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"Mataix-Cols, David"
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COGNITIVE BEHAVIOR THERAPY FOR COMORBID OBSESSIVE-COMPULSIVE DISORDER IN HIGH-FUNCTIONING AUTISM SPECTRUM DISORDERS: A RANDOMIZED CONTROLLED TRIAL
2013
Background High rates of anxiety disorders, particularly obsessive compulsive disorder (OCD) are reported in people with Autism spectrum disorders (ASD). Group cognitive behavioral treatment (CBT) has been found effective for anxiety in young people with ASD but not been OCD specific. One uncontrolled pilot study of individual CBT for OCD for adults with ASD showed good treatment efficacy. Methods Forty‐six adolescents and adults (mean age 26.9 years, 35 Males) with ASD and comorbid OCD were randomized to CBT for OCD or anxiety management (AM), a plausible control treatment. Treatments were matched in duration (mean of 17.4 sessions CBT; 14.4 sessions AM), the Yale–Brown Obsessive Compulsive Severity Scale (YBOCS) as primary outcome measure and evaluations blind to treatment group. Treatment response was defined as > 25% reduction in YBOCS total severity scores. Results Both treatments produced a significant reduction in OCD symptoms, within‐group effect sizes of 1.01 CBT group and 0.6 for the AM group. There were no statistically significant differences between the two groups at end of treatment, although more responders in the CBT group (45 versus 20%). Effect sizes for self‐rated improvement were small (0.33 CBT group; –0.05 AM group). Mild symptom severity was associated with improvement in the AM but not the CBT group. Family/carer factors were important for both groups, in that increased family accommodation was associated with poorer outcome. Conclusions Evidence‐based psychological interventions, both AM and CBT, were effective in treating comorbid OCD in young people and adults with ASD.
Journal Article
Stress related disorders and subsequent risk of life threatening infections: population based sibling controlled cohort study
by
Fall, Katja
,
Erlendsdóttir, Helga
,
Fang, Fang
in
Central nervous system
,
Cohort analysis
,
Diagnosis
2019
AbstractObjectiveTo assess whether severe psychiatric reactions to trauma and other adversities are associated with subsequent risk of life threatening infections.DesignPopulation and sibling matched cohort study.SettingSwedish population.Participants144 919 individuals with stress related disorders (post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions) identified from 1987 to 2013 compared with 184 612 full siblings of individuals with a diagnosed stress related disorder and 1 449 190 matched individuals without such a diagnosis from the general population.Main outcome measuresA first inpatient or outpatient visit with a primary diagnosis of severe infections with high mortality rates (ie, sepsis, endocarditis, and meningitis or other central nervous system infections) from the Swedish National Patient Register, and deaths from these infections or infections of any origin from the Cause of Death Register. After controlling for multiple confounders, Cox models were used to estimate hazard ratios of these life threatening infections.ResultsThe average age at diagnosis of a stress related disorder was 37 years (55 541, 38.3% men). During a mean follow-up of eight years, the incidence of life threatening infections per 1000 person years was 2.9 in individuals with a stress related disorder, 1.7 in siblings without a diagnosis, and 1.3 in matched individuals without a diagnosis. Compared with full siblings without a diagnosis of a stress related disorder, individuals with such a diagnosis were at increased risk of life threatening infections (hazard ratio for any stress related disorder was 1.47 (95% confidence intervals1.37 to 1.58) and for PTSD was 1.92 (1.46 to 2.52)). Corresponding estimates in the population based analysis were similar (1.58 (1.51 to 1.65) for any stress related disorder, P=0.09 for difference between sibling and population based comparison, and 1.95 (1.66 to 2.28) for PTSD, P=0.92 for difference). Stress related disorders were associated with all studied life threatening infections, with the highest relative risk observed for meningitis (sibling based analysis 1.63 (1.23 to 2.16)) and endocarditis (1.57 (1.08 to 2.30)). Younger age at diagnosis of a stress related disorder and the presence of psychiatric comorbidity, especially substance use disorders, were associated with higher hazard ratios, whereas use of selective serotonin reuptake inhibitors in the first year after diagnosis of a stress related disorder was associated with attenuated hazard ratios.ConclusionIn the Swedish population, stress related disorders were associated with a subsequent risk of life threatening infections, after controlling for familial background and physical or psychiatric comorbidities.
