To our knowledge, this study is the first to show localized structural abnormalities of the amygdala in individuals with psychopathy. In this study, psychopathic individuals were found to show bilateral amygdala volume reductions compared with controls. Significant regional deformations were found to be most prominent in the vicinity of the basolateral, lateral, cortical, and central nuclei of the amygdala in individuals with psychopathy. In addition, negative correlations were found between amygdala volumes and all 4 psychopathy facet scores, with correlations being most pronounced for the affective and interpersonal facets of psychopathy. Results could not be attributed to demographic group differences in socioeconomic status or substance/alcohol dependence. Findings provide initial evidence indicating amygdala structural abnormalities as 1 key element in the neurobiological bases of psychopathy.
Findings of amygdala volume reductions in individuals with psychopathy are consistent with lesion studies showing that damage to the amygdala results in emotional impairments similar to those of psychopathy. Animals with selective lesions to the amygdala have been found to show substantial impairments in fear conditioning and abnormal responsivity to threatening objects. For example, Hitch-cock and Davis59
demonstrated that lesions to the amygdala impaired fear-potentiated startle response in rats. In a recent study, Machado and Bachevalier60
found that rhesus monkeys with selective lesions to the amygdala showed profound behavioral changes that precluded positive social interactions (eg, decreased affiliation and popularity within the group) and decreased reactivity to threatening gestures. Similar findings have been reported showing that monkeys with bilateral amygdala lesions displayed blunted emotional response (ie, lack of fear) and decreased defensive behavior to threats (ie, a fake snake).61,62
These behavioral changes found in animals with amygdala lesions may suggest, albeit indirectly, that amygdala structural abnormalities may contribute to the classic findings of poor fear conditioning and impaired emotion recognition observed in individuals with psychopathy.7,9,63
In humans, selective lesions to the amygdala are rare, making it difficult to draw clear conclusions regarding the role such lesions play in modulating the emotion and behavior of patients. However, evidence suggests that there are similarities between the affective and social impairments resulting from amygdala lesions and the behavioral dysfunctions characterizing individuals with psychopathy. For example, Adolphs et al19
demonstrated in a case study that extensive bilateral amygdala damage (as a result of Urbach-Wiethe disease) led to difficulty in recognizing emotions in facial expressions, particularly when the patient was responding to a highly arousing facial expression such as fear, similar to the impairments observed in individuals with psychopathy.64
Several subsequent studies reported similar findings and show a consistent pattern of intact facial identification and impaired recognition of the facial expression of fear in patients with amygdala lesions such as those caused by disease (eg, encephalitis) and/or resection (eg, lobectomy or amygdalotomy).15,65–71
Observations from studies of patients with temporal lobe epilepsy (TLE) may also provide evidence in support of our findings linking altered amygdala morphology with psychopathy. Although amygdala damage in patients with TLE often occurs in conjunction with damage to other regions of the brain, pathological findings are regionally isolated in some cases.72–74
Volumetric reductions indicating pathology of the amygdala are frequently documented in patients with TLE (with reports ranging between 10%–57% amygdala volume reductions),75
where the lateral and basal nuclei appear most susceptible to seizure-induced damage.72,75–77
Patients who have TLE and exhibit concomitant amygdala damage have been found to show impairments in emotion recognition. For example, Houghton et al78
reported that impairments in the ability to recognize negative emotional expressions were associated with reduced amygdala volume in patients with TLE. In addition, several studies have shown that TLE-induced amygdala damage also results in impaired social judgment (ie, rate aversive facial appearances as more positive) because of the difficulty in recognizing negative facial emotions,79,80
again consistent with behavioral dysfunction reported in individuals with psychopathy. These human lesion studies demonstrate that amygdala lesions lead to outcomes of affective impairments that parallel to some extent the profile of individuals with psychopathy7,12,81
and support the findings of this study in suggesting that structural impairments in the amygdala may predispose to the emotional and social dysfunction in individuals with psychopathy.
