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Dorsolateral and ventrolateral prefrontal cortex structural changes relative to suicidal ideation in patients with depression

Published online by Cambridge University Press:  09 January 2020

Ran Zhang
Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
Shengnan Wei
Brain Function Research Section, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
Miao Chang
Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
Xiaowei Jiang
Brain Function Research Section, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
Yanqing Tang*
Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China Brain Function Research Section, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China Department of Geriatric Medicine, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
Fei Wang*
Department of Psychiatry, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China Brain Function Research Section, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China Department of Radiology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China
Author for correspondence: Yanqing Tang and Fei Wang, Emails: or
Author for correspondence: Yanqing Tang and Fei Wang, Emails: or


The prefrontal cortex (PFC) is enormously important in suicide and major depressive disorder (MDD). However, little is known about the structural alterations in the brains of people with MDD and suicidal ideation. We examined the gray matter volume (GMV) of the PFC of individuals with MDD and suicidal ideation to determine if PFC volumetric differences contribute to suicidal ideation in patients with MDD. Thirty-five subjects with MDD and suicidal ideation, 38 subjects with MDD but without suicidal ideation, and 43 age- and gender-matched healthy control (HC) subjects underwent T1-weighted imaging. A voxel-based morphometric analysis was conducted to compare the PFC GMVs of the three groups. Further GMV reductions in the left and right dorsolateral PFC (DLPFC) and right ventrolateral PFC (VLPFC) were detected in the MDD with suicidal ideation group compared with those in the HC group and the MDD without suicidal ideation group, whereas the MDD without suicidal ideation group only exhibited significant differences in the left DLPFC relative to the HC group. Our findings demonstrated that left DLPFC reductions were associated with MDD and suicidal ideation, and diminished GMV reductions in the right DLPFC and right VLPFC were only associated with suicidal ideation. These results help us better understand the neuropathological changes in MDD with suicidal ideation.

Original Article
© Scandinavian College of Neuropsychopharmacology 2020

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The two authors contributed equally to this work.


Aaltonen, K, Naatanen, P, Heikkinen, M, Koivisto, M, Baryshnikov, I, Karpov, B, Oksanen, J, Melartin, T, Suominen, K, Joffe, G, Paunio, T and Isometsa, E (2016) Differences and similarities of risk factors for suicidal ideation and attempts among patients with depressive or bipolar disorders. Journal of Affective Disorders 193, 318330.CrossRefGoogle ScholarPubMed
Abdollahi, A, Talib, MA, Yaacob, SN and Ismail, Z (2016) Problem-solving skills and suicidal ideation among Malaysian college students: the mediating role of hopelessness. Academic Psychiatry 40, 261267.CrossRefGoogle ScholarPubMed
Amico, F, Meisenzahl, E, Koutsouleris, N, Reiser, M, Moller, HJ and Frodl, T (2011) Structural MRI correlates for vulnerability and resilience to major depressive disorder. Journal of Psychiatry & Neuroscience 36, 1522.CrossRefGoogle ScholarPubMed