Journal Article
SEXUAL OBSESSIONS IN PEDIATRIC OBSESSIVE-COMPULSIVE DISORDER: CLINICAL CHARACTERISTICS AND TREATMENT OUTCOMES
by
Barrow, Faye
,
Nakatani, Eriko
,
Fernández de la Cruz, Lorena
in
Adolescent
,
adolescents
,
Child
2013
Background Sexual obsessions are common in adults with obsessive‐compulsive disorder (OCD), cause great distress, and are sometimes misinterpreted as indicating risk to others. Little is known about the prevalence, clinical correlates, and prognosis of such symptoms in young people. Methods Three hundred and eighty‐three patients referred to a specialist pediatric OCD clinic were administered a series of measures at intake and, for those treated at the clinic, again after treatment. Patients with and without sexual obsessions were compared on socio‐demographic and clinical characteristics. Mixed model analyses of variance compared treatment outcomes in both groups. Results A quarter of patients had sexual obsessions at baseline (age range 8–17); they had slightly more severe OCD symptoms and were more depressed than those without sexual obsessions. Aggressive and religious obsessions, magical thinking, fear of saying certain things, repeating rituals, superstitious games, mental rituals, and the need to tell, ask, or confess were more frequent in participants with sexual obsessions. Crucially, no differences in treatment outcome were found between the groups. Conclusions Sexual obsessions are common in pediatric OCD, even in very young children. Although they may be associated with particular clinical features, they do not interfere with treatment response. The occurrence of sexual obsessions in children should be recognized and these symptoms understood as ordinary, nonthreatening OCD symptoms, which pose no risk to others. They respond to the standard treatment strategies, so children and families should receive the usual message of optimism regarding the chances of recovery.
Journal Article
The genetic epidemiology of obsessive-compulsive disorder: a systematic review and meta-analysis
by
Blanco-Vieira, Thiago
,
Mataix-Cols, David
,
Bloch, Michael
in
Epidemiology
,
Meta-analysis
,
Neuroses
2023
The first systematic review and meta-analysis of obsessive-compulsive disorder (OCD) genetic epidemiology was published approximately 20 years ago. Considering the relevance of all the studies published since 2001, the current study aimed to update the state-of-art knowledge on the field. All published data concerning the genetic epidemiology of OCD from the CENTRAL, MEDLINE, EMBASE, BVS, and OpenGrey databases were searched by two independent researchers until September 30, 2021. To be included, the articles had to fulfill the following criteria: OCD diagnosis provided by standardized and validated instruments; or medical records; inclusion of a control group for comparison and case-control, cohort or twin study designs. The analysis units were the first-degree relatives (FDRs) of OCD or control probands and the co-twins in twin pairs. The outcomes of interest were the familial recurrence rates of OCD and the correlations of OCS in monozygotic compared with dizygotic twins. Nineteen family, twenty-nine twin, and six population-based studies were included. The main findings were that OCD is a prevalent and highly familial disorder, especially among the relatives of children and adolescent probands, that OCD has a phenotypic heritability of around 50%; and that the higher OCS correlations between MZ twins were mainly due to additive genetic or to non-shared environmental components.
Journal Article
Benzodiazepine prescribing for children, adolescents, and young adults from 2006 through 2013: A total population register-linkage study
by
Isomura, Kayoko
,
Franck, Johan
,
Hellner, Clara
in
Adolescent medicine
,
Adolescents
,
Anxiolytics
2018
Pharmacoepidemiological studies have long raised concerns on widespread use of benzodiazepines and benzodiazepine-related drugs (BZDs), in particular long-term use, among adults and the elderly. In contrast, evidence pertaining to the rates of BZD use at younger ages is still scarce, and the factors that influence BZD utilisation and shape the different prescribing patterns in youths remain largely unexplored. We examined the prevalence rates, relative changes in rates over time, and prescribing patterns for BZD dispensation in young people aged 0-24 years in Sweden during the period January 1, 2006-December 31, 2013, and explored demographic, clinical, pharmacological, and prescriber-related attributes of BZD prescribing in this group.
