The role of psychosis and clozapine load in excessive checking in treatment-resistant schizophrenia: longitudinal observational study.

BACKGROUND: A significant proportion of people with clozapine-treated schizophrenia develop 'checking' compulsions, a phenomenon yet to be understood. AIMS: To use habit formation models developed in cognitive neuroscience to investigate the dynamic interplay between psychosis, clozapine dose and obsessive-compulsive symptoms (OCS). METHOD: Using the anonymised electronic records of a cohort of clozapine-treated patients, including longitudinal assessments of OCS and psychosis, we performed longitudinal multi-level mediation and multi-level moderation analyses to explore associations of psychosis with obsessiveness and excessive checking. Classic bivariate correlation tests were used to assess clozapine load and checking compulsions. The influence of specific genetic variants was tested in a subsample. RESULTS: A total of 196 clozapine-treated individuals and 459 face-to-face assessments were included. We found significant OCS to be common (37.9%), with checking being the most prevalent symptom. In mediation models, psychosis severity mediated checking behaviour indirectly by inducing obsessions (r = 0.07, 95% CI 0.04-0.09; P < 0.001). No direct effect of psychosis on checking was identified (r = -0.28, 95% CI -0.09 to 0.03; P = 0.340). After psychosis remission (n = 65), checking compulsions correlated with both clozapine plasma levels (r = 0.35; P = 0.004) and dose (r = 0.38; P = 0.002). None of the glutamatergic and serotonergic genetic variants were found to moderate the effect of psychosis on obsession and compulsion (SLC6A4, SLC1A1 and HTR2C) survived the multiple comparisons correction. CONCLUSIONS: We elucidated different phases of the complex interplay of psychosis and compulsions, which may inform clinicians' therapeutic decisions.

Lessons from a multicenter, international, large sample size analysis of patients with obsessive-compulsive disorders: an overview of the ICOCS Snapshot studies.

Obsessive-compulsive disorder (OCD) is a prevalent and highly disabling condition, characterized by a range of phenotypic expressions, potentially associated with geo-cultural differences. This article aims to provide an overview of the published studies by the International College of Obsessive-Compulsive Spectrum Disorders, in relation to the Snapshot database which has, over the past 10 years, gathered clinical naturalistic data from over 500 patients with OCD attending various research centers/clinics worldwide. This collaborative effort has provided a multi-cultural worldwide perspective of different socio-demographic and clinical features of patients with OCD. Data on age, gender, smoking habits, age at onset, duration of illness, comorbidity, suicidal behaviors, and pharmacological treatment strategies are presented here, showing peculiar differences across countries.

The relationship between cognitive phenotypes of compulsivity and impulsivity and clinical variables in obsessive-compulsive disorder: A systematic review and Meta-analysis.

BACKGROUND: This systematic review and meta-analysis explored the relationship between cognitive phenotypes of compulsivity and impulsivity and clinical variables in obsessive-compulsive disorder (OCD). METHODS: We searched Pubmed, Scopus, Cochrane Library and PsychINFO databases until February 2023 for studies comparing patients with OCD and healthy controls on cognitive tests of compulsivity and impulsivity. The study followed PRISMA guidelines and was pre-registered on PROSPERO (CRD42021299017). RESULTS: Meta-analyses of 112 studies involving 8313 participants (4289 patients with OCD and 4024 healthy controls) identified significant impairments in compulsivity (g = -0.58, [95%CI -0.68, -0.47]; k = 76) and impulsivity (g = -0.48, [95%CI -0.57, -0.38]; k = 63); no significant difference between impairments. Medication use and comorbid psychiatric disorders were not significantly related to impairments. No associations were revealed with OCD severity, depression/anxiety, or illness duration. CONCLUSION: Cognitive phenotypes of compulsivity and impulsivity in patients with OCD appear to be orthogonal to clinical variables, including severity of OCD symptomatology. Their clinical impact is poorly understood and may require different clinical assessment tools and interventions.

Clozapine-related obsessive-compulsive symptoms and their impact on wellbeing: a naturalistic longitudinal study.

BACKGROUND: Obsessive-compulsive symptoms (OCS) are commonly associated with clozapine treatment but are frequently overlooked by clinicians despite their potential impact on patients' quality of life. In this study, we explored whether OCS severity impacted subjective wellbeing and general functioning, independently of depressive and psychotic symptoms. METHODS: We used anonymised electronic healthcare records from a large cohort of patients who were treated with clozapine and assessed annually for OCS, wellbeing, general functioning, and psychopathology using standardised scales as part of routine clinical practice. We used statistical mixed linear model techniques to evaluate the longitudinal influence of OCS severity on wellbeing and general functioning. RESULTS: A total of 184 patients were included, with 527 face-to-face assessments and 64.7% evaluated three or more times. Different linear mixed models demonstrated that OCS in patients treated with clozapine were associated with significantly worse wellbeing scores, independently of depression and psychotic symptoms, but OCS did not impair general functioning. Obsessional thinking and hoarding behaviour, but not compulsions, were significantly associated with the impact on wellbeing, which may be attributable to the ego-syntonic nature of the compulsions. CONCLUSIONS: Given the frequent occurrence of OCS and their negative impact on wellbeing, we encourage clinicians to routinely assess and treat OCS in patients who are taking clozapine.

