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SMALL ANIMALS
with obsessive-compulsive disorder:
126 cases (1989–2000)
Karen L. Overall, VMD, PhD, DACVB, and Arthur E. Dunham, PhD
JAVMA, Vol 221, No. 10, November 15, 2002 Scientific Reports: Retrospective Study 1445
er (serious or show), breeder (backyard), Society for tion of the drug was maintained and treatment was con-
the Prevention of Cruelty to Animals or humane shel- sidered successful. If a patient was treated initially with
ter, breed rescue service, newspaper adoption adver- amitriptyline and acceptable results were not obtained,
tisement (not breeder), pet store, friend, and other. clomipramine was administered instead; if acceptable
Training or schooling categories included no school, results were obtained with clomipramine, treatment
trained by client, puppy kindergarten, group lessons with amitriptyline was considered a failure and treat-
(basic), group lessons (advanced), private trainer at ment with clomipramine was considered a success.
house, and private trainer (sent to trainer). Patients for whom treatment with clomipramine failed
The general behavior modification scheme for dogs were likewise treated with another medication.
consisted of 3 basic steps designed to stop unwanted Dosage protocols13 were used consistently and
behaviors and reward preferable behaviors that were included amitriptyline (1 mg/kg [0.45 mg/lb], PO, q 12
directly competitive with the undesirable behaviors. In h for 10 days; if no change in behavior was detected,
step 1, clients were to cease even unintentional reward the dosage was increased to 2 mg/kg [0.91 mg/lb] for
for the undesirable behavior. In step 2, clients were 10 days; if still no change was detected, the medication
asked to follow a passive behavior modification pro- was changed [if treatment was efficacious it was con-
gram designed to teach dogs to sit quietly, look at the tinued for a minimum of 1 month]); doxepin (3 to 5
person from whom they were seeking attention or with mg/kg [1.4 to 2.3 mg/lb], PO, q 8 h to q 12 h for a min-
whom the interaction was occurring, and wait to take imum of 1 month); clomipramine (1 mg/kg, PO, q 12
the cues about the appropriateness of their behavior h for 14 days, then 2 mg/kg, PO, q 12 h for 14 days,
from those people (ie, Protocol for Deference8). In step then 3 mg/kg, PO, q 12 h for 1 month, for a minimum
3, clients were requested to begin active behavior mod- of 2 months of treatment [the gradual increase in
ification designed to teach the dogs to relax when they dosage was intended to minimize gastrointestinal dis-
would otherwise be engaged in the behavior, in orders]); and the SSRIs, sertraline and fluoxetine (1
exchange for which the dog was given a food or play mg/kg, PO, q 24 h for 2 months initially). Treatment
reward (ie, Protocol for Relaxation: Tier 18). was then continued at the minimum effective dose nec-
For clients with feline patients, steps 1 and 3 were essary to control the behavior.
recommended; step 2 was modified to recommend that All patients received full physical and laboratory
the client only interact with the cat when the cat was evaluation prior to treatment. Any nonspecific derma-
calm. Cats were not required to sit in step 3, although tologic, medical, or neurologic signs potentially associ-
this was encouraged, but the clients were advised to ated with OCD were evaluated by the veterinarians
engage the cat in an enjoyable behavior that was direct- trained in the respective specialty prior to behavioral
ly competitive with the undesirable behavior. treatment. When warranted, patients also received var-
Behavior modification was assessed on the basis of ious nonroutine diagnostic procedures (eg, assessment
client responses and clinician opinion. of thyroid function and magnetic resonance spec-
For some of the patients, medication had been pre- troscopy of the brain).
scribed by the referring veterinarian. When the first Eight clinicians were involved in evaluation of the
patient in this study was treated, treatment with tricyclic dogs reported here. All clinicians adhered to the same
antidepressants (TCAs; eg, clomipramine and specific diagnostic criteria, and at least 2 clinicians reviewed each
serotonin reuptake inhibitors [SSRIs]) was cost pro- diagnosis. Although many records contained detailed out-
hibitive (> $10/d). Clomipramine is now affordable and come data, quality of the description of the behaviors
available in a canine formulation.b Accordingly, the TCA depended on clinician expertise versus resident expertise,
(amitriptyline) was the first drug of choice for all whether the behaviors were videotaped, client capability
patients with conditions that primarily involved anxiety and motivation in keeping data logs, and knowledge
and were enrolled in the early portion of the study. accrued by managing increasing numbers of these dogs.
