Is it medical or is it behavioral? (Proceedings)

Monitoring and assessing behavioural signs is a critical component of every veterinary visit. Virtually any medical condition can present with behavioural signs and behavioural signs may be the first indicators of disease (e.g. irritability, anxiety, aggression, anorexia, depression, decreased response to stimuli, housesoiling, night waking, etc). Behavioral signs can also be used to monitor improvement or response to therapy. Therefore to insure early diagnosis and intervention, owners should be asked about behavior problems at each visit and pet owners should be encouraged to seek guidance as soon as signs arise.

Rather than directly initiating the signs, medical factors may play a contributory role in how a pet might behave in certain situations or respond to specific stimuli which may vary with genetics, previous experience, environment, the stimulus, etc. Signalment is also an important consideration since, for example, the onset of behaviour problems in older pets may increase the suspicion of a medical cause.

Stress and its effects on health and behaviour

While it is common to consider the effects of disease on behaviour, both acute and chronic stress can have an impact on health as well as behaviour, through its effects on the HPA axis and activation of the noradrenergic system. Stress is an altered stated of homeostasis which can be caused by physical or emotional factors. Stress triggers psychological, behavioural, endocrine and immune effects that are designed to handle stress. The first component is the HPA axis, in which the hypothalamus releases corticocotropic releasing hormone (CRH), which stimulates the release of ACTH. The second component is the sympathetic-adrenal-medullary system which releases noradrenaline and adrenaline. Noradrenaline is associated with sensitization and fear conditioning. If stress is persistent or chronic there is continued stimulation of the HPA axis and an increase in cortisol with a depression of the catecholamine system, leading to alterations in the immune system and the possible development of stress related diseases. In humans there may be a correlation between stress and poor health, poor immune function, cardiovascular disease, and cellular aging. In pets, stress has been shown to be a contributing factor to some forms of feline interstitial cystitis (FIC), gastrointestinal diseases, dermatologic conditions and behavioral disorders.

Cats with FIC have altered bladder permeability during stress when compared to cats in an enriched environment. An increase in plasma norepinephrine has been demonstrated in cats with interstitial cystitis. Cats receiving MEMO (multimodal environmental modification) had a significant reduction in FIC, respiratory disease, fearfulness, and nervousness and less inflammatory bowel disease and aggression. In a placebo controlled study there were less bouts of FIC when a Feliway™ diffuser was installed.

Stress and anxiety can alter bacterial flora, inhibit gastric emptying, increase colonic activity, and increase intestinal permeability leading to irritable bowel syndrome, gastrointestinal reflux, stress induced hypersensitivity, and heartburn. In pets, acute fear and anxiety in pets can lead to a decrease in appetite or anorexia such as what might be observed in a pet with separation anxiety that does not eat until the owner returns home. A more chronic form of anxiety may arise with the introduction of a new pet or moving (especially in cats) while the loss of a human or pet in family can cause a "grief" response in some dogs and cats that can affect appetite and health. Stress and anxiety can also lead to diarrhoea, vomiting, colitis, housesoiling, and crate soiling. Picas, polyphagia, and polydypsia may also be stress induced.

In humans, anxiety might contribute to pruritus in humans, since stress can lead to an increase in cytokines, release of opioids, serotonin and other vasoactive peptides, and a reduction in cortisol especially in atopic individuals. A link has also been found between stress and increased epidermal permeability. If this were also the case in dogs, lead a genetically predisposed individual to develop atopic disease. Opioid peptides released during stress may further potentiate pruritus.

Chronic anxiety, stress, conflict and frustration, may lead to behavioral disorders in humans including panic disorders, separation anxiety, social and other phobias, obsessive-compulsive disorders, generalized anxiety disorders, post-traumatic stress disorders, impulse control disorders, and sleep disorders which likely have similar animal correlates. A recent study in dogs identified higher prolactin levels with chronic stress and high anxiety, that was associated with stereotypic and displacement behaviors, fear aggression and autonomic signs. Lower levels of prolactin were associated with fear and phobias.

Medical causes of behavioral signs

A change in personality or mood, inability to recognize or respond appropriately to stimuli, and loss of previously learned behavior might be indicative of forebrain involvement. Alterations in awareness, responsiveness to stimuli and consciousness might arise from any disease that involves the brainstem or forebrain. Altered responsiveness to stimuli can also arise from sensory or motor dysfunction. The limbic system is associated with emotion. Diseases affecting the hypothalamus can also have an effect on behavior. Therefore any disease that directly (intracranial) or indirectly (extracranial) affects the CNS can affect behavior. While there may be identifiable medical signs such as alterations in mental status (stupor, coma), cranial nerve and sensory deficits, seizures, tremors or motor deficits (gait abnormalities, weakness, altered appetite, drinking, and elimination or emesis), this is not always the case. In addition, when pets are presented with behavior changes such as vocalization, unexpected aggression, or loss of housetraining, a neurological cause should be suspected if the pet also sleeps more, appears blind or lost, paces constantly, circles to one side, head presses, or has an increase in thirst. Pets should also be monitored over time, since many neurological problems are progressive and new signs may arise. Diseases that affect behavior may be intracranial (e.g. congenital, neoplasia, degenerative) or extracranial (e.g. toxin, hepatic encephalopathy, endocrinopathies, or disease that affect brain oxygenation). Primary behavioral diseases or pathology may also exist such as compulsive or depressive disorders. Cognitive dysfunction syndrome (CDS) is a degenerative neurologic disorder of senior pets which will be discussed in a later seminar.

