ADVANCES IN THE NEUROBIOLOGY OF OBSESSIVE-COMPULSIVE DISORDER: Implications for Conceptualizing Putative Obsessive-Compulsive and Spectrum Disorders

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For many decades, obsessive-compulsive disorder (OCD) was considered one of the exemplars of a psychogenic condition.88 In the past 20 years, however, data about the neurobiological underpinnings of OCD have steadily accumulated. Interest in OCD also has encouraged work on a hypothesized spectrum of related disorders that are characterized by an overlapping phenomenology and psychobiology.25, 38, 64, 86, 111

Nevertheless, the question of how best to delineate this spectrum remains unanswered,82 perhaps partly because the underlying mechanisms of OCD and putative spectrum disorders remain incompletely understood. This article reviews current advances in the neurochemistry, neuroanatomy, neurogenetics, neuroimmunology, and neuroethology of OCD and then uses this information to consider different approaches toward the concept of an obsessive-compulsive spectrum and its neurobiology.

Section snippets

NEUROBIOLOGY

This section focuses on the neurochemistry, neuroanatomy, neurogenetics, neuroimmunology, and neuroethology of OCD. Although understanding in each of these areas has grown remarkably, many questions remain unanswered. This discussion highlights the main findings.

SEROTONIN SELECTIVITY

Clomipramine, an SRI, is more effective than desipramine, a predominantly noradrenergic reuptake inhibitor, in adults and younger patients with OCD. The notion that different psychiatric conditions can be pharmacologically dissected was put forward early on by Klein,48 who demonstrated that the TCA imipramine was effective in decreasing episodic spontaneous panic, whereas benzodiazepines decreased chronic fearlike anxiety; however, the TCAs per se do not allow for a specific pharmacologic

ANATOMIC SPECIFICITY

The influenza pandemic early in the 1900s provided some of the first evidence that obsessive-compulsive symptoms might be mediated by specific neuroanatomic circuits. Patients developed not only postencephalitic parkinsonism but also psychiatric symptoms, including obsessive-compulsive behavior. At autopsy, findings included lesions in the basal ganglia.11 Later work demonstrated that several neurologic disorders of the basal ganglia are associated with obsessive-compulsive symptoms. Patients

GENETIC SPECIFICITY

The disorder most closely linked with OCD in family studies is TS. In a fascinating brain imaging study, Moriarty et al68 found that in patients with obsessive-compulsive symptoms, regional cerebral blood flow patterns differed depending on whether a family history of TS was present, and patterns were similar to those seen in TS in patients from families with TS. Family studies of TS, however, arguably also demonstrate a link with several other disorders, including ADHD, mood disorders, conduct

IMMUNOLOGIC SPECIFICITY

Swedo et al107 suggested several diagnostic criteria for PANDAS: presence of OCD or a CMT disorder, prepubertal symptom onset, episodic course of symptom severity, association with group A β-hemolytic streptococcal infection, and association with neurologic abnormalities. Patients with PANDAS also may demonstrate several other psychological abnormalities, however, including emotional liability, separation anxiety, oppositional behaviors, and motoric hyperactivity. Symptoms such as hair pulling

ETHOLOGIC SPECIFICITY

Arguably the best-studied neuroethologic model of OCD is canine acral lick dermatitis. Nevertheless, several other stereotypical symptoms occur in veterinary practice,92 including locomotory stereotypies in horses, chewing in sows, hoarding in cats, feather picking in birds, and self-grooming in primates. These various conditions may involve overlapping neurobiological mechanisms; evidence shows that the serotonergic, dopaminergic, and opioid systems and corticostriatal circuits, may have a

SUMMARY

Several approaches to the spectrum of obsessive-compulsive spectrum disorders have been put forward, each based on a rather different framework. To some extent, overlaps exist among these approaches, indicating that the neurobiology of OCD and related disorders is increasingly consolidated; however, important differences exist between these approaches, and many questions are unanswered, demonstrating that more work is necessary to fully delineate OCD and its subtypes and their relationships to

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    Address reprint requests to Dan J. Stein, MB, Medical Research Council Unit on Anxiety Disorders, University of Stellenbosch, Tygerberg 7505, South Africa, e-mail: [email protected]

    This work was supported by the Medical Research Council Unit of South Africa.

    *

    Medical Research Council Unit on Anxiety Disorders, University of Stellenbosch, Cape Town, South Africa

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    Copyright © 2000 W. B. Saunders Company. Published by Elsevier Inc. All rights reserved.