Clomipramine was only used instead of amitriptyline if Accordingly, outcomes were broadly grouped and statisti-
amitriptyline was not efficacious or caused gastrointesti- cally treated as class variables to evaluate older and newer
nal disorders. Because of its histamine-1 receptor antag- cases equivalently. Response variables for outcome were
onist properties, the TCA doxepin was the first drug of small decrease in intensity (≤ 50%), large decrease in
choice for conditions that primarily involved pruritus, intensity (> 50%), small decrease in frequency (≤ 50%),
followed by amitriptyline.8,12-14 Other medications were large decrease in frequency (> 50%), the behavior stopped
occasionally prescribed as dictated by alterations in the totally, no change, small increase in intensity (< 50%),
patients’ behaviors, and for some animals, combinations large increase in intensity (> 50%), small increase in fre-
of medications were both more efficacious and more quency (< 50%), large increase in frequency (> 50%),
cost-effective for clients, as described elsewhere.13 died, euthanatized because of OCD, euthanatized for
When the senior author was awarded a grant pro- other reasons, placed, other, and unknown. Patients clas-
viding clomipramine at no cost, clomipramine was used sified with unknown outcomes were those lost to follow-
as the first drug of choice for treating OCD, as it has up. For patients with concurrent behavioral diagnoses,
been in humans. This circumstance allowed us to retro- alterations in intensity and severity reported here pertain
spectively compare the relative effects of amitriptyline only to OCD.
and clomipramine for patients that met the criteria for Data were analyzed by use of the log-likelihood
OCD. If a patient was administered amitriptyline and ratio test, and relevant nonparametric tests as indicat-
acceptable results were obtained (marked decrease in ed for categoric data.c
1446 Scientific Reports: Retrospective Study JAVMA, Vol 221, No. 10, November 15, 2002
SMALL ANIMALS
One hundred three dogs met inclusion criteria, hood ratio test) between sex and neuter status catego-
including 5 sexually intact females, 26 spayed females, ry of affected dogs and the category of OCD they had.
20 sexually intact males, and 52 neutered males. However, compared with the sex and neuter data for
Twenty-three cats (1 sexually intact female, 14 spayed the entire veterinary teaching hospital canine popula-
females, 1 sexually intact male, and 7 neutered males) tion during the study period (n = 47,473), male dogs
that met the diagnostic criteria had sufficiently com- were significantly over-represented in the OCD popu-
plete records to be included in the study. lation (log likelihood ratio test statistic, Gadjusted (adj) =
13.256 [P < 0.05]). In addition, neutered males were
Category of OCD—The most common category of over-represented in the OCD population, compared
OCD in dogs was that associated with grooming or with non-neutered males (log likelihood ratio test sta-
self-mutilation, followed by OCD involving locomo- tistic, Gadj = 36.641 [P ≤ 0.001]).
tion and OCD involving signs of hallucinations (Fig 1).
For cats, the most common category of OCD involved Breed—The population of dogs with OCD com-
grooming or self-mutilation (Fig 2). prised 18 mixed-breed dogs; 12 German Shepherd
Dogs; 7 Rottweilers; 6 Golden Retrievers; 5 each of
Dalmatians, Labrador Retrievers, and Lhasa Apsos; 3
each of Doberman Pinschers, Poodles, Soft-Coated
Wheaten Terriers, and English Springer Spaniels; 2
each of American Pit Bull Terriers, Bulldogs, Great
Danes, Miniature Schnauzers, and Cocker Spaniels;
and 1 dog each of 22 other breeds. This distribution
did not differ significantly from that in the overall
canine population of the Behavior Clinic or of the vet-
erinary teaching hospital. Further examination of the
most common breeds of dogs (mixed breeds, German
Shepherd Dogs, Rottweilers, Dalmations, and
Bulldogs) revealed interesting patterns among the
breeds. The specific manifestations of the OCD
appeared to be associated with the tasks for which the
dogs were developed. Dogs of herding breeds often had
excessive tail chasing. Dogs of guarding breeds and
those selected for intense focus and tenacity (eg,
Dalmatians, Rottweilers, and German Shepherd Dogs)
often had signs of hallucinations. All Rottweilers and
all but 1 Dalmatian had signs of hallucinations. Nine of
Figure 1—Frequency (%) distribution of categories of obsessive- 12 German Shepherd Dogs chased their tails.