A cost-of-illness analysis of the economic burden of obsessive-compulsive disorder in the United Kingdom.

OBJECTIVES: Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition, with diagnosed patients typically experiencing moderate or severe symptoms. This study evaluated the cost-of-illness (CoI) of OCD in the UK, capturing the annual costs accrued to the National Health Service (NHS) and Personal Social Services (PSS), people with OCD, caregivers and society. METHODS: The UK OCD population was estimated and stratified by age group (children, adults, elderly), symptom severity (mild, moderate, severe) and treatment received (including no treatment). Costs for each subpopulation were estimated through a prevalence-based approach. Cost inputs were sourced from national databases, while additional inputs were informed by literature searches or expert clinician opinion. Scenario analyses explored other factors including comorbid depression treatment and presenteeism. RESULTS: The base-case analysis estimated a total annual CoI of £378,356,004 to the NHS, rising to £5,095,759,464 when a societal perspective was considered. The annual cost of care per person with OCD increased with severity (mild: £174; moderate: £365; severe: £902) due to increasing healthcare resource utilisation. The largest contributor to healthcare costs was cognitive behavioural therapy, while societal costs were driven by lost productivity through absenteeism. The base-case results likely underestimated the true economic burden of OCD; including comorbid depression led to a 132% increase in treatment costs, while presenteeism in people with OCD and lost productivity in caregivers amplified indirect costs. CONCLUSIONS: The economic burden of OCD in the UK is substantial and extends beyond direct treatment costs, highlighting a need for research into alternative treatments with greater efficacy.

Feasibility, acceptability and practicality of transcranial stimulation in obsessive compulsive symptoms (FEATSOCS): A randomised controlled crossover trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive form of neurostimulation with potential for development as a self-administered intervention. It has shown promise as a safe and effective treatment for obsessive compulsive disorder (OCD) in a small number of studies. The two most favourable stimulation targets appear to be the left orbitofrontal cortex (L-OFC) and the supplementary motor area (SMA). We report the first study to test these targets head-to-head within a randomised sham-controlled trial. Our aim was to inform the design of future clinical research studies, by focussing on the acceptability and safety of the intervention, feasibility of recruitment, adherence to and tolerability of tDCS, and the size of any treatment-effect. METHODS: FEATSOCS was a randomised, double-blind, sham-controlled, cross-over, multicentre study. Twenty adults with DSM-5-defined OCD were randomised to treatment, comprising three courses of clinic-based tDCS (SMA, L-OFC, Sham), randomly allocated and delivered in counterbalanced order. Each course comprised four 20-min 2 mA stimulations, delivered over two consecutive days, separated by a 'washout' period of at least four weeks. Assessments were carried out by raters who were blind to stimulation-type. Clinical outcomes were assessed before, during, and up to four weeks after stimulation. Patient representatives with lived experience of OCD were actively involved at all stages. RESULTS: Clinicians showed willingness to recruit participants and recruitment to target was achieved. Adherence to treatment and study interventions was generally good, with only two dropouts. There were no serious adverse events, and adverse effects which did occur were transient and mostly mild in intensity. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores were numerically improved from baseline to 24 h after the final stimulation across all intervention groups but tended to worsen thereafter. The greatest effect size was seen in the L-OFC arm, (Cohen's d = -0.5 [95% CI -1.2 to 0.2] versus Sham), suggesting this stimulation site should be pursued in further studies. Additional significant sham referenced improvements in secondary outcomes occurred in the L-OFC arm, and to a lesser extent with SMA stimulation. CONCLUSIONS: tDCS was acceptable, practicable to apply, well-tolerated and appears a promising potential treatment for OCD. The L-OFC represents the most promising target based on clinical changes, though the effects on OCD symptoms were not statistically significant compared to sham. SMA stimulation showed lesser signs of promise. Further investigation of tDCS in OCD is warranted, to determine the optimal stimulation protocol (current, frequency, duration), longer-term effectiveness and brain-based mechanisms of effect. If efficacy is substantiated, consideration of home-based approaches represents a rational next step. TRIAL REGISTRATION: ISRCTN17937049. https://doi.org/10.1186/ISRCTN17937049.

Mental fatigue in individuals with psychiatric disorders: a scoping review.

