December 20, 2011
Note: I wrote this review in 2011 during my graduate work in animal behavior and psychology at Hunter College. The research is older, but the core finding still matters to how I work: aggressive dogs, especially those showing defensive, fear-based aggression, often have measurably different stress and serotonin levels. Fear is not a choice, and it is not a training failure. That is why my program focuses on reducing the underlying anxiety, not just suppressing the behavior.
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The Neurobiology of Pathological Aggression in Dogs:
A Review of a Study Entitled “Blood concentrations of serotonin, cortisol and dehydroepiandrosterone in aggressive dogs” by Rosado, et al.
Introduction
In 2009 there were approximately 77.5 million dogs living in homes in the United States, with 39% of households having at least one dog (ASPCA, 2009). We have more dogs per capita in the United States than in any other country in the world (Beaver, 1999). Unfortunately, with this high rate of dog ownership comes the increased societal risk of dog bite incidents, which occur approximately 4.5 million times per year (Sacks, Kresnow & Houston, 1996; Quinlan & Sacks, 1999). Approximately 800,000 bites per year (one out of every six) cause serious enough injury to require medical attention (Weiss, Friedman & Coben, 1998). The fifth most common reason for emergency room visits by children is a dog bite (Weiss, et al., 1998).
In addition to the toll that dog bite incidents take on society as a whole, dogs who express aggressive behavior tend to suffer emotionally from fear and/or anxiety, leading to a low quality of life (Rosado, Garcia-Belenguer, Marta Leon, Gema Chacon, Villegas & Palacio, 2010a). The owners of aggressive dogs also face potential emotional problems from the stress and anxiety of managing their dog and keeping others safe (Rosado, et al., 2010a). The majority of dog behavior problems presented to veterinarians and behaviorists involve aggressive behavior towards humans (Reisner, Mann, Stanley, Huang & Houpt, 1996), which has led to an increased interest in the aetiology of canine aggression.
Discussion
Identifying Pathological Aggression in Dogs
There are a number of research studies that have explored the biological mechanism of canine aggression (e.g., Rosado, et al., 2010a; Vermeire, Audenaert, Meester, Vandermeulen, Waelbers, Bart De Spiegeleer, Dobbeleir & Peremans, 2010; Jacobs, Van Den Broeck & Simoens, 2007). Since aggression is a normal part of a dog’s social behavior, it is important for these studies to first determine how to distinguish normal from pathological behavior (Jacobs, Van Den Broeck & Simoens, 2006). In a 2001 study entitled “Diagnosis and treatment of aggression in dogs and cats”, (Beata, 2001), an aggression test was established that is used in a number of other studies. In this test, dogs are considered normal if they first display a warning signal before biting, and only proceed to bite if provoked further, (Beata, 2001). The normal dog will also stop biting and display a stop signal to express that no further aggression will follow (Beata, 2001). Dogs who alter this sequence and show no warning signal and/or stop signal are classified as pathologically aggressive (Beata, 2001).
Article Summary
In the study by Rosado, et. al., published in 2010, the authors investigated whether the serotonergic system and the hypothalamic–pituitary–adrenal (HPA) axis are involved with aggressive behavior in dogs. The purpose of the study was to provide possible future diagnostic and treatment approaches for this type of behavior problem. The blood was tested for serotonin, cortisol and dehydroepiandrosterone (DHEA) levels (Rosado, et al., 2010a). Aggressive dogs showed significantly higher levels of cortisol, and significantly lower levels of serotonin in the blood, compared to normally behaving dogs, with the lowest levels found in dogs showing defensive forms of aggression (Rosado, et al., 2010a). Males were also found to have significantly higher DHEA levels and cortisol levels than females (Rosado, et al., 2010a).
Methods and Procedures
Rosado and colleagues obtained their dogs for this study from two veterinary teaching hospitals in Spain. A total of 80 dogs were used (52 males and 28 females), in the aggressive dog category, including 23 different breeds and mixes. The mean age was 4.9 years old (ranging from 3 months to 14 years). The control dogs included 19 dogs (8 males and 11 females) of nine different breeds. The mean age was 4.3 years old (ranging from 11 months to 9.3 years).
