White matter microstructural abnormalities and their association with anticipatory anhedonia in depression

https://doi.org/10.1016/j.pscychresns.2017.04.005Get rights and content

Highlights

  • We examined the association between anhedonia and white matter integrity in major depressive disorder.

  • Reduced fractional anisotropy in the cingulum and the corpus callosum.

  • Anticipatory anhedonia was significantly correlated with increased radial diffusivity.

Abstract

Anhedonia is associated with dysfunction of the neural circuitry of reward in patients with major depressive disorder (MDD). However, its neurobiological basis is not fully understood. The present study examined the association between anhedonia and white matter (WM) characteristics in patients with first-episode MDD. We recruited 30 patients with first-episode drug-naive MDD and 28 healthy controls (HC) to undergo diffusion weighted imaging. We examined specifically the correlation between WM characteristics and anhedonia measured with the Temporal Experience of Pleasure Scale (TEPS) in MDD patients. Using Track-Based Spatial Statistics (TBSS), we found that MDD patients exhibited reduced fractional anisotropy (FA) in the left cingulum and the forceps minor. These patients also exhibited increased radial diffusivity (RD) in several major tracts including the bilateral anterior thalamic radiation, the corticospinal tract, the superior longitudinal fasciculus and the uncinate fasciculus in the left hemisphere. Correlational analysis showed that increased RD was significantly correlated with anticipatory anhedonia in the MDD group, while reduced mean FA was correlated with consummatory anhedonia in HC. These preliminary findings suggest that left-sided WM tracts abnormalities may contribute to the development of anhedonia in MDD patients.

Introduction

Anhedonia is an important symptom of major depressive disorder (MDD) that reflects deficits in reward processing (Buckner et al., 2008), and continues to be present even after reduction in other depressive symptoms (Treadway and Zald, 2011). However, surprisingly few studies have examined the neurobiological basis of anhedonia in depressed patients. Emerging evidence suggests that anhedonia reflects disturbances in the reward circuitry including the orbitofrontal cortex (OFC), the striatum, and in particular the nucleus accumbens (NAcc), when MDD patients process rewarding stimuli (Pizzagalli et al., 2009, Smoski et al., 2009, Wacker et al., 2009). Our previous work (Yang et al., 2016) also found that diminished caudate nucleus responses were correlated with lower motivation in first-episode MDD patients. The present study aimed to extend this line of work by investigating the relationship between white matter (WM) characteristics of first-episode medication-naive MDD patients and anhedonia severity.

Diffusion tensor imaging (DTI) has been developed to reflect WM microstructure (Song et al., 2002). Fractional anisotropy (FA) is the most widely used measure to quantify white matter anisotropy with different eigenvalues. Other parameters, including mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) can be used to reflect different aspects of WM characteristics (Jones et al., 2013). Only four studies to date have examined the relationship between anhedonia and WM abnormality in MDD. The first study reported that higher levels of anhedonia was correlated with disruption in tracts connecting reward-related regions in depressed adolescents (Keedwell et al., 2012). The second study demonstrated that reduced FA was correlated with anhedonia severity in melancholic MDD patients in segments of the superior-lateral medial forebrain bundle (MFB) (Bracht et al., 2014). Subsequently, they further identified that mean FA of the left superior-lateral MFB was associated negatively with hedonic capacity in remitted MDD patients (Bracht et al., 2015). However, another study failed to identify any significant correlation between microstructure of the superior-lateral MFB and anhedonia in MDD patients (Blood et al., 2010). In brief, these findings suggest that altered WM in reward circuitries may be associated with anhedonia. However, these findings might be confounded by medication effects and methodological and sampling differences. Thus, a study of patients with medication-naive MDD could better address this question.

The present study aimed to use DTI to examine the WM characteristics of first-episode medication-naive MDD patients. We further assessed relationships between WM characteristics and anhedonia within the MDD group. We used the Temporal Experience of Pleasure Scale (TEPS) to evaluate anhedonia (Chan et al., 2012) and took the FA, AD, RD and MD values from the DTI data as indices of WM characteristics. Given that MDD may be correlated with abnormalities in subcortical reward circuitry (Bracht et al., 2015, Bracht et al., 2014), we hypothesized that MDD patients would show disruptions in WM tracts connecting reward-related regions involving the cingulum and the corpus callosum compared with controls. We also hypothesized that disruptions in these WM tracts would be correlated with anhedonia severity in patients with MDD.