OBJECTIVE: The aim of this study was to complete a scoping review of the published literature describing the relationship between mental fatigue and various psychiatric disorders, to better understand its frequency and clinical impact, and to provide recommendations for future clinical research. METHODS: A scoping review using PubMed/MEDLINE, Cochrane and PsychArticles databases was conducted using the keywords 'mental fatigue', 'mental tiredness' or 'mental exhaustion', and completed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols Extension for Scoping Reviews 2018 checklist. RESULTS: We extracted 10 studies fulfilling our inclusion criteria from a total of 2937 publications. Mental fatigue was studied within mood disorders, anxiety disorders, obsessive compulsive disorder and obsessive-compulsive personality disorder. A commonly used tool to measure mental fatigue in these samples was the Multidimensional Fatigue Inventory-20. Specific cognitive factors (unhelpful beliefs about sleep, symptom-focussed rumination) and personality risk factors (harm avoidance, self-directedness, cooperativeness, persistence) were relevant to predicting mental fatigue symptoms and rates of mental fatigue may vary with gender and diagnosis. CONCLUSION: Research into mental fatigue in adult psychiatric sample was limited to a few psychiatric disorders and requires further investigation.Key pointsA commonly used tool to measure mental fatigue was the Multidimensional Fatigue Inventory-20. However, more research into the validity and reliability for illness specific instruments to measure mental fatigue in psychiatric population is required.Reduction of mental fatigue was associated with improvement on quality of life.Specific cognitive factors (unhelpful beliefs about sleep, symptom-focussed rumination) and personality risk factors (harm avoidance, self-directedness, cooperativeness, persistence) were relevant to predicting mental fatigue symptoms and rates of mental fatigue may vary with gender.Reviewed articles indicated that mental fatigue presence was associated with lower odds of OCD. In addition, the results suggested that mental fatigue symptoms were more common in individuals with OCPD rather than OCD.Research into mental fatigue in adult psychiatric sample was limited to a few psychiatric disorders and requires further investigation to prevent potential misattribution as mental fatigue symptoms overlap between different psychiatric disorders.

Effects of exercise on obsessive-compulsive disorder symptoms: a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis assessed the efficacy of exercise in reducing OCD symptoms. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials, MEDLINE, Scopus and grey literature until March 2022. The study was preregistered at Prospero (CRD42021283931). We included randomised controlled and pre-post trials assessing physical activity as an intervention for OCD. Risk of bias was assessed using the Cochrane ROBINS-I tool and the RoB2 tool. RESULTS: The analysis included 6 trials (N = 92); 2 were RCTS and 4 were pre-post design studies. A random-effects meta-analysis of pre-post data identified a large reduction of OCD symptoms following exercise (g = 1.33 [95%CI 1.06-1.61]; k = 6). Exercise was also associated with significant pre-post reductions in anxiety (g = 0.71 [95%CI 0.37-1.05; k = 4) and depression (g = 0.57 [95%CI 0.26-0.89]; k = 2). Risk of bias was moderate-high in uncontrolled trials on the ROBINS-I and RCTs showed 'some concerns' on the RoB2. CONCLUSION: Exercise was associated with a large pre-post reduction of OCD symptoms; however, few trials were of robust quality and all were at risk of bias. Further well-powered and better quality RCTs are required to assess the role of exercise as an intervention for OCD.KEY POINTSStudies exploring exercise as an adjunct therapy for OCD have small participant numbers, therefore a systematic review and meta-analysis is needed to estimate potential efficacy.Pre-post analysis shows that exercise was associated with a large reduction of OCD symptomsThe current systematic review and meta-analysis points to the potential for exercise to be beneficial for the treatment for OCD symptoms. However, more well-powered and better controlled RCTs are required to fully assess the benefit of exercise for the treatment of OCD symptoms.

Problematic internet use during the COVID-19 pandemic: A systematic review and meta-analysis of prevalence data.

AIMS: This study sought to synthesize prevalence rates of problematic internet use (PIU) during the COVID-19 pandemic in the general adult (age over 18 years old) population and to investigate its possible moderators. METHODS: A preregistered systematic literature review using the PubMed/MEDLINE, EBSCOhost/PsycINFO, Web of Science, Cochrane Library, GSK Clinical Study Register, and ClinicalTrials.gov databases was conducted. Research was completed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 checklist. RESULTS: A total of 22 publications were identified, fulfilling inclusion criteria from a total of 595 studies. The analysis revealed that the prevalence of PIU during the COVID-19 pandemic period was 25%, however applying a stringent threshold for the PIU, resulted in a much lower prevalence of 7.9%. CONCLUSION: The PIU prevalence rate during the COVID-19 pandemic in the general population was 7.9%. Measuring the prevalence of PIU remains complicated due to the large methodological and cultural diversity that exists, so global prevalence estimates of PIU vary substantially. More methodologically sound research on psychodiagnostic assessment and cultural variances is required. (Neuropsychopharmacol Hung 2023; 25(3): 131-141) Keywords: COVID-19; internet addiction; problematic usage of the internet; prevalence; systematic review, meta-analysis Systematic review registration: PROSPERO registration number: CRD42021284619.

Meta-analysis of cognitive behaviour therapy and selective serotonin reuptake inhibitors for the treatment of hypochondriasis: Implications for trial design.

