Optimizing first line treatments for adults with OCD.

OCD is characterized by obsessions (recurrent, intrusive, unwanted thoughts, images or impulses and compulsions (repetitive behaviors or mental acts that the individual feels compelled to perform), which can manifest together or separately (Fineberg et al., 2020). NICE guidelines suggest that low intensity psychological treatments (including ERP) is the first line treatment for OCD, and that a "stepped care" treatment approach for OCD reserves combination treatment for adults with OCD with severe functional impairment, and for adults without an adequate response to: 1) treatment with an SSRI alone (12 weeks duration) or 2) CBT (including ERP) alone (NICE, 2005). Existing US treatment guidelines (APA guidelines) suggest that there are three first-line treatments for OCD (SSRI, CBT, SSRI+CBT) and recommends combined treatment for patients with an unsatisfactory response to monotherapy or for patients with severe OCD. Although, systematic review and meta-analysis of studies published in 1993-2014 suggest that combination treatment was not significantly better than CBT plus placebo (Ost et al., 2015), based on data from a recent systematic and meta-analysis which searched the two controlled trials registers maintained by the Cochrane Collaboration Common Mental Disorders group, the combination treatment approach is likely to be more effective than psychotherapeutic interventions alone, at least in severe obsessive-compulsive disorder (Skapinakis et al., 2016a). Based on data from Optimal treatment for OCD study conducted by Fineberg et al., (2018) combined treatment appeared to be the most effective especially when compared to CBT monotherapy, but SSRI monotherapy was found as the most cost effective. In this review we summarize available treatment recommendations.

The Future of Obsessive-Compulsive Spectrum Disorders: A Research Perspective.

Obsessive-compulsive disorder (OCD) sits at the epicenter of a spectrum of related conditions (often referred to as obsessive-compulsive related disorders (OCRD) or obsessive-compulsive spectrum disorders (OCSD)) that can be as disabling as they are varied in presentation. Research in the field now encompasses diverse disciplines ranging from inflammatory mechanisms to computational psychiatry, to neurocognitive endophenotypes to functional imaging to pharmacogenomics to brain stimulation approaches. As these disorders become more clearly elucidated, there is a need to continually re-evaluate the implications of research findings and to incorporate these findings into new treatment approaches that benefit both patients and clinicians. Even the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) is intended to be flexible and to incorporate validated and reliable biomarkers and neuroscience findings as they become available. This concluding chapter highlights just a few areas of study that promise to influence our understanding of the pathophysiology and clinical practice of OCRD. These include patient-centered outcomes research, the study of developmental brain trajectories in spectrum conditions, robot models of OCRDs, goal-directed versus habit-based behaviors, pharmacogenomics, problematic use of the Internet, and digital interventions. For example, digital medicine may become increasingly useful by identifying patients early on in the course of their illness; providing biomarkers to subtype patients; predicting treatment response; serving as a more proximal outcome measure of treatment response; or providing easily accessible and less costly forms of care. In order to address unmet clinical needs in OCRD, it is helpful to take an interdisciplinary perspective, and the work described in this collection of articles is likely to be invaluable in shaping the future of the field.

Overlap of obsessive-compulsive personality disorder and autism spectrum disorder traits among OCD outpatients: an exploratory study.

Background: Whereas the phenomenology of obsessive-compulsive personality disorder (OCPD) shows similarities to that of obsessive compulsive and related disorders (OCRDs) as well as with autism spectrum disorder (ASD), the relationship between these disorders is poorly understood.Aims: Within a clinical sample, we aimed to investigate the distribution of OCD, OCPD and ASD symptoms and traits and their interrelationship, as well as to evaluate insight and treatment refractoriness.Methods: Consecutive adult OCD outpatients were assessed for OCPD traits (Compulsive Personality Assessment Scale (CPAS)), OCD symptoms (Yale-Brown Obsessive Compulsive Scale (Y-BOCS)), ASD traits (Autism Spectrum Quotient (AQ)), insight (Brown Assessment of Beliefs Scale (BABS)) and treatment resistance (clinical records). Those scoring highly on the AQ underwent a diagnostic interview for ASD.Results: Sixty-seven consenting individuals completed the CPAS, BABS and AQ, and 65 completed the Y-BOCS. Twenty-four patients (35.8%) were diagnosed with OCPD. Patients with OCPD were less likely to be employed (p=.04). They demonstrated elevated AQ scores (p=.004) and rates of ASD diagnosis (54.2%) (p <.001). OCPD traits (CPAS) showed a highly significant correlation with ASD traits (AQ) (p<.001), and no association with Y-BOCS, BABS or treatment resistance.Conclusions: In an OCD cohort limited by small size, OCPD associated strongly with unemployment and ASD, with implications for diagnosis, treatment and outcome.KEY POINTSClinicians should exercise a high level of vigilance for OCPD and ASD in patients presenting with obsessive compulsive symptoms.The presence of OCPD may indicate a likelihood of disabling ASD traits, including cognitive inflexibility, poor central coherence and poor social communication.These neuropsychological factors may require separate clinical intervention strategies.

