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State-of-Science Review: E7 The Neural Basis of Resilience



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.
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.
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
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.
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).
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
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.
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.
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
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First published September 2008.
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Individuals with anxiety disorders demonstrate altered cognitive performance including (1) cognitive biases towards negative stimuli (affective biases) and (2) increased cognitive rigidity (e.g., impaired conflict adaptation) on affective Stroop tasks. Threat of electric shock is frequently used to induce anxiety in healthy individuals, but the extent to which this manipulation mimics the cognitive impairment seen in anxiety disorders is unclear. In this study, 31 healthy individuals completed an affective Stroop task under safe and threat-of-shock conditions. We showed that threat (1) enhanced aversive processing and abolished a positive affective bias but (2) had no effect on conflict adaptation. Threat of shock thus partially models the effects of anxiety disorders on affective Stroop tasks. We suggest that the affective state of anxiety-which is common to both threat and anxiety disorders-modulates the neural inhibition of subcortical aversive processing, whilst pathologies unique to anxiety disorders modulate conflict adaptation.
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Genetic variation in the cholinergic muscarinic-2 (M(2)) receptor gene (CHRM2) has been associated with the risk for developing depression. We previously reported that M(2)-receptor distribution volume (V(T)) was reduced in depressed subjects with bipolar disorder (BD) relative to depressed subjects with major depressive disorder (MDD) and healthy controls (HCs). In this study, we investigated the effects of six single-nucleotide polymorphisms (SNPs) for CHRM2 on M(2)-receptor binding to test the hypotheses that genetic variation in CHRM2 influences M(2)-receptor binding and that a CHRM2 polymorphism underlies the deficits in M(2)-receptor V(T) observed in BD. The M(2)-receptor V(T) was measured using positron emission tomography and [(18)F]FP-TZTP in unmedicated, depressed subjects with BD (n=16) or MDD (n=24) and HCs (n=25), and the effect of genotype on V(T) was assessed. In the controls, one SNP (with identifier rs324650, in which the ancestral allele adenine (A) is replaced with one or two copies of thymine (T), showed a significant allelic effect on V(T) in the pregenual and subgenual anterior cingulate cortices in the direction AA<AT<TT. In contrast, in BD subjects with the TT genotype, V(T) was significantly lower than in BD subjects with the AT genotype in these regions. The BD subjects homozygous for the T -allele also showed markedly lower V(T) (by 27 to 37% across regions) than HCs of the same genotype. Post hoc analyses suggested that T homozygosity was associated with a more severe illness course, as manifested by lower socioeconomic function, poorer spatial recognition memory and a greater likelihood of having attempted suicide. These data represent novel preliminary evidence that reduced M(2)-receptor V(T) in BD is associated with genetic variation within CHRM2. The differential impact of the M(2)-receptor polymorphism at rs324650 in the BD and HC samples suggests interactive effects with an unidentified vulnerability factor for BD.
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The purpose of this study was to examine whether appraisals of desirable and undesirable effects of military service mediated the effect of combat stress on posttraumatic stress disorder (PTSD) symptoms in later life in 1,287 male veterans, aged 44-91 years (M = 63.56, SD = 7.46), 40% of whom had been in combat. The men reported more desirable effects of military service (e.g., mastery, self-esteem, and coping skills) than undesirable ones; both increased linearly with combat exposure (r = .17 and .33, p < .001, respectively). Path analysis revealed that the appraisals were independent and opposite mediators, with undesirable effects increasing and desirable effects decreasing the relationship between combat exposure and PTSD, even controlling for depression and response style. Although lifelong negative consequences of combat exposure were observed, perceiving positive benefits from this stressful experience mitigated the effect.
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The development of competence holds great interest for parents and society alike. This article considers implications from research on competence and resilience in children and adolescents for policy and interventions designed to foster better outcomes among children at risk. Foundations of competence in early development are discussed, focusing on the role of attachment relationships and self-regulation. Results from studies of competence in the domains of peer relations, conduct, school, work, and activities are highlighted. Lessons are drawn from studies of naturally occurring resilience among children at risk because of disadvantage or trauma and also from efforts to deliberately alter the course of competence through early childhood education and preventive interventions. Converging evidence suggests that the same powerful adaptive systems protect development in both favorable and unfavorable environments.
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Echoplanar functional magnetic resonance imaging (fMRI) was used in normal human subjects to investigate the role of the amygdala in conditioned fear acquisition and extinction. A simple discrimination procedure was employed in which activation to a visual cue predicting shock (CS+) was compared with activation to another cue presented alone (CS-). CS+ and CS- trial types were intermixed in a pseudorandom order. Functional images were acquired with an asymmetric spin echo pulse sequence from three coronal slices centered on the amygdala. Activation of the amygdala/periamygdaloid cortex was observed during conditioned fear acquisition and extinction. The extent of activation during acquisition was significantly correlated with autonomic indices of conditioning in individual subjects. Consistent with a recent electrophysiological recording study in the rat (Quirk et al., 1997), the profile of the amygdala response was temporally graded, although this dynamic was only statistically reliable during extinction. These results provide further evidence for the conservation of amygdala function across species and implicate an amygdalar contribution to both acquisition and extinction processes during associative emotional learning tasks.
