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Using resting-state intrinsic network connectivity to identify suicide risk in mood disorders

  • Jonathan P. Stange (a1), Lisanne M. Jenkins (a2), Stephanie Pocius (a3), Kayla Kreutzer (a1), Katie L. Bessette (a1), Sophie R. DelDonno (a1), Leah R. Kling (a1), Runa Bhaumik (a1), Robert C. Welsh (a3), John G. Keilp (a4), K. Luan Phan (a5) and Scott A. Langenecker (a3)...



Little is known about the neural substrates of suicide risk in mood disorders. Improving the identification of biomarkers of suicide risk, as indicated by a history of suicide-related behavior (SB), could lead to more targeted treatments to reduce risk.


Participants were 18 young adults with a mood disorder with a history of SB (as indicated by endorsing a past suicide attempt), 60 with a mood disorder with a history of suicidal ideation (SI) but not SB, 52 with a mood disorder with no history of SI or SB (MD), and 82 healthy comparison participants (HC). Resting-state functional connectivity within and between intrinsic neural networks, including cognitive control network (CCN), salience and emotion network (SEN), and default mode network (DMN), was compared between groups.


Several fronto-parietal regions (k > 57, p < 0.005) were identified in which individuals with SB demonstrated distinct patterns of connectivity within (in the CCN) and across networks (CCN-SEN and CCN-DMN). Connectivity with some of these same regions also distinguished the SB group when participants were re-scanned after 1–4 months. Extracted data defined SB group membership with good accuracy, sensitivity, and specificity (79–88%).


These results suggest that individuals with a history of SB in the context of mood disorders may show reliably distinct patterns of intrinsic network connectivity, even when compared to those with mood disorders without SB. Resting-state fMRI is a promising tool for identifying subtypes of patients with mood disorders who may be at risk for suicidal behavior.


Corresponding author

Author for correspondence: Scott A. Langenecker, E-mail:


