Obsessive-compulsive disorder and global mental health.

The discipline of global mental health has emphasized the importance of the treatment gap in mental disorders, and of addressing this gap via changes in health policy, an emphasis on human rights, and innovations such as task-shifting. Although global mental health research has focused on both common mental disorders such as depression, and serious mental disorders such as schizophrenia, it has paid relatively little attention to obsessive-compulsive and related disorders (OCRDs). Nevertheless, international collaborations have recently paid a good deal of attention to the nosology and neurobiology of OCRDs, and given the prevalence and morbidity of these conditions, further work along these lines should be encouraged. This article provides a brief overview of recent international collaborations on OCRDs, and outlines future directions for such work.

INTRODUCTION

Cross-cultural psychiatry has long played an important role in providing insights into overlaps and discrepancies in psychopathology across the globe, and in emphasizing the extent to which divergent explanatory models of mental disorder may impact on the experience of mental illness as well as on outcomes.[1] More recently, global mental health has built on these foundations, adding in a range of other disciplines and perspectives, and has played a key role in emphasizing the importance of the treatment gap in mental disorders, and of addressing this gap via changes in health policy, an emphasis on human rights, and innovations such as task-shifting.[2]

Global mental health research has focused on both common mental disorders such as depression, as well as serious mental disorders such as schizophrenia. Thus, for example, randomized controlled trials have been undertaken on task-shifting interventions for postnatal depression in Pakistan, and community-based interventions for schizophrenia in India.[3] Nevertheless, in a systematic review of task-shifting interventions for mental disorders, no study was found on obsessive-compulsive and related disorders (OCRDs).[3] Although the prevalence of obsessive compulsive disorder (OCD) may be lower than that of depression, taken together the OCRDs constitute a common and disabling set of conditions.[4]

Fortunately, international collaborations have recently paid a good deal of attention to the nosology and neurobiology of OCRDs. These include the work of the International Classification of Diseases-11 (ICD) workgroup on OCRDs, the OCD workgroup of the Psychiatric Genetics Consortium (PGC) on OCD, the OCD workgroup of Enhancing Neuroimaging Meta-Analysis (ENIGMA), a number of cross-national treatment studies in OCD, and the work of the Cochrane Collaboration. In this paper, a number of these collaborations and their contributions are outlined, and future directions at the intersection of OCD, global mental health, and international research are considered.

NOSOLOGY

Two key classification systems in psychiatry are the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM) and the World Health Organization's ICD. Both systems have recently undergone revision; the fifth edition of DSM (DSM-5) has been published, and the 11th Edition of ICD is currently being finalized. Notably, both systems have elected to alter the classification of OCD, and to include for the first time a separate chapter on OCRDs. Nevertheless, a number of differences in the approach of these systems in general, and in the classification of OCRDs in particular, are worth emphasizing.

DSM is developed by a specific national professional organization, and sales of the volume are an important source of its income. Nevertheless, DSM has long been used by a range of different countries, and DSM-5 committees included a number of experts from outside of the United States. In contrast, ICD is developed under the auspices of an international health institution, is translated into key international languages as part of the developmental process, and WHO products are made freely available throughout the world. Furthermore, ICD-11 committees were specifically formulated to be representative of different geographical regions.

At the start of the DSM-5 revision process, it was emphasized that there was a need for increased diagnostic validity of mental disorders, and it was hoped that neuroscience would provide a foundation for psychiatric nosology.[5] The DSM-5 workgroup on OCRDs emphasized that these disorders had a specific neurobiology, and that this differed in good part from that of the anxiety disorders.[6] In contrast, ICD-11 has emphasized the importance of clinical utility and global applicability, targeting use by nonspecialist clinicians in primary care settings.[7] The ICD-11 workgroup emphasized that classifying the OCRDs together would usefully increase recognition and appropriate treatment of these conditions.[8] That said, it is important to recognize that diagnostic validity provides a crucial base for clinical utility.[9]

The idea that neuroscience will inform future psychiatric nosology continues to be influential, as exemplified by the emphasis of the National Institute of Mental Health in the United States on the Research Domain Criteria (RDoC) framework.[10] This framework emphasizes a translational and dimensional approach to psychopathology, noting that behavioral dimensions relevant to mental disorders exist across species, and that symptoms themselves lie on dimensions. While this point seems unarguable, it remains to be seen how much impact this approach will have on clinical practice in the short-term.[11] Nevertheless, as discussed below, it is key that exploration of RDoC constructs is not confined to high-income countries, but is also done globally.

