Abstract
Introduction: Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associated with suicide-related personality traits. The objective of our study was to clarify this. Methods: Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA), and 40 without SA, and 35 healthy controls (HCs). The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Results: BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression, and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. Conclusion: These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits.
Journal Section:
Research Article
References
1.
Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, et al. Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry. 2011 Mar;68(3):241–51.
2.
Dong M, Lu L, Zhang L, Zhang Q, Ungvari GS, Ng CH, et al. Prevalence of suicide attempts in bipolar disorder: a systematic review and meta-analysis of observational studies. Epidemiol Psychiatr Sci. 2019 Oct 25;29:e63.
3.
Hantouche EG, Akiskal HS. Bipolar II vs. unipolar depression: psychopathologic differentiation by dimensional measures. J Affect Disord. 2005 Feb;84(2–3):127–32.
4.
Soloff P, White R, Diwadkar VA. Impulsivity, aggression and brain structure in high and low lethality suicide attempters with borderline personality disorder. Psychiatry Res. 2014 Jun 30;222(3):131–9.
5.
Jonckheere D, Coutino-Gonzalez E, Baekelant W, Bueken B, Reinsch H, Stassen I, et al. Silver-induced reconstruction of an adeninate-based metal-organic framework for encapsulation of luminescent adenine-stabilized silver clusters. J Mater Chem C Mater. 2016 May 21;4(19):4259–68.
6.
Johnston JAY, Wang F, Liu J, Blond BN, Wallace A, Liu J, et al. Multimodal neuroimaging of frontolimbic structure and function associated with suicide attempts in adolescents and young adults with bipolar disorder. Am J Psychiatry. 2017 Jul 1;174(7):667–75.
7.
Lan MJ, Rizk MM, Pantazatos SP, Rubin-Falcone H, Miller JM, Sublette ME, et al. Resting-state amplitude of low-frequency fluctuation is associated with suicidal ideation. Depress Anxiety. 2019 May;36(5):433–41.
8.
Smith SM, Vidaurre D, Beckmann CF, Glasser MF, Jenkinson M, Miller KL, et al. Functional connectomics from resting-state fMRI. Trends Cogn Sci. 2013 Dec;17(12):666–82.
9.
Weng JC, Chou YS, Tsai YH, Lee CT, Hsieh MH, Chen VC. Connectome analysis of brain functional network alterations in depressive patients with suicidal attempt. J Clin Med. 2019 Nov 14;8(11):1966.
10.
Ding Y, Lawrence N, Olie E, Cyprien F, le Bars E, Bonafe A, et al. Prefrontal cortex markers of suicidal vulnerability in mood disorders: a model-based structural neuroimaging study with a translational perspective. Transl Psychiatry. 2015 Feb 24;5(2):e516.
11.
Fan S, Lippard ETC, Sankar A, Wallace A, Johnston JAY, Wang F, et al. Gray and white matter differences in adolescents and young adults with prior suicide attempts across bipolar and major depressive disorders. J Affect Disord. 2019 Feb 15;245:1089–97.
12.
Fan L, Li H, Zhuo J, Zhang Y, Wang J, Chen L, et al. The human brainnetome atlas: a new brain atlas based on connectional architecture. Cereb Cortex. 2016 Aug;26(8):3508–26.
13.
Glikmann-Johnston Y, Oren N, Hendler T, Shapira-Lichter I. Distinct functional connectivity of the hippocampus during semantic and phonemic fluency. Neuropsychologia. 2015 Mar;69:39–49.
14.
Howard LR, Javadi AH, Yu Y, Mill RD, Morrison LC, Knight R, et al. The hippocampus and entorhinal cortex encode the path and Euclidean distances to goals during navigation. Curr Biol. 2014 Jun 16;24(12):1331–40.
15.
Fateh AA, Long Z, Duan X, Cui Q, Pang Y, Farooq MU, et al. Hippocampal functional connectivity-based discrimination between bipolar and major depressive disorders. Psychiatry Res Neuroimaging. 2019 Feb 28;284:53–60.
16.
Blum S, Habeck C, Steffener J, Razlighi Q, Stern Y. Functional connectivity of the posterior hippocampus is more dominant as we age. Cogn Neurosci. 2014;5(3–4):150–9.
17.
Kesner RP, Lee I, Gilbert P. A behavioral assessment of hippocampal function based on a subregional analysis. Rev Neurosci. 2004;15(5):333–51.
18.
Strange BA, Witter MP, Lein ES, Moser EI. Functional organization of the hippocampal longitudinal axis. Nat Rev Neurosci. 2014 Oct;15(10):655–69.
19.
Hutchison RM, Womelsdorf T, Gati JS, Everling S, Menon RS. Resting-state networks show dynamic functional connectivity in awake humans and anesthetized macaques. Hum Brain Mapp. 2013 Sep;34(9):2154–77.