Manifesto for a European research network into Problematic Usage of the Internet.

The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.

A trans-diagnostic perspective on obsessive-compulsive disorder.

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.

The classification of Obsessive-Compulsive and Related Disorders in the ICD-11.

BACKGROUND: To present the rationale for the new Obsessive-Compulsive and Related Disorders (OCRD) grouping in the Mental and Behavioural Disorders chapter of the Eleventh Revision of the World Health Organization's International Classification of Diseases and Related Health Problems (ICD-11), including the conceptualization and essential features of disorders in this grouping. METHODS: Review of the recommendations of the ICD-11 Working Group on the Classification for OCRD. These sought to maximize clinical utility, global applicability, and scientific validity. RESULTS: The rationale for the grouping is based on common clinical features of included disorders including repetitive unwanted thoughts and associated behaviours, and is supported by emerging evidence from imaging, neurochemical, and genetic studies. The proposed grouping includes obsessive-compulsive disorder, body dysmorphic disorder, hypochondriasis, olfactory reference disorder, and hoarding disorder. Body-focused repetitive behaviour disorders, including trichotillomania and excoriation disorder are also included. Tourette disorder, a neurological disorder in ICD-11, and personality disorder with anankastic features, a personality disorder in ICD-11, are recommended for cross-referencing. LIMITATIONS: Alternative nosological conceptualizations have been described in the literature and have some merit and empirical basis. Further work is needed to determine whether the proposed ICD-11 OCRD grouping and diagnostic guidelines are mostly likely to achieve the goals of maximizing clinical utility and global applicability. CONCLUSION: It is anticipated that creation of an OCRD grouping will contribute to accurate identification and appropriate treatment of affected patients as well as research efforts aimed at improving our understanding of the prevalence, assessment, and management of its constituent disorders.

Disorders of compulsivity: a common bias towards learning habits.

Why do we repeat choices that we know are bad for us? Decision making is characterized by the parallel engagement of two distinct systems, goal-directed and habitual, thought to arise from two computational learning mechanisms, model-based and model-free. The habitual system is a candidate source of pathological fixedness. Using a decision task that measures the contribution to learning of either mechanism, we show a bias towards model-free (habit) acquisition in disorders involving both natural (binge eating) and artificial (methamphetamine) rewards, and obsessive-compulsive disorder. This favoring of model-free learning may underlie the repetitive behaviors that ultimately dominate in these disorders. Further, we show that the habit formation bias is associated with lower gray matter volumes in caudate and medial orbitofrontal cortex. Our findings suggest that the dysfunction in a common neurocomputational mechanism may underlie diverse disorders involving compulsion.

Evidence-based treatment pathways for translational studies in obsessive-compulsive disorders.