Angst, F, Stassen, HH, Clayton, PJ and Angst, J (2002) Mortality of patients with mood disorders: follow-up over 34–38 years. Journal of Affective Disorders 68, 167181.CrossRefGoogle ScholarPubMed
Aron, AR, Robbins, TW and Poldrack, RA (2014) Inhibition and the right inferior frontal cortex: one decade on. Trends in Cognitive Sciences 18, 177185.CrossRefGoogle Scholar
Ashburner, J and Friston, KJ (2000) Voxel-based morphometry--the methods. Neuroimage 11, 805821.CrossRefGoogle Scholar
Bari, A and Robbins, TW (2013) Inhibition and impulsivity: behavioral and neural basis of response control. Progress in Neurobiology 108, 4479.CrossRefGoogle ScholarPubMed
Beck, AT, Kovacs, M and Weissman, A (1979) Assessment of suicidal intention: the scale for suicide ideation. Journal of Consulting and Clinical Psychology 47, 343352.CrossRefGoogle ScholarPubMed
Berlim, MT, Van den Eynde, F, Tovar-Perdomo, S, Chachamovich, E, Zangen, A and Turecki, G (2014) Augmenting antidepressants with deep transcranial magnetic stimulation (DTMS) in treatment-resistant major depression. The World Journal of Biological Psychiatry 15, 570578.CrossRefGoogle Scholar
Bland, RC (1997) Epidemiology of affective disorders: a review. Canadian Journal of Psychiatry 42, 367377.CrossRefGoogle ScholarPubMed
Botsis, AJ, Soldatos, CR and Stefanis, CN (1997) Suicide: Biopsychosocial Approaches. Amsterdam: Elsevier Science Health Science Division.Google Scholar
Bozorgmehr, A, Alizadeh, F, Ofogh, SN, Hamzekalayi, MRA, Herati, S, Moradkhani, A, Shahbazi, A and Ghadirivasfi, M (2018) What do the genetic association data say about the high risk of suicide in people with depression? A novel network-based approach to find common molecular basis for depression and suicidal behavior and related therapeutic targets. Journal of Affective Disorders 229, 463468.CrossRefGoogle ScholarPubMed
Braun, C, Bschor, T, Franklin, J and Baethge, C (2016) Suicides and suicide attempts during long-term treatment with antidepressants: a meta-analysis of 29 placebo-controlled studies including 6,934 patients with major depressive disorder. Psychotherapy and Psychosomatics 85, 171179.CrossRefGoogle ScholarPubMed
Buckner, JD, Lemke, AW, Jeffries, ER and Shah, SM (2017) Social anxiety and suicidal ideation: test of the utility of the interpersonal-psychological theory of suicide. Journal of Anxiety Disorders 45, 6063.CrossRefGoogle ScholarPubMed
Coryell, W, Nopoulos, P, Drevets, W, Wilson, T and Andreasen, NC (2005) Subgenual prefrontal cortex volumes in major depressive disorder and schizophrenia: diagnostic specificity and prognostic implications. American Journal of Psychiatry 162, 17061712.CrossRefGoogle ScholarPubMed
Desmyter, S, Duprat, R, Baeken, C, Bijttebier, S and van Heeringen, K (2014) The acute effects of accelerated repetitive Transcranial Magnetic Stimulation on suicide risk in unipolar depression: preliminary results. Psychiatr Danub 26, 4852.Google ScholarPubMed
Ding, Y, Lawrence, N, Olie, E, Cyprien, F, le Bars, E, Bonafe, A, Phillips, ML, Courtet, P and Jollant, F (2015) Prefrontal cortex markers of suicidal vulnerability in mood disorders: a model-based structural neuroimaging study with a translational perspective. Translational Psychiatry 5, e516.CrossRefGoogle ScholarPubMed
Du, L, Zeng, J, Liu, H, Tang, D, Meng, H, Li, Y and Fu, Y (2017) Fronto-limbic disconnection in depressed patients with suicidal ideation: a resting-state functional connectivity study. Journal of Affective Disorders 215, 213217.CrossRefGoogle ScholarPubMed
Dutta, R, Ball, HA, Siribaddana, SH, Sumathipala, A, Samaraweera, S, McGuffin, P and Hotopf, M (2017) Genetic and other risk factors for suicidal ideation and the relationship with depression. Psychological Medicine 47, 24382449.CrossRefGoogle ScholarPubMed
