Skip to main content Accessibility help

Dissociable brain correlates for depression, anxiety, dissociation, and somatization in depersonalization-derealization disorder

  • Erwin Lemche (a1), Simon A. Surguladze (a1), Michael J. Brammer (a2), Mary L. Phillips (a3), Mauricio Sierra (a1), Anthony S. David (a1), Steven C. R. Williams (a2) and Vincent P. Giampietro (a2)...



The cerebral mechanisms of traits associated with depersonalization-derealization disorder (DPRD) remain poorly understood.


Happy and sad emotion expressions were presented to DPRD and non-referred control (NC) subjects in an implicit event-related functional magnetic resonance imaging (fMRI) design, and correlated with self report scales reflecting typical co-morbidities of DPRD: depression, dissociation, anxiety, somatization.


Significant differences between the slopes of the two groups were observed for somatization in the right temporal operculum (happy) and ventral striatum, bilaterally (sad). Discriminative regions for symptoms of depression were the right pulvinar (happy) and left amygdala (sad). For dissociation, discriminative regions were the left mesial inferior temporal gyrus (happy) and left supramarginal gyrus (sad). For state anxiety, discriminative regions were the left inferior frontal gyrus (happy) and parahippocampal gyrus (sad). For trait anxiety, discriminative regions were the right caudate head (happy) and left superior temporal gyrus (sad).


The ascertained brain regions are in line with previous findings for the respective traits. The findings suggest separate brain systems for each trait.


Our results do not justify any bias for a certain nosological category in DPRD.


Corresponding author

*Address for correspondence: Erwin Lemche, PhD, Section of Cognitive Neuropsychiatry, Box PO69, Institute of Psychiatry, King's College School of Medicine, De Crespigny Park, London SE5 8AF, UK. (Email:


Hide All

We thank The Wellcome Trust, ARC Programme, and The Pilkington Family Trust for support of this work.