Obsessive-compulsive disorder (OCD) and related disorders are costly and burdensome long-term illnesses. Whilst evidence-based pharmacological and psychological treatments are available for OCD, a significant proportion of OCD patients fail to respond and for many of the OCD-related disorders no validated treatments are as yet recognised. In addition, predictors of treatment response/non-response to guide clinicians in the management of individual patients are lacking. The introduction of personalised medicine to psychiatry is expected to offer the novel prospect of identifying the most effective treatment for a patient in a timely and cost-effective way. Translational research that investigates endophenotype predictors of treatment response in OCD and related disorders may pave the way toward personalised medicine. Such research is likely to require multidisciplinary collaboration between neuroscientists and clinicians, so that the right clinical questions are addressed, and large datasets, entailing multinational, multicentre sampling. In order to facilitate the translational investigation of the key aspects of the treatment response, these studies would require access to standardised treatment paradigms that are internationally recognised. In this chapter, we introduce some of the most important outstanding questions for personalised medicine that translational research could be expected to address within the next 10 years. We review the available tools and techniques for standardised clinical assessment and the criteria that are used to define the degree of therapeutic response (response, remission, relapse, resistance) that would naturally dictate the direction of treatment. We also present a series of consecutive stepped treatment algorithms based on evidence-based practice and modelled on naturalistic care that we believe could be adapted to multicentre settings as a template for the translational researcher to aid in the design of pragmatic treatment trials that are capable of identifying biomarkers of treatment response or non-response at each key stage of the evidence-based canon.

Manifesto for a European research network into obsessive-compulsive and related disorders.

Obsessive-compulsive and related disorders (O-CRDs) are highly disabling psychiatric illnesses of early-onset. They are responsible for considerable morbidity and socioeconomic burden. Existing treatments are usually only partially successful and there is an urgent need to understand the aetiological factors and neurobiological bases of the disorders in order to develop new and more effective strategies for prevention, early detection and effective treatment. Emerging data from the neurosciences supports the reconceptualisation of obsessive-compulsive disorder as a spectrum disorder, related to but different from the anxiety disorders and closely aligned with other less well understood psychiatric disorders characterised by compulsive acts such as body dysmorphic disorder, trichotillomania, skin-picking disorder, hoarding disorder; and possibly extending to tic disorders and other neurodevelopmental disorders such as autism. A new, O-CRDs research network, supported by the Networks Initiative of the European College of Neuropsychopharmacology and comprising leading figures in preclinical and clinical research, has been established. It aims to provide a European perspective on the current debate around internationally-accepted diagnostic criteria and treatment strategies for O-CRDs. Its objectives include; (1) identifying the key outstanding research questions that depend upon cross-centre collaborative investigation, (2) setting a research agenda that is likely to produce an impact on health-outcomes, and (3) strengthening existing projects and collaborative enterprises with these objectives in mind. This paper reviews some of these critical research priorities. By establishing shared multinational databases, collaborative research networks, multicentre studies and joint publications, it is hoped that progress will be achieved.

Punishment promotes response control deficits in obsessive-compulsive disorder: evidence from a motivational go/no-go task.

BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with response inhibition deficits under motivationally neutral contingencies. We examined response inhibition performance in the presence of reward and punishment. We further investigated whether the hypothesized difficulties in flexibly updating behaviour based on external feedback in OCD would also lead to a reduced ability to adjust to changes in the reward and punishment contingencies. METHOD: Participants completed a go/no-go task that used punishments or rewards to promote response activation or suppression. The task was administered to OCD patients free of current Axis-I co-morbidities including major depression (n = 20) and a group of healthy controls (n = 32). RESULTS: Compared with controls, patients with OCD had increased commission errors in punishment conditions, and failed to slow down immediately after receiving punishment. The punishment-induced increase in commission errors correlated with self-report measures of OCD symptom severity. Additionally, patients did not differ from controls in adapting their overall response style to the changes in task contingencies. CONCLUSIONS: Individuals with OCD showed reduced response control selectively under punishment conditions, manifesting in an impulsive response style that was related to their current symptom severity. This stresses failures of cognitive control in OCD, particularly under negative motivational contingencies.

Translational approaches to obsessive-compulsive disorder: from animal models to clinical treatment.

Obsessive-compulsive disorder (OCD) is characterized by obsessions (intrusive thoughts) and compulsions (repetitive ritualistic behaviours) leading to functional impairment. Accumulating evidence links these conditions with underlying dysregulation of fronto-striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. However, the brain bases of these conditions and treatment mechanisms are still not fully elucidated. Animal models simulating the behavioural and clinical manifestations of the disorder show great potential for augmenting our understanding of the pathophysiology and treatment of OCD. This paper provides an overview of what is known about OCD from several perspectives. We begin by describing the clinical features of OCD and the criteria used to assess the validity of animal models of symptomatology; namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) neurobehavioural models. We also discuss their advantages and shortcomings in relation to their capacity to identify potentially efficacious new compounds. It is of interest that there has been rather little evidence of 'false alarms' for therapeutic drug effects in OCD models which actually fail in the clinic. While it is more difficult to model obsessive cognition than compulsive behaviour in experimental animals, it is feasible to infer cognitive inflexibility in certain animal paradigms. Finally, key future neurobiological and treatment research areas are highlighted.

