Meta-analytic methods for neuroimaging data explained

The number of neuroimaging studies has grown exponentially in recent years and their results are not always consistent. Meta-analyses are helpful to summarize this vast literature and also offer insights that are not apparent from the individual studies. In this review, we describe the main methods used for meta-analyzing neuroimaging data, with special emphasis on their relative advantages and disadvantages. We describe and discuss meta-analytical methods for global brain volumes, methods based on regions of interest, label-based reviews, voxel-based meta-analytic methods and online databases. Regions of interest-based methods allow for optimal statistical analyses but are affected by a limited and potentially biased inclusion of brain regions, whilst voxel-based methods benefit from a more exhaustive and unbiased inclusion of studies but are statistically more limited. There are also relevant differences between the different available voxel-based meta-analytic methods, and the field is rapidly evolving to develop more accurate and robust methods. We suggest that in any meta-analysis of neuroimaging data, authors should aim to: only include studies exploring the whole brain; ensure that the same threshold throughout the whole brain is used within each included study; and explore the robustness of the findings via complementary analyses to minimize the risk of false positives

Prevalence of hoarding disorder: A systematic review and meta-analysis

Currently there is uncertainty concerning the prevalence of Hoarding Disorder (HD) due to methodological issues in the evidence base. Estimates have widely ranged from between 1.5% and 6% of the general population. This systematic review and meta-analysis therefore aimed to summarise and reliably estimate the prevalence of HD by employing strict inclusion criteria and using studies with sufficiently large samples. A systematic literature search was conducted to identify all relevant prevalence studies. Inclusion criteria were studies that reported working age adult HD prevalence rates and had sample sizes of at least 1009 participants. Eleven studies met criteria (n = 53,378), had low risk of bias and were originally based in developed countries. A random effects meta-analysis was then conducted, with subgroup moderator analysis and meta-regression. The pooled estimated prevalence for HD was 2.5% (CI 1.7–3.6%) and subgroup analyses revealed that prevalence rates were similar for both males and females. Guidance on the manner in which HD is assessed in future prevalence studies is provided and the clinical implications of the results discussed

Síndrome d'Acumulació Compulsiva: "M'ho guardo. No sigui cas que..."

El 50% de les persones que pateixen aquesta síndrome no presenten un quadre de Transtorn Obsessiu Compulsiu. Una dada clau per entendre més a fons una variant poc estudiada i que cal diferenciar de la síndrome de Diògenes. Es tracta de persones de qualsevol edat, majoritàriament dones, que els resulta difícil desprendre's d'objectes sense valor i amb els que, en gran part dels casos, estableixen un vincle emocional. Una situació que deriva en espais inhabitables de la llar i condiciona el dia a dia del pacient. El següent estudi, encapçalat pel Departament de Psiquiatria de l'Hospital de Bellvitge, i amb la col·laboració de l'Institute of Psychiatry de Londres, obre el camí per continuar investigant. De moment, el mes d'octubre passat, l'article va ser publicat a la revista American Journal of Psychiatry.El 50% de las personas que sufren este síndrome no presentan un cuadro de Trastorno Obsesivo Compulsivo. Un dato clave para entender más a fondo una variante poco estudiada y que hay que diferenciar del síndrome de Diógenes. Se trata de personas de cualquier edad, mayoritariamente mujeres, que les resulta difícil desprenderse de objetos sin valor y con los que, en gran parte de los casos, establecen un vínculo emocional. Una situación que deriva en espacios inhabitables del hogar y condiciona el día a día del paciente. El siguiente estudio, encabezando por el Departamento de Psiquiatría del Hospital de Bellvitge, y con la colaboración de l'Institute of Psychiatry de Londres, abre el camino para continuar investigando. De momento, el pasado mes de octubre, el artículo fue publicado en la revista American Journal of Psychiatry