It is notable that a global mental health approach to diagnosis may have a number of features in common with the clinical neuroscience approach of RDoC. In particular, both frameworks emphasize the importance of not reifying psychiatric entities, and instead focus on understanding the multiple causal mechanisms that contribute to spectrums of psychopathology. Categorical and dimensional approaches can certainly be complementary,[12] and it is notable that although the ICD-11 approach is more categorical than dimensional, its attempt to remove pseudo-specific criteria and its recognition of spectra such as the OCDRs, is consistent with an emphasis on avoiding reification, and on embracing complexity.

A particular strength of the ICD-11 revision process was the development and deployment of a global practice network for doing empirical research on psychiatric nosology.[13] This research provided an efficient and cost-effective way of addressing a range of questions, and for supporting particular decisions made by various ICD-11 workgroups, including the workgroup on OCRDs. Going forwards, such global efforts to research psychiatric nosology should be strongly encouraged. With advances in modern technology it is possible that they could be extended to include a range of additional data, including self-rated patient measures. Indeed, there is considerable scope for establishing integration between the somewhat different, but potentially synergetic, fields of clinical neuroscience and global mental health.[14]

NEUROBIOLOGY

Research on the psychobiology of OCRs in recent decades has drawn on a wide range of data, including from animal modeling, cases with neurological lesions, and neuropsychological investigation.[15] Neuroimaging has been particularly influential, however, in establishing current neurocircuitry models of OCRDs; structural, functional, and molecular imaging findings have supported the role of cortico-striatal-thalamic-cortical circuitry in OCD. Advances in neurogenetics have also been important; current methods are able to contribute to understanding the genetic architecture of OCD, as well as overlaps and distinctions with other disorders.

Neuroimaging is a relatively expensive methodology, and early work was confined to relatively small samples in specialized centers. In more recent years, magnetic resonance imaging (MRI) has also been established in a range of countries around the world. A key development has been the collaboration of different centers on mega-and meta-analyses of their work. Such collaboration addresses a key limitation of single-center work, the relative low statistical power of small sample brain imaging studies. ENIGMA is the largest such international collaboration, and exemplifies the extraordinary productivity that such collaborations potentially allow.[16]

In the case of OCD, an initial collaboration was formed to mega-analyze existing structural scans. Proof-of-principle analyses focused on 1.5T brain scans, and used voxel-based morphometry and cortical thickness measures.[1718] Subsequently contributors to this consortium established an ENIGMA-OCD workgroup; this provided access to pipelines for meta-analytic work using summary statistics generated at each participating site. ENIGMA-OCD has published subcortical and cortical data comparing OCD patients and healthy controls around the world.[1920] Ongoing efforts will focus on diffusion tensor imaging and resting-state MRI data, and will also incorporate additional methodologies such as machine learning analyses, and integration with genetic data.

While ENIGMA analyses have the huge advantage of robust statistical power, they are limited to the extent that different sites have used different methodologies, including heterogeneous brain scanning parameters and clinical assessments. ENIGMA-OCD provided the rationale for a successful NIMH application to prospectively study individuals with OCD and healthy controls, with sites across the world (Brazil, India, Netherlands, South Africa, United States). Led by Drs. Blair Simpson and Melanie Wall, with collaborators Drs. Euripedes Miguel. Janardhan Reddy, Dan Stein, and Odile van den Heuvel, this international collaboration will hopefully not only inform our understanding of brain signatures of OCD, but will do so in a way that has global applicability.

The sequencing of the human genome, and subsequent decreases in the cost of genotyping, have provided enormous impetus to work on the genetic basis of medical disorders. OCD demonstrates significant heritability, and a strong foundation of early work on family studies has provided a useful basis for subsequent genetics research. Furthermore, the establishment of a PGC has again provided a model and a mechanism for productive collaboration, with pooling of data from around the world in order to ensure samples that are sufficiently powered to allow robust genome wide association studies (GWAS). Future such work may also provide key insights into gene x environment mechanisms that contribute to mental disorders.

PGC-OCD research has suggested that OCD has a complex genetic architecture, with multiple genes of small effect size contributing.[2122] In the first PGC-OCD GWAS, the lowest two P values were located within DLGAP1, a gene that influences glutamatergic neurotransmission;[21] a finding that is consistent with growing evidence of the role of this neurotransmitter system in the pathogenesis of OCD.[23] In addition, this work has allowed a comparison of the genetic architecture of OCD and of Tourette's disorders; it is notable that despite the strong clinical overlap of these two conditions, there are key differences in this architecture.[22] The hope is that such work will ultimately lead to novel treatment targets.

