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Anxiety disorders adversely affect millions of people and account for substantial morbidity in the United States. Anxiety disrupts an individual’s ability to effectively engage and interact in social and non-social situations. The onset of anxiety disorders may begin at an early age or occur in response to life events. Thus, the effects of anxiety are broad ranging, affecting both family and work dynamics, and may limit an individual’s quality of life.

While there has been a great deal of research focused on anxious behavior and anxiety disorders in the past few decades, there is still much we do not know. In order to better understand anxiety disorders, and to develop novel options for those who are nonresponsive to current treatments, scientists need to investigate the biobehavioral mechanisms that underlie the expression of anxiety related behavior. Research with humans subjects is one strategy used to gain insight on how to effectively treat anxiety disorders. However, there are inherent difficulties with such studies, including complex life histories and differences in access to resources (such as health care), as well as ethical issues. Common physiology between humans and other animals allow for the development of animal models that allow scientists to examine the neurobiological underpinnings of anxiety disorders. The non-human primate (NHP) has been used in the study of anxiety due to the physiological, behavioral and neural commonalities we share.

One type of anxiety assessment in non-human primates relies on direct behavioral observations, either in the animal’s ‘home environment’ or in a situation in which the animal is mildly challenged to induce an anxious state. In these procedures, observers typically look for the presence of behaviors indicative of anxiety, including fear and displacement behaviors (normal behaviors that may occur at seemingly inappropriate times). For example, in certain stressful situations, macaques may pick at their hair, a behavior similar to hair twirling in humans. Importantly anxiolytic drugs that reduce the occurrence of these behaviors in humans have been shown to reduce these behaviors in non-human primates, suggesting a common biological mechanism.

One commonly used procedure to assess anxiety in non-human primates is the “Human Intruder Test” (HIT). This procedure was designed to evaluate an animal’s response to the “uncertainty” of the presence of an unfamiliar human. The species appropriate response when presented with this mild challenge is to remain still and vigilant; however, there is a range of responses, with some animals showing little response and others excessive freezing behavior. Variations of this procedure have used similar stimuli, including unfamiliar conspecifics and predatory threats (e.g., stuffed predator) to measure anxiety-related responses. Animals that exhibit heightened anxiety responses in the Human Intruder Test also show alterations in the same neurobiological systems affected in humans with anxiety disorders.

Another class of anxiety tests in non-human primates relies on measuring physiological response following the presentation of an unexpected auditory or motor stimulus. For example, anxious people are more likely than others to react to a brief, unexpected sound with an exaggerated heart rate. Researchers have adopted similar methodology to assess startle response for nonhuman primates using a wide range of stimuli and physiological parameters.

Other research has focused on the cognitive processes involved in the regulation of anxiety responses. These tests of “cognitive bias” are based on the idea that an individual’s tendency to attend to potentially noxious stimuli tell us something about how the individual processes or weighs the experience. Therefore, an individual’s “anxious” state can be by assessed from his or her judgment about or attention to stimuli with different potentials to evoke anxiety. Cognitive bias procedures have been adapted and successfully employed in humans and other animals with similar response strategies across species, making these tests valuable comparative tools in our understanding of anxious behavior behavior.

Our review presents non-human primate models used by scientists in an effort to understand the biobehavioral mechanisms that mediate anxiety. The cross-species approach of modeling human psychopathology aims to discover targets for treatment toward the goal of reducing human suffering caused by anxiety disorders. Additionally, the knowledge gained from our investigation of anxiety-like behavior inform captive care of non-human primates. The studies reviewed have refined our understanding of factors that may result in anxiety-like behavior and provide information on how to manage them. Modeling psychopathology in non-human primates is necessary and critical to our understanding and treatment of these disorders in humans and nonhuman primates.

The post Anxiety in non-human primates appeared first on OUPblog.