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Anestis, MD and Joiner, TE (2011) Examining the role of emotion in suicidality: negative urgency as an amplifier of the relationship between components of the interpersonal–psychological theory of suicidal behavior and lifetime number of suicide attempts. Journal of Affective Disorders 129, 261269.
Behzadi, Y, Restom, K, Liau, J and Liu, TT (2007) A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage 37, 90101.
Bekh Bradley, D, DeFife, JA, Guarnaccia, C, Phifer, MJ, Fani, MN, Ressler, KJ and Westen, D (2011) Emotion dysregulation and negative affect: association with psychiatric symptoms. Journal of Clinical Psychiatry 72, 685691.
Birn, RM, Molloy, EK, Patriat, R, Parker, T, Meier, TB, Kirk, GR, Nair, VA, Meyerand, ME and Prabhakaran, V (2013) The effect of scan length on the reliability of resting-state fMRI connectivity estimates. Neuroimage 83, 550558.
Brady, RO Jr., Tandon, N, Masters, GA, Margolis, A, Cohen, BM, Keshavan, M and Öngür, D (2017) Differential brain network activity across mood states in bipolar disorder. Journal of Affective Disorders 207, 367376.
Brett, M, Anton, J-L, Valabregue, R and Poline, J-B (2002) Region of interest analysis using an SPM toolbox [abstract]. Presented at the 8th International Conference on Functional Mapping of the Human Brain. Available on CD-ROM in NeuroImage 16.
Brown, GK, Beck, AT, Steer, RA and Grisham, JR (2000) Risk factors for suicide in psychiatric outpatients: a 20-year prospective study. Journal of Consulting and Clinical Psychology 68, 371377.
Buckner, RL, Andrews-Hanna, JR and Schacter, DL (2008) The brain's default network. Annals of the New York Academy of Sciences 1124, 138.
Burke, TA, Connolly, SL, Hamilton, JL, Stange, JP, Abramson, LY and Alloy, LB (2016) Cognitive risk and protective factors for suicidal ideation: a two year longitudinal study in adolescence. Journal of Abnormal Child Psychology 44, 11451160.
Bzdok, D and Yeo, BT (2017) Inference in the age of big data: future perspectives on neuroscience. Neuroimage 155, 549564.
Cao, J, Chen, JM, Kuang, L, Ai, M, Fang, WD, Gan, Y, Wang, W, Chen, XR, Xu, XM, Wang, HG and Lv, Z (2015) Abnormal regional homogeneity in young adult suicide attempters with no diagnosable psychiatric disorder: a resting state functional magnetic imaging study. Psychiatry Research: Neuroimaging 231, 95102.
Chang, BP, Franklin, JC, Ribeiro, JD, Fox, KR, Bentley, KH, Kleiman, EM and Nock, MK (2016) Biological risk factors for suicidal behaviors: a meta-analysis. Translational Psychiatry 6, e887.
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.
Chawla, NV, Bowyer, KW, Hall, LO and Kegelmeyer, WP (2002) SMOTE: synthetic minority over-sampling technique. Journal of Artificial Intelligence Research 16, 321357.
Clasen, PC, Beevers, CG, Mumford, JA and Schnyer, DM (2014) Cognitive control network connectivity in adolescent women with and without a parental history of depression. Developmental Cognitive Neuroscience 7, 1322.
Connolly, CG, Wu, J, Ho, TC, Hoeft, F, Wolkowitz, O, Eisendrath, S, Frank, G, Hendren, R, Max, JE, Paulus, MP, Tapert, SF, Banerjee, D, Simmons, AN and Yang, TT (2013) Resting-state functional connectivity of subgenual anterior cingulate cortex in depressed adolescents. Biological Psychiatry 74, 898907.
Desmyter, S, Bijttebier, S and van Heeringen, K (2013) The role of neuroimaging in our understanding of the suicidal brain. CNS & Neurological Disorders-Drug Targets 12, 921999.
Dolcos, F, Kragel, P, Wang, L and McCarthy, G (2006) Role of the inferior frontal cortex in coping with distracting emotions. NeuroReport 17, 15911594.
Drysdale, AT, Grosenick, L, Downar, J, Dunlop, K, Mansouri, F, Meng, Y, Fetcho, RN, Zebley, B, Oathes, DJ, Etkin, A, Schatzberg, AF, Sudheimer, K, Keller, K, Mayberg, HS, Gunning, FM, Alexopoulos, GS, Fox, MD, Pascual-Leone, A, Voss, HU, Casey, BJ, Dubin, MJ and Listen, C (2017) Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nature Medicine 23, 2838.
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.
Fischer, AS, Keller, CJ and Etkin, A (2016) The clinical applicability of functional connectivity in depression: pathways toward more targeted intervention. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 1, 262270.
Franklin, JC, Ribeiro, JD, Fox, KR, Bentley, KH, Kleiman, EM, Huang, X, Musacchio, KM, Jaroszewski, AC, Chang, BP and Nock, MK (2017) Risk factors for suicidal thoughts and behaviors: a meta-analysis of 50 years of research. Psychological Bulletin 143, 187232.
