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Mental Capital and Wellbeing:
Making the most of ourselves in the 21st century
State-of-Science Review: E7
The Neural Basis of Resilience
Dr Rebecca Elliott
Neuroscience and Psychiatry Unit, University of Manchester
Professor Barbara Sahakian
Department of Psychiatry, University of Cambridge
Professor Dennis Charney
Mount Sinai School of Medicine, Mount Sinai Hospital, New York, USA
This review has been commissioned as part of the UK Government’s Foresight Project,
Mental Capital and Wellbeing. The views expressed do not represent the policy of
any Government or organisation.
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Summary
Resilience can be characterised as adaptive responding to stressful or traumatic
circumstances or events. Stress and trauma are major precipitants of mental health problems
in vulnerable individuals and therefore understanding why resilient people are protected
from these effects is important for mental health research. Resilience has been studied in
psychosocial research for some time. However, the neurobiology of resilience is a more recent
and less developed research area. Important reviews have emphasised the importance of
multiple interacting factors, with clear roles for both biological and environmental influences.
This review considers briefly how specific biological factors impact on resilience, with
reference to post-traumatic stress disorder (PTSD) and depression. We consider cognitive
factors, particularly the coping strategies that resilient individuals employ. Neurochemical
factors are also important, and we discuss evidence implicating neuropeptide Y and
dehydroepiandrosterone in the mediation of stress and resilience. Brain imaging provides a
tool for assessing in vivo brain structure and function, with several studies suggesting that
regions of the extended limbic system are likely to play key roles in determining resilience.
Finally, genetic research is showing how genetic markers underpin personality traits
including resilience to stress and trauma. These biological factors interact with each another
as well as environmental triggers to determine how an individual responds to stressful or
traumatic events. Understanding these interactions may offer clues to help us strengthen
resilience in individuals vulnerable to stress-induced mental health problems.
1. Introduction
Although the concept of resilience has been of interest for thousands of years, empirical study of human
resilience has only developed in the last few decades. Resilience can be defined as an individual’s successful
adaptation and functioning in the face of stress or trauma. Psychological resilience is a relatively stable
feature of personality that allows an individual to bounce back from stress or adversity. Much of the initial
empirical research on resilience was psychosocial. However, a seminal review by Curtis and Cicchetti
(2003) emphasised the biological aspects of resilience, and the concept is now attracting increasing interest
among neuroscientists.
Cicchetti and Blender (2006) recently presented a perspective on resilience research that stressed the
need for multiple levels of analysis. Although there is clear evidence for biological factors (neuroendocrine
markers, genetic factors and neuroimaging indices of brain structure and function), these occur in the
context of environmental influences. Key questions concern how environmental factors produce the
biological influences that underpin resilience.
An important concept for research is plasticity in neural development. Experiences affect neural structure
and function, and plasticity relates to the brain’s ability to respond and recover. There are at least two
distinct mechanisms for the brain basis of resilience. One possibility is that resilient individuals have a
particularly enhanced ability to recover from adversity or trauma (a type of ’super-plasticity’). Alternatively,
individuals may have a better-than-average resistance to environmental impact. That is, stress or trauma
produce less significant detrimental effects on neural function. Both mechanisms may contribute to
resilience, and modern neuroscience techniques are allowing these possibilities to be explored.
The neuroscience of resilience has largely been studied in three contexts. The first is developmental
psychology/psychopathology: specifically studying why childhood adversity leads to maladjustment in some
children but not others. The second is post-traumatic stress disorder (PTSD) and why some individuals
develop PTSD in response to trauma while others do not. Finally, the third is depression. Environmental
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stressors and adverse life events are important triggers for depression in vulnerable individuals, but others
are resilient in the face of life stress.
Understanding mechanisms of vulnerability is a typical focus for studying the aetiology of mental health
problems. However, understanding resilience provides a valuable counterpoint. This review briefly explores
the role of four neuroscience factors in resilience: cognitive psychology; neurochemistry; brain structure and
function; and genetic factors, with examples from research on post-traumatic stress disorder and depression.