BACKGROUND: Classification of hypochondriasis as an obsessive-compulsive and related disorder in the International Classification of Diseases 11th Revision (ICD-11) has generated new heuristics for treatment of this common, chronic and disabling disorder. Standard treatment involves cognitive behaviour therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs), but no meta-analysis has so far considered hypochondriasis as a structured diagnosis or assessed the role of medication. A clearer understanding of the relative effectiveness of these interventions and identification of clinically relevant factors moderating the treatment response is needed for clinical guideline development. METHODS: The current systematic review and meta-analysis of interventions for hypochondriasis was preregistered on PROSPERO (CRD42020185768) and follows PRISMA guidelines. We searched MEDLINE, PsycINFO, and Cochrane Library databases until July 2021 for randomized controlled trials (RCTs) of interventions for patients diagnosed with hypochondriasis (or historical diagnostic equivalents). We assessed aspects of study quality using: the CONSORT Checklist for evaluation of RCTs, the Cochrane Risk of Bias 2 tool, researcher allegiance and treatment fidelity. The primary outcome was improvement in hypochondriasis symptoms, comparing intervention and control groups at trial endpoint. Moderator variables were assessed using subgroup and meta-regression analyses. RESULTS: Searches identified 13 randomised controlled trials (RCTs) (N = 1405); 12 included CBT (N = 1212) and three included SSRI (N = 193) arms as the experimental intervention. Random effects meta-analysis yielded a moderate-to-large effect size for CBT versus all controls (g = -0.70 [95% CI -0.99 to -0.41], k = 18, I2 = 81.1%). Funnel plot asymmetry indicated possible publication bias and two potentially missing trials, reducing the effect size (g = -0.60 [95% CI -0.88 to -0.32]). Subgroup analysis showed that choice of control significantly moderated effect size, with those in CBT vs. wait-list (g = -1.32 [95% CI -1.75 to -0.90], k = 7, I2 = 0%) being double those of CBT vs. psychological or pharmacological placebo controls (g = -0.58 [95% CI -0.95 to -0.22], k = 7, I2 = 82%). Analysis of studies directly comparing CBT and SSRIs found a numerical, but not statistical advantage for SSRIs (g = 0.21 [95% CI -0.46 to 0.87], k = 2, I2 = 58.34%) and a modest effect size emerged for SSRIs vs. pill placebo (g = -0.29 [95% CI -0.57 to -0.01], k = 3, I2 = 0%). Most studies (11/13) were rated as high on potential researcher allegiance bias in favour of CBT. Meta-regressions revealed that effect sizes were larger in younger participants, and smaller in better quality and more recent RCTs and those with greater CBT fidelity. CONCLUSION: CBT and SSRIs are effective in the acute treatment of hypochondriasis, with some indication that intervention at a younger age produces better outcomes for CBT. In the case of CBT, effect sizes appear to have been significantly inflated by the use of wait list controls, and researcher allegiance bias. We recommend that a definitive, adequately controlled trial, designed with respect to the methodological issues raised in this meta-analysis, is needed to determine the magnitude effects for CBT and SSRIs with confidence and the long-term effect of treatments, to inform mental health service provision for this overlooked patient group.

Repetitive transcranial magnetic stimulation (r-TMS) and selective serotonin reuptake inhibitor-resistance in obsessive-compulsive disorder: A meta-analysis and clinical implications.

INTRODUCTION: Despite promising results from several randomized controlled trials (RCTs) and meta-analyses, the efficacy of r-TMS as a treatment for OCD remains controversial, at least in part owing to inconsistency in the trial methodologies and heterogeneity in the trial outcomes. This meta-analysis attempts to explain some of this heterogeneity by comparing the efficacy of r-TMS in patients with or without resistance to treatment with selective serotonin reuptake inhibitors (SSRI), defined using standardized criteria. METHODS: We conducted a pre-registered (PROSPERO ID: 241381) systematic review and meta-analysis. English language articles reporting blinded RCTs were retrieved from searches using MEDLINE, PsycINFO, and Cochrane Library databases. Studies were subjected to subgroup analysis based on four stages of treatment resistance, defined using an adaptation of published criteria (1 = not treatment resistant, 2 = one SSRI trial failed, 3 = two SSRI trials failed, 4 = two SSRI trials failed plus one or more CBT trial failed). Meta-regression analyses investigated patient and methodological factors (age, duration of OCD, illness severity, stage of treatment-resistance, or researcher allegiance) as possible moderators of effect size. RESULTS: Twenty-five independent comparisons (23 studies) were included. Overall, r-TMS showed a medium-sized reduction of Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores (Hedge's g: -0.47; 95%CI: - 0.67 to -0.27) with moderate heterogeneity (I2 = 39.8%). Assessment of publication bias using Trim and Fill analysis suggested a reduced effect size that remained significant (g: -0.29; 95%CI: -0.51 to -0.07). Subgroup analysis found that those studies including patients non-resistant to SSRI (stage 1) (g: -0.65; 95%CI: -1.05 to -0.25, k = 7) or with low SSRI-resistance (stage 2) (g:-0.47; 95%CI: -0.86 to -0.09, k = 6) produced statistically significant results with low heterogeneity, while studies including more highly resistant patients at stage 3 (g: -0.39; 95%CI: -0.90 to 0.11, k = 4) and stage 4 (g: -0.36; 95%CI: -0.75 to 0.03, k = 8) did not. Intriguingly, the only significant moderator of the effect size found by meta-regression was the severity of baseline depressive symptoms. All trials showed evidence of researcher allegiance in favour of the intervention and therefore caution is required in interpreting the reported effect sizes. CONCLUSION: This meta-analysis shows that r-TMS is an effective treatment for OCD, but largely for those not resistant to SSRI or failing to respond to only one SSRI trial. As a consequence, r-TMS may be best implemented earlier in the care pathway. These findings would have major implications for clinical service development, but further well-powered RCTs, which eliminate bias from researcher allegiance, are needed before definitive conclusions can be drawn.

