Altered Intrinsic Brain Functional Connectivity in Suicidal Patients with Major Depressive Disorder
Ziqi Chen1, Mingrui Xia2, Jia Liu1, Zhiyun Jia1,3, Xin Xu1,4, Weihong Kuang4, Yong He2, and Qiyong Gong1,5

1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, 2State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China, People's Republic of, 3Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, 4Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, China, People's Republic of, 5Department of Psychology, School of Public Administration, Sichuan University, Chengdu, China, People's Republic of

Synopsis

The underlying neural correlates of suicide attempts in major depressive disorder (MDD) at the connectivity or circuit level remains incompletely understood. Therefore, we utilized a graph-theory approach—functional connectivity strength (FCS) to identify resting-state functional connectivity alterations of whole-brain networks in MDD patients with a history of suicide attempts. Relative to healthy controls, two MDD patient groups (attempters and non-attempters) showed overlapping reduced FCS in the middle and inferior occipital gyrus (IOG), insula, superior temporal gyrus, thalamus and limbic regions, while attempters showed more decreased FCS in right insula and left IOG. The depression severity was positively correlated with FCS in right thalamus in suicide attempters. Disconnection of the insula and IOG could be biological correlates of impaired decision making and emotional information processing in MDD patients with a history of suicide attempt.

Purpose

Although many studies have suggested brain structural and functional alterations related to suicide behavior, the underlying neural correlates of suicide attempts in major depressive disorder (MDD) at the connectivity or circuit level remains incompletely understood. Here, we seek to investigate the whole-brain functional connectivity patterns in MDD patients with a history of a suicide attempt relative to MDD patients without such history.

Methods

The participants were 36 medication-free MDD patients, with (N = 15) and without (N = 35) a history of a suicide attempt, and 37 healthy controls matched for age and gender. We utilized a graph-theory approach—functional connectivity strength (FCS)1,2 to compare the resting-state functional connectivity of whole-brain networks among these three groups. Correlation analyses were conducted between the depression severity, illness duration and FCS values extracted from the altered brain regions in MDD patients, with and without a history of a suicide attempt.

Results

Relative to the healthy controls, the two MDD patient groups showed overlapping reduced FCS the middle and inferior occipital gyrus (IOG), insula, superior temporal gyrus, thalamus and limbic regions, while suicide attempters showed more decreased FCS in the right insula and left IOG (Figure 1). The correlation analysis showed that depression severity was positively correlated with FCS values in the right thalamus in suicide attempters (Figure 2).

Discussion

The insula is thought to act as an integral hub, in mediating dynamic interactions between large-scale brain networks to generate appropriate behavioral responses to salient stimuli and coordinate executive control functions related to decision-making.3 The reduction of FCS in the insula suggests that the suicidal behavior in MDD patients are associated with disruption in a neural system that subserves cognitive control functions, and may be related to biased decision-making. The IOG has been implicated in the perceptual processing of emotional stimuli.4 The decreased FCS in the IOG may lead to the disconnection in the neural system of perceptual processing of emotional stimuli which could explain the emotional information processing deficits in MDD patients with a history of suicide attempts.

Conclusion

Disconnection of the insula and inferior occipital gyrus could be a biological correlate of impaired decision making and emotional information processing in MDD patients with a history of suicide attempt. Future studies with longitudinal designs, large samples and combined analysis of multimodal imaging data are needed to better characterize the neurobiological mechanisms of suicidal behavior.

Acknowledgements

This study was supported by the National Natural Science Foundation (Grant Nos.81220108013, 81271532, 81227002, 30900378 and 81030027), National Key TechnologiesR&D Program (Program No. 2012BAI01B03) and Program for Changjiang Scholars andInnovative Research Team in University (PCSIRT, Grant No. IRT1272)of China. Dr. Gong would like to acknowledges the support from his Changjiang Scholar Professorship Award(Award No. T2014190) of China and the CMB Distinguished Professorship Award (AwardNo. F510000/G16916411) administered by the Institute of International Education, USA.

References

1. Buckner RL, Sepulcre J, Talukdar T, et al. Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer's disease. J neurosci. 2009; 29(6): 1860-1873.

2. Liang X, Zou Q, He Y, et al. Coupling of functional connectivity and regional cerebral blood flow reveals a physiological basis for network hubs of the human brain. Proc Natl Acad Sci U S A. 2013; 110(5): 1929-1934.

3. Menon V, Uddin LQ. Saliency, switching, attention and control: a network model of insula function. Brain struct funct. 2010; 214(5-6): 655-667.

4. Haxby JV, Hoffman EA, Gobbini MI. The distributed human neural system for face perception. Trends Cogn Sci. 2000; 4(6): 223-233.

Figures

Figure 1. Difference of functional connectivity strength maps between major depressive disorder patients with and without a history of a suicide attempt and healthy controls. p<0.05 (corrected) Abbreviation: nSA: major depressive disorder patients without a history of a suicide attempt; SA: major depressive disorder patients with a history of a suicide attempt; HC: healthy control.

Figure 2. Correlation map of 17-items Hamilton Rating Scale for Depression (HAMD) score and functional connectivity strength values in the right thalamus in major depressive disorder patients with a history of a suicide attempt.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
4155