Tuesday, January 12, 2010

The Neurochemistry of Psychological Adversity and Resilience

A nice little piece from Psychiatry Weekly on how to identify resilience. Below this article, I want to present a new study that suggests that the timing of childhood stress is a major determinant in resiliency.

Identifying Psychological Resilience

December 21, 2009

Norman Sussman, MD, DFAPA

Editor, Primary Psychiatry and Psychiatry Weekly, Professor of Psychiatry, Interim Chairman, Department of Psychiatry, New York University

First published in Psychiatry Weekly, Volume 4, Issue 30, on December 21, 2009

Psychiatry is identified with a focus on the causes and management of maladaptive emotional responses that lead to symptoms and disorders. The paradigm has long been to explore an individual’s vulnerabilities. Psychoanalysts have looked at the obverse, describing defense mechanisms that are considered healthy and associated with adaptive responses. In recent years an increasing number of researchers have identified the concept of resilience as a framework for identifying factors that make some individuals more successful at coping with adversity than others. There is growing interest in why some people not only adapt, but also grow in the face of adversity.

While much evidence shows that stress in early childhood increases the likelihood of adult mental disorder, there is some evidence that exposure to early life stress diminishes subsequent psychopathology. Called “stress inoculation,” it may increase exploration of novel situations, decreases stress levels of pituitary-adrenal hormones and enhance prefrontal-dependent cognitive control of behavior. It is known that patients with bipolar disorder often become ill when subjected to stress. Activity in the prefrontal cortex may differentiate bipolar disorder patients who became symptomatic compared to those who do not.

Efforts are being made to develop resilience scales that might be used to evaluate coping skills and possibly predict response to treatment.1 The military is looking into ways to mitigate the effects of post traumatic stress disorder by training soldiers to be more mentally resilient in advance. In light of the high rates of PTSD associated with combat veterans, the military now sees the need for soldiers to be both physically and mentally fit to avoid the problems associated with PTSD. The United States Army is developing a “Global Assessment Tool” to help assess soldiers’ fitness.

Dr. Dennis Charney has been a leading proponent for more research into resilience. He has described distinct neurochemical response patterns to acute stress,2 and he emphasizes the importance of optimism, “cognitive reappraisal” and a supportive social network in improving response to adversity.


1. Lopez CT. Soldiers may better handle trauma with resilience training (http://www.army.mil/-news/2009/03/23/18611-soldiers-may-better-handle-trauma-with-resilience-training/) Accessed 12/3/09.

2. Charney DS. Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am J Psychiatry. 2004;161(2):195-216.

The idea of a global assessment tool is very cool - (it will include physical, emotional, social, spiritual and family elements) - but I wonder how effective it will be at revealing issues that might lessen resiliency.

A recent review article in Frontiers of Human Neuroscience looks at the developmental timing of adversity (stress) and how it impacts brain development. Here is the title and abstract.
A review of adversity, the amygdala and the hippocampus: a consideration of developmental timing

Department of Society, Human Development, and Health, School of Public Health, Harvard University, USA

A review of the human developmental neuroimaging literature that investigates outcomes following exposure to psychosocial adversity is presented with a focus on two subcortical structures – the hippocampus and the amygdala. Throughout this review, we discuss how a consideration of developmental timing of adverse experiences and age at measurement might provide insight into the seemingly discrepant findings across studies. We use findings from animal studies to suggest some mechanisms through which timing of experiences may result in differences across time and studies. The literature suggests that early life may be a time of heightened susceptibility to environmental stressors, but that expression of these effects will vary by age at measurement.
Here is an explanation of why the researchers focused on the hippocampus and amygdala, and not on the frontal lobes as suggested by Sussman above.
Because the systemic output of the HPA axis, glucocorticoids (cortisol in humans), can pass through the blood-brain barrier, the HPA axis is one of the major pathways through which the effects of stress can shape brain development. The amygdala and hippocampus are rich with receptors for cortisol and are therefore major targets of the HPA axis. Thus, we see narrowing our review to the amygdala and hippocampus as one reasonable way to limit the scope of the neural effects of adversity that we examine here. We will describe some specific examples of when amygdala and hippocampal development are disrupted by negative psychosocial environments. By describing these associations, we hope to distill potential mechanisms by which exposure to adversity could become biologically embedded resulting in increased susceptibility to mental illness.
This explanation will come as no surprise to those familiar with the literature on post-traumatic stress disorder (PTSD) in children who are physically and/or sexually abused over time. In fact, the second article cited by Sussman (Charney, 2004) explains the negative impact of cortisol (the primary stress hormone) on the brain:
Cortisol serves to mobilize and replenish energy stores; it contributes to increased arousal, vigilance, focused attention, and memory formation; inhibition of the growth and reproductive system; and containment of the immune response. Cortisol has important regulatory effects on the hippocampus, amygdala, and prefrontal cortex (4). Glucocorticoids can enhance amygdala activity, increase corticotropin-releasing hormone (CRH) mRNA concentrations in the central nucleus of the amygdala (5–7), increase the effects of CRH on conditioned fear (8), and facilitate the encoding of emotion-related memory (9). Adrenal steroids such as cortisol have biphasic effects on hippocampal excitability and cognitive function and memory (10). These effects may contribute to adaptive alterations in behaviors induced by cortisol during the acute response to stress.