compulsive disorder (OCD) in 103 dogs. M = Self-mutilation The cat population consisted of 14 Domestic
(grooming). L = Locomotor (spinning, chasing). H = Hallucinatory. Shorthairs, 6 Siamese, 1 Devon Rex, 1 Russian Blue,
P = Pica. V = Vocalization. K = Licking. C = Coprophagy. S =
Sucking. D = Digging. O = Other. and 1 Bengal. Siamese cats commonly had pica involv-
ing sucking, chewing, or ingestion of fabrics; 2 of the 6
Siamese cats in the study chewed, sucked, or ingested
fabric; and 1 ingested electric cords. All cats that
ingested fabric were Siamese, but neither cats that
licked plastic substrate or had sucking behavior cate-
gory were. The Bengal cat had over-grooming and
urine marking, both anxiety-related conditions. The
small number of cats we evaluated precluded statistical
comparisons among breeds. The behaviors associated
with OCD appeared after trauma in 3 cats and after
changes in feline or human social circumstances or
relationships in 7 cats. The changes in the feline or
human relationships were also often associated with
intercat aggression or elimination abnormalities (9
cats). Grooming or self-mutilation involved 16 of the
cats, 3 of which had a previous diagnosis of hyperes-
thenia and 3 of which had a diagnosis of atopy.
Age of onset—Age of onset was known or confi-
dently estimated for 95 of the 103 dogs. Mean ± SD age
at onset was 20.3 ± 23.7 months; however, the fre-
quency distribution of age at onset was highly skewed
Figure 2—Frequency (%) distribution of categories of OCD in 23 (skewness, 3.214). Age of onset for cats was 28.2 ±
cats. See Figure 1 for key. 30.1 months (n = 21), and the frequency distribution
JAVMA, Vol 221, No. 10, November 15, 2002 Scientific Reports: Retrospective Study 1447
1448 Scientific Reports: Retrospective Study JAVMA, Vol 221, No. 10, November 15, 2002
SMALL ANIMALS
ure in 89 dogs and 20 cats with obsessive-compulsive disorder Stereotypic behaviors may or may not be associat-
ed with OCD.1-5,7 Differential diagnoses for other
No. of No. of Probability
Drug Successes Failures of success
behavioral conditions in which the nonspecific signs
d
associated with OCD can occur include environmental
Amitriptyline 32 22 0.593 causes, management, humane considerations (eg,
b,e
Clomipramine 30 6 0.833
f
those involving understimulation, neglect, or excessive
Fluoxetine
g
8 1 0.889 confinement), separation anxiety, attention-seeking
Buspirone 1 1 0.500
Alprazolam *
h,
1 0 1.000
behavior, generalized anxiety, and hyperactivity.7,8
i,†
Obsessive-compulsive disorder in all species is
Hydroxyzine 3 0 1.000 characterized by repetitive, ritualistic behaviors, in
j,‡
Doxepin 1 2 0.333
Sertraline
k
1 0 1.000 excess of any required for normal function, the execu-
§ tion of which interferes with normal, daily activities
Prednisone 1 0 1.000
Pentazocine
l
1 0 1.000 and functioning. Inherent in this description is a
Diazepam
m,II
3 0 1.000 behavior that is exaggerated in form as well as dura-
tion. The diagnostic criteria employed here have dual
*Used in combination with clomipramine to treat signs of panic. †Used for
pruritus associated with lesion caused by grooming in cats. ‡Used for pruri-
advantages. First, they permit separation of nonspecif-
tus associated with lesions caused by grooming in dogs. §For treatment of ic signs from diagnostic criteria. This allows the non-
putative intervertebral disk disease. IIUsed in combination with amitriptyline specific signs to be used to evaluate changes in the con-
(2 animals) and clomipramine (1 animal) for signs of panic.
dition and to further describe populations afflicted
with different manifestations of the condition.15,16
affected relatives and 15 did not. Of the 15 dogs with Second, they do not require definition or assessment of
affected relatives, 7 had 1 known affected relative (3 underlying motivational states, which is difficult to
male littermates, 3 sires, and 1 dam), 7 had 2 known accomplish in a meaningful manner in other species.
