An Evolutionary Perspective on Obsessive-Compulsive Disorder

Evolutionary models may help clinicians and patients gain a better understanding of the causes and symptoms of OCD, while animal models provide a heuristic for further research of the psychobiological basis and testing for possible treatment.

Obsessive-compulsive disorder (OCD) has now been established as a common and disabling syndrome found in many parts of the globe. The Epidemiological Catchment Area (ECA) Study (Robins et al., 1984) found OCD to be the fourth most common psychiatric disorder in the United States, with a lifetime prevalence of 2.5% and remarkably similar prevalence rates have since been reported across diverse cultures (Weissman et al., 1994).

Furthermore, OCD has been identified as the tenth most disabling medical disorder (Murray and Lopez, 1996) and costs the economy of the United States several billion dollars each year (Dupont et al., 1996; Greenberg et al., 1999). These findings have stimulated growing interest and important advances, in our understanding of the disorder.

Obsessions and compulsions

OCD is characterized by obsessions and compulsions. Obsessions are intrusive, anxietyprovoking thoughts, ideas or images, while compulsions are repetitive rituals or mental actions performed in response to obsessions in order to decrease anxiety (APA, 2000).

Patients with OCD are typically aware that their symptoms are excessive or unreasonable, but are unable to resist repeating them. Although patients report a range of different kinds of obsessions and compulsions, there is notable consistency of themes across patients.

These themes include contamination concerns with associated purification compulsions (e.g. washing, showering), pathological doubt accompanied by checking or praying, concerns about symmetry that elicit ordering behaviours and hoarding concerns and behaviours (Rasmussen and Eisen, 1992).

Striking similarity

Aside from some culturally-specific details in OCD phenomena which may be shaped by religious belief systems, these core themes are strikingly similar across cultural settings (Rapoport and Fiske, 1998; Stein and Rapoport, 1996).

The similarity of OCD prevalence rates across cultures and the globally consistent specificity of OCD themes, lend support to the diverse lines of evidence that suggest universal mechanisms underlie the disorder. These mechanisms may be both "proximal" and "distal" (Nesse, 1999).

Proximal mechanisms refer to the psychobiological factors involved in the pathogenesis of symptoms; OCD appears to be associated with specific neurocircuitry and neurobiological processes. Distal mechanisms refer to the evolutionary roots of the psychobiological structures and processes relevant to OCD (Hofer, 2002; Stein et al., 1992; Swedo, 1989).

Behavioural exaggeration or deficit

An evolutionary perspective proposes that pathological anxiety constitutes an exaggeration of or deficit in behaviours that were originally adaptive; anxiety has always played an important role in protecting humans and other organisms from real physical and social dangers (Marks and Nesse, 1994; Stein and Bouwer, 1997).

The consistently recurring themes of OCD symptoms represent survival concerns that were particularly salient for our early ancestors.Washing, cleaning and other kinds of grooming are behaviours that strengthen social ties in mammals and may also be a defence against micro-organisms.

Checking behaviour in defence of supplies, territory and mates, ordering of the environment and hoarding of food and possessions, were all necessary to ensure survival and may have been actively selected for through mammalian evolution (Joiner and Sachs-Ericsson, 2001; Stevens and Price, 1996).

While its unlikely that humans are selected to groom or to hoard, we may still have the relevant structures because of our mammalian evolutionary past and these may be inadvertently released if there is damage to these structures.

Fixed action patterns

Possible support for evolutionary perspectives on OCD comes from the identification of fixed action patterns (Eibl-Eibesfeld, 1970; Lorenz, 1966; Tinbergen, 1953) in animals. Fixed action patterns are innate and adaptive behaviour sequences that are actualised by a releasing stimulus and are seen in all members of a species, even when they are raised in isolation.

Initial ethological work focused on the notion of excessive or inappropriate release of action patterns, in the form of "displacement behaviours".

Animal stereotypies

More recent work has focused on a range of animal stereotypies that are produced by confinement, by particular medications, or that seem to arise de novo. For example, in veterinary practice, pathological stereotypies include the paw-licking of dogs with acral lick dermatitis (a grooming disorder characterized by excessive licking or biting of the extremities leading to localized alopecia and subsequent granulomatous lesions), hair-pulling in cats with psychogenic alopecia and feather-pulling in birds with excessive preening.

Many of the repetitive symptoms seen in OCD and OCDrelated disorders such as trichotillomania (compulsive hair-pulling), Tourette's syndrome (repetitive motoric patterns) and compulsive picking or self-mutilitation, are reminiscent of these animal behaviours.

