Alexithymia and reduced white matter integrity in schizophrenia: A diffusion tensor imaging study on impaired emotional self-awareness

https://doi.org/10.1016/j.schres.2012.08.026Get rights and content

Abstract

Alexithymia is characterized by deficits in emotional self-awareness. A number of previous studies have revealed impaired emotional self-awareness in schizophrenia. Although the pathology of schizophrenia is thought to involve disrupted white matter integrity, its relationship with alexithymia remains unclear. The present study investigated associations between alexithymia and white matter integrity, to seek the neural basis of impaired emotional self-awareness in schizophrenia. Forty-four patients with schizophrenia and 44 age-, gender- and predicted IQ level-matched healthy controls underwent diffusion-weighted imaging. Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20). We applied tract-based spatial statistics to investigate the correlation between the TAS-20 total score and white matter fractional anisotropy (FA). TAS-20 scores were significantly higher in patients than in controls. In the patient group only, FA was negatively correlated with the TAS-20 total score in the corpus callosum, mostly the left part of the superior and inferior longitudinal fasciculi, the inferior occipito-frontal fasciculus, the anterior and posterior thalamic radiation, and the precuneus white matter. These results suggest that schizophrenia is associated with alexithymia, and that reduced white matter integrity within these regions constitutes an important pathology underlying impaired self-emotional awareness in schizophrenia.

Introduction

Alexithymia is characterized by deficits in emotional self-awareness, and refers to a cognitive-affective disturbance that affects the way individuals recognize and verbalize emotions (Sifneos, 1972). Alexithymic individuals show difficulty in recognizing and describing their own feelings, and in discriminating between emotional states and bodily sensations (Taylor, 1984). Their communicative style is characterized by markedly reduced or absent symbolic thinking, so that inner attitudes, feelings, wishes, and drives are not revealed (Taylor, 1984).

The phenomenon was first described in patients with psychosomatic disorders (Sifneos, 1972). A number of subsequent studies reported that alexithymia is shown in other psychiatric disorders, including eating disorders (Taylor et al., 1996, Bydlowski et al., 2005), dissociative disorders (Elzinga et al., 2002, Sayar et al., 2005), posttraumatic stress disorder (Frewen et al., 2008), and pervasive developmental disorders (Fitzgerald and Molyneux, 2004, Szatmari et al., 2008). Alexithymia is also found in schizophrenia (Stanghellini and Ricca, 1995, Maggini and Raballo, 2004, Todarello et al., 2005, van't Wout et al., 2007, Kubota et al., 2011).

Meanwhile, magnetic resonance imaging (MRI) studies on patients with schizophrenia have consistently reported gray matter (GM) volume reductions in frontal, temporal and parietal cortical regions, medial temporal lobe structures, the basal ganglia, and the thalamus (Shenton et al., 2001, Ellison-Wright et al., 2008). This disorder is thought to arise as a result of disrupted connectivity among these GM regions (Friston, 1998). Diffusion tensor imaging (DTI) techniques have recently been developed to provide information about white matter (WM) tracts and their organization based on water diffusion. Fractional anisotropy (FA) is the fraction of the total “magnitude” of the diffusion tensor that we can ascribe to anisotropic diffusion (Basser, 1995). FA ranges from 0 to 1, where 0 represents no preferred direction (isotropic diffusion), and 1 represents unidirectional movement (anisotropic diffusion) (Thomason and Thompson, 2011). It is the most commonly used index of DTI, and reduction of FA implies decreased WM tract integrity. A number of studies have demonstrated FA reductions in diverse areas including frontal and temporal WM, the corpus callosum (CC), the cingulum, the fornix, fronto-temporal tracts, and fronto-occipital fascicule in patients with schizophrenia (Walterfang et al., 2006, Kubicki et al., 2007). These findings suggest that WM abnormalities may be an anatomical substrate for the ‘disconnection hypothesis’ (Friston, 1998) of schizophrenia.

