsessions and washing compulsions, the most common OCD symptom dimension. METHOD: Participants consisted of 12 OCD patients who underwent symptom provocation with contamination-related images during functional magnetic resonance imaging (fMRI) scanning prior to 12 weeks of CBT. RESULTS: Patterns of brain activity during symptom provocation were correlated with a decrease on the Yale-Brown Obsessive Compulsive Scale (YBOCS) after treatment, even when controlling for baseline scores on the YBOCS and the Beck Depression Inventory (BDI) and improvement on the BDI during treatment. Specifically, activation in brain regions involved in emotional processing, such as the anterior temporal pole and amygdala, was most strongly associated with better treatment response. By contrast, activity in areas involved in emotion regulation, such as the dorsolateral prefrontal cortex, correlated negatively with treatment response mainly in the later stages within each block of exposure during symptom provocation. CONCLUSIONS: Successful recruitment of limbic regions during exposure to threat cues in patients with contamination-based OCD may facilitate a better response to CBT, whereas excessive activation of dorsolateral prefrontal regions involved in cognitive control may hinder response to treatment. The theoretical implications of the findings and their potential relevance to personalized care approaches are discussed.

Aetiological overlap between obsessive-compulsive and depressive symptoms: a longitudinal twin study in adolescents and adults.

BACKGROUND: Depression is commonly co-morbid with obsessive-compulsive disorder (OCD). However, it is unknown whether depression is a functional consequence of OCD or whether these disorders share a common genetic aetiology. This longitudinal twin study compared these two hypotheses. METHOD: Data were drawn from a longitudinal sample of adolescent twins and siblings (n = 2651; Genesis 12-19 study) and from a cross-sectional sample of adult twins (n = 4920). The longitudinal phenotypic associations between OCD symptoms (OCS) and depressive symptoms were examined using a cross-lag model. Multivariate twin analyses were performed to explore the genetic and environmental contributions to the cross-sectional and longitudinal relationship between OCS and depressive symptoms. RESULTS: In the longitudinal phenotypic analyses, OCS at time 1 (wave 2 of the Genesis 12-19 study) predicted depressive symptoms at time 2 (wave 3 of the Genesis 12-19 study) to a similar extent to which depressive symptoms at time 1 predicted OCS at time 2. Cross-sectional twin analyses in both samples indicated that common genetic factors explained 52-65% of the phenotypic correlation between OCS and depressive symptoms. The proportion of the phenotypic correlation due to common non-shared environmental factors was considerably smaller (35%). In the adolescent sample, the longitudinal association between OCS at time 1 and subsequent depressive symptoms was accounted for by the genetic association between OCS and depressive symptoms at time 1. There was no significant environmental association between OCS and later depressive symptoms. CONCLUSIONS: The present findings show that OCS and depressive symptoms co-occur primarily due to shared genetic factors and suggest that genetic, rather than environmental, effects account for the longitudinal relationship between OCS and depressive symptoms.

Localized grey matter atrophy in multiple sclerosis: a meta-analysis of voxel-based morphometry studies and associations with functional disability.

Grey matter (GM) damage in Multiple Sclerosis (MS) occurs largely independent of white matter (WM) lesions and shows stronger correlation with clinical parameters than WM damage but no clear pattern of GM atrophy distribution has emerged in the literature. We used Signed Differential Mapping (SDM), a novel neuroimaging meta-analytical method, to assess global and regional GM volume differences in MS. Meta-regression methods were used to explore potential effects of disease duration and degree of functional disability. We found a highly localized pattern of regional GM volume loss in Relapsing Remitting MS involving bilateral thalamus, basal ganglia structures, pre/postcentral regions and cingulate gyrus. These results remained largely unchanged after subgroup and sensitivity analyses. Furthermore, GM volume loss in left pre/postcentral regions correlated with increasing functional disability in MS. These results demonstrate that GM atrophy occurs as a regional rather than global process in MS, and that functional disability is specifically associated with atrophy of the left pre/post central gyrus. Further investigation is needed to determine whether these structures are targeted by neurodegenerative processes and to establish their clinical and neurocognitive correlates.

Neurological soft signs in obsessive-compulsive disorder: two empirical studies and meta-analysis.