High-dose selective serotonin reuptake inhibitors in OCD: a systematic retrospective case notes survey.

This article presents a systematic, retrospective case-note survey of a specialist obsessive-compulsive disorder (OCD) outpatient service. We explore the frequency of 'high-dose' selective serotonin reuptake inhibitor (SSRI) prescribing and describe clinical outcomes in a naturalistic clinical setting. Patients receiving high doses were compared with 'control' cases at the following three time-points: referral, initiation of high-dose SSRI and last clinical assessment.Twenty-six (13.5%) out of 192 patients received high-dose treatment for 3-364 weeks (mean 81.5 weeks; SD = ±95.1). At referral, high-dose patients were significantly more likely than controls to be male, and to have received Cognitive Behavioural Therapy (CBT), although illness severity and complexity did not differ. At initiation of dose escalation, however, high-dose patients were significantly more symptomatic than controls (Yale-Brown Obsessive Compulsive Scale score [Y-BOCS 25.4 vs. 17.7]). At the last assessment, patients on high-dose treatment showed significant within-group improvements (Y-BOCS 25.35 vs. 20.95), although endpoint scores for the high-dose group remained significantly higher than control patients treated for a matched period (Y-BOCS 21.0 vs. 15.5), suggesting enduring treatment-resistance. Frequency of adverse effects did not significantly differ between the two groups. Our results suggest that high-dose SSRI was associated with clinical improvement and well-tolerated in a particularly refractory OCD sample.

Inhibition of thoughts and actions in obsessive-compulsive disorder: extending the endophenotype?

BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with impairments in stop-signal inhibition, a measure of motor response suppression. The study used a novel paradigm to examine both thought suppression and response inhibition in OCD, where the modulatory effects of stimuli relevant to OCD could also be assessed. Additionally, the study compared inhibitory impairments in OCD patients with and without co-morbid depression, as depression is the major co-morbidity of OCD. METHOD: Volitional response suppression and unintentional thought suppression to emotive and neutral stimuli were examined using a novel thought stop-signal task. The thought stop-signal task was administered to non-depressed OCD patients, depressed OCD patients and healthy controls (n=20 per group). RESULTS: Motor inhibition impairments were evident in OCD patients, while motor response performance did not differ between patients and controls. Switching to a new response but not motor inhibition was affected by stimulus relevance in OCD patients. Additionally, unintentional thought suppression as measured by repetition priming was intact. OCD patients with and without depression did not differ on any task performance measures, though there were significant differences in all self-reported measures. CONCLUSIONS: Results support motor inhibition deficits in OCD that remain stable regardless of stimulus meaning or co-morbid depression. Only switching to a new response was influenced by stimulus meaning. When response inhibition was successful in OCD patients, so was the unintentional suppression of the accompanying thought.

The neuropsychology of the schizo-obsessive subtype of schizophrenia: a new analysis.

BACKGROUND: Interest in the neuro-cognitive profile of patients with schizophrenia and co-morbid obsessive compulsive disorder (schizo-OCD) is rising in response to reports of high co-morbidity rates. Whereas schizophrenia has been associated with global impairment in a wide range of neuro-cognitive domains, OCD is associated with specific deficits featuring impaired performance on tasks of motor and cognitive inhibition involving frontostriatal neuro-circuitry. METHOD: We compared cognitive function using the CANTAB battery in patients with schizo-OCD (n=12) and a schizophrenia group without OCD symptoms (n=16). The groups were matched for IQ, gender, age, medication, and duration of illness. RESULTS: The schizo-OCD patients made significantly more errors on a task of attentional set-shifting (ID-ED set-shift task). By contrast, no significant differences emerged on the Stockings of Cambridge task, the Cambridge Gamble Task or the Affective Go/NoGo tasks. No correlation emerged between ID-ED performance and severity of schizophrenia, OCD or depressive symptoms, consistent with neurocognitive impairment holding trait rather than state-marker status. Schizo-obsessives also exhibited a trend toward more motor tics emphasizing a neurological contribution to the disorder.ConclusionOur findings reveal a more severe attentional set-shifting deficit and neurological abnormality that may be fundamental to the neuro-cognitive profile of schizo-OCD. The clinical implications of these impairments merit further exploration in larger studies.