Problematic use of the internet during the COVID-19 pandemic: Good practices and mental health recommendations.

With the onset of the COVID-19 pandemic and the accelerated spread of the SARS-CoV-2 virus came jurisdictional limitations on mobility of citizens and distinct alterations in their daily routines. Confined to their homes, many people increased their overall internet use, with problematic use of the internet (PUI) becoming a potential reason for increased mental health concerns. Our narrative review summarizes information on the extent of PUI during the pandemic, by focusing on three types: online gaming, gambling and pornography viewing. We conclude by providing guidance for mental health professionals and those affected by PUI (with an outline of immediate research priorities and best therapeutic approaches), as well as for the general public (with an overview of safe and preventative practices).

The role of gender in a large international OCD sample: A Report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) Network.

INTRODUCTION: Obsessive-compulsive disorder (OCD) is characterized by a range of phenotypic expressions. Gender may be a relevant factor in mediating the disorder's heterogeneity. The aim of the present report was to explore a large multisite clinical sample of OCD patients, hypothesizing existing demographic, geographical and clinical differences between male and female patients with OCD. METHODS: Socio-demographic and clinical variables of 491 adult OCD outpatients recruited in the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network were investigated with a retrospective analysis on a previously gathered set of data from eleven countries worldwide. Patients were assessed through structured clinical interviews, the Yale- Brown Obsessive-Compulsive Scale (Y-BOCS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Self-rating Depression Scale (SDS). RESULTS: Among females, adult onset (>18 years old) was significantly over-represented (67% vs. 33%, p < 0.005), and females showed a significantly older age at illness onset compared with males (20.85 ± 10.76 vs. 17.71 ± 8.96 years, p < 0.005). Females also had a significantly lower education level than males (13.09 ± 4.02 vs. 13.98 ± 3.85 years; p < 0.05), a significantly higher rate of being married (50.8% vs. 33.5%; p < 0.001) and a higher rate of living with a partner (47.5% vs. 37.6%; p < 0.001) than males. Nonetheless, no significant gender differences emerged in terms of the severity of OCD symptoms nor in the severity of comorbid depressive symptoms. No predictive effect of gender was found for Y-BOCS, MADRS and SDS severity. DISCUSSION/CONCLUSIONS: Our findings showed significant differences between genders in OCD. A sexually dimorphic pattern of genetic susceptibility may have a crucial role to OCD clinical heterogeneity, potentially requiring different specific therapeutic strategies. Further research is warranted to validate gender as an important determinant of the heterogeneity in OCD.

Advances in problematic usage of the internet research - A narrative review by experts from the European network for problematic usage of the internet.

Global concern about problematic usage of the internet (PUI), and its public health and societal costs, continues to grow, sharpened in focus under the privations of the COVID-19 pandemic. This narrative review reports the expert opinions of members of the largest international network of researchers on PUI in the framework of the European Cooperation in Science and Technology (COST) Action (CA 16207), on the scientific progress made and the critical knowledge gaps remaining to be filled as the term of the Action reaches its conclusion. A key advance has been achieving consensus on the clinical definition of various forms of PUI. Based on the overarching public health principles of protecting individuals and the public from harm and promoting the highest attainable standard of health, the World Health Organisation has introduced several new structured diagnoses into the ICD-11, including gambling disorder, gaming disorder, compulsive sexual behaviour disorder, and other unspecified or specified disorders due to addictive behaviours, alongside naming online activity as a diagnostic specifier. These definitions provide for the first time a sound platform for developing systematic networked research into various forms of PUI at global scale. Progress has also been made in areas such as refining and simplifying some of the available assessment instruments, clarifying the underpinning brain-based and social determinants, and building more empirically based etiological models, as a basis for therapeutic intervention, alongside public engagement initiatives. However, important gaps in our knowledge remain to be tackled. Principal among these include a better understanding of the course and evolution of the PUI-related problems, across different age groups, genders and other specific vulnerable groups, reliable methods for early identification of individuals at risk (before PUI becomes disordered), efficacious preventative and therapeutic interventions and ethical health and social policy changes that adequately safeguard human digital rights. The paper concludes with recommendations for achievable research goals, based on longitudinal analysis of a large multinational cohort co-designed with public stakeholders.

Functional interventions as augmentation strategies for obsessive-compulsive disorder (OCD): scoping review and expert survey from the international college of obsessive-compulsive spectrum disorders (ICOCS).

