Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-26T19:21:21.206Z Has data issue: false hasContentIssue false

Default mode dysfunction underpins suicidal activity in mood disorders

Published online by Cambridge University Press:  30 May 2019

Gin S. Malhi*
Affiliation:
Academic Department of Psychiatry, Northern Sydney Local Health District, St Leonards, NSW2065, Australia ARCHI, Sydney Medical School Northern, The University of Sydney, NSW2006, Australia Sydney Medical School Northern, The University of Sydney, NSW2006, Australia CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW2065, Australia
Pritha Das
Affiliation:
Academic Department of Psychiatry, Northern Sydney Local Health District, St Leonards, NSW2065, Australia ARCHI, Sydney Medical School Northern, The University of Sydney, NSW2006, Australia Sydney Medical School Northern, The University of Sydney, NSW2006, Australia CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW2065, Australia
Tim Outhred
Affiliation:
Academic Department of Psychiatry, Northern Sydney Local Health District, St Leonards, NSW2065, Australia ARCHI, Sydney Medical School Northern, The University of Sydney, NSW2006, Australia Sydney Medical School Northern, The University of Sydney, NSW2006, Australia CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW2065, Australia
Richard A. Bryant
Affiliation:
School of Psychology, University of New South Wales, Sydney, New South Wales, NSW2052, Australia
Vince Calhoun
Affiliation:
The Mind Research Network, Albuquerque, NM, USA Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA
J. John Mann
Affiliation:
Department of Psychiatry, Columbia University, New York, USA Molecular Imaging and the Neuropathology Division, New York State Psychiatric Institute, New York, USA
*
Author for correspondence: Gin S. Malhi, E-mail: [email protected]

Abstract

Background

Suicide is a serious and not uncommon consequence of mood disorders that occurs primarily when individuals are depressed. Understanding the neurobiology of suicidal activity (thoughts or behaviors) is likely to facilitate prevention.

Method

Seventy-nine adult depressed mood disorder patients (MDP), of which 25 had attempted suicide at least once, and 66 healthy controls (HC) participated in this study. Resting-state functional MRI was used to identify neural activity differences between suicide attempters (SA) and non-attempters (NA). Specifically, differences were examined in functional connectivity both within and between four large cognitive networks [Executive Control (ECN), Default Mode (DMN), Salience (SN), and Basal Ganglia (BGN)] and their respective associations with suicidal activity.

Results

Compared to HCs, patients had greater posterior DMN activity, but less activity in the BGN, and less low-frequency spectral power in the dorso-medial DMN. Furthermore, increased posterior DMN activity in SA was associated with recent suicidal activity, whereas NA had reduced BGN activity and less dorso-medial DMN spectral power, the latter being associated with lifelong suicidal thinking. SA also had greater activity in midline circuitry compared to both HC and NA, and the pattern of BGN and DMN co-activity differed between SA and NA.

Conclusions

DMN engagement raises the possibility that suicidal activity in mood disorder patients may be a consequence of impaired self-referential thought processing. Furthermore, differential BGN and DMN co-activation according to suicide attempt status suggests that attempting suicide perhaps alters cognitive flexibility. These insights are potentially useful for understanding the neural basis of suicide activity.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

GSM and PD are equal first authors.