Endocrine diseases, including hyperthyroidism, hyperadrenocorticism and hypothyroidism can also contribute to signs of anxiety. Hypothyroidism may increase 5HT turnover so that behavior changes may be due to alterations in serotonergic activity. Since cortisol inhibits TSH release, stress can also diminish thyroid levels. Unless low thyroid levels can be documented, thyroid therapy is not likely indicated..

Pain can be identified from either behavioral or physical signs. Studies have shown that behavioral measures are an accurate means of measuring pain, and pain assessment scoring systems have been developed both for the veterinary office and for pet owners. A trial with a product for pain management can help to confirm the diagnosis.

Medical problems and drug therapy can increase or decrease appetite or drinking and can lead to picas and licking. Pets that lick excessively may have a GI disturbance, including oral or esophageal disease or nausea. A therapeutic trial with a novel protein or hydrolyzed protein diet (d/d or z.d), an intestinal diet (i/d) or an H2 antagonist might help rule out a gastrointestinal cause.

Coprophagia may be a normal behavior for some dogs. However when a dog is eating feces, especially its own, gastrointestinal, nutritional and exocrine pancreatic insufficiency, should be ruled out. Assessing stool consistency, volume, straining and concurrent medical signs can help to determine if there is a medical cause. Some pets on a calorie restricted diet may also develop coprophagia.

Housesoiling can often be precipitated by medical problems. In a retrospective study of cats with problem elimination behavior, sixty percent of the cats had a history of FUS/FLUTD.20 Inappropriate elimination can also be due to any medical problem that causes an increased volume of urine or stool, increased discomfort during elimination, decreased control, or diseases that affect cortical control. Urinary tract disease is unlikely to be a factor in urine marking in cats. However, systemic illnesses which lead to alterations in behavior could contribute to marking in dogs or cats by altering hormonal states or increasing anxiety. Assessment of every elimination disorder should begin with a physical examination, cbc, biochemical profile and urinalysis, as well as any imaging or scoping that might be indicated. In marking cats, evidence of penile barbs or odorous urine might indicate a hormonal disorder. Although, treatment of the medical problem may resolve the problem, the soiling may persist once pets have learned a new routine.

Self traumatic disorders (such as tail mutilation, nail biting, psychogenic alopecia, acral lick dermatitis, face and neck scratching, flank sucking) can have a medical cause such as pain (possibly neuropathic), pruritus, infectious or immune mediated. Differentiating medical causes from behavioral is most difficult when there are no primary lesions and the problem is non-seasonal. If diagnostic tests do not reveal a medical cause, response to therapy may be a diagnostic option.

Is it medical or is it compulsive?

Compulsive disorders can only be diagnosed by excluding those medical problems that might cause the signs. Compulsive disorders may arise out of anxiety, conflict, or frustration. Conflict occurs when the pet is motivated to perform two opposing behaviors. Frustration refers to a situation in which the pet is motivated to perform a behavior but is not able to do so. In these situations the response might be a displacement behavior, where the response is inappropriate or out of context with respect to the stimulus (e.g. tail chasing). Pet owners may further aggravate the problem by reinforcing or punishing (which might increase anxiety and conflict).

Compulsive disorders are those in which the displacement behaviors are exhibited independent of the original context, have no apparent goal and have an element of dyscontrol in either the initiation or termination of the behavior. They may be repetitive, exaggerated, sustained or so intense that they might be difficult to interrupt. Although it has been suggested that stereotypies might be a coping mechanism leading to a reduction in arousal, this is rarely the case. Compulsive disorders are generally associated with stress or anxiety and may affect physical health. There appears to be a genetic predisposition to the development of stereotypic behaviors (e.g. wool sucking in oriental breeds of cats, spinning in Bull Terriers, tail chasing in German Shepherds).

It is possible that there is a common pathophysiology, that neurotransmitters vary between presenting complaints, or that there may be changing involvement as the problem progresses. Beta-endorphins, dopamine, and serotonin have all been implicated.

a) Differentiating neurologic from compulsive

Some of the most difficult and frustrating cases to diagnose are the neurological signs, such as fly snapping, tail chasing, pouncing, fixed staring, tail chasing, star gazing, head shaking, spinning or checking. Another group of signs are the head tremors of Boxers, Bulldogs and Dobermans, and more generalized idiopathic tremors such as those seen in "white shaker dogs" and in Great Danes.44,45 The greatest diagnostic difficulty arises when no medical causes can be identified. This then leaves the clinician to determine whether the pet may have a behavioral disorder (e.g. compulsive) or a neurological disorder such as a partial or psychomotor seizure. Simple partial seizures are due to cerebrocortical disease but do not have altered consciousness, while partial complex seizures may have altered levels of consciousness and may have a behavioral component such as hallucination or aggression ("rage"). A therapeutic response trial with phenobarbital, potassium bromide or perhaps clonazepam, gabapentin or carbamazepine might be a useful diagnostic tool, especially when there is loss of consciousness, no pattern or identifiable initiating factor and there are phases that might be indicative of a seizure focus (e.g. aura or post ictal).