BACKGROUND: Patients with obsessive-compulsive disorder (OCD) commonly exhibit a range of functional difficulties, presumed linked to neurocognitive changes. Evidence-based first-line treatments have limited effect on improving these cognitive-functional problems. Candidate interventions could be used to augment evidence-based treatments by the multi-professional mental health team. METHODS: A scoping review was performed to identify any intervention with at least one peer-reviewed report of clinical improvement in any of the 13 functional domains of the Cognitive Assessment Instrument of Obsessions and Compulsions (CAIOC-13). Next, an online survey of experts of the International College of Obsessive-Compulsive Spectrum Disorders was conducted. RESULTS: Forty-four studies were identified reporting a positive outcome for 27 different kinds of intervention. Twenty-six experts from 12 different countries, including at least one expert from each continent, completed the opinion survey. Five interventions were identified as 'highly promising', none of which was moderated by rater-related factors, suggesting global applicability. CONCLUSION: Patients with OCD may benefit from a detailed functional assessment, to identify areas of unmet need. A variety of interventions show theoretical promise for treating the complex functional difficulties in OCD as adjuncts to first-line treatments, but the published evidence is weak. Randomised controlled trials are needed to determine the clinical effectiveness of these interventions.HighlightsFunctional-cognitive problems are common in patients with OCD.First-line evidence-based treatments have limited effect on these functionalcognitive difficulties.In our scoping review we found 44 studies reporting of improved clinical outcomes in any of the 13 functional domains of the Cognitive Assessment Instrument of Obsessions and Compulsions (CAIOC-13).An online survey of experts of the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) was conducted and identified five interventions as "highly promising" candidate treatments for functional-cognitive problems in OCD.Randomised controlled trials are needed to determine the clinical effectiveness of these interventions.

A preliminary investigation of Cyberchondria and its correlates in a clinical sample of patients with obsessive-compulsive disorder, anxiety and depressive disorders attending a tertiary psychiatric clinic.

Objectives. This cross-sectional study aimed to investigate the frequency and presentation of cyberchondria (CYB) in patients with obsessive-compulsive disorder (OCD), anxiety disorders (ADs), and major depression disorder (MDD).Methods. Seventy-seven patients (OCD:25, ADs:26, MDD:26) referred to a tertiary psychiatry outpatient clinic and 27 healthy controls (HCs) were included. A 'working' definition of CYB was used to measure CYB frequency. CYB severity was measured with the Cyberchondria Severity Scale (CSS).Results. CYB as currently defined was present in just 1.3% of the combined patients' sample. Using a broader definition (omitting the disability criterion), we found a higher distribution (OCD:12%, ADs:19.2%, MDD:15.4%, HCs:3.7%) and greater CYB symptom severity. Patients with OCD (63.3 ± 18.9) and ADs (63.3 ± 25.9) showed a higher CYB severity, compared with HCs (48.4 ± 9.9, p<.05). In the combined patients' sample, a positive correlation was found between the CSS scores and measures of health anxiety or hypochondriasis. Higher CYB symptom severity emerged in patients with a positive family history of psychiatric disorders and in those prescribed benzodiazepines or mood-stabilisers.Conclusion. CYB represents a common transdiagnostic syndrome in patients with OCD, ADs, and MDD with a spectrum of severity and indicates a variable burden of illness, supporting the need for specific clinical considerations and interventions.Key pointsCyberchondria (CYB) represents a common transdiagnostic syndrome in patients with obsessive-compulsive disorder, anxiety, and depressive disorders.CYB's frequency as a syndrome of compulsive online health searches associated with an increased anxiety and distress was reported in 10-20% patients.Health anxiety/hypochondriasis showed a strong correlation with CYB.Patients with a positive family history of psychiatric disorders and those prescribed benzodiazepines or mood-stabilisers showed higher CYB symptom severity.Considering the spread of Internet use for health-related information, additional studies investigating CYB in clinical samples are encouraged.

Set-shifting-related basal ganglia deformation as a novel familial marker of obsessive-compulsive disorder.

The symptoms of obsessive-compulsive disorder (OCD) are suggestive of cognitive rigidity, and previous work identified impaired flexible responding on set-shifting tasks in such patients. The basal ganglia are central to habit learning and are thought to be abnormal in OCD, contributing to inflexible, rigid habitual patterns of behaviour. Here, we demonstrate that increased cognitive inflexibility, indexed by poor performance on the set-shifting task, correlated with putamen morphology, and that patients and their asymptomatic relatives had common curvature abnormalities within this same structure. The association between the structure of the putamen and the extradimensional errors was found to be significantly familial in OCD proband-relative pairs. The data implicate changes in basal ganglia structure linked to cognitive inflexibility as a familial marker of OCD. This may reflect a predisposing heightened propensity toward habitual response patterns and deficits in goal-directed planning.

Suicidality in patients with obsessive-compulsive and related disorders (OCRDs): A meta-analysis.

