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