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Hyperconnectivity and network inflexibility in large-scale brain networks: Linking childhood neglect to depression via task and resting-state fMRI.

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Τίτλος: Hyperconnectivity and network inflexibility in large-scale brain networks: Linking childhood neglect to depression via task and resting-state fMRI.
Συγγραφείς: Cao X; Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.; Medical Psychological Institution, Central South University, Changsha, China., Yang H; Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.; Medical Psychological Institution, Central South University, Changsha, China., Liu Z; Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.; Medical Psychological Institution, Central South University, Changsha, China., Cai S; Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China., Cheng M; Department of Clinical Psychology, Brain Hospital of Hunan Province, Changsha, China., Li C; Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.; Medical Psychological Institution, Central South University, Changsha, China., Liao H; Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China., Yi J; Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, China.; Medical Psychological Institution, Central South University, Changsha, China.; National Clinical Research Center for Mental Disorders, Changsha, China.
Πηγή: Psychiatry and clinical neurosciences [Psychiatry Clin Neurosci] 2026 Oct; Vol. 80 (10), pp. 856-865. Date of Electronic Publication: 2026 Jul 29.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Blackwell Science Country of Publication: Australia NLM ID: 9513551 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1440-1819 (Electronic) Linking ISSN: 13231316 NLM ISO Abbreviation: Psychiatry Clin Neurosci Subsets: MEDLINE
Imprint Name(s): Original Publication: Carlton, Vic., Australia : Blackwell Science
Ιατρικοί όροι (MeSH): Major Depressive Disorder*/physiopathology , Major Depressive Disorder*/diagnostic imaging , Major Depressive Disorder*/etiology , Nerve Net*/physiopathology , Nerve Net*/diagnostic imaging , Default Mode Network*/physiopathology , Default Mode Network*/diagnostic imaging , Connectome* , Adult Survivors of Child Abuse*, Humans ; Magnetic Resonance Imaging ; Female ; Male ; Adult ; Inhibition, Psychological ; Young Adult
Περίληψη: Background: Childhood neglect is a potent risk factor for major depressive disorder (MDD), yet its underlying neural mechanisms linking neglect to depression remain poorly understood. This study aimed to investigate brain network alterations and task-rest functional connectivity (FC) similarity associated with childhood neglect and to clarify their mechanistic roles in depression.
Methods: Participants included MDD patients with childhood neglect (n = 42), MDD patients without childhood trauma (n = 23), and healthy controls without childhood trauma (n = 66). All participants completed clinical scales and underwent both resting-state and task-based fMRI during a Go/No-Go response inhibition task.
Results: (1) A distinct subnetwork comprising 207 edges across 170 nodes (P < 0.05) exhibited hyperconnectivity in the MDD-Neglect group compared to both the MDD-No Trauma group (P < 0.001) and healthy controls (P < 0.001), with prominent involvement of the default mode network and dorsal attention network. (2) The connectivity strength of the significant subnetwork positively predicted depressive symptom severity (β = 0.438, P < 0.001) and significantly mediated the relationship between childhood neglect and depressive symptoms. (3) The task-rest FC similarity of the significant subnetwork also positively predicted depressive symptom severity (β = 0.328, P < 0.001) and mediated the relationship between childhood neglect and depressive symptoms.
Conclusion: Childhood neglect may exacerbate depression through two complementary neurofunctional mechanisms: heightened static connectivity within a cognitive control subnetwork and diminished dynamic flexibility in brain network reconfiguration. These complementary network-level features advance a network-based understanding of how early adversity confers lasting depression risk.
Significant Outcomes: Patients with major depressive disorder and a history of childhood neglect exhibited a distinct pattern of hyperconnectivity within a large-scale brain subnetwork (primarily involving the DMN, DAN, and SAN) during response inhibition. Both increased functional connectivity strength and higher task-rest FC similarity within the network independently mediated the relationship between childhood neglect and depressive symptom severity.
Limitations: The cross-sectional design of this study limits causal inferences about the directional relationships among childhood neglect, brain network alterations, and depressive symptoms. Childhood neglect was assessed retrospectively via self-report, which may be subject to recall bias. The study is specific to the domain of response inhibition and functional connectivity measures, limiting generalization to other cognitive or emotional processes and to multimodal neural mechanisms.
(© 2026 The Author(s). Psychiatry and Clinical Neurosciences © 2026 Japanese Society of Psychiatry and Neurology.)
References: Otte C, Gold SM, Penninx BW et al. Major depressive disorder. Nat. Rev. Dis. Primers. 2016; 2: 16065.
Cui L, Li S, Wang S et al. Major depressive disorder: Hypothesis, mechanism, prevention and treatment. Signal Transduct. Target. Ther. 2024; 9: 30.
Price JL, Drevets WC. Neurocircuitry of mood disorders. Neuropsychopharmacology 2010; 35: 192–216.
van den Heuvel MP, Scholtens LH, Kahn RS. Multiscale neuroscience of psychiatric disorders. Biol. Psychiatry 2019; 86: 512–522.
