Introduction

Diagnoses are not diseases; correlation is not causality. Conditions for which there is putative etiologic and pathophysiologic heterogeneity (multi-factorial disorders) are complex, and there is nowhere that this is more true than for the topic of fears, phobias, and anxieties. Diagnosis and treatment will be, by definition, complex. Fear and anxiety are probably closely related, but may not be identical at the neurophysiological level. It is worth remembering that when one diagnoses a problem related to fear, anxiety, or aggression one is doing so at the level of the phenotypic or functional diagnosis; when psychotropic medication is used such conditions are treated at the neurophysiological level. Phenotypic (functional, phenomenological) diagnoses are open to various mechanistic bases of all subsequent levels. Some of these more reductionistic levels can be tested using treatment (specific pharmacologic agents), but few phenotypic diagnoses can be specifically tested using behavior modification. Regardless, the logic for using very specific phenomenological diagnoses related to fear and anxiety is to (a) enumerate and identify the particular behavioral manifestation that needs to be altered or assessed, and (b) to identify areas where specific behavioral intervention can be useful.

Neuroanatomy of fear, anxiety, and obsessive-compulsive disorder: The extent to which learning and memory play roles in fear, anxiety, phobias, and OCD has been poorly studied because it is difficult to do so given the complexity of the neurochemical systems involved. What is know is that: (1) a functioning amygdala is required to learn fear, (2) a functioning forebrain is required to unlearn fear (i.e., to effect habituation), and (3) many human fears appear to be the result of the inability to inhibit a fear response. Accordingly, it has been hypothesized that fear is, in part, due to chronic amygdala over-reaction and, or failure of the amygdala to turn off after the threat has passed. The specific neuroanatomy of a fear response involves the locus ceruleus (LC), the principal norepinerphrinergic (noradrenergic) nucleus in the brain. Dysregulation of the LC appears to lead to panic and phobias in humans. The LC directly supplies the limbic systems and may be responsible for many correlated "limbic" signs. Patients with true panic and phobic responses are more sensitive to pharmacologic stimulation and suppression of the LC than are controls.

Some dogs and cats respond either more quickly to a stimulus, or react more intensely to a given stimulus than other dogs. At some level this "hyper-reactivity" is probably truly pathological and represents yet another phenotypical manifestation of some neurochemical heterogeneity associated with anxiety. These dogs are different and it can be very difficult or impossible to interrupt them once they reach that level where they "fire" indiscriminately. For cats, stimulation of the VMH, VLH, and PLH can have profound stereotypic consequences (active biting attach v quiet attack). The degree of stimulation has made cats excellent models for "kindling" behaviors, but this also means that, once stimulated, these cats stay reactive for a period of time that can exceed 24 h. Intense anticipation is critical for these individuals. Other animals just react with a higher level of intensity, but may still be workable. Behaviors that can be used to ascertain levels of reactivity or arousal include alertness (hyper-vigilance), restlessness (motor activity), vocalization (whining / growling in dogs; howling / hissing in cats), systemic effects (emesis, urination, or defecation), displacement or stereotypic behaviors, and changes in content or quantity of solicitous behaviors.

Separation anxiety as a model case: First and foremost, it is critical to realize that client complaints like elimination inside the house and destruction are both non-specific signs that can occur for a variety of reasons. Non-specific signs, themselves, are extremely useful because they allow the client and the practitioner to keep a log of the patient's behaviors and to chart progress, or lack there of. Also, the pattern of the signs can also be essential in helping the clinician decide if the patient meets the necessary and sufficient criteria. For example, if the practitioner thinks that the destruction and elimination are associated with separation anxiety, having the client monitor each of the signs and the frequency with which they occur can insure that the correct diagnosis is made and treated. If the client notes that none of the separation anxiety-associated behaviors ever seem to occur in a way that allows them to answer the questions on the screen in the affirmative, then the dog likely does not have separation anxiety.

Alternative diagnoses / conditions / causes to rule out for the non-specific signs of "elimination" and "destruction" involved in separation anxiety.

The first step in making the diagnosis is to learn the pattern for each of these transgressions and then to ask if the pattern meets the necessary and sufficient criteria for a specific diagnosis. By using these conditions practitioners can ask if any signs exhibited by the patient-even if the signs are odd and, or rare-meet these definitional criteria. If the signs meet the criteria-even if the signs are not commonly associated with the condition-the dog is likely afflicted with the condition, regardless of whether it involves aggression, elimination, obsessive-compulsive behavior patterns, et cetera.

Necessary and sufficient conditions for defining selected behavioral conditions listed above:

1.  Separation anxiety-Necessary conditions: Physical or behavioral signs of distress exhibited by the animal only in the absence of, or lack of access to the client. Sufficient conditions: Consistent, intensive destruction, elimination, vocalization, or salivation exhibited only in the virtual or actual absence of the client; behaviors are most severe close to the separation, and many anxiety-related behaviors (autonomic hyperactivity, increased motor activity, and increased vigilance and scanning) may become apparent as the client exhibits behaviors associated with leaving.

2.  Incomplete house training-Necessary conditions: consistent, and age-inappropriate elimination in undesirable locations or at undesirable times that is not associated with any lack of access or opportunity, other behavioral conditions, or any physical or physiological condition. Sufficient conditions: the above in an animal for whom this has always been true and for whom the complaint does not involve a change in behavior.