Ge, R, Blumberger, DM, Downar, J, Daskalakis, ZJ, Dipinto, AA, Tham, JC, Lam, R and Vila-Rodriguez, F (2017) Abnormal functional connectivity within resting-state networks is related to rTMS-based therapy effects of treatment resistant depression: a pilot study. Journal of Affective Disorders 218, 7581.
Hamilton, M (1960) A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.
Hamilton, M (1959) The assessment of anxiety states by rating. British Journal of Medical Psychology 32, 5055.
Hamilton, JP, Furman, DJ, Chang, C, Thomason, ME, Dennis, E and Gotlib, IH (2011) Default-mode and task-positive network activity in major depressive disorder: implications for adaptive and maladaptive rumination. Biological Psychiatry 70, 327333.
Hasler, G and Northoff, G (2011) Discovering imaging endophenotypes for major depression. Molecular Psychiatry 16, 604.
Hawton, K, Sutton, L, Haw, C, Sinclair, J and Harriss, L (2005) Suicide and attempted suicide in bipolar disorder: a systematic review of risk factors. Journal of Clinical Psychiatry 66, 693704.
Hawton, K, i Comabella, CC, Haw, C and Saunders, K (2013). Risk factors for suicide in individuals with depression: a systematic review. Journal of Affective Disorders 147, 1728.
Insel, TR and Cuthbert, BN (2015) Brain disorders? Precisely. Science 348, 499500.
Insel, T, Cuthbert, B, Garvey, M, Heinssen, R, Pine, DS, Quinn, K, Sanislow, C and Wang, P (2010) Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. American Journal of Psychiatry 167, 748751.
Jacobs, RH, Jenkins, LM, Gabriel, LB, Barba, A, Ryan, KA, Weisenbach, SL, Verges, A, Baker, AM, Peters, AT, Crane, NA and Gotlib, IH (2014) Increased coupling of intrinsic networks in remitted depressed youth predicts rumination and cognitive control. Public Library of Science One 9, e104366.
Jacobs, RH, Barba, A, Gowins, JR, Klumpp, H, Jenkins, LM, Mickey, BJ, Ajilore, O, Peciña, M, Sikora, M, Ryan, KA and Hsu, DT (2016) Decoupling of the amygdala to other salience network regions in adolescent-onset recurrent major depressive disorder. Psychological Medicine 46, 10551067.
Jo, HJ, Gotts, SJ, Reynolds, RC, Bandettini, PA, Martin, A, Cox, RW and Saad, ZS (2013) Effective preprocessing procedures virtually eliminate distance-dependent motion artifacts in resting state FMRI. Journal of Applied Mathematics
Jollant, F, Lawrence, NL, Olié, E, Guillaume, S and Courtet, P (2011) The suicidal mind and brain: a review of neuropsychological and neuroimaging studies. The World Journal of Biological Psychiatry 12, 319339.
Just, N, Abramson, LY and Alloy, LB (2001) Remitted depression studies as tests of the cognitive vulnerability hypotheses of depression onset: a critique and conceptual analysis. Clinical Psychology Review 21, 6383.
Kaiser, RH, Andrews-Hanna, JR, Wager, TD and Pizzagalli, DA (2015) Large-scale network dysfunction in major depressive disorder: a meta-analysis of resting-state functional connectivity. JAMA Psychiatry 72, 603611.
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.
Keilp, JG, Gorlyn, M, Oquendo, MA, Burke, AK and Mann, JJ (2008) Attention deficit in depressed suicide attempters. Psychiatry Research 159, 717.
Keilp, JG, Sackeim, HA, Brodsky, BS, Oquendo, MA, Malone, KM and Mann, JJ (2001) Neuropsychological dysfunction in depressed suicide attempters. American Journal of Psychiatry 158, 735741.
Keilp, JG, Gorlyn, M, Russell, M, Oquendo, MA, Burke, AK, Harkavy-Friedman, J and Mann, JJ (2013) Neuropsychological function and suicidal behavior: attention control, memory and executive dysfunction in suicide attempt. Psychological Medicine 43, 539551.
Keilp, JG, Beers, SR, Burke, AK, Melhem, NM, Oquendo, MA, Brent, DA and Mann, JJ (2014a) Neuropsychological deficits in past suicide attempters with varying levels of depression severity. Psychological Medicine 44, 29652974.
Keilp, JG, Wyatt, G, Gorlyn, M, Oquendo, MA, Burke, AK and Mann, JJ (2014b) Intact alternation performance in high lethality suicide attempters. Psychiatry Research 219, 129136.
Kim, K, Kim, SW, Myung, W, Han, CE, Fava, M, Mischoulon, D, Papakostas, GI, Seo, SW, Cho, H, Seong, JK and Jeon, HJ (2017) Reduced orbitofrontal-thalamic functional connectivity related to suicidal ideation in patients with major depressive disorder. Scientific Reports 7, 15772.
Kleiman, EM and Nock, MK (2018) Real-time assessment of suicidal thoughts and behaviors. Current Opinion in Psychology 22, 3337.
Kleiman, EM, Riskind, JH, Stange, JP, Hamilton, JL and Alloy, LB (2014) Cognitive and interpersonal vulnerability to suicidal ideation: a weakest link approach. Behavioral Therapy 45, 778790.