This second summary article from an epidemiological review of the health of former prisoners of war (POWs) and other Australian veterans, commissioned by the Sir Edward Dunlop Medical Research Foundation, reports on studies of mortality. The MEDLARS database, from 1966 to the present, under the terms military personnel, veterans, veterans' disability claims, combat disorders and prisoners (matched against war); databases of the Department of Veterans' Affairs (Victoria) and the Central Library, Commonwealth Department of Defense, under the term "prisoner of war"; and the microfiche listings of the Department of Veterans' Affairs, under "prisoner of war" and "repatriation". Only studies in English or French were reviewed, reaching a total of 172. Four studies in this paper constitute the main evidence about postwar mortality in Australians who were POWs of World War II or Vietnam veterans. Other mortality studies are cited in the complete literature review published elsewhere. Only the data with an epidemiological basis are considered here. All-cause mortality rates were no greater in former POWs or Vietnam veterans than in the general Australian male population. There was, however, evidence of increased mortality among former POWs compared with other non-POW veterans, and among Vietnam veterans in one particular corps compared with veterans of the same era who served in Australia. Elevated early postwar mortality of young former POWs implicates diseases with short latent periods (including psychiatric disorders). This is consistent with the greater health risks of this group of survivors that were identified in the earlier review of morbidity. Mortality among former POWs and other veterans requires continued surveillance because a "healthy worker effect" (or exclusion of unfit persons from the armed forces) may partly conceal increased morbidity or mortality that should be attributed to war service.
It has been suggested that patients with unipolar depression show abnormal responses to negative feedback in the performance of cognitive tasks. Positron emission tomography (PET) has previously identified blood flow abnormalities in depressed patients during cognitive performance. We have also used PET to identify regions where there is differential neural response to performance feedback in normal volunteers. In this study we aimed to test the hypothesis that blood flow in these regions, the medial caudate and ventromedial prefrontal cortex, would be abnormal in depressed patients. Six patients with unipolar depression and six matched controls were scanned using PET while performing cognitive tasks in the presence and absence of feedback. Compared with controls, depressed patients failed to show significant activation in the medial caudate and ventromedial orbitofrontal cortex. Blood flow was lower and a differential response, observed in normals, under different task and feedback conditions was not seen in the patients. The findings suggest that the behavioural response to feedback in depressed patients is associated with an abnormal neural response within the medial caudate and ventromedial orbitofrontal cortex, regions implicated in reward mechanisms. We argue that the observed abnormalities may depend on a combination of psychological factors, with both cognitive and emotive components.
Anticipatory anxiety is a complex combination of a future-oriented cognitive state, negative affect, and autonomic arousal. A dual-task paradigm of anticipation of electric shocks and a motor-learning task was used to examine the changes in neural patterns of activation associated with modulation of the cognitive state in anxiety by a distracting motor task. We used positron emission tomography (PET) and 15O-water to measure regional cerebral blood flow (rcbf) in 10 healthy male volunteers. A 2x2 factorial design-(shock vs no shock) x (low vs high distraction) was used with three scans per condition. Twelve PET scans were performed on each subject. In six of these scans, subjects were given electric shocks. In all scans, subjects also simultaneously performed a motor repetition (low distraction) or learning (high distraction) task. Galvanic skin conductance (GSR), Spielberger State and Trait Anxiety Inventory (STAI), and self-report data were also collected. In comparisons between the shock and no-shock conditions, the main finding was of increased rcbf in the left insula (-38,8,8) (z = 4.85, P<0.05 corrected) and a homologous area in the right insula at a lower threshold (z =3.20, P = 0.001 uncorrected). Other areas activated were the right superior temporal sulcus, left fusiform, and left anterior cingulate. Using the STAI-state scores as a covariate of interest, significant correlations with rCBF were seen in the left orbitofrontal cortex, left insula, and left anterior cingulate cortex. There was no significant distraction effect as measured by the STAI, self-report, GSR response or interactional analysis of the PET data. These findings support the role of paralimbic structures as neural substrates of anticipatory anxiety. The failure to demonstrate behavioral and neurophysiological changes with the distractor task may reflect the modest increases in anxiety with the shock, the relatively simple distractor task, and small sample size.
Background: Neuropeptide-Y (NPY) is present in extensive neuronal systems of the brain and is present in high concentrations in cell bodies and terminals in the amygdala. Preclinical studies have shown that injections of NPY into the central nucleus of the amygdala function as a central anxiolytic and buffer against the effects of stress. The objective of this study was to assess plasma NPY immunoreactivity in healthy soldiers participating in high intensity military training at the U.S. Army survival school. The Army survival school provides a means of observing individuals under high levels of physical, environmental, and psychological stress, and consequently is considered a reasonable analogue to stress incurred as a result of war or other catastrophic experiences. Methods: Plasma levels of NPY were assessed at baseline (prior to initiation of training), and 24 hours after the conclusion of survival training in 49 subjects, and at baseline and during the Prisoner of War (P.O.W.) experience (immediately after exposure to a military interrogation) in 21 additional subjects. Results: Plasma NPY levels were significantly increased compared to baseline following interrogations and were significantly higher in Special Forces soldiers, compared to non-Special Forces soldiers. NPY elicited by interrogation stress was significantly correlated to the subjects' behavior during interrogations and tended to be negatively correlated to symptoms of reported dissociation. Twenty-four hours after the conclusion of survival training, NPY had returned to baseline in Special Forces soldiers, but remained significantly lower than baseline values in non-Special Forces soldiers. NPY was positively correlated with both cortisol and behavioral performance under stress. NPY was negatively related to psychological symptoms of dissociation. Conclusions: These results provide evidence that uncontrollable stress significantly increases plasma NPY in humans, and when extended, produces a significant depletion of plasma NPY. Stress-induced alterations of plasma NPY were significantly different in Special Forces soldiers compared to non-Special Forces soldiers. These data support the idea that NPY may be involved in the enhanced stress resilience seen in humans.