        

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Stress seems to be everywhere we turn. Much of the daily news is stressful, whether it pertains to the recent Ebola outbreak in western Africa (and its subsequent entry into the United States), beheadings by the radical Islamic group called ISIS, or the economic doldrums that continue to plague much of the developed world. Moreover, we all experience frequent stress in our daily lives. Stress can come from your job, your family, a romantic relationship, personal attacks by way of social media, or, if you’re a student, your school performance. Counselors, psychotherapists, even self-help books and other materials may help us cope with stress, but these sources don’t usually give us very much information about what is actually happening to our brain and our body when we’re stressed.

If we think about it for a moment, it becomes clear that stress is not a recent phenomenon brought about by the features of contemporary western societies. Our hominid ancestors who evolved on the African savanna were surely stressed in the course of meeting their basic biological needs of finding food and water, acquiring shelter, and keeping safe from predators. Moreover, the principal brain and endocrine (i.e. hormonal) systems that underlie the cognitive, behavioral, and physiological responses to stress are found throughout the animal kingdom, indicating that these systems arose much earlier in evolutionary history than the appearance of the first hominids. So just what are these systems and how do they work?

A lot of research has focused on the hormonal systems that are turned on during stress. These responses are easier to access than brain responses, since researchers usually need only to obtain samples of the person’s blood, saliva, or urine to determine whether her endocrine system is showing a normal stress response or perhaps is functioning abnormally due to the effects of previous stress exposure. There are two parts to the endocrine stress response, both involving the adrenal glands. The inner part of the adrenal gland, called the adrenal medulla, rapidly secretes the hormones epinephrine and norepinephrine (also called adrenalin and noradrenalin) in response to a stressor. These hormones help prepare the person for rapid physical action by elevating heart rate and blood pressure, mobilizing sugar from the liver for instant energy, and increasing blood flow to the skeletal muscles. The outer part of the adrenal gland, called the adrenal cortex, is also activated by stressors but a bit more slowly. This part of the gland secretes glucocorticoids such as cortisol, which not only works in conjunction with epinephrine and norepinephrine but also affects inflammation, immune function, and brain activity.

For many years, researchers focused on how stress, especially chronic stress, can damage the adult brain and body. More recently, however, it has become clear that stress may be particularly destructive during development. We now know, for example, that repeated childhood maltreatment and abuse increase the child’s vulnerability to a later onset of clinical depression or post-traumatic stress disorder. But stress can exert deleterious effects even earlier in development, namely during the prenatal period. Although the fetal adrenal glands begin to function before birth, it seems likely that stress is transmitted to the fetus mainly through maternal hormones such as cortisol. The placenta breaks down much of the mother’s cortisol before it reaches the fetus, but some of the hormone manages to get through. One example that shows how prenatal stress can adversely affect offspring development stems from a terrible ice storm that hit Québec Province in Canada in January of 1998. Three million people lost electrical power for up to 40 days, resulting in significant privation. David Laplante and colleagues at Douglas Hospital of McGill University later studied 89 five-and-a-half-year-old children whose mothers had been pregnant with them during the power outage. Children whose mothers endured the greatest hardship as a result of the storm scored noticeably lower in verbal IQ scores and in a vocabulary test than children whose mother experienced low or moderate hardship.

While natural disasters like the Québec ice storm afford researchers the opportunity to investigate some of the deleterious effects of prenatal stress exposure, there are many limitations of such studies because the stress cannot be controlled experimentally and there are additional confounding variables such as differing postnatal experiences among the participants. To overcome some of these limitations and additionally permit a more detailed examination of behavioral, endocrine, and brain function than normally available with human participants, models of stress (including prenatal stress) have been developed for studying nonhuman primates such as rhesus monkeys. Offspring of rhesus monkeys exposed during mid-to-late pregnancy either to repeated mild stress or to pharmacological stimulation of cortisol release show behavioral and brain abnormalities that are still present at least several years later.

The implication of both the human and primate research is clear. We must pay closer attention to the well-being of pregnant women in order to minimize whatever life stresses can be controlled. By so doing, we can help newborn children begin life with better prospects for their future mental and physical health.

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