Preliminary communicationAltered brain response to others׳ pain in major depressive disorder
Introduction
Patients with major depressive disorder (MDD) experience significant social dysfunction, which may partly result from deficits in social cognition, involving the ability to understand and respond to the thoughts and feelings of others (Cusi et al., 2012).
Empathy is a set of constructs that enable us to understand the sensation and emotions of others by sharing their sensory and affective states, and thus has a central role in successful interpersonal engagement (Decety and Moriguchi, 2007). In recent years, functional magnetic resonance imaging (fMRI) studies during empathy for others׳ pain in healthy subjects have provided an avenue for investigating the neural basis of empathy. These studies showed the importance of brain regions implicated in cognitive and affective systems, such as the anterior cingulate cortex (ACC), middle cingulate cortex (MCC), anterior insula, and prefrontal cortices, and the regions for encoding the sensory dimension, such as somatosensory-related cortices (SRC) in the inferior parietal lobe, in terms of empathy processing (Jackson et al., 2006, Lamm et al., 2010, Lamm et al., 2011). These areas overlap with the neural network of the so-called “pain matrix”, which is activated in the direct experience of one׳s own pain (Peyron et al., 2000), thus these studies also suggest that the neural network for representing one׳s own subjective feeling states is crucial for understanding the emotional response in others.
In MDD patients, not only affective range is limited because of depressed mood and anhedonia, but also many of the cognitive and affective processes, for example, working memory and emotion regulation, are affected (Fu et al., 2008, Hasselbalch et al., 2011). Furthermore, the pain threshold of MDD patients is reported to be increased (Bär et al., 2007), therefore it is also possible that the sensory perception in this disorder might be altered. Accordingly, MDD patients would show altered empathic abilities (Cusi et al., 2011, Wilbertz et al., 2010). Indeed, it has been shown that depressed mothers are less responsive to crying of their newborn babies (Field et al., 2009). However, surprisingly, few studies have investigated the neural mechanisms underlying altered empathy in MDD patients.
To date, among many fMRI studies comparing MDD patients with healthy subjects, several studies, although not focusing on empathy, have showed differential activation in the above-mentioned brain networks that are important for empathy processing. For example, greater activation in the lateral prefrontal cortex and ACC were shown in MDD patients during a working memory task (Harvey et al., 2005). In addition, a recent study showed that neural activation in the cingulate cortex and inferior parietal cortex was reduced in MDD patients during sad facial emotion processing (Fu et al., 2008). However, to the best of our knowledge, there is no fMRI study directly investigating the neural basis of empathetic ability of MDD patients.
Here, we performed fMRI during an empathy task to test for the response to others׳ pain in MDD patients. We compared MDD patients and healthy subjects for their regional hemodynamic responses to visual perception of videos depicting human hands in painful situations. We hypothesized that the MDD patients would show reduced empathy for others׳ pain and also show different neural responses in regions related to cognitive, affective and sensory processing, such as, ACC, MCC, anterior insula, SRC, and prefrontal cortices.
Section snippets
Participants
Twelve patients who had experienced at least one episode of MDD based on the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) were recruited. Current comorbid axis I diagnoses were acceptable as long as the depressive episode was primary; one patient met the criteria for panic disorder and one patient for social anxiety disorder. The 17-item Hamilton Depression Rating Scale (HDRS) (Hamilton, 1960) was used to assess the severity of clinical symptoms. None had a previous history
Results
Demographic data are shown in Table 1. The MDD sample consisted of two euthymic patients (HDRS≤7), four patients with mild depression (8≤HDRS≤16), three patients with moderate depression (17≤HDRS≤23), and two patients with severe depression (24≤HDRS) (using the severity classification by Zimmerman et al., 2013).
MDD patients showed reduced pain ratings on the painful videos compared with healthy controls (HC, mean=66.1, SD=22.6; MDD, mean=33.9 SD=29.9, p=0.02). Both groups scored non-painful
Discussion
To the best of our knowledge, this is the first study to examine brain responses to others׳ pain in MDD patients. We found that the MDD patients rated the painful stimuli as less painful compared with healthy subjects. Furthermore, the MDD patients showed reduced cerebral activation in the left MCC and the right SRC, whereas showing greater cerebral activation in the left IFG during empathy for others׳ pain.
A previous study found that MDD patients showed reduced awareness of others׳ emotions
Role of funding source
This work was supported by Grants-in-Aid for Young Scientists B (23791326) from the Japan Society for the Promotion of Science; SENSHIN Medical Research Foundation; Grants-in-Aid for scientific research S (22220003), and on Innovative Areas (23118004), from the Ministry of Education, Culture, Sports, Science and Technology of Japan. These agencies had no further role in the study design, collection, analysis and interpretation of data, writing of the paper, or in the decision to submit the
Conflict of interest
All authors declare that they have no conflicts of interest.
Acknowledgments
The authors wish to extend their gratitude to Yusuke Tanaka, Manabu Kubota, Akihiko Sasamoto, Shiho Ubukata, Yukiko Matsumoto, Masanori Isobe, Shuraku Son, Kousuke Tsurumi, Kimito Hirose, Yasuo Mori, Naoto Yokoyama, Naho Saito, Tomomi Noda, Hideaki Takeuchi, Ema Murao and Takuro Murao for their assistance in data acquisition and processing, and, most of all, to the patients and volunteers for participating in the study. A part of this study is the result of Development of BMI Technologies for
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