اختلالات ماده خاکستری در بیماران مبتلا به اختلال شخصیت خودشیفتگی

Abstract Background Despite the relevance of narcissistic personality disorder (NPD) in clinical settings, there is currently no empirical data available regarding the neurobiological correlates of NPD. In the present study, we performed a voxel-based morphometric analysis to provide initial insight into local abnormalities of gray matter (GM) volume. Methods Structural brain images were obtained from patients with NPD (n = 17) and a sample of healthy controls (n = 17) matched regarding age, gender, handedness, and intelligence. Groups were compared with regard to global brain tissue volumes and local abnormalities of GM volume. Regions-of-interest analyses were calculated for the anterior insula. Results Relative to the control group, NPD patients had smaller GM volume in the left anterior insula. Independent of group, GM volume in the left anterior insula was positively related to self-reported emotional empathy. Complementary whole-brain analyses yielded smaller GM volume in fronto-paralimbic brain regions comprising the rostral and median cingulate cortex as well as dorsolateral and medial parts of the prefrontal cortex. Conclusion Here we provide the first empirical evidence for structural abnormalities in fronto-paralimbic brain regions of patients with NPD. The results are discussed in the context of NPD patients' restricted ability for emotional empathy.

1. Introduction As stated by the DSM-IV-TR, “a pervasive pattern of grandiosity, need for admiration, and lack of empathy” are defining features of narcissistic personality disorder (NPD; American Psychiatric Association, 2000), a serious mental disorder with a median lifetime prevalence of 1% in the general population (Pincus and Lukowitsky, 2010). Previous findings have highlighted the relevance of NPD for mental health services by showing that NPD is associated with severe impairments in psychosocial functioning (Miller et al., 2007), a high co-morbidity rate of affective as well as substance use disorders (Ritter et al., 2010; Stinson et al., 2008), and an increased rate of suicidal behavior (Blasco-Fontecilla et al., 2009; Ronningstam et al., 2008). Nonetheless, up to now, there has been a severe lack of empirical research investigating psychological and neurobiological factors related to the clinical presentation of NPD (Miller and Campbell, 2010). In particular, neurobiological abnormalities in patients with NPD are, to the best of our knowledge, currently unknown, both at a structural and a functional level. In the present study, we aimed to provide initial insight into brain structural abnormalities in patients with NPD and compared local GM volume between patients with NPD and healthy controls using voxel-based morphometry (VBM). Given the lack of previous neurobiological investigations, our main hypothesis regarding group differences in GM volume focused on a highly characteristic and experimentally supported feature in patients with NPD: “lack of empathy”. Impaired empathy is unequivocally considered to be highly characteristic of patients with NPD and has a longstanding tradition in theoretical conceptualizations of this mental disorder (Akhtar and Thomson, 1982; Blais et al., 1997; Kernberg, 1970; Ronningstam, 2010). However, it was only recently that an experimental study explicitly investigated empathic abilities in patients with NPD (Ritter et al., 2011). In accordance with multidimensional models of empathy (Blair, 2005; Decety and Meyer, 2008; Singer, 2006), Ritter et al. examined the ability to infer mental states of another person (i.e., cognitive empathy; Baron-Cohen and Wheelwright, 2004) as well as emotional responses regarding the observed emotional state of another person (i.e., emotional empathy; Eisenberg and Miller, 1987; Mehrabian and Epstein, 1972). The experimental investigation indicated that NPD patients have impaired emotional empathy, whereas cognitive aspects of empathy were found to be unaffected (Ritter et al., 2011). In other words, patients with NPD are not characterized by a general impairment in empathy, but rather a specific deficit in their ability to emotionally respond to the observed emotional state of another person. The neural representation of empathy has received considerable attention in recent years (for meta-analyses, see Fan et al., 2011a; Lamm et al., 2011). Meta-analytic evidence of functional neuroimaging findings highlighted the bilateral anterior insula, anterior and median parts of the cingulate cortex, and the supplementary motor area to represent a core network activated during empathy related processes (Fan et al., 2011a). Complementary evidence regarding the neural representation of empathy was provided by volumetric studies in patients with neurodegenerative diseases (Rankin et al., 2006) and mental disorders such as schizophrenia and autism (Hadjikhani et al., 2006; Hooker et al., 2011). For example, smaller GM volume in the ventromedial prefrontal cortex of individuals with schizophrenia significantly contributed to deficits in theory-of-mind skills (i.e. cognitive empathy, Hooker et al., 2011). Impairments in emotional empathy, in contrast, were related to smaller GM volume of the bilateral insula in adolescents with conduct disorder (Sterzer et al., 2007). The results of a recent study indicated neurofunctional abnormalities of empathy-related brain regions in healthy individuals with marked narcissistic personality traits (Fan et al., 2011b). More specifically, narcissistic participants were found to exhibit abnormal functioning of the anterior insula when asked to emotionally empathize with other individuals. Consequently, the results of this study stress again the importance of abnormalities in emotional empathy and highlight anterior parts of the insular cortex to represent a potential neurobiological correlate of these impairments in narcissism. In light of the findings presented above, and due to a lack of available neurobiological studies investigating healthy and pathological narcissism, we specifically investigated gray matter abnormalities in the anterior insula of NPD patients. To more closely associate GM abnormalities of the anterior insula with impaired emotional empathy in NPD, we additionally assessed the correlation between GM volume of this brain region and self-reported emotional empathy, as measured by the Interpersonal Reactivity Index (IRI; Davis, 1983; Sterzer et al., 2007). Finally, exploratory whole-brain analyses were calculated to provide further indications of structural abnormalities in NPD.