A trans-diagnostic perspective on obsessive-compulsive disorder

© Cambridge University Press 2017. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.Progress in understanding the underlying neurobiology of obsessive-compulsive disorder (OCD) has stalled in part because of the considerable problem of heterogeneity within this diagnostic category, and homogeneity across other putatively discrete, diagnostic categories. As psychiatry begins to recognize the shortcomings of a purely symptom-based psychiatric nosology, new data-driven approaches have begun to be utilized with the goal of solving these problems: specifically, identifying trans-diagnostic aspects of clinical phenomenology based on their association with neurobiological processes. In this review, we describe key methodological approaches to understanding OCD from this perspective and highlight the candidate traits that have already been identified as a result of these early endeavours. We discuss how important inferences can be made from pre-existing case-control studies as well as showcasing newer methods that rely on large general population datasets to refine and validate psychiatric phenotypes. As exemplars, we take 'compulsivity' and 'anxiety', putatively trans-diagnostic symptom dimensions that are linked to well-defined neurobiological mechanisms, goal-directed learning and error-related negativity, respectively. We argue that the identification of biologically valid, more homogeneous, dimensions such as these provides renewed optimism for identifying reliable genetic contributions to OCD and other disorders, improving animal models and critically, provides a path towards a future of more targeted psychiatric treatments.Peer reviewedFinal Published versio

Comparative Multimodal Meta-analysis of Structural and Functional Brain Abnormalities in Autism Spectrum Disorder and Obsessive-Compulsive Disorder

BACKGROUND: Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) share inhibitory control deficits possibly underlying poor control over stereotyped and repetitive and compulsive behaviors, respectively. However, it is unclear whether these symptom profiles are mediated by common or distinct neural profiles. This comparative multimodal meta-analysis assessed shared and disorder-specific neuroanatomy and neurofunction of inhibitory functions. METHODS: A comparative meta-analysis of 62 voxel-based morphometry and 26 functional magnetic resonance imaging (fMRI) studies of inhibitory control was conducted comparing gray matter volume and activation abnormalities between patients with ASD (structural MRI: 911; fMRI: 188) and OCD (structural MRI: 928; fMRI: 247) and control subjects. Multimodal meta-analysis compared groups across voxel-based morphometry and fMRI. RESULTS: Both disorders shared reduced function and structure in the rostral and dorsomedial prefrontal cortex including the anterior cingulate. OCD patients had a disorder-specific increase in structure and function of left basal ganglia (BG) and insula relative to control subjects and ASD patients, who had reduced right BG and insula volumes versus OCD patients. In fMRI, ASD patients showed disorder-specific reduced left dorsolateral-prefrontal activation and reduced posterior cingulate deactivation, whereas OCD patients showed temporoparietal underactivation. CONCLUSIONS: The multimodal comparative meta-analysis shows shared and disorder-specific abnormalities. Whereas the rostrodorsomedial prefrontal cortex was smaller in structure and function in both disorders, this was concomitant with increased structure and function in BG and insula in OCD patients, but a reduction in ASD patients, presumably reflecting a disorder-specific frontostriatoinsular dysregulation in OCD in the form of poor frontal control over overactive BG, and a frontostriatoinsular maldevelopment in ASD with reduced structure and function in this network. Disorder-differential mechanisms appear to drive overlapping phenotypes of inhibitory control abnormalities in patients with ASD and OCD

Exploratory analysis of obsessive compulsive symptom dimensions in children and adolescents: a Prospective follow-up study

BACKGROUND: Recent statistical approaches based on factor analysis of obsessive compulsive (OC) symptoms in adult patients have identified dimensions that seem more effective in symptom-based taxonomies and appear to be more stable over time. Although a phenotypic continuum from childhood to adulthood has been hypothesized, no factor analytic studies have been performed in juvenile patients, and the stability of OC dimensions in children and adolescents has not been assessed. METHODS: This study was designed to perform an exploratory factor analysis of OC symptoms in a sample of children and adolescents with OC disorder (OCD) and to investigate the course of factors over time (mean follow-up period: four years). RESULTS: We report for the first time that four symptom dimensions, remarkably similar to those previously described in adults, underlined the heterogeneity of OC symptoms in children and adolescents. Moreover, after follow-up, the symptom dimensions identified remained essentially unmodified. The changes observed concerned the intensity of dimensions rather than shifts from one dimension to another. CONCLUSION: These findings reinforce the hypothesis of a phenotypic continuum of OC symptoms from childhood to adulthood. They also strengthen the interest for investigating the clinical, neurobiological and genetic heterogeneity of OCD using a dimension-based approach