Klonsky, ED and May, A (2010) Rethinking impulsivity in suicide. Suicide Life-Threat Behavior 40, 612619.
Kriegeskorte, N, Simmons, WK, Bellgowan, PS and Baker, CI (2009) Circular analysis in systems neuroscience: the dangers of double dipping. Nature Neuroscience 12, 535.
Levy, BJ and Wagner, AD (2011) Cognitive control and right ventrolateral prefrontal cortex: reflexive reorienting, motor inhibition, and action updating. Annals of the New York Academy of Sciences 1224, 4062.
Lewinsohn, PM, Rohde, P and Seeley, JR (1994) Psychosocial risk factors for future adolescent suicide attempts. Journal of Consulting and Clinical Psychology 62, 297305.
Lippard, ET, Johnston, JA and Blumberg, HP (2014) Neurobiological risk factors for suicide: insights from brain imaging. American Journal of Preventative Medicine 47, S152S162.
Malhi, GS, Bargh, DM, Kuiper, S, Coulston, CM and Das, P (2013) Modeling bipolar disorder suicidality. Bipolar Disorders 15, 559574.
Marchetti, I, Koster, EH, Sonuga-Barke, EJ and De Raedt, R (2012) The default mode network and recurrent depression: a neurobiological model of cognitive risk factors. Neuropsychology Review 22, 229251.
May, AM and Klonsky, ED (2016) What distinguishes suicide attempters from suicide ideators? A meta-analysis of potential factors. Clinical Psychology: Science and Practice 23, 520.
Menon, V (2011) Large-scale brain networks and psychopathology: a unifying triple network model. Trends in Cognitive Science 15, 483506.
Miranda, R, Gallagher, M, Bauchner, B, Vaysman, R and Marroquín, B (2012) Cognitive inflexibility as a prospective predictor of suicidal ideation among young adults with a suicide attempt history. Depression and Anxiety 29, 180186.
Miranda, R, Valderrama, J, Tsypes, A, Gadol, E and Gallagher, M (2013) Cognitive inflexibility and suicidal ideation: mediating role of brooding and hopelessness. Psychiatry Research 210, 174181.
Muschelli, J, Nebel, MB, Caffo, BS, Barber, AD, Pekar, JJ and Mostofsky, SH (2014) Reduction of motion-related artifacts in resting state fMRI using aCompCor. Neuroimage 96, 2235.
Nock, MK, Hwang, I, Sampson, NA and Kessler, RC (2010) Mental disorders, comorbidity and suicidal behavior: results from the National Comorbidity Survey Replication. Molecular Psychiatry 1, 868876.
Nurnberger, JI, Blehar, MC, Kaufmann, CA, York-Cooler, C, Simpson, SG, Harkavy-Friedman, J, Severe, JB, Malaspina, D and Reich, T (1994) Diagnostic interview for genetic studies: rationale, unique features, and training. Archives of General Psychiatry 51, 849859.
Oquendo, MA, Galfalvy, H, Russo, S, Ellis, SP, Grunebaum, MF, Burke, A and Mann, JJ (2004) Prospective study of clinical predictors of suicidal acts after a major depressive episode in patients with major depressive disorder or bipolar disorder. American Journal of Psychiatry 161, 14331441.
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.
Panagioti, M, Gooding, P and Tarrier, N (2009) Post-traumatic stress disorder and suicidal behavior: a narrative review. Clinical Psychology Review 29, 471482.
Pisani, AR, Wyman, PA, Petrova, M, Schmeelk-Cone, K, Goldston, DB, Xia, Y and Gould, MS (2013) Emotion regulation difficulties, youth-adult relationships, and suicide attempts among high school students in underserved communities. Journal of Youth and Adolescence 42, 807820.
Power, JD, Barnes, KA, Snyder, AZ, Schlaggar, BL and Petersen, SE (2012) Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion. Neuroimage 59, 21422154.
Power, JD, Mitra, A, Laumann, TO, Snyder, AZ, Schlaggar, BL and Petersen, SE (2014) Methods to detect, characterize, and remove motion artifact in resting state fMRI. Neuroimage 84, 320341.
Power, JD, Plitt, M, Laumann, TO and Martin, A (2017) Sources and implications of whole-brain fMRI signals in humans. NeuroImage 146, 609625.
Rey, G, Piguet, C, Benders, A, Favre, S, Eickhoff, SB, Aubry, JM and Vuilleumier, P (2016) Resting-state functional connectivity of emotion regulation networks in euthymic and non-euthymic bipolar disorder patients. European Psychiatry 34, 5663.
Rogers, ML and Joiner, TE (2017) Rumination, suicidal ideation, and suicide attempts: a meta-analytic review. Review of General Psychology 21, 132142.
Rudd, MD (2006) Fluid vulnerability theory: a cognitive approach to understanding the process of acute and chronic risk. In Ellis, TE (ed), Cognition and Suicide: Theory, Research, and Therapy. Washington, DC: American Psychological Association, pp. 355368.
