Use of the Cross-Translational Model to Study Self-Injurious Behavior in Human and Nonhuman Primates

Abstract

Nonsuicidal self-injurious behavior occurs in the general human population, particularly among teenagers and young adults. Some rhesus macaques also develop self-injurious behavior (SIB) as adolescents or young adults. In both of these cases, the development of harmful behaviors is idiopathic, only coming to the attention of physicians or veterinarians after the disorder is established. Thus, a combination of retrospective, statistical, and empirical procedures are used to understand this disorder. Here, we identify concordances between macaques and humans across five different levels of analysis-(1) form and prevalence, (2) etiology, (3) triggering events, (4) function/maintenance, and (5) therapeutic intervention-and show the value of the cross-translational model (macaques to humans and humans to macaques) in understanding this phenomenon. Substantial concordance is present with respect to the range of severity, the presence of early life stress exposure, and emotional dysregulation. In the macaque model, additional information is available on the hypothalamic-pituitary-adrenal axis stress response system, possible genetic involvement, and the immediate contextual situations that appear to trigger or exacerbate SIB episodes. In contrast, considerably more information is available from human studies on the effectiveness of various treatment regimens. Veterinarians have drawn on this information to explore these therapeutic interventions in monkeys. We expect that models of SIB will continue to have cross-translational impact as scientists and practitioners move from preclinical to clinical research and treatment.

Self‐injurious behaviours in rhesus macaques: Potential glial mechanisms

“…; Novak et al . ). This fact is especially important when considering the prevalence of SIB in populations with neurodevelopmental disorders.…”

“…; Novak et al . ) and growth in children and adolescence, most commonly in cases of depression or neurodevelopment (Jacobson and Gould ). Macaques have been noted to spontaneously develop SIB (Novak ), an important distinguishing factor from other animal models (namely rodents) which tend to be induced (with some exceptions (Bechard et al .…”

“…Self-Injurious Behaviour (SIB), which has been defined as intentional, direct injuring of body tissue without suicidal intent (Baguelin-Pinaud et al 2009), is a serious global health problem occurring in several high risk populations with neuropsychiatric diseases/disorders (including borderline personality disorder, PTSD, depression, autism spectrum disorders) and in other neurodevelopmental disorders (Zlotnick et al 1997;Al-Sharqi et al 2012;Mork et al 2013). Of particular concern is its lack of effective treatment (Navines et al 2013;Novak et al 2014) and growth in children and adolescence, most commonly in cases of depression or neurodevelopment (Jacobson and Gould 2007). Macaques have been noted to spontaneously develop SIB (Novak 2003), an important distinguishing factor from other animal models (namely rodents) which tend to be induced (with some exceptions (Bechard et al 2017)), making the macaque model a closer match with the human analog (Tiefenbacher et al 2005;Davenport et al 2008;Novak et al 2014).…”

Rhesus macaques ( Macaca mulatta ) displaying self-injurious behavior show more sleep disruption than controls

“…The prevalence of this condition ranges from 5–14% depending on the facility and methodologies used to assess SIB (Lutz et al, 2003; Rommeck et al, 2009). A decade of research on rhesus macaques suggests that there are commonalities with human SIB, not only with regard to prevalence but also with respect to etiology, triggering events, function, and therapeutic intervention (reviewed in Novak, et al, 2014). …”

“…Because only a small percentage of monkeys housed in similar laboratory environments spontaneously acquire this disorder, comparisons of those that develop SIB with those that do not provide insight into this condition (Novak, 2003; Novak et al, 2014). Based on our working model, at least two factors presumably play an initial role in the development of SIB in rhesus monkeys (Tiefenbacher et al, 2005): exposure to significant early life stress events (Lutz et al, 2003) in concert with differential sensitivity to stress as determined by the presence of gene polymorphisms associated with anxiety (Chen et al, 2010).…”