The question “Is it medical or behavioral?” is often part of our clinical reasoning. However, this question does not always have a simple answer. The reciprocal link between behavior and the inflammatory and immune response has been extensively documented in the scientific literature, and it is known to be influenced by the host microbiome.^1-3 Activation of proinflammatory cytokines induces a depressed state (sickness), which helps the individual to cope with the disease (e.g., an infection by exogenous pathogens) that triggered the inflammatory response. Circulating proinflammatory cytokines can enter the brain, where they have a direct inflammatory action and stimulate the production of other pro-inflammatory cytokines and prostaglandins.

Although this inflammatory response does not produce tissue damage, it induces a negative behavioral change. Circulating pro-inflammatory cells also exercise their action on the brain indirectly through neuronal pathways, for example, activating a vagal response.¹ The endogenous microorganisms constituting the intestinal microbiome may influence the behavior of their animal hosts through a similar action.

The presence of pain (e.g., osteoarthritis, trauma, otitis, neuropathic pain) is of particular relevance, not only because of the involvement of inflammation, but also because of the possible learned association between touching/handling an animal and triggering pain. The animal may therefore learn that interacting with other individuals is a potential source of pain (classical conditioning) and may display fear and defensive pain-related aggression. Painful condition, e.g., hip dysplasia, have been associated with an onset of aggressive behavior in dogs with no history of aggression. When compared with dogs in pain with a history of aggression preceding the pain-inducing condition, dogs with no previous history showed less warning signs preceding aggression, were more likely to display aggression when handled, and showed more defense signs in their body posture.⁴

Dogs with a late onset of fear of loud noises should be screened for possible presence of musculoskeletal pain, as suggested by Fagundes et al.⁵ Radiological signs of osteoarthritis are very common in cats, even in absence of clinical signs,⁶ and acute or chronic pain has to be considered as a possible contributing factor to behavior changes observed in cats (e.g., house soiling).

Metabolic disease should also be ruled out as a possible cofactor for observed behavior changes in dogs and cats. Aggression has been reported to be a sign of hypothyroidism in some cases,⁷ but no significant difference has been found between aggressive and non-aggressive dogs in the concentrations of biomarkers most commonly used to diagnose canine hypothyroidism.⁸

Pathologies that alter perception and/or proprioception, neurological and sensory problems, should be investigated as possible causes of or contributing factors to behavioral changes, including aggression. Because of the link between immune response and behavior changes, inflammatory diseases (e.g., dermatitis, gastroenteritis…) comorbid to aggression or other behavior problems should be adequately treated.

Feline interstitial cystitis (FIC) represents the perfect example of a disease in which it is not possible to draw a clear line between behavior and medical causes and symptoms. The environmental distress experienced by cats with FIC contributes to the creation of painful lesions in the urine bladder that in turn worsen the distress, creating a syndrome that can be effectively addressed only through a multimodal (behavioral and medical) treatment.⁹

Treatment that affect the immune response may cause long-term changes in the behavior of dogs.³ Dogs with a history of corticosteroid treatment (of at least one week) are significantly more likely to be in a negative affective state and to exhibit aggression towards people than dogs that did not receive corticosteroids.¹⁰ A late onset of behavior changes in geriatric patients can be secondary to a comorbid medical problem or a sign of canine cognitive dysfunction.

Behavioral changes can be a sign of medical diseases and, therefore, should not be overlooked even in absence of typical medical symptoms, in order to maximize the health and welfare of our patients.

References

1.  Dantzer D, O’Connor JC, Freund GC, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9:46–56.

2.  Foster JA, McVey Neufeld K. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013;36:305–312.

3.  Siracusa C. Treatments affecting dog behavior: something to be aware of. Vet Rec. 2016;179:460–461.

4.  Camps T, Amat M, Mariotti VM, Le Brech S, Manteca X. Pain-related aggression in dogs: 12 clinical cases. J Vet Behav. 2012;7:99–102.

5.  Lopes Fagundes AL, Hewison L, McPeake KJ, Zulch H, Mills DS. Noise sensitivities in dogs: an exploration of signs in dogs with and without musculoskeletal pain using qualitative content analysis. Front Vet Sci. 2018;5:17.

6.  Kerwin SC. Osteoarthritis in cats. Top Companion Anim Med. 2010;25:218–223.

7.  Fatjó J, Stub C, Manteca X. Four cases of aggression and hypothyroidism in dogs. Vet Rec. 2002;151:547–548.

8.  Radosta LA, Shofer FS, Reisner IR. Comparison of thyroid analytes in dogs aggressive to familiar people and in non-aggressive dogs. Vet J. 2012;192:472–475.

9.  Buffington CA. Idiopathic cystitis in domestic cats beyond the lower urinary tract. J Vet Intern Med. 2011;25:784–796.

10.  Notari L, Burman O, Mills D. Is there a link between treatments with exogenous corticosteroids and dog behaviour problems? Vet Rec. 2016;179:462.