2. Psychological factors
A number of psychological characteristics have been associated with resilience. Studies of children raised in
a variety of adverse situations have consistently revealed that successful adaptation is predicted by factors
including high levels of intellectual functioning, strong attachment behaviour, optimism, altruism and active
coping styles (Masten and Coatsworth, 1998; Bell, 2001). In adults employed in stressful professions (military
forces, fire-fighting, police), resilience to stress is associated with group bonding, altruism and effective
performance under stress.
Other important psychological constructs related to resilient responses to stress and trauma include
positive affectivity or optimism, cognitive reserve, cognitive flexibility and the development of coping
strategies (Yehuda et al., 2006; Barnett et al., 2006).
2.1. Positive affectivity
Positive affectivity has been explored in studies of patients with depression and mania. Elliott et al. (1998)
studied how patients with depression and healthy controls responded to performance feedback on
cognitive tasks. The feedback was ‘rigged’ such that, in some conditions, feedback was positive regardless
of performance. In others, it was negative, while in a control condition, no feedback was provided. Both
patients and controls performed better when the feedback was positive compared to when it was negative.
In the absence of feedback, controls performed as though receiving positive feedback, while patients
performed as though receiving negative feedback. This suggests that, unlike depressed patients, controls
assume they are performing well in the absence of information to the contrary; they have a form of positive
affectivity that may confer resilience to depression.
In another study of depression, Erickson et al. (2005) used an affective ‘Go/No-go’ task. Subjects were
presented with blocks of emotional words, some happy and some sad. In some blocks, subjects had to
respond to the happy words and ignore the sad, while in others the reverse pattern of responding was
required. Depressed patients responded more slowly and made more errors for happy words. Healthy
subjects were slower and less accurate for sad words, suggesting a positive affective bias that may be
associated with resilience. The functional neural basis of these effects has also been studied (see below).
Interestingly, it is possible that there is an optimum level of positive affectivity for psychological resilience.
Individuals who are vulnerable to mania may experience excess positive affect. Farmer et al. (2006)
performed a study in which they induced positive mood in stable subjects with bipolar depression and
controls. Positive mood was induced in both groups but was more sustained in the subjects with mania,
suggesting that extremes of positive affectivity may be maladaptive.
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2.2. Cognitive flexibility
The salient aspect of cognitive flexibility is the ability to reinterpret an adverse event to find meaning or
opportunity. In studies of combat veterans, PTSD is less prevalent in those who have this characteristic
(Baldwin et al., 1994). Cognitive flexibility may be correlated with general cognitive functioning. There
is evidence that patients with PTSD have impaired cognitive function on various measures (e.g. Golier
et al., 2002), and Kanagaratnam and Asbjornsen (2006) have suggested there may be some specificity
of impairment on laboratory measures of cognitive flexibility. However, it is not clear whether this is a
vulnerability factor or a consequence of developing PTSD.
In a recent study (Kremen et al., 2007), a large sample of Vietnam veterans were considered. Cognitive
ability scores had been obtained at the onset of military service (i.e. prior to trauma exposure) and higher
levels of cognitive ability were associated with lower risk of PTSD after stress exposure, which may reflect
resilience. Similarly Barnett et al. (2006) have suggested that superior cognitive function, or cognitive
reserve, may be a resilience factor in schizophrenia (and other psychiatric disorders).
2.3. Coping strategies
Active coping strategies involve adopting a problem-solving approach to a stressful situation, and this type
of strategy (as opposed to passive approaches like denial) has been associated with resilience in a number
of contexts. This strategic approach may confer a mastery over the situation which prevents a sense of
‘learned helplessness’ (see, for example, Amat et al., 2005; Robbins, 2005). For example, Gulf War veterans
who employ active coping strategies show lower levels of stress-related symptoms (Sharkansy et al., 2000).