Future global research on the neurobiology of OCRDs should also address disorders such as body dysmorphic disorder, trichotillomania, and skin-picking disorder; entities that are often overlooked in research priority exercises, despite their high prevalence and associated morbidity. The Trichotillomania Learning Center Foundation for Body Focused Repetitive Behaviors is currently funding a large prospective multi-site study of trichotillomania, which includes one site outside of the United States. Such work provides enormous potential for integrating clinical neuroscience and global health, and for providing insights into both biological and socio-cultural factors influencing the expression and experience of mental disorders. There is a clear need for the current GWAS database of studies to be extended to include more diverse samples.[24] Indeed, discovery research in LMIC settings may play a key role in advancing the field.[25]

INTERVENTION

Work on OCD was given significant impetus by early findings that clomipramine, a serotonergic antidepressant, and exposure and response prevention, a behavioral technique, were efficacious in reducing symptoms. Such work was often initiated by a single researcher at a single site with a single patient, before being expanded by a bigger research group into a case series or small controlled trial, and then researched in a well-powered multi-site randomized controlled trial. Clomipramine, for example, was reported as useful in OCD by a Spanish psychiatrist, was rigorously studied in series of patients by a Swedish group, and was then registered by the Food and Drug Administration for the treatment of OCD on the basis of two large multi-site studies in the United States.[26]

With the subsequent introduction of the serotonin selective reuptake inhibitors (SSRIs), the pharmaceutical industry sponsored a number of cross-national studies of these agents in the pharmacotherapy of OCD. For example, studies of escitalopram for OCD were undertaken at sites in a range of countries around the world, including work in Africa, Asia, Australia, Europe, and North America, and resulted in both a short-term efficacy study, as well as a relapse prevention study.[2728] Such cross-national studies again have the potential advantage of allowing more robust statistical power. At the same time, it is noteworthy that several large multi-sites of the SSRIs for OCD had lower effect sizes than the original clomipramine work.[29] This may in part be due to the higher placebo response that is seen in less well controlled work with more heterogeneous samples.

While explanatory trials for drug registration purposes have been crucial for clinical practice, there is a clear need to supplement such work with pragmatic studies of patients in “real-life” settings.[30] To date there have, however, been very few such studies. In an early controlled trial, patients with OCD and phobia being treated in primary care were assigned to behavioral psychotherapy from a nurse therapist or to routine care from their general practitioner. At the end of 1 year clinical outcome was significantly better in patients cared for by the nurse therapist, and there was evidence for cost-efficacy.[31] Key questions for future such work include how best to sequence different medications, and how best to sequence pharmacotherapy and psychotherapy in OCD, particularly in individuals who do not response to first-line intervention. There are also opportunities for international collaborations to study less well researched interventions for OCD, such as repetitive transcranial magnetic stimulation. Finally, given preliminary success with computer-guided and online interventions for OCRDs, further work incorporating these interventions into daily practice across cultures is needed.

The Cochrane Collaboration is an important international effort that has focused on the importance of establishing evidence-based recommendations, based on rigorous synthesis of existing interventional data. Cochrane reviews have been undertaken on OCD, on body dysmorphic disorder, on trichotillomania, as well as on treatment-resistant anxiety disorders (including OCD).[32333435] These reviews are arguably useful not only in synthesizing the current evidence-base, but also in pointing to areas where further research is needed. Cochrane reviews can, however, be time- and energy-consuming and mechanisms are needed to ensure that existing reviews are updated in an ongoing way.

Perhaps one of the most important gaps in the field regards task-shifting interventions for OCRDs. Given the relatively high prevalence of OCRDs globally, and given the relative lack of human resources with expertise in their management, the global mental health approach of empowering nonspecialized health workers to assist in interventions, seems sensible. It is notable that considerable consumer advocacy has been done in the field of OCRDs, including peer-led interventions.[36] That said, additional effort is needed to ensure that task-shifting or task-sharing interventions are feasible and acceptable, and to assess whether they are efficacious and cost-effective. Lessons gained from work in other conditions, including depression, may, however, be useful in informing such research.

CONCLUSION

The uniformity of OCD phenomenology around the world has been emphasized by a number of authors, a point consistent with a paradigm that has emphasized a neuropsychiatric model of this condition. At the same time, the expression and experience of all mental disorders is influenced by sociocultural context, a point that cross-cultural psychiatry has long emphasized. Today, with the advent of contemporary global mental health and clinical neuroscience, it is timely to integrate these perspectives and to ensure their application to OCRDs.

The value of such a perspective has been exemplified by productive international collaborations that have advanced the nosology and neurobiology of the OCRDs. Much additional global work is however needed in this area given the significant prevalence and morbidity of these conditions, and given important advances in the research methodologies that are needed to further our scientific understanding of their underlying mechanisms. There is a particular need for pragmatic trials in the management of OCRDs, as well as for work on task-shifting and task-sharing interventions for these conditions.

Financial support and sponsorship

Nil.

Conflicts of interest

In the past 3 years, the author has received research grants and/or consultancy honoraria from Biocodex, Lundbeck, and Sun.