The first step in this study was to diagnose the dogs with aggressive or non-aggressive behavior. Diagnosis was made through a questionnaire given to the dog owners, focusing on three primary criteria: target, context and communication signals. All dogs were also given a medical examination to determine if any medical conditions were related to their aggression. After diagnosis, the dogs were placed in one of four categories: 1) SCA: social conflict-related aggression directed towards family members; 2) DA: defensive aggression towards unfamiliar people; 3) OA: offensive aggression towards unfamiliar people; 4) Other forms: including aggression related to medical causes. Blood samples were then collected from each subject and tested for levels of 5-HT, cortisol and DHEA.
Results
Within the aggressive dog group, 71.25%, were in the SCA category. In addition, 63.6% of the dogs in the aggressive group showed aggression towards other dogs, and 77.5% showed other behavior problems such as noise phobias, anxiety, fear and compulsive disorders. This information is outlined in Table 1, which shows the number of dogs displaying aggression within the different categories of aggression. The table is clear and well formulated.
A multifactorial multivariate ANOVA was performed, which found a significant effect of the factors of aggression (P<.01), and gender (P<.05) on the parameters in the study. There was no significant interaction between those factors. These results are shown in Table 2, which clearly shows the mean concentrations of biochemical variables according to the group and the gender of the animals.
The dogs in the aggressive category showed significantly lower serum concentrations of 5-HT and higher plasma concentrations of cortisol than the control dogs. Males also showed significantly higher plasma concentrations of DHEA and DHEA/cortisol ratio mean values than females. A significant effect was shown for the category of aggression, shown in Table 3 in the article. The table clearly shows the mean concentrations of the biochemical variables for each category of aggression compared to the control group.
Discussion
The discussion section of the article thoroughly discusses all relevant results in the context of prior research. They explain how the results support their own preliminary study of 28 aggressive and 10 non-aggressive dogs, where lower concentrations of 5-HT were found in the blood of the aggressive dogs (Leon, 2006; Leon, Garcia-Belenguer, Rosado, Chacon, & Palacio, 2008). A number of other studies were discussed that suggest an altered 5-HT activity is linked to aggression in dogs. One study found differences in the uptake of 5-HT2A radioligand in different brain areas of aggressive and non-aggressive dogs (Peremans, et al., 2003). Another study also found a difference between aggressive and non-aggressive dogs in the 5-HT uptake in the platelets (Rosado, et al., 2009).
The article discusses the fact that the majority of the dogs in the study, and those referred to animal behaviorists for aggression, are males. In the study, males as a whole (in both the aggressive and control groups) showed significantly higher plasma concentrations of DHEA and values of DHEA/cortisol ratio than did females. A study was referenced that suggested that testosterone may have a stimulatory effect and estradiol an inhibitory effect on adrenal androgen levels (Laughlin & Barrett-Connor, 2000).
A number of limitations were noted in regards to this study. First, the reliance on owner reports for clinical categorization of aggressive behavior. To counteract this limitation the authors also used the clinical history of the animals in their assessments. Next, the use of parametric tests for variables showing non-normal distributions, here with cortisol and DHEA, limited the generalization of the results. Finally, there was an unbalanced number of dogs in the different categories of aggression, which may have influenced the assessment of the role of gender in the different groups.
Summary and Conclusions
Overall this study was well formulated, and presented in a clear and concise manner in the article. The results showed that aggressive dogs had significantly higher levels of cortisol, and significantly lower levels of serotonin in the blood, compared to normally behaving dogs, with the lowest levels found in dogs showing defensive forms of aggression (Rosado, et al., 2010a). Males were also found to have significantly higher DHEA levels and cortisol levels than females (Rosado, et al., 2010a). These findings are significant and could help lead to new diagnostic and therapeutic approaches for pathological aggression in dogs.
Next Step
Further studies could include more homogeneous groups of dogs, such as dogs with or without stress-related problems, in order to study individual differences. Also, a more balanced distribution of animals in the categories of aggression would allow for a better assessment of the role of gender in the different groups of aggressive dogs.
Other Relevant Research
There are a number of other studies that also suggest the involvement of the serotonergic system in pathological dog aggression.