INTRODUCTION: Previous meta-analyses showed that OCD is associated with a substantial risk of suicidal behaviours. Conclusive rates of suicidal ideation (current and lifetime) and suicide attempts based on pooled prevalence rates have not so far been calculated using meta-analysis for the other DSM-5 Obsessive-Compulsive and Related Disorders (OCRDs). OBJECTIVES: This meta-analysis aims to separately calculate the pooled prevalence rates of lifetime suicide attempts and current or lifetime suicidal ideation in BDD, Hoarding Disorder (HD), Skin Picking Disorder (SPD) and Trichotillomania (TTM) and to identify factors associated with increased suicide rates. METHODS: Our protocol was pre-registered with PROSPERO (CRD42020164395). A systematic review and meta-analysis following PRISMA reporting guidelines was performed by searching in PubMed/Medline, PsycINFO, Web of Science and CINAHL databases from the date of the first available article to April 20th, 2020. Stata version 15 was used for the statistical analysis. Given the small number of studies in TTM and SPD, the two grooming disorders were grouped together. Meta-analyses of proportions based on random effects (Der-Simonian and Laird method) were used to derive the pooled estimates. RESULTS: Thirty-eigth studies (N = 4559 participants) were included: 23 for BDD, 8 for HD, 7 for Grooming Disorders. For BDD, the pooled prevalence of lifetime suicide attempts, current and lifetime suicidal ideation was, respectively 35.2% (CI:23.4-47.8), 37.2% (CI:23.8-51.6) and 66.1% (CI:53.5-77.7). For HD, the pooled prevalence of lifetime suicide attempts, current and lifetime suicidal ideation was 24.1% (CI:12.8-37.6), 18.4% (CI:10.2-28.3) and 38.3% (CI:35.0-41.6), respectively. For Grooming Disorders, the pooled prevalence of lifetime suicide attempts and current suicidal ideation were 13.3% (CI:5.9-22.8) and 40.4% (CI:35.7-45.3), respectively (no data available for lifetime suicidal ideation). CONCLUSIONS: The OCRDs as a group are associated with relatively high rates of suicidal behaviour. Through indirect comparisons, we infer that BDD has the greatest risk. Comorbid substance abuse, possibly reflecting poor underlying impulse control, is associated with higher rates of suicidal behaviour in BDD. Our data emphasize the need for clinicians to consider the risk of suicidal behaviour in the management of patients presenting with all forms of OCRDs.

Cognitive behavioural therapy with exposure and response prevention in the treatment of obsessive-compulsive disorder: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Cognitive behavioural therapy (CBT), incorporating exposure and response prevention (ERP) is widely recognised as the psychological treatment of choice for obsessive-compulsive disorder (OCD). Uncertainty remains however about the magnitude of the effect of CBT with ERP and the impact of moderating factors in patients with OCD. METHOD: This systematic review and meta-analysis assessed randomised-controlled trials of CBT with ERP in patients of all ages with OCD. The study was preregistered in PROSPERO (CRD42019122311). The primary outcome was end-of-trial OCD symptom scores. The moderating effects of patient-related and study-related factors including type of control intervention and risk of bias were examined. Additional exploratory analyses assessed the effects of treatment fidelity and impact of researcher allegiance. RESULTS: Thirty-six studies were included, involving 2020 patients (537 children/adolescents and 1483 adults) with 1005 assigned to CBT with ERP and 1015 to control conditions. When compared against all control conditions, a large pooled effect size (ES) emerged in favour of CBT with ERP (g = 0.74: 95% CI = 0.51 to 0.97 k = 36), which appeared to diminish with increasing age. While CBT with ERP was more effective than psychological placebo (g = 1.13 95% CI 0.71 to 1.55, k = 10), it was no more effective than other active forms of psychological therapy (g = -0.05: 95% CI -0.27 to 0.16, k = 8). Similarly, whereas CBT with ERP was significantly superior when compared to all forms of pharmacological treatment (g = 0.36: 95% CI 0.7 to 0.64, k = 7), the effect became marginal when compared with adequate dosages of pharmacotherapy for OCD (g = 0.32: 95% CI -0.00 to 0.64, k = 6).A minority of studies (k = 8) were deemed to be at low risk of bias. Moreover, three quarters of studies (k = 28) demonstrated suspected researcher allegiance and these studies reported a large ES (g = 0.95: 95% CI 0.69 to 1.2), while those without suspected researcher allegiance (k = 8) indicated that CBT with ERP was not efficacious (g = 0.02: 95% CI -0.29 to 0.33). CONCLUSIONS: A large effect size was found for CBT with ERP in reducing the symptoms of OCD, but depends upon the choice of comparator control. This meta-analysis also highlights concerns about the methodological rigor and reporting of published studies of CBT with ERP in OCD. In particular, efficacy was strongly linked to researcher allegiance and this requires further future investigation.

Pharmacotherapy for trichotillomania.