affected relatives (female littermate-male littermate, It appears that dogs, as do humans, may perceive
sire-male offspring, sire-other, grandsire-other, dam- that their behaviors are abnormal and control their
male littermate, dam-second degree relative), and 1 behaviors to the extent that the behavior is performed
had 3 known affected relatives. Only 3 clients with cats only minimally, or not at all, in the presence of others.
knew about affected relatives, and only 2 of these defi- Dogs who flank suck or tail chase may, after frequent
nitely had an affected relative (1 sire, 1 offspring). reprimands and corrections, remove themselves from
view and then commit the behavior elsewhere. Upon
Concurrent behavioral diagnoses—Seventy-seven approach, the behavior ceases, only to begin again
(74.8%) dogs had concurrent behavioral conditions, as when no one is watching or when the animal removes
determined via published diagnostic criteria.8 Thirty- itself from view. Results of this study support the exis-
three (32.0%) dogs met the criteria for a diagnosis of tence of this evasive behavior pattern. If the desire to
attention-seeking behavior (eg, excessive solicitation perform the behavior is present, despite restraint
and neediness), 29 (28.2%) met the criteria for a diag- because of punishment, training, or physical incarcer-
nosis of dominance or impulse-control aggression, 23 ation, the condition is present. The key is that if such
(23.3%) met the criteria for a diagnosis of separation control is removed and the animal can commit the
anxiety, and 16 (15.5%) met the criteria for a diagnosis behavior, it will commit the behavior. Ignoring this
of generalized anxiety disorder. Thirty other miscella- crucial point will result in underdiagnosis of OCD and
neous behavioral and medical diagnoses were also underestimation of its frequency in canine and feline
noted. There was no association between duration that populations.
the dog had been affected before treatment and the The presence of this and other cognitive compo-
number of concurrent behavioral diagnoses (r = 0.13; nents suggests that the problem is rooted at a higher
P = 0.23). Because many dogs in this study had multi- level than the behavior alone may indicate (ie, a
ple concurrent behavioral diagnoses, the sample sizes of Doberman Pinscher may be flank sucking, but not
each diagnostic combination were insufficient to deter- because anything is wrong with its flank). Such exam-
mine whether the associations were random, as has ples support the contention that obsessions are a valid
been performed elsewhere.15 The data were also insuffi- component of OCD. We evaluate obsessions in
cient to assess whether dogs that had been affected humans by asking them about repetitive, invasive
longer had more intense or more frequent signs of thoughts.17 It is inappropriate to apply a criterion (eg,
OCD, compared with dogs affected for a short period. assessment that relies on a verbal response) to 1
In contrast with dogs, only 9 of 23 (39.1%) cats species that has a divergent phylogeny (eg, nonverbal)
met the criteria for concurrent behavioral diagnoses, a that prohibits the use of that tool or criteria.10 The
difference that was significant (log likelihood ratio test, extent to which the patients in our study focused on
Gadj = 10.04; P < 0.05). In contrast with dogs, most of their behaviors, avoided those who sought to interfere
the concurrent behavioral diagnoses were associated with them, and were avoided by clinically normal or
with elimination disorders; 3 cats also sprayed, 2 cats unaffected canine and feline housemates strongly sug-
urine-marked without spraying, 1 cat marked with gests that a cognitive component was present, albeit
feces, and 1 cat had a substrate aversion to the litter. difficult to assess.
Only 1 cat met the criteria for separation anxiety, a Obsessive-compulsive disorder in humans fre-
major concurrent diagnosis in dogs. quently appears in adolescence, at the onset of social
JAVMA, Vol 221, No. 10, November 15, 2002 Scientific Reports: Retrospective Study 1449
cats, OCD also appears during this indistinct period of finding supports the hypothesis that OCD in dogs is
social maturity (range for dogs, 12 to 36 months; based in some primary neurochemical or neurogenetic
mean, approx 18 to 24 months; range for cats, 24 to 48 dysfunction, and that the mechanisms driving OCD
months; mean, approx 30 to 36 months)8 and if left may differ between dogs and cats.
untreated, whether by behavioral or pharmacologic Obsessive-compulsive disorder affects at least 2%
intervention, it worsens. Given the relatively early age of the human population, and this is believed to be an
at which this condition develops and the probability of underestimate.19-21 Some forms of OCD have a familial
profound deterioration when left untreated, young ani- genetic component22-24; however, most instances of
mals should be routinely screened for OCD and treat- human OCD appear to be sporadic. It is important to
ed appropriately early. Dogs and cats from families recognize that the development of specific animal
with a history of OCD should be carefully watched for breeds and the practice of inbreeding within those
its appearance, albeit possibly in a different form than breeds suggest that the prevalence of OCD in dogs
that of their relatives. could be higher than that reported for humans.