References

Allen, EA, Erhardt, EB, Damaraju, E, Gruner, W, Segall, JM, Silva, RF, Havlicek, M, Rachakonda, S, Fries, J, Kalyanam, R, Michael, AM, Caprihan, A, Turner, JA, Eichele, T, Adelsheim, S, Bryan, AD, Bustillo, J, Clark, VP, Feldstein Ewing, SW, Filbey, F, Ford, CC, Hutchison, K, Jung, RE, Kiehl, KA, Kodituwakku, P, Komesu, YM, Mayer, AR, Pearlson, GD, Phillips, JP, Sadek, JR, Stevens, M, Teuscher, U, Thoma, RJ and Calhoun, VD (2011) A baseline for the multivariate comparison of resting-state networks. Frontiers in Systems Neuroscience 5, 2. eCollection 2011.CrossRefGoogle ScholarPubMed
Angst, J, Angst, F, Gerber-Werder, R and Gamma, A (2005) Suicide in 406 mood-disorder patients with and without long-term medication: a 40 to 44 years’ follow-up. Archives of Suicide Research 9, 279300.CrossRefGoogle Scholar
Arsalidou, M, Duerden, EG and Taylor, MJ (2013) The centre of the brain: topographical model of motor, cognitive, affective, and somatosensory functions of the basal ganglia. Human Brain Mapping 34, 30313054.CrossRefGoogle ScholarPubMed
Balcioglu, YH and Kose, S (2018) Neural substrates of suicide and suicidal behaviour: from a neuroimaging perspective. Psychiatry and Clinical Psychopharmacology 28, 314328.CrossRefGoogle Scholar
Balsters, JH, Robertson, IH and Calhoun, VD (2013) BOLD frequency power indexes working memory performance. Frontiers in Human Neuroscience 7, 207.CrossRefGoogle ScholarPubMed
Bell, AJ and Sejnowski, TJ (1995) An information-maximization approach to blind separation and blind deconvolution. Neural Computation 7, 11291159.CrossRefGoogle ScholarPubMed
Calhoun, VD, Adali, T, Pearlson, GD and Pekar, JJ (2001) A method for making group inferences from functional MRI data using independent component analysis. Human Brain Mapping 14, 140151.CrossRefGoogle ScholarPubMed
Cao, J, Chen, X, Chen, J, Ai, M, Gan, Y, Wang, W, Lv, Z, Zhang, S, Zhang, S, Wang, S, Kuang, L and Fang, W (2016) Resting-state functional MRI of abnormal baseline brain activity in young depressed patients with and without suicidal behavior. Journal of Affective Disorders 205, 252263.CrossRefGoogle ScholarPubMed
Chase, HW, Segreti, AM, Keller, TA, Cherkassky, VL, Just, MA, Pan, LA and Brent, DA (2017) Alterations of functional connectivity and intrinsic activity within the cingulate cortex of suicidal ideators. Journal of Affective Disorders 212, 7885.CrossRefGoogle ScholarPubMed
Damaraju, E, Allen, EA, Belger, A, Ford, JM, McEwen, S, Mathalon, DH, Mueller, BA, Pearlson, GD, Potkin, SG, Preda, A, Turner, JA, Vaidya, JG, van Erp, TG and Calhoun, VD (2014) Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia. Neuroimage: Clinical 5, 298308.CrossRefGoogle Scholar
Das, P, Calhoun, V and Malhi, GS (2014) Bipolar and borderline patients display differential patterns of functional connectivity among resting state networks. Neuroimage 98, 7381.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
Erhardt, EB, Rachakonda, S, Bedrick, EJ, Allen, EA, Adali, T and Calhoun, VD (2011) Comparison of multi-subject ICA methods for analysis of fMRI data. Human Brain Mapping 32, 20752095.CrossRefGoogle ScholarPubMed
Fan, T, Wu, X, Yao, L and Dong, J (2013) Abnormal baseline brain activity in suicidal and non-suicidal patients with major depressive disorder. Neuroscience Letters 534, 3540.CrossRefGoogle ScholarPubMed
Freire, L and Mangin, JF (2001) Motion correction algorithms may create spurious brain activations in the absence of subject motion. Neuroimage 14, 709722.CrossRefGoogle ScholarPubMed
Isometsa, E (2014) Suicidal behaviour in mood disorders – who, when, and why? The Canadian Journal of Psychiatry 59, 120130.CrossRefGoogle Scholar
Jafri, MJ, Pearlson, GD, Stevens, M and Calhoun, VD (2008) A method for functional network connectivity among spatially independent resting-state components in schizophrenia. Neuroimage 39, 16661681.CrossRefGoogle Scholar
Johnson, MK, Nolen-Hoeksema, S, Mitchell, KJ and Levin, Y (2009) Medial cortex activity, self-reflection and depression. Social Cognitive and Affective Neuroscience 4, 313327.CrossRefGoogle ScholarPubMed
Kang, SG, Na, KS, Choi, JW, Kim, JH, Son, YD and Lee, YJ (2017) Resting-state functional connectivity of the amygdala in suicide attempters with major depressive disorder. Progress in Neuro-psychopharmacology and Biological Psychiatry 77, 222227.CrossRefGoogle ScholarPubMed
Li, YO, Adali, T and Calhoun, VD (2007) Estimating the number of independent components for functional magnetic resonance imaging data. Human Brain Mapping 28, 12511266.CrossRefGoogle ScholarPubMed
Malhi, GS, Outhred, T, Das, P, Morris, G, Hamilton, A and Mannie, Z (2018) Modeling suicide in bipolar disorders. Bipolar Disorders 20, 334348.CrossRefGoogle ScholarPubMed
