Outstanding Research Questions for OCD

Genetics of OCD

Defining OCD Phenotypes

Neuropsychological Theories of OCD

The OCD Brain

Neural Mechanisms of OCD

Treatments for OCD: Neuroscientific Basis and Future Prospects

Summary and Conclusions

REFERENCES

Introduction

Most people have had intrusive thoughts or irresistible behavioral urges. When these tendencies become excessive and life disrupting, in the form of obsessions and compulsions, they may receive a diagnosis of obsessive-compulsive disorder (OCD), which is surprisingly common in the general population (2.5%–۳%) and constitutes a major health-economic burden on society. OCD can be a severe and disabling disorder that is expressed in a bewildering variety of ways, including most obviously checking and washing, associated with excessive worrying and contamination fears. It has seriously afflicted numerous famous individuals, reportedly including Martin Luther, Samuel Johnson, Hans Christian Andersen, and Howard Hughes. One of the most remarkable facets of the disorder in many patients is their preservation of insight about what often presents as bizarre behavior. The mismatch between their subjective goals and their behavior is often called ‘‘egodystonia’’ and is one of many of the puzzles that OCD presents to the clinician or neuroscientist. Solving some of these questions and puzzles will undoubtedly advance the entire field of the cognitive neuroscience of mental health. Without attempting to review in detail all of the facets of OCD, we list below some of the major issues, and we will attempt to address them during the course of this article. Many of the classical references are to be found in the reviews provided in the monumental recent volume summarizing the massive amount of work in this field (Pittenger, 2017a).

Developmental versus Adult Perspectives

As with many other psychiatric disorders, there is increasing emphasis on understanding early-onset (i.e., before puberty, mean age 11 years) versus late-onset adult expression (mean age 23 years), as these may indicate distinct etiological and biological factors, as well as clinical factors. Early-onset OCD tends to be more severe, more familial, and male predominant and is associated with tic disorders, other comorbidities, and poorer treatment response (Taylor, 2011). Other precise phenotypic differences and variation in brain network structure organization are more controversial. There are obvious difficulties in naive cross-sectional comparisons between the two populations. Thus, a brain region shown to be different in children with OCD may well be different from an adult expression simply because of investigating them at different stages of brain development. Taylor (2011) judged it unwise to make strong conclusions about differences in brain regions between early- and late-onset OCD, because none of the studies had adequate statistical power to do so, and the necessary longitudinal studies have been lacking. Similarly, unless duration of symptoms is equated, differences (e.g., in severity) may originate simply as a function of this greater exposure to the disorder, especially if untreated. A more intriguing and counterintuitive claim has been that early-onset OCD patients, despite greater clinical severity, have no evidence of ‘‘cold’’ cognitive deficits (e.g., Hybel et al., 2017).