20.
Preti MG, Bolton TA, Van De Ville D. The dynamic functional connectome: state-of-the-art and perspectives. Neuroimage. 2017 Oct 15;160:41–54.
21.
Zhang J, Cheng W, Liu Z, Zhang K, Lei X, Yao Y, et al. Neural, electrophysiological and anatomical basis of brain-network variability and its characteristic changes in mental disorders. Brain. 2016 Aug;139(Pt 8):2307–21.
22.
Liao W, Li J, Duan X, Cui Q, Chen H, Chen H. Static and dynamic connectomics differentiate between depressed patients with and without suicidal ideation. Hum Brain Mapp. 2018 Oct;39(10):4105–18.
23.
Li J, Duan X, Cui Q, Chen H, Liao W. More than just statics: temporal dynamics of intrinsic brain activity predicts the suicidal ideation in depressed patients. Psychol Med. 2019 Apr;49(5):852–60.
24.
Watson S, Gallagher P, Ritchie JC, Ferrier IN, Young AH. Hypothalamic-pituitary-adrenal axis function in patients with bipolar disorder. Br J Psychiatry. 2004 Jun;184:496–502.
25.
Belvederi Murri M, Pariante C, Mondelli V, Masotti M, Atti AR, Mellacqua Z, et al. HPA axis and aging in depression: systematic review and meta-analysis. Psychoneuroendocrinology. 2014 Mar;41:46–62.
26.
Mann JJ, Currier D, Stanley B, Oquendo MA, Amsel LV, Ellis SP. Can biological tests assist prediction of suicide in mood disorders?Int J Neuropsychopharmacol. 2006 Aug;9(4):465–74.
27.
Kamali M, Saunders EF, Prossin AR, Brucksch CB, Harrington GJ, Langenecker SA, et al. Associations between suicide attempts and elevated bedtime salivary cortisol levels in bipolar disorder. J Affect Disord. 2012 Feb;136(3):350–8.
28.
Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology. 2000 Nov;23(5):477–501.
29.
Bschor T, Adli M, Baethge C, Eichmann U, Ising M, Uhr M, et al. Lithium augmentation increases the ACTH and cortisol response in the combined DEX/CRH test in unipolar major depression. Neuropsychopharmacology. 2002 Sep;27(3):470–8.
30.
Pfennig A, Kunzel HE, Kern N, Ising M, Majer M, Fuchs B, et al. Hypothalamus-pituitary-adrenal system regulation and suicidal behavior in depression. Biol Psychiatry. 2005 Feb 15;57(4):336–42.
31.
Lindqvist D, Isaksson A, Traskman-Bendz L, Brundin L. Salivary cortisol and suicidal behavior: a follow-up study. Psychoneuroendocrinology. 2008 Sep;33(8):1061–8.
32.
Belvederi Murri M, Prestia D, Mondelli V, Pariante C, Patti S, Olivieri B, et al. The HPA axis in bipolar disorder: systematic review and meta-analysis. Psychoneuroendocrinology. 2016 Jan;63:327–42.
33.
McEwen BS. Protection and damage from acute and chronic stress: allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders. Ann N Y Acad Sci. 2004 Dec;1032:1–7.
34.
Horta M, Kaylor K, Feifel D, Ebner NC. Chronic oxytocin administration as a tool for investigation and treatment: a cross-disciplinary systematic review. Neurosci Biobehav Rev. 2020 Jan;108:1–23.
35.
Sun X, Ming Q, Zhong X, Dong D, Li C, Xiong G, et al. The MAOA gene influences the neural response to psychosocial stress in the human brain. Front Behav Neurosci. 2020;14:65.
36.
Shields GS, Hostinar CE, Vilgis V, Forbes EE, Hipwell AE, Keenan K, et al. Hypothalamic-pituitary-adrenal Axis activity in childhood predicts emotional memory effects and related neural circuitry in adolescent girls. J Cogn Neurosci. 2021 Apr 1;33(5):872–86.
37.
Kiem SA, Andrade KC, Spoormaker VI, Holsboer F, Czisch M, Samann PG. Resting state functional MRI connectivity predicts hypothalamus-pituitary-axis status in healthy males. Psychoneuroendocrinology. 2013 Aug;38(8):1338–48.
38.
Mareckova K, Holsen L, Admon R, Whitfield-Gabrieli S, Seidman LJ, Buka SL, et al. Neural: hormonal responses to negative affective stimuli–impact of dysphoric mood and sex. J Affect Disord. 2017 Nov;222:88–97.
39.
Colla M, Schubert F, Bubner M, Heidenreich JO, Bajbouj M, Seifert F, et al. Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol. Mol Psychiatry. 2009 Jul;14(7):696–704.
40.
Barzilay S, Apter A. Psychological models of suicide. Arch Suicide Res. 2014;18(4):295–312.