Patterns of Nonrandom Mating Within and Across 11 Major Psychiatric Disorders

Psychiatric disorders are heritable, polygenic traits, which often share risk alleles and for which nonrandom mating has been suggested. However, despite the potential etiological implications, the scale of nonrandom mating within and across major psychiatric conditions remains unclear

Association of Tourette Syndrome and Chronic Tic Disorder With Violent Assault and Criminal Convictions

IMPORTANCE Tic disorders are associated with multiple social adversities, but little is known about the experience of violent assault (including sexual assault) and criminality in this group. OBJECTIVE To establish if Tourette syndrome (TS) and chronic tic disorder (CTD) are associated with an increased risk of experiencing violent assault and criminal convictions. DESIGN, SETTING, AND PARTICIPANTS In this cohort study, all individuals living in Sweden at any time between January 1, 1973, and December 31, 2013, were identified from Swedish nationwide health and administrative registers. Cox proportional hazards regression models were used to estimate the risk of violent assault and criminal convictions among people with TS or CTD, compared with the general population and unaffected full siblings. Data analyses were conducted between September 1 and October 22, 2021. EXPOSURES The Swedish version of the International Classification of Diseases, Eighth Revision ( ICD-8 ), ICD-9 , and ICD-10 diagnoses of TS or CTD in the Swedish National Patient Register. MAIN OUTCOMES AND MEASURES Records of sexual and nonsexual violent assault and death due to violent assaults were obtained from the National Patient Register and the Cause of Death Register, respectively. Convictions for violent and nonviolent criminal offenses were obtained from the Crime Register. Covariates included sex and birth year. RESULTS The study cohort included 13 819 284 individuals living in Sweden between 1973 and 2013. A total of 7791 individuals with TS or CTD were identified (median [IQR] age at first diagnosis, 13.4 [10.0-21.8] years; 5944 [76%] male). Compared with unaffected individuals from the general population, people with TS or CTD had a 2-fold increased risk of experiencing any violent assault (sexual and nonsexual) (adjusted hazard ratio [aHR], 2.21; 95% CI, 2.00-2.43), a 3-fold increased risk of violent convictions (aHR, 3.13; 95% CI, 2.92-3.36), and a 1.6-fold increased risk of nonviolent crime convictions (aHR, 1.62; 95% CI, 1.54-1.71). Among people with TS or CTD, 37.0% (114 of 308; 95% CI, 31.6%-42.4%) of individuals who had experienced violent assault also had a violent crime conviction, compared with 17.9% (16 067 of 89 920; 95% CI, 17.6%-18.1%) in the general population. Exclusion of individuals with attention-deficit/hyperactivity disorder and substance use disorders partially attenuated the associations. Similarly, within-sibling models attenuated but did not eliminate the associations (any violent assault: aHR, 1.32; 95% CI, 1.08-1.61; violent crime: aHR, 2.23; 95% CI, 1.86-2.67; nonviolent crime: aHR, 1.34; 95% CI, 1.20-1.50). CONCLUSIONS AND RELEVANCE Results of this cohort study suggest that most individuals with TS or CTD are not assaulted nor are perpetrators of crime. However, individuals with TS or CTD diagnosed in specialist settings were more likely to both experience violent assault and be perpetrators of violence compared with the general population. The risk was highest in individuals with comorbid attention-deficit/hyperactivity disorder and substance use disorders. The increased risk found in specialty clinics will need to be better understood in the general population.Peer reviewe

Association of Tourette Syndrome and Chronic Tic Disorder With Subsequent Risk of Alcohol- or Drug-Related Disorders, Criminal Convictions, and Death : A Population-Based Family Study