Elliott, R, Rubinsztein, JS, Sahakian, BJ and Dolan, RJ (2002) The neural basis of mood-congruent processing biases in depression. Archives of General Psychiatry 59, 597604.CrossRefGoogle ScholarPubMed
Frodl, T, Reinhold, E, Koutsouleris, N, Reiser, M and Meisenzahl, EM (2010) Interaction of childhood stress with hippocampus and prefrontal cortex volume reduction in major depression. Journal of Psychiatric Research 44, 799807.CrossRefGoogle ScholarPubMed
Ghaziuddin, N, King, CA, Welch, K and Ghaziuddin, M (2014) Depressed suicidal adolescent males have an altered cortisol response to a pharmacological challenge. Asian Journal of Psychiatry 7, 2833.CrossRefGoogle ScholarPubMed
Gliatto, MF and Rai, AK (1999) Evaluation and treatment of patients with suicidal ideation. American Family Physician 59, 15001506.Google ScholarPubMed
Goldin, PR, McRae, K, Ramel, W and Gross, JJ (2008) The neural bases of emotion regulation: reappraisal and suppression of negative emotion. Biological Psychiatry 63, 577586.CrossRefGoogle ScholarPubMed
Gonzalez-Maeso, J and Meana, JJ (2006) Heterotrimeric g proteins: insights into the neurobiology of mood disorders. Current Neuropharmacology 4, 127138.CrossRefGoogle ScholarPubMed
Horwitz, AG, Berona, J, Czyz, EK, Yeguez, CE and King, CA (2017) Positive and negative expectations of hopelessness as longitudinal predictors of depression, suicidal ideation, and suicidal behavior in high-risk adolescents. Suicide and Life-Threatening Behavior 47, 168176.CrossRefGoogle ScholarPubMed
Hsu, DT, Langenecker, SA, Kennedy, SE, Zubieta, JK and Heitzeg, MM (2010) fMRI BOLD responses to negative stimuli in the prefrontal cortex are dependent on levels of recent negative life stress in major depressive disorder. Psychiatry Research 183, 202208.CrossRefGoogle ScholarPubMed
Hugdahl, K, Rund, BR, Lund, A, Asbjornsen, A, Egeland, J, Ersland, L, Landro, NI, Roness, A, Stordal, KI, Sundet, K and Thomsen, T (2004) Brain activation measured with fMRI during a mental arithmetic task in schizophrenia and major depression. American Journal of Psychiatry 161, 286293.CrossRefGoogle ScholarPubMed
Hunter, AM, Leuchter, AF, Cook, IA and Abrams, M (2010) Brain functional changes (QEEG cordance) and worsening suicidal ideation and mood symptoms during antidepressant treatment. Acta Psychiatrica Scandinavica 122, 461469.CrossRefGoogle ScholarPubMed
Jia, Z, Wang, Y, Huang, X, Kuang, W, Wu, Q, Lui, S, Sweeney, JA and Gong, Q (2014) Impaired frontothalamic circuitry in suicidal patients with depression revealed by diffusion tensor imaging at 3.0 T. Journal of Psychiatry and Neuroscience 39, 170177.CrossRefGoogle ScholarPubMed
Kang, HJ, Bae, KY, Kim, SW, Shin, IS, Hong, YJ, Ahn, Y, Jeong, MH, Yoon, JS and Kim, JM (2017) Genetic predisposition toward suicidal ideation in patients with acute coronary syndrome. Oncotarget 8, 9495194958.CrossRefGoogle ScholarPubMed
Kiosses, DN, Gross, JJ, Banerjee, S, Duberstein, PR, Putrino, D and Alexopoulos, GS (2017) Negative emotions and suicidal ideation during psychosocial treatments in older adults with major depression and cognitive impairment. The American Journal of Geriatric Psychiatry 25, 620629.CrossRefGoogle ScholarPubMed
Klonsky, ED, May, AM and Saffer, BY (2016) Suicide, suicide attempts, and suicidal ideation. Annual Review of Clinical Psychology 12, 307330.CrossRefGoogle ScholarPubMed
Ko, JK, Han, KM, Shin, C, Lee, SH, Han, C, Kim, YK, Yoon, HK and Ko, YH (2019) Association of metabolic syndrome and its components with suicidal ideation and depression in adults: a nationally representative sample of the Korean population. Journal of Affective Disorders 249, 319326.CrossRefGoogle ScholarPubMed