3.  Marking behavior-Necessary condition: urination or defecation that occurs in frequencies and, or locations inconsistent solely with evacuation of bladder and bowel, but consistent with social and olfactory stimuli. Sufficient condition: repeated urination or defecation, associated with species-typical postures distinct form those used in simple elimination, that occurs in frequencies and, or locations inconsistent solely with evacuation of bladder and bowel, but consistent with limited and identifiable social and olfactory stimuli.

4.  Obsessive-compulsive disorder-Necessary Condition: Repetitive, stereotypic motor, locomotory, grooming, ingestive, or hallucinogenic behaviors that occur out-of-context to their "normal" occurrence, or in a frequency or duration that is in excess of that required to accomplish the ostensible goal. Sufficient Condition: As above, in a manner that interferes with the animal's ability to otherwise function in his or her social environment.

It is important to note that for all of these conditions, distress and anxiety may be at the neurobehavioral genetic root. The extent to which non-specific signs are shared among diagnoses and the manner in which non-specific signs cluster may be clues about shared underlying mechanisms. Understanding these mechanisms would lead to better treatment.

Daily logs in combination with video surveillance can be extremely useful in elucidating patterns of the condition. Understanding these patterns is critically important for treatment. For example, if the client learns that the dog can be left for 4 hours without elimination, but not 6 hours then they can avoid longer absences. Avoidance is key in the treatment of almost all behavioral problems since every time the behavior-no matter how undesirable or abnormal-is repeated, the dog will be reinforced for the behavior. Furthermore, learning at the molecular level is reinforced every time the animal repeats the behavior or is rewarded for repeating it.

Studies that have examined client behavior and the development of separation anxiety have demonstrated no association between the former and the development of the latter. Studies specifically seeking to find causal associations between client attachment to their pet and separation anxiety have failed to do so, although one manifestation of separation anxiety, that involving "virtual" absences may involve dogs that are abnormally needy.

Some dogs respond either more quickly to a stimulus, or react more intensely to a given stimulus than other dogs. The extent to which dogs "panic" is being investigated currently, but true panic may be a co-morbid diagnosis for a variety of conditions (e.g., thunderstorm phobias, noise phobias, separation anxiety, fear of humans or dogs, et cetera). In one study examining some of the cases in which panic could be involved, the observed frequency of a co-morbid diagnosis of any combination of separation anxiety, thunderstorm phobia, and noise phobia was significantly different than expected were the associations independent. This finding supports that noise and thunderstorm phobias are different from each other and affect the frequency and intensity of related behaviors in co-morbid diagnoses differently. Also, the interaction of multiple pathological responses to noise likely either reflects an altered, dysfunctional, underlying neurochemical substrate, or is the result of one. The extent to which such dynamic interactions shape expressed behavioral phenotypes is supported by differential responses to behavioral medications. Accordingly, anticipation and early treatment is critical for these individuals. It is likely that the high co-morbidity of separation anxiety and noise and thunderstorm phobias is a function of some arousal system, so thorough behavioral screening and early intervention is essential for any dog exhibiting any sign of increased reactivity to noises.

Prior to incorporating behavioral pharmacology into any treatment program, the practitioner should have: (1) a reasonable diagnosis of list of diagnoses, (2) an appreciation for the putative mechanism of action of the available behavioral drugs, (3) a clear understanding of any potential side effects, and (4) some clear concept of how the drug that they are considering will be specifically alter the behavior in question. Most medications used to treat separation anxiety are tricyclic antidepressants or selective serotonin re-uptake inhibitors (TCAs or SSRIs). One of the drugs used most successfully in the treatment of canine separation anxiety is clomipramine. Clomipramine is a TCA that is relatively specific in its effects on the serotonin receptor most associated with anxiety (the 5-HT_1A subtype receptor). In placebo-controlled, double-blind studies clomipramine, in combination with passive behavior modification like that described here, successfully controlled the signs of separation anxiety after 2-3 months of treatment, and dogs treated with clomipramine improved at a significantly greater rate than did dogs treated with the passive behavior modification, alone. Prolonged treatment may be necessary for some pets to prevent relapse, but with good physical and laboratory monitoring there are very few associated risks.

It should be noted that treatment for noise and thunderstorm phobias is on an as needed basis, but that for separation anxiety is daily. Combination treatment is likely to be the most successful treatment for patients with these conditions. Key to the success of combination treatment is three-fold: (1) use the benzodiazepines sufficiently early before the provocative event that the dog does not react before receiving the medication (e.g., if there is a 50% chance or greater of the noise occurring or if you can medicate the dog 2 h before the anticipated noise; (2) give smaller doses of the benzodiazepines more frequently so that the intermediate metabolites can also be efficacious and reach a steady state (e.g., given ½ the dose 2 hours before the event and ½ the dose 30 minutes before the event); and (3) use the TCAs or SSRIs for a sufficiently long time to minimize the risk of any recidivistic event (e.g., a minimum of 4-6 months). The side effects are relatively minor compared with the potential for either worsening of the condition or recidivism in the absence of potentially beneficial medication.

References

References are available on request.