Sacchet, MD, Ho, TC, Connolly, CG, Tymofiyeva, O, Lewinn, KZ, Han, LK, Blom, EH, Tapert, SF, Max, JE, Frank, GK and Paulus, MP (2016) Large-scale hypoconnectivity between resting-state functional networks in unmedicated adolescent major depressive disorder. Neuropsychopharmacology 41, 29512960.
Sebastian, A, Jung, P, Neuhoff, J, Wibral, M, Fox, PT, Lieb, K, Fries, P, Eickhoff, SB, Tüscher, O and Mobascher, A (2016) Dissociable attentional and inhibitory networks of dorsal and ventral areas of the right inferior frontal cortex: a combined task-specific and coordinate-based meta-analytic fMRI study. Brain Structure and Function 221, 16351651.
Seeley, WW, Menon, V, Schatzberg, AF, Keller, J, Glover, GH, Kenna, H, Reiss, AL and Greicius, MD (2007) Dissociable intrinsic connectivity networks for salience processing and executive control. Journal of Neuroscience 27, 13491356.
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,
Shankman, SA, Funkhouser, CJ, Klein, DN, Davila, J, Lerner, D and Hee, D (2018) Reliability and validity of severity dimensions of psychopathology assessed using the Structured Clinical Interview for DSM-5 (SCID). International Journal of Methods in Psychiatric Research 27, e1590.
Smith, SM, Fox, PT, Miller, KL, Glahn, DC, Fox, PM, Mackay, CE, Filippini, N, Watkins, KE, Toro, R, Laird, AR and Beckmann, CF (2009) Correspondence of the brain's functional architecture during activation and rest. Proceedings of the National Academy of Sciences of the USA 106, 1304013045.
Spreng, RN (2012) The fallacy of a ‘task-negative’ network. Frontiers in Psychology 3, 145.
Stange, JP, Sylvia, LG, da Silva Magalhães, PV, Miklowitz, DJ, Otto, MW, Frank, E, Berk, M, Hansen, NS, Dougherty, DD, Nierenberg, AA and Deckersbach, T (2014) Extreme attributions predict suicidal ideation and suicide attempts in bipolar disorder: prospective data from STEP-BD. World Psychiatry 13, 9596.
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.
Stange, JP, Bessette, KL, Jenkins, LM, Peters, AT, Feldhaus, C, Crane, NA, Ajilore, O, Jacobs, RH, Watkins, ER and Langenecker, SA (2017) Attenuated intrinsic connectivity within cognitive control network among individuals with remitted depression: temporal stability and association with negative cognitive styles. Human Brain Mapping 38, 29392954.
Stange, JP, Kleiman, EM, Mermelstein, RJ, and Trull, TJ (in press) Using ambulatory assessment to measure dynamic risk processes in affective disorders. Journal of Affective Disorders
Surrence, K, Miranda, R, Marroquín, BM and Chan, S (2009) Brooding and reflective rumination among suicide attempters: cognitive vulnerability to suicidal ideation. Behaviour Research and Therapy 47, 803808.
Valtonen, HM, Suominen, K, Mantere, O, Leppamaki, S, Arvilommi, P and Isometsa, ET (2006) Prospective study of risk factors for attempted suicide among patients with bipolar disorder. Bipolar Disorders 8, 576585.
van Heeringen, K, Godfrin, K and Bijttebier, S (2011). Understanding the suicidal brain: a review of neuropsychological studies of suicidal ideation and behavior. In O'Connor, RC, Platt, S and Gordon, J (eds.), International Handbook of Suicide Prevention: Research, Policy and Practice. New York: Wiley, pp. 151167.
van Heeringen, K, Bijttebier, S, Desmyter, S, Vervaet, M and Baeken, C (2014) Is there a neuroanatomical basis of the vulnerability to suicidal behavior? A coordinate-based meta-analysis of structural and functional MRI studies. Frontiers Human Neuroscience 8, 824.
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.
Yeo, BT, Krienen, FM, Sepulcre, J, Sabuncu, MR, Lashkari, D, Hollinshead, M and Roffman, JL (2011) The organization of the human cerebral cortex estimated by intrinsic functional connectivity. Journal of Neurophysiolog 106, 11251165.
Zhang, H, Chen, Z, Jia, Z and Gong, Q (2014) Dysfunction of neural circuitry in depressive patients with suicidal behaviors: a review of structural and functional neuroimaging studies. Progress in Neuro-Psychopharmacology and Biological Psychiatry 53, 6166.
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.


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Using resting-state intrinsic network connectivity to identify suicide risk in mood disorders

  • Jonathan P. Stange (a1), Lisanne M. Jenkins (a2), Stephanie Pocius (a3), Kayla Kreutzer (a1), Katie L. Bessette (a1), Sophie R. DelDonno (a1), Leah R. Kling (a1), Runa Bhaumik (a1), Robert C. Welsh (a3), John G. Keilp (a4), K. Luan Phan (a5) and Scott A. Langenecker (a3)...


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