41.
Pompili M, Innamorati M, Giupponi G, Pycha R, Rihmer Z, Casale A, et al. Predicting risk of suicide in bipolar and unipolar depression: correlation between temperament and personality. Nervenarzt. 2009 Mar;80(3):315–23.
42.
Bryan CJ, Johnson LG, David Rudd M, Joiner TEJr. Hypomanic symptoms among first-time suicide attempters predict future multiple attempt status. J Clin Psychol. 2008 Apr;64(4):519–30.
43.
Su MH, Chen HC, Lu ML, Feng J, Chen IM, Wu CS, et al. Risk profiles of personality traits for suicidality among mood disorder patients and community controls. Acta Psychiatr Scand. 2018 Jan;137(1):30–8.
44.
Zakowicz P, Skibińska M, Wasicka-Przewoźna K, Skulimowski B, Waśniewski F, Chorzepa A, et al. Impulsivity as a risk factor for suicide in bipolar disorder. Front Psychiatry. 2021;12:706933.
45.
Petek Eric A, Eric I, Curkovic M, Dodig-Curkovic K, Kralik K, Kovac V, et al. The temperament and character traits in patients with major depressive disorder and bipolar affective disorder with and without suicide attempt. Psychiatr Danub. 2017 Jun;29(2):171–8.
46.
He Z, Lu F, Sheng W, Han S, Pang Y, Chen Y, et al. Abnormal functional connectivity as neural biological substrate of trait and state characteristics in major depressive disorder. Prog Neuro-Psychopharmacol Biol Psychiatry. 2020 Aug 30;102:109949.
47.
Wu X, He H, Shi L, Xia Y, Zuang K, Feng Q, et al. Personality traits are related with dynamic functional connectivity in major depression disorder: a resting-state analysis. J Affect Disord. 2019 Feb 15;245:1032–42.
48.
Wasserman D, Geijer T, Sokolowski M, Rozanov V, Wasserman J. Genetic variation in the hypothalamic-pituitary-adrenocortical axis regulatory factor, T-box 19, and the angry/hostility personality trait. Genes Brain Behav. 2007 Jun;6(4):321–8.
49.
O’Connor DB, Branley-Bell D, Green JA, Ferguson E, O’Carroll RE, O’Connor RC. Resilience and vulnerability factors influence the cortisol awakening response in individuals vulnerable to suicide. J Psychiatr Res. 2021 Oct;142:312–20.
50.
Wasserman D, Geijer T, Sokolowski M, Rozanov V, Wasserman J. Nature and nurture in suicidal behavior, the role of genetics: some novel findings concerning personality traits and neural conduction. Physiol Behav. 2007 Sep 10;92(1–2):245–9.
51.
Braquehais MD, Picouto MD, Casas M, Sher L. Hypothalamic-pituitary-adrenal axis dysfunction as a neurobiological correlate of emotion dysregulation in adolescent suicide. World J Pediatr. 2012 Aug;8(3):197–206.
52.
Yan CG, Wang XD, Zuo XN, Zang YF. DPABI: data processing & analysis for (Resting-State) brain imaging. Neuroinformatics. 2016 Jul;14(3):339–51.
53.
Hakamata Y, Komi S, Sato E, Izawa S, Mizukami S, Moriguchi Y, et al. Cortisol-related hippocampal-extrastriate functional connectivity explains the adverse effect of cortisol on visuospatial retrieval. Psychoneuroendocrinology. 2019 Nov;109:104310.
54.
Leonardi N, Van De Ville D. On spurious and real fluctuations of dynamic functional connectivity during rest. Neuroimage. 2015 Jan 1;104:430–6.
55.
Liao W, Wu GR, Xu Q, Ji GJ, Zhang Z, Zang YF, et al. DynamicBC: a MATLAB toolbox for dynamic brain connectome analysis. Brain Connect. 2014 Dec;4(10):780–90.
56.
Cheng X, Chen J, Zhang X, Zhang Y, Wu Q, Ma Q, et al. Alterations in resting-state global brain connectivity in bipolar I disorder patients with prior suicide attempt. Bipolar Disord. 2021 Aug;23(5):474–86.
57.
Pan LA, Ramos L, Segreti A, Brent DA, Phillips ML. Right superior temporal gyrus volume in adolescents with a history of suicide attempt. Br J Psychiatry. 2015 Apr;206(4):339–40.
58.
McLellan Q, Wilkes TC, Swansburg R, Jaworska N, Langevin LM, MacMaster FP. History of suicide attempt and right superior temporal gyrus volume in youth with treatment-resistant major depressive disorder. J Affect Disord. 2018 Oct 15;239:291–4.
59.
Gong J, Chen G, Zhou M, Jia Y, Zhong S, Chen F, et al. Characteristics of temporal dynamics of intrinsic brain activity in unmedicated bipolar disorder with suicidality. Aust N Z J Psychiatry. 2020 Nov;54(11):1115–24.