Marchand, W (2012) Self-referential thinking, suicide, and function of the cortical midline structures and striatum in mood disorders: possible implications for treatment studies of mindfulness-based interventions for bipolar depression. Depression Research and Treatment 2012, 246725.CrossRefGoogle ScholarPubMed
Marchand, WR and Yurgelun-Todd, D (2010) Striatal structure and function in mood disorders: a comprehensive review. Bipolar Disorders 12, 764785.CrossRefGoogle ScholarPubMed
Marzuk, PM, Hartwell, N, Leon, AC and Portera, L (2005) Executive functioning in depressed patients with suicidal ideation. Acta Psychiatrica Scandinavica 112, 294301.CrossRefGoogle ScholarPubMed
Menon, V (2011) Large-scale brain networks and psychopathology: a unifying triple network model. Trends in Cognitive Sciences 15, 483506. Epub 2011 Sep 9.CrossRefGoogle ScholarPubMed
Northoff, G and Bermpohl, F (2004) Cortical midline structures and the self. Trends in Cognitive Sciences 8, 102107.CrossRefGoogle ScholarPubMed
Northoff, G, Heinzel, A, de Greck, M, Bermpohl, F, Dobrowolny, H and Panksepp, J (2006) Self-referential processing in our brain – a meta-analysis of imaging studies on the self. Neuroimage 31, 440457.CrossRefGoogle Scholar
Ordaz, SJ, Goyer, MS, Ho, TC, Singh, MK and Gotlib, IH (2018) Network basis of suicidal ideation in depressed adolescents. Journal of Affective Disorders 226, 9299.CrossRefGoogle ScholarPubMed
Pan, PM, Sato, JR, Salum, GA, Rohde, LA, Gadelha, A, Zugman, A, Mari, J, Jackowski, A, Picon, F, Miguel, EC, Pine, DS, Leibenluft, E, Bressan, RA and Stringaris, A (2017) Ventral striatum functional connectivity as a predictor of adolescent depressive disorder in a longitudinal community-based sample. American Journal of Psychiatry 174, 11121119.CrossRefGoogle Scholar
Posner, K, Brown, GK, Stanley, B, Brent, DA, Yershova, KV, Oquendo, MA, Currier, GW, Melvin, GA, Greenhill, L, Shen, S and Mann, JJ (2011) The Columbia-suicide severity rating scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. American Journal of Psychiatry 168, 12661277.CrossRefGoogle ScholarPubMed
Pu, S, Setoyama, S and Noda, T (2017) Association between cognitive deficits and suicidal ideation in patients with major depressive disorder. Scientific Reports 7, 11637.CrossRefGoogle ScholarPubMed
Renteria, ME, Schmaal, L, Hibar, DP, Couvy-Duchesne, B, Strike, LT, Mills, NT, de Zubicaray, GI, McMahon, KL, Medland, SE, Gillespie, NA, Hatton, SN, Lagopoulos, J, Veltman, DJ, van der Wee, N, van Erp, TGM, Wittfeld, K, Grabe, HJ, Block, A, Hegenscheid, K, Volzke, H, Veer, IM, Walter, H, Schnell, K, Schramm, E, Normann, C, Schoepf, D, Konrad, C, Zurowski, B, Godlewska, BR, Cowen, PJ, Penninx, B, Jahanshad, N, Thompson, PM, Wright, MJ, Martin, NG, Christensen, H and Hickie, IB (2017) Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group. Translational Psychiatry 7, e1116.CrossRefGoogle ScholarPubMed
Rogers, ML and Joiner, TE (2017) Rumination, suicidal ideation, and suicide attempts: a meta-analytic review. Review of General Psychology 21, 132142.CrossRefGoogle Scholar
Serafini, G, Pardini, M, Pompili, M, Girardi, P and Amore, M (2016) Understanding suicidal behavior: the contribution of recent resting-state fMRI techniques. Frontiers in Psychiatry 7, 69.CrossRefGoogle ScholarPubMed
Sher, L, Oquendo, MA and Mann, JJ (2001) Risk of suicide in mood disorders. Clinical Neuroscience Research 1, 337344.CrossRefGoogle Scholar
Stange, JP, Hamilton, JL, Burke, TA, Kleiman, EM, O'Garro-Moore, JK, Seligman, ND, Abramson, LY and Alloy, LB (2015) Negative cognitive styles synergistically predict suicidal ideation in bipolar spectrum disorders: a 3-year prospective study. Psychiatry Research 226, 162168.CrossRefGoogle ScholarPubMed
Surrence, K, Miranda, R, Marroquin, BM and Chan, S (2009) Brooding and reflective rumination among suicide attempters: cognitive vulnerability to suicidal ideation. Behaviour Research and Therapy 47, 803808.CrossRefGoogle ScholarPubMed
Van Dijk, KR, Hedden, T, Venkataraman, A, Evans, KC, Lazar, SW and Buckner, RL (2010) Intrinsic functional connectivity as a tool for human connectomics: theory, properties, and optimization. Journal of Neurophysiology 103, 297321.CrossRefGoogle Scholar
Vijayakumar, L (2015) Suicide in women. Indian Journal of Psychiatry 57, S233S238.CrossRefGoogle ScholarPubMed
Whitfield-Gabrieli, S and Ford, JM (2012) Default mode network activity and connectivity in psychopathology. Annual Review of Clinical Psychology 8, 4976.CrossRefGoogle ScholarPubMed
Zhang, S, Chen, JM, Kuang, L, Cao, J, Zhang, H, Ai, M, Wang, W, Zhang, SD, Wang, SY, Liu, SJ and Fang, WD (2016) Association between abnormal default mode network activity and suicidality in depressed adolescents. BMC Psychiatry 16, 337.CrossRefGoogle ScholarPubMed
Supplementary material: PDF

Malhi et al. supplementary material

Malhi et al. supplementary material 1

Download Malhi et al. supplementary material(PDF)
PDF 57.1 KB