More recently, studies have shown that individuals affected by the 9/11 terrorist attacks in New York
reported lower levels of distress and PTSD six months after the attacks if they used active coping strategies
(Silver et al., 2002).
Other important aspects related to coping strategies are religious coping and social support. Various studies
have suggested that people with strong religious affiliation are more resilient (Hill and Pargament, 2003),
although it is unclear whether this is due to religious faith per se or the social support offered by religious
communities. It is certainly clear that strong social support networks of various forms promote resilience in
the face of stress or trauma (Cohen et al., 2000).
3. Neurochemical factors
A variety of neurochemical compounds have been suggested to influence resilience. For example, a review
by Charney (2004) identified 11 compounds involved in mediating psychobiological responses to stress
and thus may contribute to resilience. A detailed account of stress neurochemistry is beyond the scope of
this review. However, two key neurochemicals that have been empirically associated with resilience will be
discussed briefly below.
3.1. Neuropeptide Y (NPY)
NPY is a peptide that influences the function of the hippocampus and may act as an anxiolytic (Heilig, 2004).
Patients with PTSD show reduced baseline levels of NPY (Morgan et al., 2003) and, conversely, individuals
with high levels of NPY show enhanced performance under stressful conditions (Morgan et al., 2000).
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Findings in combat veterans also support the idea that high levels of NPY serve as a biological marker for
resilience to, or recovery from, stress and trauma (Yehuda et al., 2006b).
3.2. Dehydroepiandrosterone (DHEA)
DHEA and cortisol are adrenal steroids released in response to stress. Both DHEA levels and DHEA/
cortisol ratios have been suggested as biological markers of resilience. Morgan et al. (2004) reported
positive correlations between DHEA levels (and DHEA/cortisol ratios) and the performance of military
recruits under stressful conditions.
Rasmusson et al. (2004) found a negative correlation between DHEA reactivity to stress and PTSD
symptom severity, which may suggest that high levels of DHEA protect against the adverse effects of
stress and trauma. Negative associations have also been reported between DHEA levels and depressive
symptoms in adolescents, again implicating a role for elevated DHEA levels in psychological resilience
(Goodyer et al., 2001).
4. Brain structure and function
Neuroimaging techniques, particularly functional magnetic resonance imaging (fMRI), can be used to
examine how individual differences in brain structure and function may relate to resilience. This kind of
research is very much in its infancy. However, there are two established lines of imaging evidence that are
relevant to resilience.
The first is research examining normal responses to anxiogenic and other emotional stimuli, and the second
is research in depressed patients and patients with PTSD. Both these avenues are important in establishing
likely functional mechanisms of resilience, which can then be explored in more explicit studies.
4.1. Neuroimaging of emotional stimuli
Imaging studies of responses to various emotional stimuli have identified the amygdala and regions of the
medial prefrontal cortex (mPFC) as particularly important. LaBar et al. (1998) reported amygdala activation
during a fear conditioning task, suggesting that this region is an important mediator of acquired anxiety.
Chua et al. (1999) reported areas including the anterior cingulate (part of the mPFC) associated with
anticipatory anxiety.
Differences between anticipatory responses to aversive stimuli and responses to the stimuli themselves have
been reported in prefrontal regions (Nitschke et al., 2006). However, this study also found common amygdala
and mPFC response to both anticipation and actual exposure. Kalisch et al. (2006) suggested that anticipatory
responses in mPFC/anterior cingulate may reflect higher-level cognitive appraisal of emotional material.
These findings have clear implications for resilience research. If normal responses to aversive or anxiogenic
stimuli involve the amygdala and mPFC, it is reasonable to hypothesise that the trait of resilience may be
associated with significant modulation of these responses. Some evidence for this comes from Kalisch
et al. (2005; 2006b) who have shown that using strategies to reduce anxiety during anticipatory anxiety
paradigms is associated with altered function in prefrontal regions, including mPFC.