Commentary on STAR*D: a summary and UK perspective.

The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) program attempted to determine whether some treatment sequences are better than others in the management of depression. Application of the findings to UK treatment settings is difficult because depression is an inhomogeneous condition and to regard it as a unitary entity, to which a unitary stratagem can be applied, is possibly misguided.

Obsessive-compulsive disorder in UK clozapine-treated schizophrenia and schizoaffective disorder: a cause for clinical concern.

The association between schizophrenia and obsessive-compulsive disorder (OCD) is complex. This study systematically examined a UK cohort of clozapine-treated individuals with schizophrenia/schizoaffective disorder. Fourteen of 59 cases (24%) scored positively on item H of the Mini-International Neuropsychiatric Interview (MINI) for OCD. The mean Yale- Brown Obsessive-Compulsive Scale (Y-BOCS) score in MINI-positive cases was 17.6 (SD+/-6.3). Sixty-four percent scored 16 or more on the Y-BOCS, representing clinically meaningful illness severity. Seven (50%) patients with OCD had previously received the diagnosis by their treating clinicians and were already receiving with selective serotonin re-uptake inhibitors (SSRIs) treatment. OCD cases scored significantly worse than their non-OCD counterparts on the Abnormal Involuntary Movement Scale (P=0.01) and the Simpson Angus Scale (SAS; P=0.01). There was also a non-significant trend toward higher ratings for OCD cases on the Clinical Global Impression-Schizophrenia scale (P=0.06). Comparing the OCD cases taking SSRI (n=7) with those not on SSRI (n=7), significant differences emerged on the SAS (P=0.03). Our results suggest that OCD is common among patients receiving clozapine for schizophrenic disorders and that the comorbidity is associated with greater motoric impairment. The role of medication in this condition remains unclear.

The neuropsychology of obsessive compulsive disorder: the importance of failures in cognitive and behavioural inhibition as candidate endophenotypic markers.

Obsessive compulsive disorder (OCD) is a highly debilitating neuropsychiatric condition with estimated lifetime prevalence of 2-3%, more than twice that of schizophrenia. However, in contrast to other neuropsychiatric conditions of a comparable or lesser prevalence, relatively little is understood about the aetiology, neural substrates and cognitive profile of OCD. Despite strong evidence for OCD being familial, with risk to first-degree relatives much greater than for the background population, its genetic underpinnings have not yet been adequately delineated. Although cognitive dysfunction is evident in the everyday behaviour of OCD sufferers and is central to contemporary psychological models, theory-based studies of neurocognitive function have yet to reveal a reliable cognitive signature, and interpretation has often been confounded by failures to control for co-morbidities. The neuroimaging findings in OCD are amongst the most robust reported in the psychiatric literature, with structural and functional abnormalities frequently reported in orbitofrontal cortex, anterior cingulate cortex, and caudate nucleus. In spite of this, our relative lack of understanding of OCD neurochemical processes continues to impede progress in the development of novel pharmacological treatment approaches. Integrating the neurobiological, cognitive, and clinical findings, we propose that OCD might usefully be conceptualised in terms of lateral orbitofrontal loop dysfunction, and that failures in cognitive and behavioural inhibitory processes appear to underlie many of the symptoms and neurocognitive findings. We highlight existing limitations in the literature, and the potential utility of endophenotypes in overcoming these limitations. We propose that neurocognitive indices of inhibitory functions may represent a useful heuristic in the search for endophenotypes in OCD. This has direct implications not only for OCD but also for putative obsessive-compulsive spectrum conditions including attention deficit hyperactivity disorder, Tourette's syndrome, and trichotillomania (compulsive hair pulling).