Section snippets

Participants

Thirty medication-naive patients with first-episode MDD meeting the diagnostic criteria of the DSM-IV (APA, 2000) were recruited from the outpatient clinic of the Second Xiangya Hospital, the Central South University. The inclusion and exclusion criteria were the same as our previous study (Yang et al., 2016). In brief, all patients had a total score of ≥20 on the Hamilton Rating Scale for Depression (HAMD) (Williams, 1988), and had no history of drug treatment. Potential participants were

Demographic information

Demographic and clinical characteristics of the participants are shown in Table 1. The two groups did not differ in age, gender, years of education and IQ (all p>0.05). However, the MDD group reported significantly higher levels of trait anticipatory and consummatory anhedonia measured by the TEPS and higher levels of state anhedonia measured by the SHAPS than healthy controls (p<0.001). As expected, healthy controls reported significantly lower level of depressive symptoms on the BDI than the

Discussion

Consistent with our hypothesis, we found decreased FA in the left cingulum and the forceps minor of the corpus callosum in the medication-naïve patients with first-episode MDD. We also observed increased RD in patients with MDD in several tracts, including the bilateral anterior thalamic radiation, the corticospinal tract, the inferior fronto-occipital fasciculus, the cingulate gyrus, the forceps minor, the uncinate fasciculus and the superior longitudinal fasciculus in the left hemisphere.

Competing interests

None declared.

Contributors

Xin-hua Yang implemented the method, collected the original imaging data, and wrote the manuscript. Yi Wang analyzed and interpreted the imaging data. Dong-fang Wang and Kai Tian administered the tests and collected imaging data. Eric F C Cheung commented on the manuscript significantly. Guang-rong Xie supervised the clinical data collection and conducted the clinical interview. Raymond C K Chan generated the idea of the study, interpreted the findings and commented significantly on the drafts

Acknowledgements

This study was supported by the “Strategic Priority Research Program (B)” of the Chinese Academy of Sciences (XDB02030002), the Beijing Municipal Science and Technology Commission Grant (Z161100000216138), the Beijing Training Project for the Leading Talents in Science and Technology (Z151100000315020), the National Science Fund China (81571317), the CAS Key Laboratory of Mental Health, and the CAS/SAFEA International Partnership Programme for Creative Research Teams (Y2CX131003) to RCKC. XHY

References (37)

  • M.J. Smoski et al.

    fMRI of alterations in reward selection, anticipation, and feedback in major depressive disorder

    J. Affect. Disord.

    (2009)
  • S.K. Song et al.

    Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water

    NeuroImage

    (2002)
  • M.T. Treadway et al.

    Reconsidering anhedonia in depression: lessons from translational neuroscience

    Neurosci. Biobehav. Rev.

    (2011)
  • J. Wacker et al.

    The role of the nucleus accumbens and rostral anterior cingulate cortex in anhedonia: integration of resting EEG, fMRI, and volumetric techniques

    NeuroImage

    (2009)
  • X.H. Yang et al.

    Diminished caudate and superior temporal gyrus responses to effort-based decision making in patients with first-episode major depressive disorder

    Prog. Neuropsychopharmacol. Biol. Psychiatry

    (2016)
  • M. Annett

    A classification of hand preference by association analysis

    Br. J. Psychol.

    (1970)
  • APA

    Diagnostic and Statistical Manual of Mental Disorders

    (2000)
  • A.J. Blood et al.

    Microstructural abnormalities in subcortical reward circuitry of subjects with major depressive disorder

    PLoS One

    (2010)
  • Cited by (36)

    • Alterations in white matter microarchitecture in adolescents and young adults with major depressive disorder: A voxel-based meta-analysis of diffusion tensor imaging

      2022, Psychiatry Research - Neuroimaging
      Citation Excerpt :

      For the results of the meta-regression analysis, we ignored abnormalities that were not present in the main meta-analysis findings. The systematic searches retrieved a total of 884 possible articles, of which 9 articles were selected for the final meta-analysis(Bessette et al., 2014; Cullen et al., 2010; Guo et al., 2012; Henderson et al., 2013; Ma et al., 2007; Peng et al., 2013; Xiao et al., 2015; Yang et al., 2017; Zhu et al., 2011). The final sample in these included studies consisted of 205 adolescents and young adults with MDD (92 males and 113 females; mean age: 23.00 years) compared with 194 HCS (88 males and 106 females; mean age: 22.37 years).

    • Heterogeneous alterations in thalamic subfields in major depression disorder

      2021, Journal of Affective Disorders
      Citation Excerpt :

      Despite the lack of studies based upon structural MRI in the thalamic subregions in MDD patients, the findings from studies using diffusional or functional MRI were similar to ours. A study using diffusion tensor imaging reported that, compared with NC, FEDN patients showed increased radial diffusivity in the bilateral anterior thalamic radiation (Yang et al., 2017). Moreover, a meta-analysis using resting-state positron emission tomography or single-photon emission computed tomography reported that MDD patients had significantly more activity in the bilateral pulvinar nuclei of the thalamus than NC (Hamilton et al., 2012).

    View all citing articles on Scopus
    View full text