Serotonin 5-HT and 5-HIAA. In a follow up study to the one discussed above, Rosado, et al., examined the role of the serotonin (5-HT) transporter (5-HTT) in canine aggression (Rosado, et al., 2010b). It is believed that a dysfunction in serotonergic neurotransmission, in particular low 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF), plays a role in impulsivity and aggression in several species, including dogs (Rosado, et al., 2010b). The results of this study are consistent with prior studies, finding lower concentrations of 5-HT and CSF 5-HIAA in aggressive dogs compared to the control group (Rosado, et al., 2010b). These results suggest that aggressive dogs may benefit from the SSRI fluoxetine (Rosado, et al., 2010b).
Serotonin-1B-Receptor. In a 2007 study by Jacobs, et al., the authors measured the number of serotonin-1B-receptor-positive neurons in the basolateral nuclear group (BNG) of the amygdala to assess whether this receptor is involved in dog aggression (Jacobs, et al., 2007). This was a follow up to their previous study in 2006 where they found that pathologically aggressive dogs had a bilaterally enlarged BNG of the amygdala, and significantly higher numbers of BNG neurons, than normally behaving dogs (Jacobs, et al., 2006), and proposed the explanation that stress can lead to the formation of new dendrite spines in the BNG resulting in enhanced synaptic activity (Jacobs, et al., 2006). In that study they also suggest that neurotrophins can be induced in several brain areas as a result of psychological stressors, which may lead to the production of new neurons, although it is still unknown whether neurogenesis occurs in the amygdaloid body (Jacobs, et al., 2006).
Serotonin is thought to play a role in emotional processes, and its pathways reach important brain regions like the cerebral cortex, hippocampus, caudate nucleus, putamen, globus pallidus, septum and several hypothalamic areas (Jacobs, et al., 2007). A number of human affective disorders, such as depression, anxiety, schizophrenia, impulsivity and aggression are reported to be involved with the serotonergic system (Jacobs, et al., 2007). The involvement of the serotonergic system in human and animal aggressiveness and anxiety disorders has been demonstrated through the successful use of serotonergic drugs used in humans, rats, dogs and pigeons (Vermeire, et al., 2010). The serotonin-1B receptor acts pre and post synaptically, and is both an autoreceptor regulating the release of serotonin and a heteroreceptor on non-serotonergic terminals, modulating the release of other neurotransmitters such as acetylcholine, dopamine, glutamate, GABA and vasopressin (Jacobs, et al., 2006).
The Jacobs, et. al., study found a statistically significant difference between the mean number of serotonin-1B receptive positive neurons in the aggressive dog compared to the normally behaving dog (Jacobs, et al., 2006). They also found positive correlations between the number of serotonin-1B-receptor-positive neurons and the BNG volume, as well as between the number of those neurons and the total number of neurons in the BNG (Jacobs, et al., 2006). Jacobs and colleagues stated that these findings suggest the involvement of the serotonergic system in pathological dog aggression, but are not conclusive because there are multiple factors that influence the number and function of the serotonin-1B receptor, and many ways that serotonin can impact behavior.
Serotonin-2A-receptor. A more recent study also looked at the role of serotonin in dog aggression and anxiety, evaluating the role of the serotonin-2A-receptor (Vermeire, et al., 2010). Rather than dissecting the brain of the subject dogs in this study, they used an innovative, non-invasive tool, a Single Photon Emission Tomography (SPECT), to get in vivo images of regional brain neuronal function and neurotransmitter receptors and transporters (Vermeire, et al., 2010). The study revealed impaired binding indices of the serotonin-2A receptor in both impulsively aggressive and anxious dogs in the frontal, temporal and occipital cortex, going in opposite directions (Vermeire, et al., 2010). These results were consistent with prior studies, and showed that their use of SPECT neuro-imaging can be a useful tool for therapeutic interventions based on individual neurobiological need (Vermeire, et al., 2010).
References
American Society for the Prevention of Cruelty to Animals (ASPCA), US Pet Ownership Statistics (2009). www.aspca.org/about-us/faq/pet-statistics.html
Beata, C. A. (2001). Diagnosis and treatment of aggression in dogs and cats. Recent advances in companion animal behavior problems: International Veterinary. Information Service. Ithaca, New York
Beaver, B. V. (1999). Canine Behavior: a guide for veterinarians. Philadelphia: WB Saunders Co.
