Structural brain abnormalities in MDD patients with suicideļ¼š A DARTEL-enhanced voxel-based morphometry study
Huiru Li1, Huawei Zhang1, Li Yin2, Zhiyun Jia1, and Qiyong Gong1

1Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China, 2Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, China


We performed a VBM analysis with DARTEL to analysis the different structure in healthy controls, MDD patients with or without suicidal actors. The result shows suicidal patients had reduced GMV than patient controls in precuneus/cuneus, anterior cingulate cortex and orbital frontal gyrus. Particularly, we found suicidal ideators have reduced GMV in middle frontal gyrus compared to suicidal attempters. Negative correlation was found between clinical characters and volume of some regions. The dysfunction of self-awareness, emotional processing and impulsivity control function caused by the abnormalities of these brain regions may be associated suicidal behavior.


The aetiology of suicidal behavior is complex, and the depression is an important predisposing factor to suicidal behavior. But knowledge about its neurobiological mechanisms is limited and there is no consensus opinion on structure MRI imaging findings of the suicidal brain of depression. This study aims to find more detailed insight into grey matter structure and to obtain evidence for neuroanatomical difference in suicidal brain.


This study was approved by the local ethics committee, and all subjects provided written informed consent. Participant was included 47 healthy controls, 30 depressions without suicide (patient controls) and 40 depressions with suicidal behaviors (20 suicidal ideators and 20 suicidal attempters). Age and sex were matched among the three groups. Clinical symptoms were assessed with the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA) and Barratt Impulsiveness Scale (BIS) among patient controls and suicidal behaviors.

We performed a voxel-based morphometry (VBM) with Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) to analysis the different structure. The analysis was performed using an automated Computational Anatomy Toolbox (CAT12) within Statistical Parametric Mapping (SPM12) while running MATLAB (R2013b). T1 images were normalized to a template space and segmented into gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). And then smoothed using a 6-mm full-width-at-half-maximum (FWHM) Gaussian kernel. We using an analysis of covariance (ANCOVA) with whole-brain volume, age, and gender as covariates to compare group differences of gray matter volume (GMV) and then a subsequent post-hoc analysis used a two-sample t-test. Statistical inferences were performed with a threshold of p<0.05 with family wise error correction (FWE). Then we particularly performed a two-sample t-test between SAs and SIs.


GMV across all three groups differed in bilateral precuneus, right cuneus, bilateral anterior cingulate cortex, and left superior orbital frontal gyrus. And the post-hoc t-tests showed that suicidal patients had reduced GMV than patient controls in bilateral precuneus, right cuneus, bilateral anterior cingulate cortex, and left superior orbital frontal gyrus. Moreover, we also found the patients controls showed increased GMV in bilateral precuneus and right cuneus than healthy controls. The t test analysis between SAs and SIs shows increased GMV in SAs than SIs in left middle frontal gyrus. Significant negative correlations with HAMD and HAMA scores were observed in left precuneus, and BIS scores was negatively correlated in right cuneus for GMV in suicidal groups.


The precuneus plays an important role in processing of self-relevant information, especially self-awareness1,2. High self-awareness may increase motivation to suicide3. Previous MRI studies found abnormal structure and decreased activation in precuneus/cuneus in SAs of MDD4-6. The decreased volume of precuneus and negative correlation in depression level suggest the deficits of precunes/cuneus function is associated to suicide behavior in MDD.

Both anterior cingulate cortex and orbital frontal gyrus are involved in emotional processing7, 8.Self-referential suicidal ideation such as hopelessness may be related to the alteration of ACC9. In previous studies, the alteration of structure and function of ACC were found in suicidal brain9-12. Abnormal orbitofrontal cortex makes patients more prone to making dangerous choices such as suicide13. Previous fMRI studies found in suicidal brain the OFC has reduced volume and performed less actively during decision-making some tasks13-15. Current findings of ACC and OFC are consistent with these results.

The middle frontal gyrus includes the dorsolateral prefrontal area, which plays a critical role in the development of SAs. DLPFC is a region associated with executive functions16. A systematic review shows suicidality may be associated with executive function deficits17. Previous studies found functional abnormality of the frontal cortex in SAs is related to the degree of impulsivity18, 19. Particularly, a PET study investigated rCMRglu was different in suicidal ideators and suicidal plans20. Our result may suggest MFG contributes to impulsive traits, which is associated with a vulnerability of suicidal behavior.


We found the GMV changes in the precuneus/cuneus, anterior cingulate cortex, orbital frontal gyrus and middle frontal gyrus in suicidal attempters. The dysfunction of self-awareness, emotional processing and impulsivity control function caused by the abnormalities of these brain regions may be associated with the vulnerability for suicidal behavior in MDD.


This study was supported by the National Natural Science Foundation (Grant Nos. 81771718, 81621003, 81571637 and 81271532). Q.G. received the support from 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.


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Significant GMV differences are observed among healthy controls, patients controls and suicidal actors in right precuneus/cuneus (A), left orbital frontal gyrus (B) and left anterior cingulate cortex (C) shown projected onto the gray matter template built using DARTEL (corrected for multiple comparisons using a family-wise-error rate with p < 0.05). Significant GMV decrease in suicidal ideators compared with suicidal attempters in left middle frontal gyrus (D).

Abbreviation: GMV=Gray matter volume.

Both HAMD scores and HAMA scores are negatively corelated with GMV of left precuneus (A and B). BIS scores are negatively corelated with GMV of right cuneus (C).

Abbreviation: HAMD=Hamilton Depression Rating Scale; HAMA=Hamilton Anxiety Rating Scale; BIS=Barratt Impulsiveness Scale; GMV=Gray matter volume.

Table 1: Demographic and clinical characteristics of participants (n = 117).

Abbreviation: HAMD=Hamilton Depression Rating Scale; HAMA=Hamilton Anxiety Rating Scale; BIS=Barratt Impulsiveness Scale; BDI= Beck Depression Inventory.

Table 2: Demographic and clinical characteristics of suicidal actors (n = 40).

Abbreviation: HAMD=Hamilton Depression Rating Scale; HAMA=Hamilton Anxiety Rating Scale; BIS=Barratt Impulsiveness Scale; BDI= Beck Depression Inventory.

Table 3: Voxel-based analysis of gray matter volumes in MDD patients with or without suicidal history and healthy controls.

Abbreviation: SA=Suicidal attempters; SI=Suicidal ideators.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)