BACKGROUND: Neurological soft signs (NSS) have been inconsistently reported in obsessive-compulsive disorder (OCD) but may make an impact on treatment response. Method The current study examined the presence of NSS in two independent European samples of OCD patients (combined 85 patients and 88 matched healthy controls) using a standardized instrument and conducted a meta-analysis of all published studies identified in the literature with the aim to provide a more definitive answer to the question of whether OCD patients are characterized by increased NSS. RESULTS: Both empirical studies found elevated NSS scores in patients compared with matched controls. The results of the meta-analysis, which included 15 studies (combined 498 patients and 520 controls) showed large effect sizes (Hedges' g=1.27, 95% confidence interval 0.80-1.75), indicating that OCD patients have significantly higher rates of NSS than matched controls on both sides of the body and in multiple domains (motor coordination, sensory integration and primitive reflexes). The results were robust and remained largely unchanged in our reliability analyses, which controlled for possible outliers. Meta-regression was employed to examine the role of potential variables of interest including sociodemographic variables, symptom severity, medication effects and the use of different instruments, but none of these variables was clearly associated with NSS. CONCLUSIONS: As a group, OCD patients are characterized by increased rates of NSS, compared with healthy controls. However, their origins and potential clinical importance remain to be clarified. Future directions for research are discussed.

The London field trial for hoarding disorder.

BACKGROUND: A new diagnostic category, hoarding disorder (HD), has been proposed for inclusion in DSM-5. This study field-tested the validity, reliability and perceived acceptability of the proposed diagnostic criteria for HD. Method Fifty unselected individuals with prominent hoarding behavior and 20 unselected, self-defined 'collectors' participated in thorough psychiatric assessments, involving home visits whenever possible. A semi-structured interview based on the proposed diagnostic criteria for HD was administered and scored by two independent raters. 'True' diagnoses were made by consensus according to the best-estimate diagnosis procedure. The percentage of true positive HD cases (sensitivity) and true negative HD cases (specificity) was calculated, along with inter-rater reliability for the diagnosis and each criterion. Participants were asked about their perceptions of the acceptability, utility and stigma associated with the new diagnosis. RESULTS: Twenty-nine (58%) of the hoarding individuals and none of the collectors fulfilled diagnostic criteria for HD. The sensitivity, specificity and inter-rater reliability of the diagnosis, and of each individual criterion and the specifiers, were excellent. Most participants with HD (96%) felt that creating a new disorder would be very or somewhat acceptable, useful (96%) and not too stigmatizing (59%). CONCLUSIONS: The proposed HD criteria are valid, reliable and perceived as acceptable and useful by the sufferers. Crucially, they seem to be sufficiently conservative and unlikely to overpathologize normative behavior. Minor changes in the wording of the criteria are suggested.

A general approach for combining voxel-based meta-analyses conducted in different neuroimaging modalities.

Meta-analyses are useful to summarize the exponential amount of inconsistent and conflicting neuroimaging data. However, they are usually separately conducted for each different neuroimaging modality, preventing the multimodal integration of different imaging findings in a given neuropsychiatric disorder. Here, we describe an innovative method to meta-analytically combine the results of different imaging modalities, such as structural and functional paradigms. The method accounts for the presence of noise in the estimation of the p-values, and can be easily applied to any meta-analytical software. We hope that with this advanced imaging tool, researchers will be able to provide more complete multimodal pictures of the brain regions affected in different neuropsychiatric disorders.

Multimodal meta-analysis of structural and functional brain changes in first episode psychosis and the effects of antipsychotic medication.

Structure and function in the human brain are closely related. At the onset of psychosis, brain imaging studies have identified robust changes in brain function and structure, but no data are available relating these two domains. After systematic literature searches, we included all available studies reporting whole-brain structural or cognitive functional imaging findings in first-episode (FEP) subjects in multimodal Signed Differential Mapping (SDM). Forty-three studies met the inclusion criteria. The structural database comprised 965 FEP subjects matched with 1040 controls whilst the functional cohort included 362 FEP subjects matched with 403 controls. The analysis identified conjoint structural and functional differences in the insula/superior temporal gyrus and the medial frontal/anterior cingulate cortex bilaterally. In these regions, large and robust decreases in grey matter volume were found with either reduced or enhanced activation. Meta-regression analyses indicated that grey matter volume in the anterior cingulate and left insular clusters was influenced by exposure to antipsychotics: patients receiving medication were more likely to show structural abnormalities in these regions.

Independent validation of the dimensional Yale-Brown obsessive-compulsive scale (DY-BOCS).

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition characterized by a few consistent, temporally stable symptom dimensions. The dimensional Yale-Brown obsessive-compulsive scale (DY-BOCS) is a recently developed instrument that allows patient and clinician ratings of dimension-specific symptom severity, as well as estimates of global symptom severity in patients with OCD. METHODS: We examined the psychometric properties of the DY-BOCS in a sample of 128 European adult patients with OCD. RESULTS: The results of the psychometric analyses were overall excellent. The internal consistency across the domains of time, distress and interference for each dimension was high. The subscales of the DY-BOCS were largely independent from one another. The convergent and discriminant validity of the DY-BOCS subscales were adequate. The Global Severity and Interference scales were largely intercorrelated, suggesting that they may be redundant. The level of agreement between self-report and expert ratings was adequate although somewhat lower than in the original validation study. CONCLUSION: The results of the present study confirm the excellent psychometric properties of the DY-BOCS reported in the original validation study.