Results Comparing global volumes of gray matter, white matter, cerebrospinal fluid, and total intracranial volume between healthy controls and patients with narcissistic personality disorder yielded no significant differences in global volumes of the respective tissue maps (all ps > .10). Results are presented in Table 2. Table 2. Global tissue volumes of patients with narcissistic personality disorder (NPD) and healthy controls (HC). HC NPD T P d Mean SD Mean SD Global brain volumes Gray matter 730.0 80.5 691.4 50.3 1.68 .10 .57 White matter 573.1 72.7 537.3 60.5 1.56 .13 .53 Cerebrospinal fluid 250.1 34.3 246.6 36.2 0.29 .78 .10 Total intracranial volume 1553.3 172.6 1475.3 122.9 1.52 .14 .52 Table options Relative to healthy controls, NPD patients presented significantly smaller GM volumes in the left anterior insula ([−41,6,−5], T = 3.32, p < .05 [FWE], d = 1.09; see also Fig. 1). A similar, albeit marginally significant, effect was found in the right anterior insula ([42,6,1], T = 3.01, p < .10 [FWE], d = .98). 1 Visualization of the reported group difference (red) and the positive ... Fig. 1. Visualization of the reported group difference (red) and the positive association of emotional empathy with GM volume (green) as well as the overlap of both effects (blue) in the anterior insula. Results are overlaid on a template provided by MRIcron and the result threshold was set at p < .005 uncorrected for visualization purposes. The scatterplot illustrates the relation between lower levels of self-reported empathic concern and gray matter volume for the left anterior insula. The effects of global GM volume (covariate in the statistical analysis) on local estimates of gray matter volume in the anterior insula were regressed. Therefore, the scatterplots depicts the relation between unstandardized residuals and empathic concern. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.) Figure options The complementary whole-brain analysis illustrated pathological narcissism to be characterized by smaller GM volume in a fronto-paralimbic network (Fig. 2). In particular, patients with NPD showed smaller GM volumes in the left anterior insular region, the bilateral superior frontal gyrus (including dorsolateral and medial areas) and the bilateral middle frontal gyrus. Furthermore, smaller GM volume in patients with NPD was found in the right rostral and left median cingulate cortex, as well as in parts of the pre- and post-central gyrus (see Table 3). The reverse contrast (indicating greater GM volume in NPD patients) revealed no significant clusters. Significantly smaller GM volume in patients with narcissistic personality ... Fig. 2. Significantly smaller GM volume in patients with narcissistic personality disorder compared to healthy controls as determined using a cluster extent correction procedure (height threshold of p < .005 uncorr. and cluster extent threshold of k > 169 voxels). Significant voxels are overlaid on the mean anatomical image of all participants (see also Table 3). Smaller GM volume was found in rostral parts of the anterior cingulate cortex (ACC), medial parts of the prefrontal cortex (mPFC) and in the median cingulate cortex (CC). Figure options Table 3. Results of the whole-brain analysis comparing local gray matter volume between healthy controls and patients with narcissistic personality disorder. Whole-brain results were corrected using cluster-extent correction procedures. The reverse contrast yielded no significant results. Significant clusters are presented from anterior to posterior. Healthy controls > patients with narcissistic personality disorder Left hemisphere Right hemisphere Region BA [X Y Z] k T d Region BA [X Y Z] k T d Sup. frontal g., medial 10 −3 59 25 236 3.61 1.25 Anterior cingulate g. 24 9 33 6 231 3.17 1.07 Middle frontal g. 10 −32 39 16 274 3.69 1.05 Middle frontal g. 8 29 17 42 639 4.10 1.47 Insula 13 −41 6 −5 300 3.32 1.23 Sup. frontal g., dl. 6 20 −4 57 222 3.54 1.10 Median cingulate g. 24 −5 −9 42 1259 3.84 1.51 Middle frontal g. 6 42 −4 60 440 3.43 1.18 Postcentral g. 4 −51 −10 49 647 4.56 1.34 BA – Brodman Area, dl. – dorsolateral, g. – gyrus, k – cluster size in voxels, T – T-value of the peak voxel, d – Cohen's d of the significant cluster. Table options In order to test whether GM volume of the anterior insula is associated with self-reported empathy, regression analyses were calculated. Independent of the factor group, GM volume of the left anterior insula was marginally, positively correlated with emotional empathy (left anterior insula: [−35,5,−14], T = 3.01, p < .10 [FWE], r = .62; right anterior insula [39,0,−15], T = 2.25, p > .30 [FWE]). For visualization see Fig. 1. Neither group specific effects nor relations of cognitive empathy with GM volume of the anterior insula were found.