Animal studies and animal models suggest that the neurocircuitry and neurobiology of excessive and inappropriate repetitive behaviours in animals and in humans may have significant overlap.

Neurocircuitry

Given that OCD symptoms involve stereotypical behaviour, there is a possibility that OCD involves dysfunction in the procedural strategies whereby the brain selects, initiates and maintains cognitive and motoric activity in response to environmental stimuli (c.f. Mishkin and Petri, 1984; Robins and Brown, 1990; Saint- Cyr et al., 1995).

It is likely that cortical-striatal-thalamic-cortical (CSTC) systems play a crucial role in the implicit learning of procedural strategies and their subsequent automatic execution.Ventral CSTC circuits, which include the basal ganglia, in particular appear to play an important role in recognizing behaviourally significant stimuli (and in error detection), and in regulating autonomic and goal-directed responses (including response inhibition and suppression of negative emotion) according to pre-existing "rules" for guiding behaviour in particular environmental contexts (Wise et al., 1996).

These circuits are therefore a good candidate for involvement in OCD (Davidson et al., 2001; Rauch and Baxter, 1998; Zald and Kim, 1996).

Several strands of evidence

There are several strands of evidence that CSCT circuits are disrupted in OCD. First, patients with neurological conditions involving the basal ganglia (e.g. Tourette's syndrome, Sydenham's syndrome and Huntington's disease) have increased rates of comorbidity with OCD (Cummings and Cunningham, 1992; Swedo et al., 1989).

Second, OCD patients may have comorbid tics (Pitman et al., 1987) or increased neurological soft signs (Hollander et al., 1990), consistent with basal ganglia damage.

Third, persuasive evidence from structural and functional brain imaging point to basal ganglia abnormalities in OCD patients (Rauch and Baxter, 1998): some CT and MRI studies have demonstrated decreased caudate volume in OCD patients (Luxenberg et al., 1988; Robinson et al., 1995), while functional imaging studies have found increased pre-frontal activity prior to treatment and decreased caudate activity after effective treatment of OCD symptoms (Insel, 1992).

Fourth, surgical lesions to frontalbasal ganglia pathways may result in improvement in OCD symptoms (Martuza et al., 1990).

Additionally, a core emotion in the contamination themes that are common to OCD may be disgust, which appears to be processed by the CSTC system (Stein et al., 2001).

Faulty recognition

The many links betweens OCD and basal ganglia functioning suggest that OCD may indeed involve faulty recognition of a behavioural context that does not exist, and/or a dysfunction in the selection of pre-existing "rules" to guide behaviour in response to the immediate environmental context; this releases behaviours (the obsessive thoughts and compulsive rituals of OCD) outside of an appropriate context (Rapoport and Fiske, 1998).

Like repetitive behaviours in humans, the learning and execution of fixed action patterns and repetitive motor habits in animals is a function of the basal ganglia (Lehrman, 1964; Mishkin et al., 1984). For example, an interesting recent study of spontaneous stereotypic behaviour in deermice has demonstrated the role of the striatum in mediating such behaviours (Lewis, 2003).

Similarly, lesion studies demonstrate the role of the striatum in behaviours such as hoarding (Stein et al., 1999).

Cause remains unsolved

However, the cause of CSTC dysfunction in OCD remains unresolved: mechanisms may involve genetic factors, the marked sensitivity of striatal circuits to anoxic damage, the development of disordered striatal architecture after emotional deprivation (Martin et al., 1991) and a broad spectrum of potential neurochemical, neuroimmunological and neuroendocrinological factors (Stein, 2003).

Serotonin and dopamine

CSTC circuits have significant input from serotonergic and dopaminergic neurons. Indeed, the serotonergic and dopaminergic systems have been implicated in both OCD in humans and fixed action patterns/stereotypies.

An important role for the serotonin system in OCD is suggested by several findings. OCD responds to treatment with the serotonergic reuptake inhibitor (SRI) clomipramine, but not to the noradrenergic tricyclic antidepressant desipramine (Zohar and Insel, 1987); a subset of patients with OCD in some studies have elevated cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) (Thoren et al., 1980); and the administration of the serotonin agonist, mchlorophenylpiperazine (m-CPP), leads to exacerbation of OCD symptoms in some patients, which remits after treatment with clomipramine or a SSRI (Hollander et al., 1991; Zohar et al., 1988).

Non-serotonergic systems may also play a role

However, the absence of elevated CSF 5-HIAA, of symptom exacerbation after m-CPP and of response to SRIs among other OCD patients, raises the possibility that non-serotonergic systems may also play a role in OCD. Evidence from pre-clinical and clinical studies suggest that dopamine is a likely candidate (Goodman et al., 1990).