Liu, W, Mao, Y, Wei, D, Yang, J, Du, X, Xie, P and Qiu, J (2016) Structural asymmetry of dorsolateral prefrontal cortex correlates with depressive symptoms: evidence from healthy individuals and patients with major depressive disorder. Neuroscience Bulletin 32, 217226.CrossRefGoogle ScholarPubMed
Liu, YY, Wang, XT, Qiu, HM, Xu, AQ and Jia, CX (2017) Functional and dysfunctional impulsivity and attempted suicide in rural China: a paired case-control study. Psychiatry Research 253, 2227.CrossRefGoogle ScholarPubMed
Mann, JJ, Apter, A, Bertolote, J, Beautrais, A, Currier, D, Haas, A, Hegerl, U, Lonnqvist, J, Malone, K, Marusic, A, Mehlum, L, Patton, G, Phillips, M, Rutz, W, Rihmer, Z, Schmidtke, A, Shaffer, D, Silverman, M, Takahashi, Y, Varnik, A, Wasserman, D, Yip, P and Hendin, H (2005) Suicide prevention strategies: a systematic review. JAMA 294, 20642074.CrossRefGoogle ScholarPubMed
Mann, JJ, Waternaux, C, Haas, GL and Malone, KM (1999) Toward a clinical model of suicidal behavior in psychiatric patients. American Journal of Psychiatry 156, 181189.Google Scholar
Marchand, WR, Lee, JN, Johnson, S, Thatcher, J, Gale, P, Wood, N and Jeong, EK (2012) Striatal and cortical midline circuits in major depression: implications for suicide and symptom expression. Progress in Neuro-Psychopharmacology and Biological Psychiatry 36, 290299.CrossRefGoogle ScholarPubMed
Matthews, S, Spadoni, A, Knox, K, Strigo, I and Simmons, A (2012) Combat-exposed war veterans at risk for suicide show hyperactivation of prefrontal cortex and anterior cingulate during error processing. Psychosomatic Medicine 74, 471475.CrossRefGoogle ScholarPubMed
Minzenberg, MJ, Lesh, TA, Niendam, TA, Cheng, Y and Carter, CS (2016) Conflict-related anterior cingulate functional connectivity is associated with past suicidal ideation and behavior in recent-onset psychotic major mood disorders. The Journal of Neuropsychiatry and Clinical Neurosciences 28, 299305.CrossRefGoogle ScholarPubMed
Myung, W, Han, CE, Fava, M, Mischoulon, D, Papakostas, GI, Heo, JY, Kim, KW, Kim, ST, Kim, DJ, Kim, DK, Seo, SW, Seong, JK and Jeon, HJ (2016) Reduced frontal-subcortical white matter connectivity in association with suicidal ideation in major depressive disorder. Translational Psychiatry 6, e835.CrossRefGoogle ScholarPubMed
Nitschke, JB, Heller, W, Etienne, MA and Miller, GA (2004) Prefrontal cortex activity differentiates processes affecting memory in depression. Biological Psychology 67, 125143.CrossRefGoogle ScholarPubMed
Nitschke, JB and Mackiewicz, KL (2005) Prefrontal and anterior cingulate contributions to volition in depression. International Review of Neurobiology 67, 7394.CrossRefGoogle ScholarPubMed
Nixon, NL, Liddle, PF, Worwood, G, Liotti, M and Nixon, E (2013) Prefrontal cortex function in remitted major depressive disorder. Psychological Medicine 43, 12191230.CrossRefGoogle ScholarPubMed
Olie, E, Ding, Y, Le Bars, E, de Champfleur, NM, Mura, T, Bonafe, A, Courtet, P and Jollant, F (2015) Processing of decision-making and social threat in patients with history of suicidal attempt: a neuroimaging replication study. Psychiatry Research 234, 369377.CrossRefGoogle ScholarPubMed
Phillips, ML, Drevets, WC, Rauch, SL and Lane, R (2003) Neurobiology of emotion perception II: implications for major psychiatric disorders. Biological Psychiatry 54, 515528.CrossRefGoogle ScholarPubMed
Picouto, MD, Villar, F and Braquehais, MD (2015) The role of serotonin in adolescent suicide: theoretical, methodological, and clinical concerns. International Journal of Adolescent Medicine and Health 27, 129133.CrossRefGoogle ScholarPubMed
Pulay, AJ and Rethelyi, JM (2016) Multimarker analysis suggests the involvement of BDNF signaling and microRNA biosynthesis in suicidal behavior. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 171, 763776.CrossRefGoogle ScholarPubMed
