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Abnormal Local Functional Connectivity Density in Major Depressive Disorder Patients with Suicidal Behavior1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, People's Republic of China, 2State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, People's Republic of China, 3Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, People's Republic of China, 4Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, People's Republic of China, 5State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, 6Department of Psychology, Sichuan University, Chengdu, People's Republic of China
Synopsis
Previous studies suggested abnormal functional connectivity related to suicide behavior, which however relied on priori selection of seed regions. We applied functional connectivity density (FCD) to investigate the short-range and long-range functional connectivity patterns in major depressive disorder (MDD) patients with suicidal behavior. Relative to healthy controls, MDD patients with suicidal behavior showed reduced short-range FCD in bilateral thalamus, left hippocampus and increased short-range FCD in left precuneus. This study demonstrated altered local connectivity density at voxel level in MDD patients with suicidal behavior and highlighted that the thalamus, hippocampus and precuneus were important brain network hubs for these patients.
Purpose
Previous studies have suggested abnormal brain functional connectivity related to suicide behavior. However, these studies usually relied strongly on a priori selection of seed regions and may not be able to identify hubs with connection number changes at voxel level. Here, we applied functional connectivity density (FCD)1,2, a graph-theory approach to investigate the short-range (implicated in functional specialization) and long-range (implicated in functional integration) functional connectivity patterns in major depressive disorder (MDD) patients with suicidal behavior.Methods
The participants were 15 medication-free MDD patients with a history of a suicide attempt, and 37 healthy controls matched for age and gender. Using the FCD method, both short-range (local) FCD and long-range (distal) FCD were compared between these two groups. Correlation analyses were conducted between the depression severity, illness duration and FCD values extracted from the altered brain regions in MDD patients with suicidal behavior.Results
Relative to the healthy controls, the MDD patients with suicidal behavior showed significantly reduced short-range FCD in the bilateral thalamus, left hippocampus and increased short-range FCD in the left precuneus (Figure 1). All the clusters survived two-tailed Gaussian Random Field (GRF) correction at p <0.05 (voxel z value >2.58). No marked long-range FCD alterations were found in MDD patients with suicidal behavior. These abnormalities were not correlated with depression severity or illness duration.Discussion
The thalamus mediates information flow between the limbic system (including the hippocampus) and cerebral cortex, which are together involved in the neural processing of cognition and mood3.The left hippocampus is important in memory and contextual learning4. Previous studies have reported that structural alterations of the thalamus and hippocampus were associated with suicide and/or depression3,5. The decreased short-range FCD in the thalamus and hippocampus may suggest impaired cognitive control of memory and emotional dysregulation in MDD patients with suicidal behavior. As an important node of default mode network, the precuneus has been implicated in visuo-spatial imagery, episodic memory retrieval and self-processing6. The increased short-range FCD in the precuneus may suggest the highly active role of this brain region in MDD patients with suicidal behavior.Conclusion
This study demonstrated alterations of local connectivity density at voxel level in MDD patients with suicidal behavior. Our findings highlighted that the thalamus, hippocampus and precuneus were important brain network hubs for MDD patients with suicidal behavior and provided new evidence of the dysfunction of connection hubs in the neuropathology of suicidal behavior. To better characterize the neurobiological mechanisms of suicidal behavior, further attempts should be made with larger sample sizes and multimodal imaging data.Acknowledgements
This study was supported by the National Natural Science Foundation of China (Grant Nos. 81621003 and 81220108013). Dr. Gong would like to acknowledge the support from his Changjiang Scholar Professorship Award (Award No. T2014190) of China and the CMB Distinguished Professorship Award (Award No. F510000/G16916411) administered by the Institute of International Education, USA.References
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2. Dardo Tomasi, Nora D. Volkow. Functional connectivity density mapping. Proc Natl Acad Sci U S A. 2010; 25;107(21):9885-90.
3. Jia Z, Huang X, Wu Q, et al. High-Field Magnetic Resonance Imaging of Suicidality in Patients With Major Depressive Disorder. Am J Psychiatry. 2010;167(11):1381-90.
4. Burgess N, Maguire EA, O'Keefe J. The human hippocampus and spatial and episodic memory. Neuron. 2002; 35(4):625-41.
5. Colle R, Chupin M, Cury C, et al. Depressed suicide attempters have smaller hippocampus than depressed patients without suicide attempts. J Psychiatr Res. 2015;61:13-8.
6. Cavanna AE, Trimble MR. The precuneus: a review of its functional anatomy and behavioural correlates. Brain. 2006; 129(Pt 3):564-83.
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