60.
Chen CF, Chen WN, Zhang B. Functional alterations of the suicidal brain: a coordinate-based meta-analysis of functional imaging studies. Brain Imaging Behav. 2021 Aug 5;16(1):291–304.
61.
Chepenik LG, Wang F, Spencer L, Spann M, Kalmar JH, Womer F, et al. Structure-function associations in hippocampus in bipolar disorder. Biol Psychol. 2012 Apr;90(1):18–22.
62.
Cao B, Passos IC, Mwangi B, Bauer IE, Zunta-Soares GB, Kapczinski F, et al. Hippocampal volume and verbal memory performance in late-stage bipolar disorder. J Psychiatr Res. 2016 Feb;73:102–7.
63.
Sander D, Grandjean D, Pourtois G, Schwartz S, Seghier ML, Scherer KR, et al. Emotion and attention interactions in social cognition: brain regions involved in processing anger prosody. Neuroimage. 2005 Dec;28(4):848–58.
64.
Richard-Devantoy S, Berlim MT, Jollant F. Suicidal behaviour and memory: a systematic review and meta-analysis. World J Biol Psychiatry. 2015;16(8):544–66.
65.
Mitchell RL, Elliott R, Barry M, Cruttenden A, Woodruff PW. Neural response to emotional prosody in schizophrenia and in bipolar affective disorder. Br J Psychiatry. 2004 Mar;184:223–30.
66.
Reisch T, Seifritz E, Esposito F, Wiest R, Valach L, Michel K. An fMRI study on mental pain and suicidal behavior. J Affect Disord. 2010 Oct;126(1–2):321–5.
67.
Brunner J, Keck ME, Landgraf R, Uhr M, Namendorf C, Bronisch T. Vasopressin in CSF and plasma in depressed suicide attempters: preliminary results. Eur Neuropsychopharmacol. 2002 Oct;12(5):489–94.
68.
Preil J, Muller MB, Gesing A, Reul JM, Sillaber I, van Gaalen MM, et al. Regulation of the hypothalamic-pituitary-adrenocortical system in mice deficient for CRH receptors 1 and 2. Endocrinology. 2001 Nov;142(11):4946–55.
69.
Hauger RL, Risbrough V, Brauns O, Dautzenberg FM. Corticotropin releasing factor (CRF) receptor signaling in the central nervous system: new molecular targets. CNS Neurol Disord Drug Targets. 2006 Aug;5(4):453–79.
70.
Roos NP. The disconnect between the data and the headlines. Can Med Assoc J. 2000 Aug 22;163(4):411–2.
71.
Pandey GN, Rizavi HS, Bhaumik R, Ren X. Increased protein and mRNA expression of corticotropin-releasing factor (CRF), decreased CRF receptors and CRF binding protein in specific postmortem brain areas of teenage suicide subjects. Psychoneuroendocrinology. 2019 Aug;106:233–43.
72.
Drayton M. The Minnesota multiphasic personality inventory-2 (MMPI-2). Occup Med. 2009 Mar;59(2):135–6.
73.
Kim S, Lee HK, Lee K. Detecting suicidal risk using MMPI-2 based on machine learning algorithm. Sci Rep. 2021 Jul 28;11(1):15310.
74.
Pompili M, Rihmer Z, Akiskal HS, Innamorati M, Iliceto P, Akiskal KK, et al. Temperament and personality dimensions in suicidal and nonsuicidal psychiatric inpatients. Psychopathology. 2008;41(5):313–21.
75.
Lee YJ, Keum MS, Kim HG, Cheon EJ, Cho YC, Koo BH. Defense mechanisms and psychological characteristics according to suicide attempts in patients with borderline personality disorder. Psychiatry Investig. 2020 Aug;17(8):840–9.
76.
Kabbara A, Paban V, Weill A, Modolo J, Hassan M. Brain network dynamics correlate with personality traits. Brain Connect. 2020 Apr;10(3):108–20.
77.
Martins JM, Alves J, Trinca A, Grima B, do Vale S, Vasconcelos T, et al. Personality, brain asymmetry, and neuroendocrine reactivity in two immune-mediated disorders: a preliminary report. Brain Behav Immun. 2002 Aug;16(4):383–97.
78.
Gustin SM, McKay JG, Petersen ET, Peck CC, Murray GM, Henderson LA. Subtle alterations in brain anatomy may change an individual’s personality in chronic pain. PLoS One. 2014;9(10):e109664.
79.
Jokela M, Hakulinen C, Singh-Manoux A, Kivimaki M. Personality change associated with chronic diseases: pooled analysis of four prospective cohort studies. Psychol Med. 2014 Sep;44(12):2629–40.
© 2023 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2023
You do not currently have access to this content.