Radomsky, ED, Haas, GL, Mann, JJ and Sweeney, JA (1999) Suicidal behavior in patients with schizophrenia and other psychotic disorders. The American Journal of Psychiatry 156, 15901595.CrossRefGoogle ScholarPubMed
Rogers, ML, Tucker, RP, Law, KC, Michaels, MS, Anestis, MD and Joiner, TE (2016) Manifestations of overarousal account for the association between cognitive anxiety sensitivity and suicidal ideation. Journal of Affective Disorders 192, 116124.CrossRefGoogle ScholarPubMed
Rushworth, MF, Noonan, MP, Boorman, ED, Walton, ME and Behrens, TE (2011) Frontal cortex and reward-guided learning and decision-making. Neuron 70, 10541069.CrossRefGoogle ScholarPubMed
Teismann, T and Forkmann, T. (2017) Rumination, entrapment and suicide ideation: a mediational model. Clinical Psychology and Psychotherapy 24, 226234.CrossRefGoogle ScholarPubMed
Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, Crivello, F, Etard, O, Delcroix, N, Mazoyer, B and Joliot, M (2002) Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15, 273289.CrossRefGoogle ScholarPubMed
Ueda, K, Okamoto, Y, Okada, G, Yamashita, H, Hori, T and Yamawaki, S (2003) Brain activity during expectancy of emotional stimuli: an fMRI study. Neuroreport 14, 5155.CrossRefGoogle Scholar
van Heeringen, K. (2003) The neurobiology of suicide and suicidality. Canadian Journal of Psychiatry 48, 292300.CrossRefGoogle ScholarPubMed
Van Orden, KA, Witte, TK, Cukrowicz, KC, Braithwaite, SR, Selby, EA and Joiner, TE Jr (2010) The interpersonal theory of suicide. Psychological Review 117, 575600.CrossRefGoogle ScholarPubMed
Wagner, G, Koch, K, Schachtzabel, C, Schultz, CC, Sauer, H and Schlosser, RG (2011) Structural brain alterations in patients with major depressive disorder and high risk for suicide: evidence for a distinct neurobiological entity? Neuroimage 54, 16071614.CrossRefGoogle ScholarPubMed
Wagner, G, Schultz, CC, Koch, K, Schachtzabel, C, Sauer, H and Schlosser, RG (2012) Prefrontal cortical thickness in depressed patients with high-risk for suicidal behavior. Journal of Psychiatric Research 46, 14491455.CrossRefGoogle ScholarPubMed
Walter, H, Wolf, RC, Spitzer, M and Vasic, N (2007) Increased left prefrontal activation in patients with unipolar depression: an event-related, parametric, performance-controlled fMRI study. Journal of Affective Disorders 101, 175185.CrossRefGoogle ScholarPubMed
Winer, ES, Nadorff, MR, Ellis, TE, Allen, JG, Herrera, S and Salem, T (2014) Anhedonia predicts suicidal ideation in a large psychiatric inpatient sample. Psychiatry Research 218, 124128.CrossRefGoogle Scholar
World Health Organization (WHO) (2001) The WHO World Health Report 2001 New Understanding–New Hope. World Health Organization.Google Scholar
World Health Organization (WHO) (2017) Global Health Estimates: Depression and Other Common Mental Disorders. World Health Organization.Google Scholar
Xie, W, Li, H, Luo, X, Fu, R, Ying, X, Wang, N, Yin, Q, Zou, Y, Cui, Y, Wang, X and Shi, C (2014) Anhedonia and pain avoidance in the suicidal mind: behavioral evidence for motivational manifestations of suicidal ideation in patients with major depressive disorder. Journal of Clinical Psychology 70, 681692.CrossRefGoogle ScholarPubMed
Xin-tian, L (1983) The distribution of left and right handedness in Chinese people. Acta Psychologica Sinica 15, 2735.Google Scholar
Zhang, X, Xu, H, Gu, J, Lau, JT, Hao, C, Zhao, Y, Davis, A and Hao, Y (2016) Depression, suicidal ideation, and related factors of methadone maintenance treatment users in Guangzhou, China. AIDS Care 28, 851856.CrossRefGoogle ScholarPubMed
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