The surface-based mesh modeling analyses indicate regional atrophy in amygdala structure in the vicinity of the basolateral, lateral, central, and cortical nuclei in individuals with psychopathy, echoing the complexity of the clinical descriptions of this disorder. The most robust evidence suggests that the lateral, basolateral, and central nuclei of the amygdala are independently and interactively involved in emotional processing, including fear conditioning and autonomic reactivity to affective stimuli,28–30
while other studies have further linked these nuclei to reward-related learning, behavioral inhibition, and decision making.28
With regard to the cortical nuclei, the very few findings are suggestive that this region may be involved in parenting, social interaction, and the regulation of stress and anxiety.28
Therefore, the regional morphological abnormalities of the amygdala observed in this study may reflect a variety of emotional and behavioral features in individuals with psychopathy. Future research using higher-resolution imaging will be needed to identify the structural alterations within each nucleus of the amygdala, but the even greater challenge will be to delineate the human functional significance of such deformations based on the behavioral neuroscience animal literature.
In addition to the significant amygdala volume reductions in individuals with psychopathy, reduced volumes were found to correlate with increased total psychopathy scores across the entire sample. The correlations were found to be most pronounced for the affective and interpersonal facets of psychopathy. These findings are consistent with 1 abstract reporting a correlation between reduced volumes in the right amygdala and increased affective-interpersonal scores of psychopathy in a violent offender sample.82
Results are further supported by evidence from functional imaging studies showing a higher degree of abnormal activation in the amygdala to be associated with an increase in the psychopathy score during affect recognition, prisoner’s dilemma tasks, and moral decision making.83–85
The associations between reduced amygdala volume and increased psychopathy total and facet scores are in line with evidence indicating that, in addition to emotional processing, the amygdala mediates a variety of brain functions, including attention, memory, social judgment, and moral decision making, through its neural connections with the prefrontal cortex and other subcortical structures.79,86–89
Therefore, our findings support the hypothesis that a higher degree of structural abnormalities in the amygdala may contribute to a greater manifestation of the affective-interpersonal impairments and, to a lesser degree, an increase in antisocial behavior and lifestyle in individuals with psychopathy.
There are several potential limitations of the present study that need to be taken into account when interpreting the results. First, the sample size is modest, thus raising the risk of potential type II error. However, the sample size is comparable with those used in other magnetic resonance imaging studies, and the use of correlation analyses on the entire sample of 59 subjects increases the power for detecting any association between amygdala volume and psychopathy. Second, there was the lack of absolute objectivity due to the nature of manual tracing. However, the method was used to test the specific hypotheses of regional morphological deformations in the amygdala in individuals with psychopathy, which would not have been possible if an automated imaging analysis method, such as voxel-based morphometry, was used. Third, although we controlled for socioeconomic status and substance dependence, a possibility remains that other confounds may contribute to the amygdala structural alterations observed in individuals with psychopathy, such as pharmacological treatments received prior to the scanning. Another limitation of this study is that even though we were able to conduct the group comparisons on a surface point-by-point level to elucidate the approximate locations of the amygdala deformations, we were unable to test the significance values for each distinct nucleus. Therefore, while surface maps indicate a more pronounced amygdala deformation in the cortical, central, basolateral, and lateral nuclei, the possibility remains that the findings also reflect deformations of nuclei relatively less represented on the surface (eg, medial amygdaloid and basomedial nuclei). Last, the standard resolution of structural imaging data does not yet allow reliable localization of structural alterations within specific amygdala nuclei. The precise identification of the amygdala nuclei in humans requires a combination of histological/immunohistochemical methods and neurochemical and cytoarchitectonic criteria,90
which was not possible in this study using in vivo imaging with a 1.5-T scanner. As a result, it needs to be made clear that the labeling of the schematic representation of the amygdala nuclei shown in this study was based on information obtained from a single human brain atlas53
and has not been validated in any probabilistic manner. Nonetheless, this approach was chosen taking into account the methodological and technological difficulties to best illustrate the approximate locations of regional amygdala deformations in individuals with psychopathy and illuminate the need for future studies to examine the amygdala as a heterogeneous structure and identify subtle and localized structural changes within the amygdala. Although the precise localization of structural changes within specific nuclei awaits further research, this study is the first, to our knowledge, to provide an examination of localized morphological alterations in the amygdala in individuals with psychopathy. The advance in the understanding of the neuropathology in psychopathy could greatly benefit from future studies examining the mediating risk factors (eg, autonomic fear conditioning response) together with structural imaging data to translate amygdala structural impairments directly into functional impairments in individuals with psychopathy.