Menon V. Large‐scale brain networks and psychopathology: A unifying triple network model. Trends Cogn. Sci. 2011; 15: 483–506.
Seeley WW, Menon V, Schatzberg AF et al. Dissociable intrinsic connectivity networks for salience processing and executive control. J. Neurosci. 2007; 27: 2349–2356.
Raichle ME, MacLeod AM, Snyder AZ, Powers WJ, Gusnard DA, Shulman GL. A default mode of brain function. Proc. Natl. Acad. Sci. 2001; 98: 676–682.
Mao Y, Xiao H, Ding C, Qiu J. The role of attention in the relationship between early life stress and depression. Sci. Rep. 2020; 10: 6154.
Sylvester CM, Barch DM, Corbetta M, Power JD, Schlaggar BL, Luby JL. Resting state functional connectivity of the ventral attention network in children with a history of depression or anxiety. J. Am. Acad. Child Adolesc. Psychiatry 2013; 52: 1326–1336. e1325.
Yu M, Linn KA, Shinohara RT et al. Childhood trauma history is linked to abnormal brain connectivity in major depression. Proc. Natl. Acad. Sci. U. S. A. 2019; 116: 8582–8590.
Ferreira S, Pego JM, Morgado P. A systematic review of behavioral, physiological, and neurobiological cognitive regulation alterations in obsessive‐compulsive disorder. Brain Sci. 2020; 10: 797.
Vargas C, Lopez‐Jaramillo C, Vieta E. A systematic literature review of resting state network‐functional MRI in bipolar disorder. J. Affect. Disord. 2013; 150: 727–735.
Xu J, Van Dam NT, Feng CL et al. Anxious brain networks: A coordinate‐based activation likelihood estimation meta‐analysis of resting‐state functional connectivity studies in anxiety. Neurosci. Biobehav. Rev. 2019; 96: 21–30.
Marx W, Penninx BWJH, Solmi M et al. Major depressive disorder. Nat. Rev. Dis. Primers. 2023; 9: 44.
Barczyk ZA, Foulds JA, Porter RJ, Douglas KM. Childhood trauma and cognitive functioning in mood disorders: A systematic review. Bipolar Disord. 2023; 25: 263–277.
Wade M, Zeanah CH, Fox NA, Tibu F, Ciolan LE, Nelson CA. Stress sensitization among severely neglected children and protection by social enrichment. Nat. Commun. 2019; 10: 5771.
Watters ER, Aloe AM, Wojciak AS. Examining the associations between childhood trauma, resilience, and depression: A multivariate meta‐analysis. Trauma Violence Abuse 2023; 24: 231–244.
Grummitt L, Baldwin JR, Lafoa'i J, Keyes KM, Barrett EL. Burden of mental disorders and suicide attributable to childhood maltreatment. JAMA Psychiatry 2024; 81: 782–788.
McLaughlin KA, Colich NL, Rodman AM, Weissman DG. Mechanisms linking childhood trauma exposure and psychopathology: A transdiagnostic model of risk and resilience. BMC Med. 2020; 18: 1–11.
McLaughlin KA, Weissman D, Bitrán D. Childhood adversity and neural development: A systematic review. Ann. Rev. Dev. Psychol. 2019; 1: 277–312.
Johnson D, Policelli J, Li M et al. Associations of early‐life threat and deprivation with executive functioning in childhood and adolescence: A systematic review and meta‐analysis. JAMA Pediatr. 2021; 175: e212511.
Smith R, Alkozei A, Killgore WD, Lane RD. Nested positive feedback loops in the maintenance of major depression: An integration and extension of previous models. Brain Behav. Immun. 2018; 67: 374–397.
Langenecker SA, Jenkins LM, Stange JP et al. Cognitive control neuroimaging measures differentiate between those with and without future recurrence of depression. NeuroImage: Clin. 2018; 20: 1001–1009.
Buckner RL, Krienen FM, Yeo BTT. Opportunities and limitations of intrinsic functional connectivity MRI. Nat. Neurosci. 2013; 16: 832–837.
Zhang H, Meng C, Di X, Wu X, Biswal B. Static and dynamic functional connectome reveals reconfiguration profiles of whole‐brain network across cognitive states. Network Neurosci. 2023; 7: 1034–1050.
Schultz DH, Cole MW. Higher intelligence is associated with less task‐related brain network reconfiguration. J. Neurosci. 2016; 36: 8551–8561.
Cole MW. Cognitive flexibility as the shifting of brain network flows by flexible neural representations. Curr. Opin. Behav. Sci. 2024; 57: 101384.
Lee Y, Yuan JP, Winkler AM, Kircanski K, Pine DS, Gotlib IH. Task‐rest reconfiguration efficiency of the reward network across adolescence and its association with early life stress and depressive symptoms. J. Am. Acad. Child Adolesc. Psychiatry 2025; 64: 290–300.