BACKGROUND: It remains unclear if individuals with Tourette syndrome (TS) or chronic tic disorder (CTD) have an elevated risk of subsequent substance misuse. METHODS: In this population-based cohort study, we investigated the association between ICD diagnoses of TS/CTD and substance misuse outcomes, accounting for psychiatric comorbidity and familial factors. The cohort included all individuals living in Sweden at any time between January 1, 1973, and December 31, 2013. Substance misuse outcomes were defined as an ICD code of substance use-related disorder or cause of death, or as a substance use-related criminal conviction in the nationwide registers. RESULTS: The cohort included 14,277,199 individuals, of whom 7832 had a TS/CTD diagnosis (76.3% men). TS/CTD was associated with an increased risk of any subsequent substance misuse outcomes (adjusted hazard ratio [aHR], 3.11; 95% confidence interval [CI], 2.94-3.29), including alcohol-related disorder (aHR, 3.45; 95% CI, 3.19-3.72), drug-related disorder (aHR, 6.84; 95% CI, 6.32-7.40), substance-related criminal convictions (aHR, 2.56; 95% CI, 2.36-2.77), and substance-related death (aHR, 2.54; 95% CI, 1.83-3.52). Excluding psychiatric comorbidities had little effect on the magnitude of the associations, with the exception of attention-deficit/hyperactivity disorder, which attenuated the risk of any substance misuse outcomes (aHR, 2.00; 95% CI, 1.82-2.19). The risk of any substance misuse outcomes in individuals with TS/CTD was substantially attenuated but remained significant when compared with their unaffected siblings (aHR, 1.74; 95% CI, 1.53-1.97). CONCLUSIONS: TS/CTD were associated with various types of subsequent substance misuse outcomes, independently of psychiatric comorbidity and familial factors shared between siblings. Screening for drug and alcohol use should become part of the standard clinical routines, particularly in patients with comorbid attention-deficit/hyperactivity disorder.Peer reviewe

Fidelity of delivery and contextual factors influencing children’s level of engagement: Process evaluation of the Online Remote Behavioural Intervention for Tics (ORBIT) Trial (Preprint)

BACKGROUND: The Online Remote Behavioural Intervention for Tics (ORBIT) study was a multicentre randomized controlled trial of a complex intervention that consisted of an online behavioural intervention for children and young people (CYP) with tic disorders. In this first part of a two-stage process evaluation, we conducted a mixed-methods study exploring reach, dose, and fidelity of the intervention and contextual factors influencing engagement with the intervention. OBJECTIVE: This study aims to explore the fidelity of delivery and the contextual factors underpinning the ORBIT intervention. METHODS: Baseline study data and intervention usage metrics from participants in the intervention arm were used as quantitative implementation data (n=112). The experiences of being in the intervention were explored by semi-structured interviews with children (n=20) and parent (n=20) participants, therapists (n=4), and referring clinicians (n=6). A principal components analysis was used to create a comprehensive, composite measure of CYP’s engagement with the intervention. Engagement factor scores reflected relative uptake as assessed by a range of usage indices including chapters accessed, number of pages visited and number of logins. RESULTS: The intervention was implemented with high fidelity, and participants deemed the intervention acceptable and satisfactory. Engagement and adherence were high with child participants completing an average of 7.5/10 chapters and 100/112 (89.3%) participants completed a minimum of 4 chapters: the pre-defined threshold for effective dose. Compared to the total population of children with tic disorders, the sample tended to have more educated parents and live in more economically advantaged areas but socioeconomic factors were not related to engagement factor scores. Factors associated with higher engagement factor scores included participants enrolled at the London site vs. the Nottingham site (P=.011), self-referred vs. clinic-referred (P=.041), higher parental engagement as evidenced by number of parental chapters completed (ρ=0.73, n=111, P<.001) and more therapist time for parent (ρ=0.46, n=111, P<.001). A multiple linear regression indicated that parents’ chapter completion (β=.69, t110=10.18, P<.001) and therapist time for parent (β=.19, t110=2.95, P=.004) were the only significant independent predictors of engagement factor scores. CONCLUSIONS: Overall, the intervention had high fidelity of delivery and was evaluated positively by participants, although reach may have been constrained by the nature of the randomized controlled trial. Parental engagement and therapist time for parent were strong predictors of intervention implementation which has important implications for the design and implementation of digital therapeutic interventions into Child and Adolescent Mental Health Services. Clinical Trial: International Standard Randomized Controlled Trial Number (ISRCTN) 70758207; https://doi.org/10.1186/ISRCTN70758207 and ClinicalTrials.gov NCT03483493; https://clinicaltrials.gov/ct2/show/NCT0348349