Evidence for a role of mPFC in resilience also comes from studies of paradigms described in the section on
positive affectivity above. Behaviourally, control subjects show a bias towards positive material in an affective
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Go/No-go task. This bias is reflected in the functional response of the anterior cingulate which shows
enhanced activity when subjects are responding to happy targets and decreased activity when responding to
sad targets (Elliott et al., 2000).
This positive bias in healthy volunteers has been shown to be diminished or abolished by acutely reducing
brain serotonin through dietary means (Murphy et al., 2002; Rosier et al., unpublished data). Responses to
negative performance feedback have also been studied, with control subjects showing decreased amygdala
response and enhanced prefrontal (including mPFC) response (Taylor-Tavares et al., unpublished findings).
The amygydala decrease predicted the extent to which subjects suppressed any tendency to inappropriately
change behaviour in response to negative feedback information. This suggests that amygdala function may
be related to adaptive responses to potentially stressful environmental information.
In the last few years, neuroimaging research has increasingly entered the realms of social neuroscience,
with studies examining the neural basis of social behaviours. Given the clear importance of social factors
in adaptive and resilient behaviours, much of this research may prove relevant to the neuroscience of
resilience. For example, Rilling et al. (2002) showed that regions including ventral mPFC were more
responsive during mutual co-operation in an interactive game. Conversely, Eisenberger et al. (2003), using
a paradigm that modelled social exclusion, found that the anterior cingulate was more responsive during
exclusion then inclusion, and this increased response correlated with self-reported distress. Both social
cooperation and inclusion/exclusion may be relevant to understanding how social support networks
modulate resilience.
4.2. Neuroimaging in patients
Imaging studies of patients with PTSD have identified brain regions associated with a pathological response
to stress and trauma, which may also be regions associated with resilience.
Typically, structural imaging studies of PTSD have implicated the hippocampus as a potentially important
site of pathology (Rauch et al., 2006 for review). This structure is involved in the normal consolidation
of emotional memories (LaBar and Phelps, 2005) and interacts closely with the amygdala and mPFC.
Neurochemical imaging studies with magnetic resonance spectroscopy (MRS) have also suggested
hippocampal abnormalities in PTSD, while functional MRI studies have reported abnormalities within
amygdala/hippocampus/mPFC circuitry (Rauch et al., 2006).
However, the imaging results in PTSD are not always consistent. Three recent studies have found no
evidence of structural or neurochemical abnormalities in the hippocampus of three distinct, elderly
populations with PTSD: Holocaust survivors, combat veterans and former prisoners of war (Golier et al.,
2005; Freeman et al., 2005; Yehuda et al, 2006). In all three studies, subjects with PTSD were compared
to those who had experienced comparable trauma but were not symptomatic for PTSD. Yehuda et al.
suggest that the effects of normal ageing on hippocampal structure may have obscured any effects of PTSD.
Freeman et al. suggest an alternative hypothesis.
In their study of former POWs, they noted that the subjects in their elderly cohort were both longer-
lived than average and extremely fit and healthy for their age. Those with PTSD showed unusually low
levels of psychiatric co-morbidity and much lower symptom severity levels than a younger group of
combat veterans with PTSD. They therefore argued that even those of the cohort with PTSD actually
represented a rather resilient sample who had survived to advanced old age. Extreme combat stress is
associated with elevated mortality rates (Guest and Venn., 1992; Johnson et al., 2004), so those who survive
well into old age may reflect a resilient population, even those individuals experiencing symptoms of PTSD.
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Freeman et al. (2005) thus imply that normal hippocampal volumes in the face of severe stress and chronic
PTSD symptomatology may be a marker for resilience.