While the neural basis of alexithymia remains a subject of ongoing investigation, previous neuroimaging studies have suggested the importance of the anterior and posterior cingulate cortex, the orbitofrontal cortex, the dorsolateral prefrontal cortex, the insula, and transcallosal interhemispheric transfer in alexithymia of healthy subjects (Kano et al., 2003, Mantani et al., 2005, Moriguchi et al., 2007a, Romei et al., 2008, Borsci et al., 2009). On the other hand, neural underpinnings of alexithymia in schizophrenia remain mostly unclear. To the best of our knowledge, only our previous study has explored such a relationship in the whole brain in schizophrenia, and it demonstrated a negative correlation between alexithymia and GM volume in the left supramarginal gyrus, which is thought to be involved in various cognitive functions (Kubota et al., 2011). However, so far there is no study that has investigated the relationship between alexithymia and WM integrity in schizophrenia.

The present study sought to examine the association between alexithymia and WM integrity in schizophrenia, using DTI. We employed the Japanese version of the 20-item Toronto Alexithymia Scale (TAS-20; Bagby et al., 1994a, Bagby et al., 1994b, Moriguchi et al., 2007b), a well-validated test that has been used to assess alexithymia in many studies on patients with schizophrenia (Maggini and Raballo, 2004, Todarello et al., 2005, Kubota et al., 2011). We also applied a widely developed technique called tract-based spatial statistics (TBSS) (Smith et al., 2006) to perform voxelwise correlational analysis on WM integrity, and FA was used as an index of integrity. TBSS maps each subject's DTI data onto a common WM tract center (‘skeleton’), and is robust to registration confounds. We hypothesized that severity of alexithymia in patients would be correlated with FA reduction in regions that are crucial for impaired cognitive abilities in this disease.

Section snippets

Participants

The schizophrenia group comprised of 44 patients (26 men and 18 women, all right-handed) who were referred to the Department of Psychiatry, Kyoto University Hospital. Each patient fulfilled the criteria for schizophrenia based on the Structural Clinical Interview for DSM-IV Axis I Disorders-Patient Edition, Version 2.0 (SCID-P). None of the patients were comorbid with other psychiatric disorders. Predicted IQ was measured by the Japanese Version of the National Adult Reading Test short form (

Task performance of TAS-20

The demographic and clinical data as well as TAS-20 results are shown in Table 1. Many patients were in the chronic stages. Numbers of patients with mild/moderate/severe symptoms are 41/3/0 for the total score, 39/5/0 for the positive, 35/9/0 for the negative, and 41/3/0 for the general psychopathology subscale scores, respectively, indicating that many patients were with mild symptom severity.

An independent sample t-test revealed that TAS-20 total, and subscale scores of DIF, DDF, and EOT were

Discussion

To our knowledge, this is the first study to investigate the relationship between alexithymia and WM connectivity in patients with schizophrenia, using DTI. The results indicate the existence of WM pathology possibly underlying impaired emotional self-awareness in schizophrenia.

The group comparison of TAS-20 revealed an association between schizophrenia and alexithymia, consistent with previous studies (Stanghellini and Ricca, 1995, Maggini and Raballo, 2004, Todarello et al., 2005, van't Wout

Role of funding source

This work was supported by grants-in-aid for scientific research B (23390290), S (22220003), and on Innovative Areas (23118004, 23120009), from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Grants-in-Aid for Young Scientists A (23680045), B (23791329) from the Japan Society for the Promotion of Science; a grant from Research Group for Schizophrenia, Japan; a grant from Mitsubishi Pharma Research Foundation; a grant from Takeda Science Foundation, Japan; a grant

Contributors

Manabu Kubota designed the study and wrote the protocol, and also managed the literature searches and analyses and wrote the first draft of the manuscript. Manabu Kubota, Jun Miyata, Akihiko Sasamoto, Ryosaku Kawada, Shinsuke Fujimoto, and Yusuke Tanaka undertook the analysis and interpretation of clinical and psychological data. Manabu Kubota performed data processing and statistical analyses, under technical supervision by Jun Miyata, Nobukatsu Sawamoto, Hidenao Fukuyama, Hidehiko Takahashi,

Conflict of interest

All authors declare that they have no conflicts of interest.