In this study, 10 of the 23 affected cats had signs of On the basis of client interviews and complaints,
their particular form of OCD after some physical trau- OCD may be familial in Great Danes, German Short-
ma or social upheaval, and the OCD in these cats may haired Pointers, German Shepherd Dogs, Bull
have occurred concomitant with intercat aggression or Terriers,25 Jack Russell Terriers, Dalmatians, Bouvier de
elimination problems. Siamese cats were ranked as the Flanders, Salukis, Cairn Terriers, Basset Hounds, and
second most common breed in this study. Although Soft-Coated Wheaten Terriers.10 The strong correla-
this does not differ substantially from their rank in the tions between canine breeds and forms of OCD we
overall hospital population (3), it is dramatically dif- detected strongly suggest a genetic basis for OCD,
ferent from the breed rank in our Behavior Clinic pop- albeit, in part as the result of genetic limitations and
ulation (22), suggesting that when a Siamese cat is subsequent potential decreases in genetic heterogene-
evaluated because of a behavioral problem, the behav- ity associated with breed.
ior is likely associated with OCD. Siamese cats were As is true for humans, first-degree relatives usual-
most often involved in ingestion of fabric, supporting ly have a different form of OCD than the proband,
other findings regarding increased prevalence of OCD which supports the hypothesis of a heritable, neuro-
in Oriental-breed cats,18 but there were too few mem- chemically variable basis for OCD. That 50% of the
bers of each breed to reach breed-related conclusions. dogs in this study for which familial data were known
It is interesting that the only Bengal cat in the study had a relative affected with some form of OCD strong-
population had self-mutilation and urine marking. ly suggests 2 important points: certain breeds of dogs
These are both anxiety-related conditions and may appear to have a high prevalence of OCD, perhaps
have some association with the relatively recent higher than that in the human population, and a larg-
domestication of this breed. Most cats affected with er proportion of canine relatives are affected than
OCD had self-mutilation or excessive grooming. No appears true for humans. This strongly suggests a
cats were reported to have signs of hallucinating; how- genetic component for OCD in dogs.
ever, hallucinations may have been associated with tail Results of recent studies indicate that OCD in
chasing. Most owners of these cats reported that the humans is the result of dysfunction of genes involving
cats acted as if something was on or near the cat’s tail neurochemical and intracellular regulatory systems.26,27
and that the cat was either trying to chase this entity or Similar complex regulatory systems that have a genet-
escape it. Accordingly, feline hallucinations may not ic, heritable basis have also been reported for dogs28
have been adequately identified in this study. and may be involved in OCD.29
Unlike cats, few dogs had OCD after trauma or Human OCD has been postulated to be caused by
social-situational distress or upheaval, and few had aberrant serotonin metabolism.30-32 Accordingly, treat-
concurrent behavioral diagnoses involving elimination ment has been directed at affecting serotonergic metabo-
or social relationships with other dogs. These data sug- lism; pharmacological agents used for treatment are fair-
gest that the behavioral characteristics, neuroanatomic ly specific and affect subclasses—primarily the 5-HT1A
regions affected, and molecular and neurogenetic class—of serotonin receptors. Neuropharmacologic
mechanisms of OCD may differ for dogs and cats. Two approaches to treatment have sought to address such reg-
dogs had OCD after physical trauma. In both dogs, the ulatory abnormalities by augmenting serotonin through
trauma consisted of abusive training (hanging by a the use of TCAs and SSRIs.33-39 The key to the success of
choke collar). That 2% of this population of dogs with the specific TCAs and SSRIs over other classes of med-
OCD was subject to such abuse should be of concern ication is that they use the same second messenger sys-
to all veterinarians. tems and transcription pathways that are used to develop
One pet-store dog had profound coprophagia, sug- cellular memory (ie, learning).40,41
gesting that at some point coprophagia may have rep- While the best design for comparing drug efficacy