Hide All
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
2. Mula, M, Pini, S, Cassano, GB. The neurobiology and clinical significance of depersonalization in mood and anxiety. J Affect Disord. 2007; 99(1–3): 9199.
3. Yargic, LI, Sar, V, Tutkun, H, Alyanak, B. Comparison of dissociative identity disorder with other diagnostic groups. Compr Psychiatry. 1998; 39(6): 345351.
4. Rief, W, Auer, C. Cortisol and somatization. Biol Psychol. 2000; 53(1): 1323.
5. van der Kolk, BA, Pelcovitz, D, Roth, S, etal. Dissociation, somatization, and affect dysregulation: the complexity of adaptation of trauma. Am J Psychiatry. 1996; 153(7 suppl): 8393.
6. Rief, W, Broadbent, E. Explaining medically unexplained symptoms—models and mechanisms. Clin Psychol Rev. 2007; 27(7): 821841.
7. Hennings, A, Zill, P, Rief, W. Serotonin transporter gene promoter polymorphism and somatoform symptoms. J Clin Psychiatry. 2009; 70(11): 15361539.
8. Lemche, E, Giampietro, VP, Brammer, MJ, etal. Somatization severity associated with postero-medial complex structures. Sci Rep. 2012; 3: 1032.
9. Frewen, PA, Lanius, RA, Dozois, DJ, etal. Clinical and neural correlates of alexithymia in posttraumatic stress disorder. J Abnorm Psychol. 2008; 117(1): 171181.
10. Mula, M, Pini, S, Calugi, S, etal. Validity and reliability of the Structured Clinical Interview for Depersonalization-Derealization Spectrum (SCI-DER). Neuropsychiatr Dis Treat. 2008; 4(5): 977986.
11. de Ruiter, MB, Veltman, DJ, Phaf, RH, van Dyck, R. Negative words enhance recognition in nonclinical high dissociators: an fMRI study. Neuroimage. 2007; 37(1): 323334.
12. Choi, J, Jeong, B, Rohan, ML, Polcari, AM, Teicher, MH. Preliminary evidence for white matter tract abnormalities in young adults exposed to parental verbal abuse. Biol Psychiatry. 2009; 65(3): 227234.
13. Lanius, RA, Vermetten, E, Loewenstein, RJ, etal. Emotion modulation in PTSD: clinical and neurobiological evidence for a dissociative subtype. Am J Psychiatry. 2010; 167(6): 640647.
14. Felmingham, K, Kemp, AH, Williams, L, etal. Dissociative responses to conscious and non-conscious fear impact underlying brain function in post-traumatic stress disorder. Psychol Med. 2008; 38(12): 17711780.
15. Lemche, E, Surguladze, SA, Giampietro, VP, etal. Limbic and prefrontal responses to facial emotion expressions in depersonalization. Neuroreport. 2007; 18(5): 473477.
16. Mayberg, HS. Defining the neural circuitry of depression: toward a new nosology with therapeutic implications. Biol Psychiatry. 2007; 61(6): 729730.
17. Phillips, ML, Ladouceur, CD, Drevets, WC. A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Mol Psychiatry. 2008; 13(9): 829, 833857.
18. Knyazev, GG, Savostyanov, AN, Levin, EA. Alpha oscillations as a correlate of trait anxiety. Int J Psychophysiol. 2004; 53(2): 147160.
19. Etkin, A, Klemenhagen, KC, Dudman, JT, etal. Individual differences in trait anxiety predict the response of the basolateral amygdala to unconsciously processed fearful faces. Neuron. 2004; 44(6): 10431055.
20. Chua, P, Krams, M, Toni, I, Passingham, R, Dolan, R. A functional anatomy of anticipatory anxiety. Neuroimage. 1999; 9(6 pt 1): 563571.
21. World Medical Association. Code of Ethics: Declaration of Helsinki. 2013;
22. Sierra, M, Berrios, GE. The Cambridge Depersonalization Scale. Psychiatry Res. 2000; 93(2): 153164.
23. Oldfield, RC. The assessment and analysis of handedness: the Edinburgh Inventory. Neuropsychologia. 1971; 7: 97113.
24. Beck, AT, Ward, CH, Mendelson, M, Mock, J, Erbaugh, J. An inventory for measuring depression. Arch Gen Psychiatry. 1961; 4: 561571.
25. Spielberger, CD. Manual for the State-Trait Anxiety Inventory (STAI). Palo Alto, CA: Consulting Psychologists Press; 1983.
26. Bernstein-Carlson, EM, Putnam, FW. Development, reliability and validity of a dissociation scale. J Nerv Ment Dis. 1986; 174(12): 727735.
27. Rief, W, Hiller, W, Heuser, J. SOMS: The Screening for Somatoform Disorders. Berne, Switzerland: Hans Huber Verlag; 1997.
28. Surguladze, S, Brammer, MJ, Keedwell, P, etal. A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder. Biol Psychiatry. 2005; 57(3): 201209.
29. Osuch, EA, Ketter, TA, Kimbrell, TA, etal. Regional cerebral metabolism associated with anxiety symptoms in affective disorder patients. Biol Psychiatry. 2000; 48(10): 10201023.