Differentiating dermatologic from compulsive

Self-traumatic disorders including biting, chewing, licking or excessive barbering can lead to skin lesions and alopecia. Medical differentials include diseases that lead to pain or pruritus (e.g. hypersensitivity reactions, neuropathies), infections (e.g. bacterial, fungal, parasitic), endocrinopathies, tumors, or skin disorders associated with systemic diseases (e.g. hepatocutaneous syndrome). When there are no primary lesions, medical and behavioral causes may be particularly difficult to differentiate.

When presented with a cat that has hair loss or licking, the diagnostic workup should begin with an examination, anal gland expression, blood and urine testing and a viral profile. A dermatologic evaluation, including a trichogram, fungal culture, skin scraping and possible biopsy would also be indicated. Assuming no abnormal findings, a therapeutic trial of a parasiticide and a food trial of 8 weeks duration, followed by a steroid response trial might be the only practical way to differentiate pruritus from a behavioral cause. Using this protocol in 21 cases presented for psychogenic alopecia, 76.2% had a medical etiology, 9.5% were compulsive and 14.3% were combined medical and behavioral. A combination of adverse food reaction and atopy (6 cases) was the most common diagnosis. Some cats had atopy, parasitic hypersensitivity or an adverse food reaction alone. Although biopsies indicated an inflammatory response for most medical cases, some cats with histologically normal skin had a medical cause.

For acral lick dermatitis (ALD) in dogs, a physical exam, blood and urine screening and a dermatologic workup, including a skin scraping, fungal culture, cytology and biopsy may all be indicated. When diagnostic tests do not reveal the underlying cause, therapeutic trials with antibiotics, pain medication, anti-inflammatory drugs, parasiticides and / or food trials may be necessary. In some cases complete resolution can be achieved with long term antibiotic therapy alone, indicating that even if the original cause was behavioral, that infection was the maintaining factor. Owner supervision and preventive mechanisms such as bandaging or E-collars may also be necessary to allow the lesions to heal. In one of our cases, a mast cell tumor was misdiagnosed as ALD for over 2 years. In a recent publication, 6 dogs presumed to have ALD were diagnosed with lymphoblastic lymphoma, irritation from a Kirschner pin, furunculosis, a mast cell tumor, Leishmaniasis and Sporotrichosis.

Tail mutilation and hyperesthesia in cats may also be a conflict induced or compulsive disorder requiring a diagnostic workup similar to ALD and psychogenic alopecia. In addition, neurologic disorders (central, spinal) and neuropathic pain are also a consideration. For nail biting, any disease of the nails or nail beds, (immune, inflammatory or infectious including in particular Malassezia) must first be ruled out.

Treatment of compulsive disorders

Behavioral management combined with drug therapy is required for the successful control of most compulsive disorders. As a general rule, pets with compulsive disorders, should receive a more structured and stimulating daily routine. Some pets may be particularly sensitive to inconsistency or lack of predictability in their daily schedule or in their interactions with their owners. Therefore the daily routine should include regular sessions of social interaction with people (in the form of training, play and exercise) or with other pets. Owners might be encouraged to focus on play that simulates the normal activities of the species or breed, (e.g. pulling carts, retrieving, mousing). Following social interaction and training, scheduled periods of inattention may help the pet learn to expect and accept spending time alone. At these times it can be useful to have a favored bedding area, and to provide a variety of enrichment toys (feeding, chew and manipulation toys). In fact working for some or all of the daily food is an important component of treatment for most compulsive disorders.

Training should encourage behaviors that are desirable rather than punishing behaviors that are undesirable. Casual and inconsistent owner interactions should be replaced by a program of predictable rewards where the owners insure that all rewards including affection, toys, and food are only given for behaviors other that are incompatible with the compulsive disorder (e.g. resting on a mat, playing with a favored toy). Clicker training can help more immediately reinforce desirable while a leash and head halter for dog or a harness for cats can be used to prompt the desired response as well as to inhibit, disrupt or prevent undesirable behavior.

Clomipramine at 1-2 mg/kg bid for dogs or .5 mg/kg in cats or a selective serotonin reuptake inhibitor (SSRI) such fluoxetine at 1-2 mg/kg once daily for dogs or .5-1 mg/kg per day for cats are usually the first drugs of choice for compulsive disorders in dogs. After 4-6 weeks, if there is insufficient response and no adverse effects, up to double the dose may be needed. Side effects may include gastrointestinal signs include inappetance, lethargy or neurological signs such as tremors or seizures and these drugs should not be used concurrently with MAO inhibitors, other antidepressants or narcotics. SSRI's inhibit P-450 enzyme systems and may reduce clearance of drugs metabolized by these enzymes.

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