resented a nutritional strategy. Of the 103 dogs, few is a prospective, placebo-controlled, double-blind
(approx 10%) had a putative neurologic disorder, study, other statistical comparisons can be made if cri-
physical condition, or potentially painful disorder teria for switching medications are consistent, as was
associated with OCD, which could either be primary or the case here. Such techniques are underused in veteri-
secondary to OCD. One dog had a diagnosis of irrita- nary medicine, which is unfortunate since the funding
ble bowel syndrome, a diagnosis that may be simply a and large enrollment pools required for the former are
1450 Scientific Reports: Retrospective Study JAVMA, Vol 221, No. 10, November 15, 2002
SMALL ANIMALS
OCD respond well to the TCA, clomipramine,7,11,18,25 tions in 3 to 5 days, peak plasma concentrations are
and to the SSRI, fluoxetine.42-46 Results of the study attained in approximately 1 to 3 hours, the half-life of
reported here indicated that clomipramine was superi- the parent compound is 1 to 16 hours, and the half-
or for treatment of OCD in dogs, compared with life of the active intermediate metabolites is 1 to 2
amitriptyline. The difference in efficacy is likely asso- hours.52,53 These data suggest that dogs may require
ciated with specificity for the serotonin 1A subtype (5- higher dosages or more frequent dosing than do
HT1A) receptor of the parent compound and at least 1 humans treated with such medications. Should the
of the intermediate metabolites that acts as a SSRI.35,40 medication be discontinued, relapses occur in many
This specificity may also be responsible for the success cases.8,13 Signs also worsened or became more pro-
of fluoxetine in the treatment of some forms of nounced in stressful or anxiety-inducing circum-
OCD,47,48 although our sample size was not sufficient to stances for some patients in our study. Use of
test this hypothesis. clomipramine to treat OCD in animals is extralabel
Adverse effects appear rare in canine patients; the usage in the United States.
most common adverse effects have been gastrointesti-
nal disorders.11,49 Use of TCAs is contraindicated in ani- a
b
Available from corresponding author upon request.
mals with a history of urinary retention and severe, Clomicalm, Novartis Animal Health, Greensboro, NC.
c
SAS, SAS Institute Inc, Cary, NC.
uncontrolled cardiac arrhythmias.50 d
Amitriptyline, Stuart, Wilmington, Del.
It is surprising that amitriptyline was at all effica- e
Clomipramine, Ciba-Geigy, Summit, NJ.
cious (32/54 animals) in the treatment of OCD in our f
Fluoxetine, Eli Lilly & Co, Indianapolis, Ind.
study. Although not the drug of choice for treatment of g
Buspirone, Mead Johnson Pharmaceuticals, division of Bristol-
OCD in humans, this relatively nonspecific TCA may Myers Squibb Co, Princeton, NJ.
h
sufficiently decrease nonspecific anxiety so that Alprazolam, Upjohn, New York, NY.
i
Hydroxyzine, Roering, New York, NY.
patients can learn to change their behavior. At present, j
Doxepin, Roering, New York, NY.
we have no way to evaluate how advanced OCD is k
Sertraline, Pfizer Animal Health, Groton, Conn.
when it is diagnosed in dogs and cats. Early signs may l
Pentazocine, Winthrop, NC.
go unnoticed. The success associated with treatment m
Diazepam, Roche, New York, NY.
with amitriptyline may reflect that some animals have
less severe forms of OCD and fewer comorbid diag- References
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sive-compulsive disorders in dogs and cats. Vet Clin North Am Small
concurrent behavioral diagnoses improved when treat- Anim Pract 1991;21:401–413.
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39.1% of the feline patients, had concurrent behavioral 40–44.
diagnoses. When considered in light of the relative role 3. Overall KL. Recognition, diagnosis, and management of
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4. Overall KL. Recognition, diagnosis, and management of
these 2 species and the divergent evolutionary and obsessive-compulsive disorders. Canine Pract 1992;17(4):39–43.
domestication histories of dogs and cats, caution is 5. Hewson CJ, Luescher UA, Ball RO. The use of chance cor-
urged in assuming that OCD is mechanistically the rected agreement to diagnose canine compulsive disorder: an
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1452 Scientific Reports: Retrospective Study JAVMA, Vol 221, No. 10, November 15, 2002