30. Ushida, T, Ikemoto, T, Tanaka, S, etal. Virtual needle pain stimuli activates cortical representation of emotions in normal volunteers. Neurosci Lett. 2008; 439(1): 712.
31. Hennenlotter, A, Schroeder, U, Erhard, P, etal. A common neural basis for receptive and expressive communication of pleasant facial affect. Neuroimage. 2005; 26(2): 581591.
32. Mitterschiffthaler, MT, Fu, CH, Dalton, JA, Andrew, CM, Williams, SC. A functional MRI study of happy and sad affective states induced by classical music. Hum Brain Mapp. 2007; 28(11): 11501162.
33. Lee, BT, Seong Whi, C, Hyung Soo, K, etal. The neural substrates of affective processing toward positive and negative affective pictures in patients with major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31(7): 14871492.
34. Blaizot, X, Mansilla, F, Insausti, AM, etal. The human parahippocampal region: I. temporal pole cytoarchitectonic and MRI correlation. Cereb Cortex. 2010; 20(9): 21982212.
35. Vuilleumier, P, Armony, JL, Driver, J, Dolan, RJ. Distinct spatial frequency sensitivities for processing faces and emotional expressions. Nat Neurosci. 2003; 6(6): 624631.
36. Goldin, PR, McRae, K, Ramel, W, Gross, JJ. The neural bases of emotion regulation: reappraisal and suppression of negative emotion. Biol Psychiatry. 2008; 63(6): 577586.
37. Peluso, MA, Glahn, DC, Matsuo, K, etal. Amygdala hyperactivation in untreated depressed individuals. Psychiatry Res. 2009; 173(2): 158161.
38. Versace, A, Thompson, WK, Zhou, D, etal. Abnormal left and right amygdala-orbitofrontal cortical functional connectivity to emotional faces: state versus trait vulnerability markers of depression in bipolar disorder. Biol Psychiatry. 2010; 67(5): 422431.
39. Phillips, ML, Bullmore, ET, Howard, R, etal. Investigation of facial recognition memory and happy and sad facial expression perception. Psychiatry Res. 1998; 83(3): 127138.
40. Hofer, A, Siedentopf, CM, Ischebeck, A, etal. Sex differences in brain activation patterns during processing of positively and negatively valenced emotional words. Psychol Med. 2007; 37(1): 109119.
41. Sommer, M, Sodian, B, Döhnel, K, etal. In psychopathic patients emotion attribution modulates activity in outcome-related brain areas. Psychiatry Res. 2010; 182(2): 8895.
42. Winecoff, A, Labar, KS, Madden, DJ, Cabeza, R, Huettel, SA. Cognitive and neural contributors to emotion regulation in aging. Soc Cogn Affect Neurosci. 2011; 6(2): 165176.
43. Leitman, DI, Wolf, DH, Ragland, JD, etal. “It's not what you say, but how you say it”: a reciprocal temporo-frontal network for affective prosody. Front Hum Neurosci. 2010; 4: 19.
44. Longe, O, Maratos, FA, Gilbert, P, etal. Having a word with yourself: neural correlates of self-criticism and self-reassurance. Neuroimage. 2010; 49(2): 18491856.
45. Keedwell, PA, Drapier, D, Surguladze, S, etal. Subgenual cingulate and visual cortex responses to sad faces predict clinical outcome during antidepressant treatment for depression. J Affect Disord. 2010; 120(1–3): 120125.
46. Colibazzi, T, Posner, J, Wang, Z, etal. Neural systems subserving valence and arousal during the experience of induced emotions. Emotion. 2010; 10(3): 377389.
47. Vrticka, P, Andersson, F, Sander, D, Vuilleumier, P. Memory for friends or foes: the social context of past encounters with faces modulates their subsequent neural traces in the brain. Soc Neurosci. 2009; 4(5): 384401.
48. Suslow, T, Kugel, H, Reber, H, etal. Automatic brain response to facial emotion as a function of implicitly and explicitly measured extraversion. Neuroscience. 2010; 167(1): 111123.
49. Sergerie, K, Lepage, M, Armony, JL. Influence of emotional expression on memory recognition bias. Biol Psychiatry. 2007; 62(10): 11261133.
50. Daly, E, Deeley, Q, Hallahan, B, etal. Effects of acute tryptophan depletion on neural processing of facial expressions of emotion in humans. Psychopharmacology (Berl). 2010; 210(4): 499510.
51. Goldin, PR, Hutcherson, CA, Ochsner, KN, etal. The neural bases of amusement and sadness: a comparison of block contrast and subject-specific emotion intensity regression approaches. Neuroimage. 2005; 27(1): 2636.


Type Description Title
Supplementary materials

Lemche Supplementary Material
Supplementary Material

 Word (578 KB)
578 KB


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed