The motivation to avoid pain and injury is a fundamental instinct, crucial to the survival of individuals and species. Yet, each year, millions of people purposefully and directly injure themselves...

Why Do People Hurt Themselves? A New Conceptual Model of Nonsuicidal Self-Injury:

Various internal and external factors negatively affect the homeostatic equilibrium of organisms at the molecular to the whole-body level, inducing the so-called state of stress. Stress affects an organism's welfare status and induces energy-consuming mechanisms to combat the subsequent ill effects; thus, the individual may be immunocompromised, making them vulnerable to pathogens. The information presented here has been extensively reviewed, compiled, and analyzed from authenticated published resources available on Medline, PubMed, PubMed Central, Science Direct, and other scientific databases. Stress levels can be monitored by the quantitative and qualitative measurement of biomarkers. Potential markers of stress include thermal stress markers, such as heat shock proteins (HSPs), innate immune markers, such as Acute Phase Proteins (APPs), oxidative stress markers, and chemical secretions in the saliva and urine. In addition, stress biomarkers also play critical roles in the prognosis of stress-related diseases and disorders, and therapy guidance. Moreover, different components have been identified as potent mediators of cardiovascular, central nervous system, hepatic, and nephrological disorders, which can also be employed to evaluate these conditions precisely, but with stringent validation and specificity. Considerable scientific advances have been made in the detection, quantitation, and application of these biomarkers. The present review describes the current progress of identifying biomarkers, their prognostic, and therapeutic values.

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Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values.

Stressful life events have been linked to the onset of severe psychopathology and endocrine dysfunction in many patients. Moreover, vulnerability to the later development of such disorders can be increased by stress or adversity during development (e.g., childhood neglect, abuse, or trauma). This review discusses the methodological features and results of various models of stress in nonhuman primates in the context of their potential relevance for human psychopathology and endocrine dysfunction, particularly mood disorders and dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system. Such models have typically examined the effects of stress on the animals' behavior, endocrine function (primarily the HPA and hypothalamic-pituitary-gonadal systems), and, in some cases, immune status. Manipulations such as relocation and/or removal of an animal from its current social group or, alternatively, formation of a new social group can have adverse effects on all of these outcome measures that may be either transient or more persistent depending on the species, sex, and other experimental conditions. Social primates may also experience significant stress associated with their rank in the group's dominance hierarchy. Finally, stress during prenatal development or during the early postnatal period may have long-lasting neurobiological and endocrine effects that manifest in an altered ability to cope behaviorally and physiologically with later challenges. Whereas early exposure to severe stress usually results in deficient coping abilities, certain kinds of milder stressors can promote subsequent resilience in the animal. We conclude that studies of stress in nonhuman primates can model many features of stress exposure in human populations and that such studies can play a valuable role in helping to elucidate the mechanisms underlying the role of stress in human psychopathology and endocrine dysfunction.

Models of Stress in Nonhuman Primates and Their Relevance for Human Psychopathology and Endocrine Dysfunction

Cortisol obtained from hair samples represents a retrospective biomarker of chronic stress experienced by the subject in previous months. Although hair cortisol levels have been used to study the relationship between maternal and neonatal stress levels in primates, this has not yet been performed in humans using a longitudinal design and focusing specifically on this association. Therefore, the objective of this study was to determine whether a relationship existed between maternal psychological stress and hair cortisol levels during pregnancy and postpartum, and neonatal hair cortisol levels. The sample consisted of 80 pregnant women and their 80 newborn infants. We conducted a longitudinal assessment of hair cortisol levels, psychological stress, anxiety, and depression in the three trimesters of pregnancy and postpartum. After childbirth, neonatal hair cortisol levels were also measured. We found that maternal hair cortisol levels in the first trimester negatively predicted neonatal hair cortisol levels. Perceived stress in the third trimester of pregnancy also predicted lower neonatal cortisol, whereas pregnancy-specific stress in the same trimester had a positive relation with neonatal cortisol. Cortisol is essential for embryonic and fetal development; consequently, if fetal synthesis of cortisol is affected by high maternal cortisol levels, such development could be impaired.

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Newborn infants' hair cortisol levels reflect chronic maternal stress during pregnancy.

Dear Editor,

Novak and Meyer are to be congratulated for their excellent article on alopecia in nonhuman primates published in the February 2009 issue1 This article included a very useful and illustrative color serial photograph showing an extreme case of alopecia during the immediate post-paturient period and spontaneous recovery thereafter This condition was first described by Vessey and Morrison in free-ranging rhesus monkeys (Macaca mulatta) on Cayo Santiago and at La Parguera, Puerto Rico as a natural phenomenon linked to reproductive seasonality2 Alopecia was observed in males at the end of the mating season and in females shortly after parturition It generally lasted between 4 and 16 wk Vessey and Morrison provided a narrative description and serial drawings of the typical pattern and recovery from this “molt”

Veterinary staff, colony managers, behavioral, and other scientists at the Caribbean Primate Research Center in Puerto Rico have considered this seasonal molt in their rhesus macaques to be a natural phenomenon and, for many years, have pointed it out as such to inspectors, site visitors, and others not aware of the condition The current article, combined with that of Vessey and Morrison, provides strong evidence that this is a natural, reversible phenomenon in rhesus macaques maintained under a variety of conditions ranging from free-ranging to individual indoor caging Both articles can be used to make those who consider this form of alopecia a medical problem aware that it is simply a natural, cyclical, and spontaneously reversible condition that has been known for decades, sometimes with extremes, such as alopecia universalis, and that it is not related to a failure to provide adequate veterinary care, poor nutrition, inadequate sunlight, lack of environmental enrichment or manipulata, trichotillomania, or other factors

Sincerely,


Matt J Kessler, DVM, DACLAM

Associate Director, Center for Comparative Medicine, University of Virginia

Alopecia: possible causes and treatments, particularly in captive nonhuman primates.

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.

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Use of the cross-translational model to study self-injurious behavior in human and nonhuman primates.

Hair loss is common in macaque colonies. Very little is known about the relationship between psychological stress and hair loss. We initially examined alopecia and hair cortisol concentrations in 198 (89 male) rhesus macaques from three primate centers and demonstrated replicability of our previous finding that extensive alopecia (>30% hair loss) is associated with increased chronic cortisol concentrations and significantly affected by facility. A subset of these monkeys (142 of which 67 were males) were sampled twice approximately 8 months apart allowing us to examine the hypotheses that gaining hair should be associated with decreases in cortisol concentrations and vice versa. Hair loss was digitally scored using ImageJ software for the first sample. Then visual assessment was used to examine the second sample, resulting in three categories of coat condition: (i) monkeys that remained fully haired; (ii) monkeys that remained alopecic (with more than 30% hair loss); or (iii) monkeys that showed more than a 15% increase in hair. The sample size for the group that lost hair was too small to be analyzed. Consistent with our hypothesis, monkeys that gained hair showed a significant reduction in hair cortisol concentrations but this effect only held for females. Coat condition changed little across sampling periods with only 25 (11 male) monkeys showing a greater than 15% gain of hair. Twenty (7 male) monkeys remained alopecic, whereas 97 (49 males) remained fully haired. Hair cortisol was highly correlated across samples for the monkeys that retained their status (remained alopecic or retained their hair). Am. J. Primatol. 79:e22547, 2017. © 2016 Wiley Periodicals, Inc.

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Assessing significant (>30%) alopecia as a possible biomarker for stress in captive rhesus monkeys (Macaca mulatta).

Hair loss is commonly used as an indicator of well being in primate facilities, yet it has been shown to also occur in otherwise healthy pregnant and postpartum females. There is significant variability in the incidence of hair loss during these important developmental periods, reasons for which remain unclear. We studied female rhesus monkeys (Macaca mulatta, n = 47) with and without hair loss in pregnancy/postpartum. We hypothesized that, similar to previously published reports, pregnancy would result in an increased likelihood of hair loss, and that hair loss would be correlated with higher hair cortisol concentrations (HCCs). We further hypothesized that hair loss among pregnant females is related to differential maternal investment. We studied a subset of monkeys (n = 26) from mid-to-late pregnancy through peak lactation, some of which exhibited hair loss in the perinatal period (n = 15), and some of which did not (n = 11). We examined fetal measurements, infant birth weight, infant growth rate, and milk yield volume (MYV) in the first 30 days as indices of investment. We found that pregnant monkeys showed a greater incidence of hair loss across the study year (χ2(2)  = 6.55, P = 0.038), and that mothers with hair loss had significantly higher HCCs in pregnancy than those without (F(2,28)  = 3.8, P = 0.017, ηp2  = 0.21). HCCs in pregnancy were correlated with severity of hair loss in the neonatal period (r(37)  = 0.42, P = 0.008). Moreover, HCCs in pregnancy were positively correlated with infant birth weight (r(12)  = 0.56, P = 0.038), infant growth rate (r(12)  = 0.64, P = 0.014), and MYV (r(11)  = 0.85, P < 0.001) for alopecic but not non-alopecic mothers. These mothers did not differ in fetal measurements, infant birth weight/growth rate, or MYV. Our results suggest that hair loss in some monkeys, especially during the birthing season, may be a signal of greater physiological stress during pregnancy and differential investment by mothers to their offspring. Am. J. Primatol. 79:e22489, 2017. © 2015 Wiley Periodicals, Inc.

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Differential relationships between chronic hormone profiles in pregnancy and maternal investment in rhesus monkey mothers with hair loss in the neonatal period.

Saif N. El-Mallah

Papers

Use of the cross-translational model to study self-injurious behavior in human and nonhuman primates.

Assessing significant (>30%) alopecia as a possible biomarker for stress in captive rhesus monkeys (Macaca mulatta).

Differential relationships between chronic hormone profiles in pregnancy and maternal investment in rhesus monkey mothers with hair loss in the neonatal period.