It is key, however, that the stress-induced increase in cortisol ultimately be constrained through an elaborate negative feedback system involving glucocorticoid and mineral corticoid receptors. Excessive and sustained cortisol secretion can have serious adverse effects, including hypertension, osteoporosis, immunosuppression, insulin resistance, dyslipidemia, dyscoagulation, and, ultimately, atherosclerosis and cardiovascular disease (11).
So if we know how cortisol impacts the brain (as well as the rest of the body), it seems that knowing when the brain is most vulnerable to this process might be important. In fact, it has been shown that the adult brain responds differently to stress than a child's brain - which makes sense since the child's brain is still in development. However, the difference is also based on family history of PTSD and other dysfunctions (O'Brien, 2004).

Still, the developmental issue is interesting and important (for an older look at this issue, which I believe is still relevant, see Perry, 1996). From Tottenham & Sheridan:
Although the effects of sensitive periods are observed in behavior, they are properties of neural circuits (see Knudsen, 2004). Central to this concept is the notion that the process of development itself may increase the system’s likelihood of being shaped by the environment (Casey et al., 2000). These periods often coincide with rapid development of a brain system, and therefore, individual neural systems will have their own sensitive periods (Lupien et al., 2009). Once environmental exposure occurs, it modifi es the architecture of the circuit in such a way that certain patterns of future activity are preferred (Knudsen, 2004). Therefore, knowing the developmental timing of environmental exposures is critical when evaluating its effects.
Here is a summary of the stress response on the hippocampus and amygdala:
Stressful events do not impact the whole brain in a uniform fashion, but instead the effects are region specific, exhibiting some of the largest effects in the amygdala and hippocampus. The amygdala and the hippocampus exhibit differential effects of stress that occurs in adulthood, and often contrasting, such that stress decreases size, complexity, and activity of the hippocampus (reviewed in Lupien et al., 2007; Bremner et al., 2008) and shows the opposite effects in the amygdala (larger, more reactive amygdala) (Liberzon et al., 1999; Rauch et al., 2000; Armony et al., 2005). The differences between the two structures seem to be partially related to the time course of the molecular events that occur between the two structures that follows stress.
And in the conclusion, the authors write:
We argue that a developmental approach is necessary in understanding how environmental conditions such as trauma can impact outcome in these structures. While this review is limited in its scope, the restriction was purposeful in that it allowed for greater discussion of how timing of exposure and age at measurement can differentially infl uence these neural phenotypes. The hypothesis driving the manuscript was that developmental timing of adverse experiences and the age at testing would influence structure and function of the amygdala and hippocampus. The literature discussed in this review suggest that the amygdala and hippocampus are highly vulnerable to the effects of adverse early environments, although these effects may be more evident in the amygdala early in life, whereas the hippocampus effects may be more subtle early in life and may be more readily observable in humans studies later in life.
This will certainly have on impact on resiliency later in life, including any attempt by the military to look for and identify early trauma and its impact on resiliency - which is made harder by the fact that soldiers know an admission of early trauma will automatically remove them from some desired positions.

However, the Charney article offers a hopeful assessment of secure attachment outcomes:
Highly resilient children, adolescents, and adults have exceptional abilities to form supportive social attachments. Individuals who demonstrate outstanding leadership ability and courageous acts in the context of great personal danger are frequently characterized by unique altruism. Clinical studies in such individuals designed to examine the neural circuits related to social cooperation are now indicated.
Those statements read almost as a definition of secure attachment (Schore, 2001).

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