Administration of dopamine agonists may result in increased compulsive behaviours in humans (Borcherding et al., 1990; Frye and Arnold, 1981) and Tourette's disorder, which frequently presents with comorbid OCD (Hollander et al., 1989), responds well to dopamine blockers (Hyde and Weinberger, 1995).

Patients with OCD and comorbid tics who fail to respond to an SRI may respond to a combination of an SRI and a dopamine blocker (Hawkridge et al., 1996; McDougle et al., 1994). While other systems may well be involved in OCD (Leckman et al., 1994; Stein, 1996), to date proven psychopharmacological interventions for OCD remain restricted to those that target the serotonin and dopamine systems.

Interesting parallels in animals

Animal models demonstrate interesting parallels in the neurobiology of repetitive behaviours in animals and humans. Serotonergic agents have been found to inhibit laboratory-induced head-twitching in mice and the wet dog shake in rats (Grahame-Smith, 1971; Green and Heal, 1985; Jacobs, 1976).

Repetitive and stereotyped separation-induced ultrasonic vocalisations in rat pups are reduced in response to serotonin-specific reuptake inhibitors but not other anti-anxiety drugs (Olivier et al., 1994).

Excessive grooming

Furthermore, serotonin has been implicated in excessive grooming in animals: serotonin reuptake blockers suppress both ACTH and noveltyinduced grooming (Rodriguez et al., 1988; Traber et al., 1988), while selective destruction of serotonergic neurons increases ACTH induced grooming (Lucki and Kucharick, 1988).

Additionally, a subgroup of neurons in the dorsal raphe nucleus (where all serotonergic fibres originate) in cats is activated when the animal licks, chews, bites or grooms with its mouth (Jacobs et al., 1990). In an elegant study, acral lick dermatitis was found to respond to the anti-obsessional drug clomipramine but not to desipramine, paralleling earlier findings in humans with OCD (Rapoport et al., 1992).

Indeed, a number of SSRIs that are useful for OCD may also be effective in acral lick dermatitis (Stein et al., 1992; Stein et al., 1998). Our group recently demonstrated that vervet monkeys with sterotypies responded better to an SSRI than to a placebo (Hugo et al., in press).

Dopamine

With regard to dopamine, it is well known that motoric sterotypies in rodents (e.g. licking the forepaw) and primates can be induced by dopaminergic agonists and blocked by dopamine antagonists (Kelley and Lang, 1988). Additionally, hoarding behaviours in animals seem to be mediated by the dopamine system: hoarding behaviours disrupted by lesions of the dopaminergic system are restored by administration of the dopamine precursor L-dopa (Blundell et al., 1977; Kelley and Stinus, 1985).

There is thus accumulating evidence that similar neurobiological mechanisms may be responsible for both OCD and animal displacement behaviours.

Conclusion

Evolutionary perspectives provide one explanation for the apparent universality of OCD themes. Animal models help to explain the particular spectrum and relative uniformity, of OCD symptoms. If OCD is characterized by the inappropriate release of fixed action patterns, or by a disruption in implicit processing (Rauch and Baxter, 1998), this may also help explain why, once the OCD symptoms are being performed, they appear senseless to the patient.

Finally, they may also be helpful in explaining certain less common variations of OCD, such as Swedo's (1989) two cases of children with hand washing who also licked their hands in a ritualised manner.

Humans differ in fundamental ways from other animals, and animal models are arguably only applicable to humans as long as appropriate modifications are made in view of the unique aspects of humans, such as our cognitive capacity.

In OCD, cognitive symptoms play an important role; whereas sterotypies in animals may include excessive and inappropriate grooming or hoarding, in humans these may include the "cognitive stereotypies" (repeated intrusive thoughts) found in OCD. To understand OCD in humans, we also need to understand implicit cognition and behaviour and its disruption in this disorder.

While there is growing evidence for the involvement of specific neurocircuitry and neurobiology in OCD, which may be shaped by distal evolutionary processes, it is likely that the activation of these mechanisms depends on a range of proximate factors; these may include immunological mechanisms such as infection with Streptococcus (Swedo et al., 1998) as well as behavioural reinforcement (itself mediated by biological mechanisms).

While evolutionary models are thus only partial, they may help clinicians to understand OCD symptoms more empathically and to provide the patient with a useful explanatory model for making sense of their experience.

In addition, animal models provide a heuristic for further research of the psychobiological basis of OCD and perhaps a testing ground for possible treatment: indeed, certain kinds of stereotypic behaviour in animals (e.g. marbleburying) have recently been used as paradigms for testing OCD medications.

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