Imaging studies of depression have also provided clues about resilience, particularly those using cognitive/
emotional challenges. As discussed above, normal subjects show enhanced ventral anterior cingulate
responses to happy words in an affective Go/No-go task but reduced responses to sad words. Depressed
patients show exactly the opposite pattern (Elliott et al., 2002). This suggests that the ventral cingulate
mediates affective biases. A bias towards sad information may influence vulnerability to, and persistence of,
depression; while a bias towards happy information, as seen in control subjects, may confer resilience.
Performance feedback is another form of affective information that has been studied with fMRI. Elliott et
al. (1998) reported reduced medial frontal responses to feedback in depression. More specifically, Taylor-
Tavares et al. (unpublished findings) have observed an absence of the normal amygdala and prefrontal
responses to negative feedback in depressed patients, suggesting that the normal responses in these regions
may be associated with resilience.
In a more explicit imaging investigation of resilience to depression, Kruger et al. (2006) performed a PET
study of bipolar disorder. As well as bipolar patients and healthy controls, they studied patients’ siblings.
This was a group who were healthy but considered at-risk. In response to a negative mood induction
procedure, patients showed various neuronal abnormalities including decreased medial prefrontal response.
The at-risk siblings showed a number of common abnormalities. However, response in the medial prefrontal
region was increased in this group. Kruger at al. suggest that this increased medial frontal activity may reflect
‘a compensatory effect and a capacity for resilience in the siblings’.
Overall, the neuroimaging studies related to resilience suggest that a number of brain regions may mediate
these effects, with the amygdala and medial prefrontal cortex prominent among these.
5. Genetic markers
In recent years, genetic influences related to resilience have been studied. Caspi et al. (2002) investigated
the influence of genetic factors on the propensity of abused children to develop antisocial personality
disorders. A functional polymorphism in the gene encoding the enzyme monoamine oxidase A (MAOA)
was found to be important. The gene for high MAOA was associated with a greatly reduced risk of
antisocial behaviour, suggesting that this gene may confer a degree of resilience.
Caspi et al. (2003) also studied genetic influences on the development of depression in response to
stressful life events. They found that a functional polymorphism in the serotonin transporter gene (5-HTT)
modulated the interaction between life events and depression. The gene has two alleles: a long and a short
form. Individuals with either one or two short alleles were more vulnerable to depression in the face of
stressful life events. Individuals with two long alleles, by contrast, were resilient in response to life stresses,
and much less likely to develop depressive symptoms.
It is important to note that these genetic studies were considering interactions between genes and
environmental factors. In both studies, a particular genetic polymorphism was associated with a more
resilient response to stressful or traumatic life events.
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6. Conclusions
Although the neuroscience of human resilience is a relatively new research area, important clues are emerging.
Psychological factors, neurochemical balances, structural and functional brain markers and genetic influences
have all been associated with potential mechanisms of resilience to stress and trauma.
Patient studies of PTSD and depression have also provided important leads, identifying factors that may
confer vulnerability, and thus suggesting possible mediators of resilience in individuals who do not develop
psychiatric symptoms in response to comparable levels of trauma.
We emphasise, however, that the various factors described here should not be considered in isolation;
rather they interact with each other, and with environmental and psychosocial influences, in determining
levels of resilience. For example, key genetic polymorphisms are likely to dictate neurochemical
balances, while differences in brain function in response to emotional challenges may underpin crucial
psychological strategies.
Psychological constructs such as cognitive reserve, cognitive flexibility and coping strategies may depend
on top-down control of amygdala function by prefrontal cortical regions. It may, therefore, be possible
to strengthen resilience through pharmacological and non-pharmacological means, including cognitive
behavioural or other psychological therapies and education.
Recent reviews of resilience highlight the importance of maintaining an interactive perspective in future
research (Yehuda et al., 2006; Cicchetti and Blender, 2006).
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All the reports and papers produced by the
Foresight Mental Capital and Wellbeing Project may be downloaded from the Foresight website
(www.foresight.gov.uk).
Requests for hard copies may also be made through this website.
First published September 2008.
The Government Office for Science.
© Crown copyright