Jacobs, C., Van Den Broeck, W., Simoens, P. (2006). Increased volume and neuronal number of the basolateral nuclear group of the amygdala in aggressive dogs. Behavioural Brain Research, 170: 119-25.
Jacobs, C., Van Den Broeck, W., Simoens, P. (2007). Neurons expressing serotonin-1B receptor in the basolateral nuclear group of the amygdala in normally behaving and aggressive dogs. Brain Research, 1136: 102-09.
Laughlin, G., Barrett-Connor, E., 2000. Sexual dimorphism in the influence of advanced aging on adrenal hormone levels: the Rancho Bernardo study. J. Clin. Endocrinol. Metab. 85, 3561-3568.
Leon, M. (2006). Agresividad canina: epidemiolgia en la Comunidad Valenciana e implicacion de los sistemas serotoninergicos, dissertation. Universidad Cardenal Herrera-CEU, Valencia, Spain.
Leon, M., Garcia-Belenguer, S., Rosado, B., Chacon, G., Palacio, J., 2008. Usefulness of the determination of peripheral serotonin in canine aggression. Amat, M. Heath, S., Mariotti, V.M. (Eds.), Proceedings of the 14th Annual Meeting of the European Society of Veterinary Clinical Ethology, Bellaterra, Spain, p. 31.
Peremans, K., Audenaert, K., Coopman, F., Blanckaert, P., Jacobs, F., Otte, A., et al., 2003. Estimates of regional cerebral blood flow and 5-HT2A receptor density in impulsive, aggressive dogs with 99mTc-ECD and 1231-5-I-R91150. Eur. J. Nucl. Med. Mol. Imaging 30, 1538-46.
Quinlan, K. P., Sacks, J. J. (1999). Hospitalizations for dog bite injuries. Centers for Disease Control and Prevention. Atlanta, GA. http://www.cdc.gov/ncipc/duip/hospital.htm
Reisner, I., Mann, J., Stanley, M., Huang, Y., Houpt, K. (1996). Comparison of cerebrospinal fluid monoamine metabolite levels in dominant-aggressive and non-aggressive dogs. Brain Research, 714: 57-64.
Rosado, B., Garcia-Belenguer, S., Palacio, J., Chacon, G., Villegas, A., Alcalde, A.I., 2009. Serotonin transporter activity in platelets and canine aggression. Vet. J., doi: 10.1016/j.tvjl.2009.07.029.
Rosado, B., Garcia-Belenguer, S., Leon, M., Chacon, G., Villegas, A., Palacio, J. (2010a). Blood concentrations of serotonin, cortisol and dehydroepiandrosterone in aggressive dogs. Applied Animal Behavior Science, 123: 124-30.
Rosado, B., Garcia-Belenguer, S., Leon, M., Chacon, G., Villegas, A., Alcalde, A. (2010b). Serotonin transporter activity in platelets and canine aggression. The Veterinary Journal, 186: 104-05.
Sacks, J. J., Kresnow, M., Houston, B. (1996). Dog bites: how big a problem? Injury Prevention, 2: 52-54.
Vermeire, S., Audenaurt, K., Meester, R., Vandermeulen, E., Waelbers, T., De Spiegeleer, B., Eersels, J., Dobbeleir, A., Peremans, K. (2010). Neuro-imaging the serotonin 2A receptor as a valid biomarker for canine behavioural disorders. Research in Veterinary Science, doi: 10.1016/j.rvsc.2010.09.21
Weiss, H. B., Friedman, D., Coben, J. H. (1998). Incidence of dog bite injuries treated in emergency departments. Journal of the American Medical Association, 279: 51-53.
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A note on medication: Some of the research above discusses fluoxetine and other medications that affect serotonin. Decisions about medication for your dog belong to your veterinarian or a veterinary behavior specialist. In my practice, behavior modification works alongside any medical care your vet recommends, never in place of it.
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If your dog’s aggression is rooted in fear, book a free intro call to see if my program is the right fit.