Through the linkage of 3 nationwide Swedish health and administrative registers, we collected data on 17,500 children (0-11 years), 15,039 adolescents (12-17 years), and 85,200 young adults (18-24 years) with at least 1 dispensed prescription for a BZD during 2006-2013, out of 3,726,818 Swedish inhabitants aged 0-24 years. Age-specific annual prevalence rates of BZD dispensations were adjusted for population growth, and relative changes in rates were calculated between 2006 and 2013. We analysed how BZD dispensation varied by sex, psychiatric morbidity and epilepsy, concurrent dispensation of psychotropic medication, type of dispensed BZD, and type of healthcare provider prescribing the BZD. Prescribing patterns were established in relation to duration (3 months, >3 to ≤6 months, or >6 months), dosage (<0.5 defined daily dosage [DDD]/day, ≥0.5 to <1.5 DDD/day, or ≥1.5 DDD/day), and \"user category\" (\"regular users\" [≥0.5 to <1.5 DDD/day for ≥1 year], \"heavy users\" [≥1.5 DDD/day for ≥1 year], or otherwise \"occasional users\"). Multinomial regression models were fitted to test associations between BZD prescribing patterns and individual characteristics of study participants. Between 2006 and 2013, the prevalence rate of BZD dispensation among individuals aged 0-24 years increased by 22% from 0.81 per 100 inhabitants to 0.99 per 100 inhabitants. This increase was mainly driven by a rise in the rate among young adults (+20%), with more modest increases in children (+3%) and adolescents (+7%). Within each age category, overall dispensation of BZD anxiolytics and clonazepam decreased over time, while dispensation of BZD hypnotics/sedatives, including Z-drugs, showed an increase between 2006 and 2013. Out of 117,739 study participants with dispensed BZD prescriptions, 65% initiated BZD prescriptions outside of psychiatric services (92% of children, 60% of adolescents, 60% of young adults), and 76% were dispensed other psychotropic drugs concurrently with a BZD (46% of children, 80% of adolescents, 81% of young adults). Nearly 30% of the participants were prescribed a BZD for longer than 6 months (18% of children, 31% of adolescents, 31% of young adults). A high dose prescription (≥1.5 DDD/day) and heavy use were detected in 2.6% and 1.7% of the participants, respectively. After controlling for potential confounding by demographic and clinical characteristics, the characteristics age above 11 years at the first BZD dispensation, lifetime psychiatric diagnosis or epilepsy, and concurrent dispensation of other psychotropic drugs were found to be associated with higher odds of being prescribed a BZD for longer than 6 months, high dose prescription, and heavy use. Male sex was associated with a higher likelihood of high dose prescription and heavy use, but not with being prescribed a BZD on a long-term basis (> 6 months). The study limitations included lack of information on actual consumption of the dispensed BZDs and unavailability of data on the indications for BZD prescriptions.
The overall increase in prevalence rates of BZD dispensations during the study period and the unexpectedly high proportion of individuals who were prescribed a BZD on a long-term basis at a young age indicate a lack of congruence with international and national guidelines. These findings highlight the need for close monitoring of prescribing practices, particularly in non-psychiatric settings, in order to build an evidence base for safe and efficient BZD treatment in young persons.
Journal Article
Multimodal Voxel-Based Meta-Analysis of White Matter Abnormalities in Obsessive–Compulsive Disorder
by
Stein, Dan J
,
Canales-Rodríguez, Erick J
,
van den Heuvel, Odile A
in
Adult and adolescent clinical studies
,
Anisotropy
,
Anxiety disorders. Neuroses
2014
White matter (WM) abnormalities have long been suspected in obsessive-compulsive disorder (OCD) but the available evidence has been inconsistent. We conducted the first multimodal meta-analysis of WM volume (WMV) and fractional anisotropy (FA) studies in OCD. All voxel-wise studies comparing WMV or FA between patients with OCD and healthy controls in the PubMed, ScienceDirect, Google Scholar, Web of Knowledge and Scopus databases were retrieved. Manual searches were also conducted and authors were contacted soliciting additional data. Thirty-four data sets were identified, of which 22 met inclusion criteria (five of them unpublished; comprising 537 adult and pediatric patients with OCD and 575 matched healthy controls). Whenever possible, raw statistical parametric maps were also obtained from the authors. Peak and raw WMV and FA data were combined using novel multimodal meta-analytic methods implemented in effect-size signed differential mapping. Patients with OCD showed widespread WM abnormalities, but findings were particularly robust in the anterior midline tracts (crossing between anterior parts of cingulum bundle and body of corpus callosum), which showed both increased WMV and decreased FA, possibly suggesting an increase of fiber crossing in these regions. This finding was also observed when the analysis was limited to adult participants, and especially pronounced in samples with a higher proportion of medicated patients. Therefore, patients with OCD may have widespread WM abnormalities, particularly evident in anterior midline tracts, although these changes might be, at least in part, attributable to the effects of therapeutic drugs.
Journal Article
The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R): A Scale to Assist the Diagnosis of Autism Spectrum Disorder in Adults: An International Validation Study
2011
The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) is a valid and reliable instrument to assist the diagnosis of adults with Autism Spectrum Disorders (ASD). The 80-question scale was administered to 779 subjects (201 ASD and 578 comparisons). All ASD subjects met inclusion criteria: DSM-IV-TR, ADI/ADOS diagnoses and standardized IQ testing. Mean scores for each of the questions and total mean ASD vs. the comparison groups’ scores were significantly different (
p
< .0001). Concurrent validity with Constantino Social Responsiveness Scale-Adult = 95.59%. Sensitivity = 97%, specificity = 100%, test–retest reliability
r
= .987. Cronbach alpha coefficients for the subscales and 4 derived factors were good. We conclude that the RAADS-R is a useful adjunct diagnostic tool for adults with ASD.