BACKGROUND: Trichotillomania (TTM; hair-pulling disorder) is a prevalent and disabling disorder characterised by recurrent hair-pulling. Here we update a previous Cochrane Review on the effects of medication for TTM. OBJECTIVES: To assess the effects of medication for trichotillomania (TTM) in adults, children and adolescents compared with placebo or other medication. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, PsycINFO, eleven other bibliographic databases, trial registries and grey literature sources (to 26 November 2020). We checked reference lists and contacted subject experts. SELECTION CRITERIA: We selected randomised controlled trials of medication versus placebo or other medication for TTM in adults, children and adolescents. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Twelve studies were included. We identified 10 studies in adults (286 participants) with a mean sample size of 29 participants per trial; one study in children and adolescents (39 participants); and, one study in adults and adolescents (22 participants: 18 adults and 4 adolescents). All studies were single-centre, outpatient trials. Eleven studies compared medication and placebo (334 participants); one study compared two medications (13 participants). Studies were 5 to 13 weeks duration. We undertook meta-analysis only for opioid antagonists as other comparisons contained a single study, or reported insufficient data. Antioxidants versus placebo in adults There was little to no difference in treatment response between antioxidant (35.7%) and placebo groups (28.6%) after six weeks, based on a single trial of silymarin (risk ratio (RR) 2.25, 95% confidence interval (CI) 0.84 to 5.99; 36 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (18 participants; low-certainty evidence). Antioxidants versus placebo in adolescents There was little to no difference in treatment response between antioxidant (50%) and placebo groups (25%) after six weeks, based on a single trial of silymarin (RR 2.00, 95% CI 0.28 to 14.20; 8 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (8 participants; low-certainty evidence). Antipsychotics versus placebo in adults There may be greater treatment response in the antipsychotic group (85%) compared to the placebo group (17%) after 12 weeks, based on a single trial of olanzapine (RR 5.08, 95% CI 1.4 to 18.37; 25 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (25 participants; low-certainty evidence). Cell signal transducers versus placebo in adults There was little to no difference in treatment response between cell signal transducer (42.1%) and placebo groups (31.6%) after 10 weeks, based on a single trial of inositol (RR 1.33, 95% CI 0.57 to 3.11; 38 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (38 participants; low-certainty evidence). Glutamate modulators versus placebo in adults There is probably greater treatment response in the glutamate modulator group (56%) compared to the placebo group (16%) after 12 weeks, based on a single trial of N-acetylcysteine (RR 3.5, 95% CI 1.34 to 9.17; 50 participants; moderate-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (50 participants; low-certainty evidence). Glutamate modulators versus placebo in children and adolescents There was little to no difference in treatment response between the glutamate modulator (25%) and placebo groups (21.1%) in children and adolescents, based on a single trial of N-acetylcysteine (RR 1.19, 95% CI 0.37 to 3.77; 39 participants; low-certainty evidence). There was little to no difference in dropouts due to adverse events between glutamate modulator (5%) and placebo (0%) groups, based on a single trial (RR 2.86, 95% CI 0.12 to 66.11; 39 participants; low-certainty evidence). Opioid antagonists versus placebo in adults There may be little to no difference in treatment response between opioid antagonist (37.5%) and placebo groups (25%) after six to eight weeks, based on two studies of naltrexone, but the evidence is very uncertain (RR 2.14, 95% CI 0.25 to 18.17; 2 studies, 68 participants; very low-certainty evidence). No data were available regarding dropouts due to adverse events. Selective serotonin reuptake inhibitors (SSRIs) versus placebo in adults There were no data available for treatment response to SSRIs. There was little to no difference in dropouts due to adverse events in the SSRI group (5.1%) compared to the placebo group (0%) after 6 to 12 weeks, based on two trials of fluoxetine (RR 3.00, 95% CI 0.33 to 27.62; 2 studies, 78 participants; low-certainty evidence). Tricyclic antidepressants (TCAs) with predominantly serotonin reuptake inhibitor (SRI) actions versus placebo in adults There may be greater treatment response in the TCAs with predominantly SRI actions group (40%) compared to the placebo group (0%) after nine weeks, but the evidence is very uncertain, based on a single trial of clomipramine (RR 5.73, 95% CI 0.36 to 90.83; 16 participants; very low-certainty evidence). There may be increased dropouts due to adverse events in the TCAs with predominantly SRI actions group (30%) compared to the placebo group (0%), but the evidence is very uncertain (RR 4.45, 95% CI 0.27 to 73.81; 16 participants; very low-certainty evidence). TCAs with predominantly SRI actions versus other TCAs in adults There may be greater treatment response in the TCAs with predominantly SRI actions group compared to the other TCAs group after five weeks, based on a single trial comparing clomipramine to desipramine (mean difference (MD) -4.00, 95% CI -6.13 to -1.87; 26 participants; low-certainty evidence). We could not calculate differences in number of dropouts as there were no events in either group (26 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There was insufficient evidence from meta-analysis to confirm or refute the efficacy of any agent or class of medication for the treatment of TTM in adults, children or adolescents. Preliminary evidence suggests there may be beneficial treatment effects for N-acetylcysteine, clomipramine and olanzapine in adults based on four trials, albeit with relatively small sample sizes.