Acknowledgments

The authors wish to extend their gratitude to Hironobu Fujiwara and Kazuyuki Hirao for their assistance in data acquisition and are especially thankful to the patients and volunteers for participating in the study.

References (66)

  • K.J. Friston

    The disconnection hypothesis

    Schizophr. Res.

    (1998)
  • H. Guttman et al.

    Alexithymia, empathy, and psychological symptoms in a family context

    Compr. Psychiatry

    (2002)
  • K.H. Karlsgodt et al.

    Diffusion tensor imaging of the superior longitudinal fasciculus and working memory in recent-onset schizophrenia

    Biol. Psychiatry

    (2008)
  • C. Knöchel et al.

    Interhemispheric hypoconnectivity in schizophrenia: fiber integrity and volume differences of the corpus callosum in patients and unaffected relatives

    Neuroimage

    (2012)
  • M. Kubicki et al.

    A review of diffusion tensor imaging studies in schizophrenia

    J. Psychiatr. Res.

    (2007)
  • M. Kubota et al.

    Alexithymia and regional gray matter alterations in schizophrenia

    Neurosci. Res.

    (2011)
  • T. Mantani et al.

    Reduced activation of posterior cingulate cortex during imagery in subjects with high degrees of alexithymia: a functional magnetic resonance imaging study

    Biol. Psychiatry

    (2005)
  • A.K. Mattila et al.

    Age is strongly associated with alexithymia in the general population

    J. Psychosom. Res.

    (2006)
  • J. Miyata et al.

    Reduced white matter integrity as a neural correlate of social cognition deficits in schizophrenia

    Schizophr. Res.

    (2010)
  • J.D. Parker et al.

    The alexithymia construct: relationship with sociodemographic variables and intelligence

    Compr. Psychiatry

    (1989)
  • A. Pasini et al.

    Alexithymia as related to sex, age, and educational level: results of the Toronto Alexithymia Scale in 417 normal subjects

    Compr. Psychiatry

    (1992)
  • S. Patel et al.

    A meta-analysis of diffusion tensor imaging studies of the corpus callosum in schizophrenia

    Schizophr. Res.

    (2011)
  • O.R. Phillips et al.

    Fiber tractography reveals disruption of temporal lobe white matter tracts in schizophrenia

    Schizophr. Res.

    (2009)
  • M.E. Shenton et al.

    A review of MRI findings in schizophrenia

    Schizophr. Res.

    (2001)
  • S.M. Smith et al.

    Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localization in cluster inference

    Neuroimage

    (2009)
  • S.M. Smith et al.

    Advances in functional and structural MR image analysis and implementation as FSL

    Neuroimage

    (2004)
  • S.M. Smith et al.

    Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data

    Neuroimage

    (2006)
  • G.J. Taylor et al.

    Relationships between alexithymia and psychological characteristics associated with eating disorders

    J. Psychosom. Res.

    (1996)
  • L.J. van der Knaap et al.

    How does the corpus callosum mediate interhemispheric transfer? A review

    Behav. Brain Res.

    (2011)
  • M. van 't Wout et al.

    No words for feelings: alexithymia in schizophrenia patients and first-degree relatives

    Compr. Psychiatry

    (2007)
  • M. Walterfang et al.

    Neuropathological, neurogenetic and neuroimaging evidence for white matter pathology in schizophrenia

    Neurosci. Biobehav. Rev.

    (2006)
  • N.C. Andreasen et al.

    “Cognitive dysmetria” as an integrative theory of schizophrenia: a dysfunction in cortical-subcortical-cerebellar circuitry?

    Schizophr. Bull.

    (1998)
  • M. Ashtari et al.

    Disruption of white matter integrity in the inferior longitudinal fasciculus in adolescents with schizophrenia as revealed by fiber tractography

    Arch. Gen. Psychiatry

    (2007)
  • Cited by (0)

    View full text