Journal Article
Predicting remission after internet-delivered psychotherapy in patients with depression using machine learning and multi-modal data
by
Ben Abdesslem, Fehmi
,
Flygare, Oskar
,
Andersson, Evelyn
in
45/43
,
631/208/1516
,
692/699/476/1414
2022
This study applied supervised machine learning with multi-modal data to predict remission of major depressive disorder (MDD) after psychotherapy. Genotyped adult patients (
n
= 894, 65.5% women, age 18–75 years) diagnosed with mild-to-moderate MDD and treated with guided Internet-based Cognitive Behaviour Therapy (ICBT) at the Internet Psychiatry Clinic in Stockholm were included (2008–2016). Predictor types were demographic, clinical, process (e.g., time to complete online questionnaires), and genetic (polygenic risk scores). Outcome was remission status post ICBT (cut-off ≤10 on MADRS-S). Data were split into train (60%) and validation (40%) given ICBT start date. Predictor selection employed human expertise followed by recursive feature elimination. Model derivation was internally validated through cross-validation. The final random forest model was externally validated against a (i) null, (ii) logit, (iii) XGBoost, and (iv) blended meta-ensemble model on the hold-out validation set. Feature selection retained 45 predictors representing all four predictor types. With unseen validation data, the final random forest model proved reasonably accurate at classifying post ICBT remission (Accuracy 0.656 [0.604, 0.705], P vs null model = 0.004; AUC 0.687 [0.631, 0.743]), slightly better vs logit (bootstrap D = 1.730,
P
= 0.084) but not vs XGBoost (D = 0.463,
P
= 0.643). Transparency analysis showed model usage of all predictor types at both the group and individual patient level. A new, multi-modal classifier for predicting MDD remission status after ICBT treatment in routine psychiatric care was derived and empirically validated. The multi-modal approach to predicting remission may inform tailored treatment, and deserves further investigation to attain clinical usefulness.
Journal Article
Internet-Delivered Cognitive Behavior Therapy for Adolescents with Obsessive-Compulsive Disorder: An Open Trial
2014
International guidelines recommend Cognitive Behavior Therapy (CBT) as the first line treatment for pediatric obsessive-compulsive disorder (OCD). However, a substantial proportion of patients do not have access to such treatment. We developed and tested the feasibility, efficacy and acceptability of a novel therapist-guided, Internet-delivered CBT (ICBT) platform for adolescents with OCD.
An interactive, age-appropriate ICBT platform (\"BiP OCD\") was developed. Twenty-one adolescents (12-17 years) with a DSM-IV diagnosis of OCD and their parents were enrolled in the study. All participants received 12 weeks of ICBT with therapist support. The primary outcome measure was the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Acceptability was assessed at post-treatment.
Participants completed on average 8.29 (SD = 3.0) of the 12 treatment chapters. Treatment yielded significant improvements on all clinician-, parent- and most self-administered outcome measures, with a large effect size of d = 2.29 (95% CI 1.5-3.07) on the CY-BOCS. Patients continued to improve at follow-up. At 6-month follow-up, 71% were classified as responders (≥35% decrease on the CY-BOCS) and 76% as being in remission (CY-BOCS score ≤12). Average clinician support time was less than 20 minutes per patient per week. The majority of participants felt that BiP OCD was age-appropriate and rated the treatment as good or very good.
ICBT could be efficacious, acceptable, and cost-effective for adolescents with OCD. More rigorously controlled studies are needed to further evaluate the treatment.
ClinicalTrials.gov; NCT01809990.
Journal Article
Predictors of remission from body dysmorphic disorder after internet-delivered cognitive behavior therapy: a machine learning approach
by
Ljótsson, Brjánn
,
Flygare, Oskar
,
Andersson, Erik
in
Algorithms
,
Analysis
,
Behavior modification
2020
Background
Previous attempts to identify predictors of treatment outcomes in body dysmorphic disorder (BDD) have yielded inconsistent findings. One way to increase precision and clinical utility could be to use machine learning methods, which can incorporate multiple non-linear associations in prediction models.
Methods
This study used a random forests machine learning approach to test if it is possible to reliably predict remission from BDD in a sample of 88 individuals that had received internet-delivered cognitive behavioral therapy for BDD. The random forest models were compared to traditional logistic regression analyses.
Results
Random forests correctly identified 78% of participants as remitters or non-remitters at post-treatment. The accuracy of prediction was lower in subsequent follow-ups (68, 66 and 61% correctly classified at 3-, 12- and 24-month follow-ups, respectively). Depressive symptoms, treatment credibility, working alliance, and initial severity of BDD were among the most important predictors at the beginning of treatment. By contrast, the logistic regression models did not identify consistent and strong predictors of remission from BDD.
Conclusions
The results provide initial support for the clinical utility of machine learning approaches in the prediction of outcomes of patients with BDD.
Trial registration
ClinicalTrials.gov ID:
NCT02010619
.
Journal Article