Bernstein DP, Fink L, Handelsman L, Foote J. Childhood trauma questionnaire. In: Assessment of Family Violence: A Handbook for Researchers and Practitioners, APA, Washington, DC, 1998.
Xiao J, Qiu Y, He Y et al. ‘Weakest link’ as a cognitive vulnerability within the hopelessness theory of depression in Chinese university students. Stress Health 2016; 32: 20–27.
He J, Zhong X, Gao Y, Xiong G, Yao S. Psychometric properties of the Chinese version of the childhood trauma questionnaire‐short form (CTQ‐SF) among undergraduates and depressive patients. Child Abuse Negl. 2019; 91: 102–108.
Esteban O, Markiewicz CJ, Blair RW et al. fMRIPrep: A robust preprocessing pipeline for functional MRI. Nat. Methods 2019; 16: 111–116.
Schaefer A, Kong R, Gordon EM et al. Local‐global Parcellation of the human cerebral cortex from intrinsic functional connectivity MRI. Cereb. Cortex 2018; 28: 3095–3114.
McLaren DG, Ries ML, Xu G, Johnson SC. A generalized form of context‐dependent psychophysiological interactions (gPPI): A comparison to standard approaches. Neuroimage 2012; 61: 1277–1286.
Masson HL, Pillet I, Boets B, de Beeck HO. Task‐dependent changes in functional connectivity during the observation of social and non‐social touch interaction. Cortex 2020; 125: 73–89.
Zalesky A, Fornito A, Bullmore ET. Network‐based statistic: Identifying differences in brain networks. Neuroimage 2010; 53: 1197–1207.
Davies C, Martins D, Dipasquale O et al. Connectome dysfunction in patients at clinical high risk for psychosis and modulation by oxytocin. Mol. Psychiatry 2024; 29: 1241–1252.
R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria, 2020.
Rosseel Y. Lavaan: An R package for structural equation modeling. J. Stat. Softw. 2012; 48: 1–36.
Majerus S, Péters F, Bouffier M, Cowan N, Phillips C. The dorsal attention network reflects both encoding load and top–down control during working memory. J. Cogn. Neurosci. 2018; 30: 144–159.
Scalabrini A, Vai B, Poletti S et al. All roads lead to the default‐mode network—Global source of DMN abnormalities in major depressive disorder. Neuropsychopharmacology 2020; 45: 2058–2069.
Lin J, Huang J, Wu Y et al. Exploring the neural link between childhood maltreatment and depression: A default mode network rs‐fMRI study [original research]. Front. Psychiatry. 2024; 15–2024. https://doi.org/10.3389/fpsyt.2024.1450051.
Kim H. Dissociating the roles of the default‐mode, dorsal, and ventral networks in episodic memory retrieval. Neuroimage 2010; 50: 1648–1657.
Stevens MC. The contributions of resting state and task‐based functional connectivity studies to our understanding of adolescent brain network maturation. Neurosci. Biobehav. Rev. 2016; 70: 13–32.
Sheline YI, Price JL, Yan Z, Mintun MA. Resting‐state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proc. Natl. Acad. Sci. 2010; 107: 11020–11025.
Rakesh D, Allen NB, Whittle S. Longitudinal changes in within‐salience network functional connectivity mediate the relationship between childhood abuse and neglect, and mental health during adolescence. Psychol. Med. 2023; 53: 1552–1564.
DeSerisy M, Ramphal B, Pagliaccio D et al. Frontoparietal and default mode network connectivity varies with age and intelligence. Dev. Cogn. Neurosci. 2021; 48: 100928.
Sherman LE, Rudie JD, Pfeifer JH, Masten CL, McNealy K, Dapretto M. Development of the default mode and central executive networks across early adolescence: A longitudinal study. Dev. Cogn. Neurosci. 2014; 10: 148–159.
Satterthwaite TD, Elliott MA, Gerraty RT et al. An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting‐state functional connectivity data. Neuroimage 2013; 64: 240–256.
Harrewijn A, Abend R, Linke J et al. Combining fMRI during resting state and an attention bias task in children. Neuroimage 2020; 205: 116301.
Kaiser RH, Kang MS, Lew Y et al. Abnormal frontoinsular‐default network dynamics in adolescent depression and rumination: A preliminary resting‐state co‐activation pattern analysis. Neuropsychopharmacology 2019; 44: 1604–1612.
Zheng R, Chen Y, Jiang Y et al. Abnormal dynamic functional connectivity in first‐episode, drug‐naïve adolescents with major depressive disorder. J. Neurosci. Res. 2022; 100: 1463–1475.
Grant Information: 82271573 National Natural Science Foundation of China
Contributed Indexing: Keywords: childhood neglect; functional connectivity; major depressive disorder; response inhibition
Entry Date(s): Date Created: 20260729 Date Completed: 20261007 Latest Revision: 20261007
Update Code: 20261008
DOI: 10.1111/pcn.70109
PMID: 42522354
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1440-1819
DOI:10.1111/pcn.70109