Negative family and interpersonal relationship are associated with centromedial amygdala functional connectivity alterations in adolescent depression.

Publisher: Country of Publication: Germany NLM ID: 9212296 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1435-165X (Electronic) Linking ISSN: 10188827 NLM ISO Abbreviation: Eur Child Adolesc Psychiatry Subsets: MEDLINE

Publication: 2010- : Heidelberg : Springer Medizin
Original Publication: Toronto ; Lewiston, NY : Hogrefe & Huber, [1992-

Depressive Disorder, Major*/physiopathology ; Depressive Disorder, Major*/diagnostic imaging ; Magnetic Resonance Imaging* ; Interpersonal Relations*; Humans ; Adolescent ; Male ; Female ; Amygdala/physiopathology ; Amygdala/diagnostic imaging ; Family Relations/psychology ; Central Amygdaloid Nucleus/physiopathology ; Central Amygdaloid Nucleus/diagnostic imaging ; Case-Control Studies

The amygdala, known for its functional heterogeneity, plays a critical role in the neural mechanism of adolescent major depressive disorder (aMDD). However, changes in its subregional functional networks in relation to stressful factors remain unclear. We recruited 78 comorbidity-free, medication-naive aMDD patients and 40 matched healthy controls (HC) to explore changes in resting-state functional connectivity (FC) across four amygdala subregions: the centromedial nucleus (CM), the basolateral nucleus (LB), the superficial nucleus (SF), and the amygdalostriatal transition area (Astr). Then, we performed partial correlation analysis to investigate the relationship between amygdala subregional FC and stressful factors as measured by the Chinese Version of Family Environment Scale (FES-CV) and the Adolescent Self-Rated Life Events Scale (ASLEC). Compared to HC, aMDD patients demonstrated significantly decreased functional connectivity between the left CM and left precentral gyrus, as well as between left SF and left precentral gyrus, and between left LB and posterior cingulate gyrus (PCC)/precuneus. In aMDD group, left CM-precentral gyrus FC exhibited negative correlation with interpersonal relationship and punishment, and positive correlation with family cohesion and expressiveness. This study reveals distinct patterns of abnormal functional connectivity among amygdala subregions in aMDD. Our findings suggest that the CM network, in particular, may be involved in stress-related factors in aMDD, which provide a potential target for the prevention and treatment of adolescent depression.
Competing Interests: Declarations. Ethical approval: This research was approved by the Ethics Committee of the Third People’s Hospital of Mianyang, and it is all done in accordance with the ethical standards set out in the 1964 Declaration of Helsinki and its subsequent amendments. Informed consent: Not applicable Competing interests: On behalf of all authors, the corresponding author states that there is no conflict of interest.
(© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Malhi GS, Mann JJ (2018) Depress Lancet 392:2299–2312. (PMID: 10.1016/S0140-6736(18)31948-2)
Chi S, Song M, Lee J-h, Ko M, Suh S-i, Lee M-S (2021) Prospective study on resting state functional connectivity in adolescents with major depressive disorder after antidepressant treatment. J Psychiatr Res 142:369–375. (PMID: 3442548910.1016/j.jpsychires.2021.08.026)
Miller L, Campo JV (2021) Depression in adolescents. N Engl J Med 385:445–449. (PMID: 3432028910.1056/NEJMra2033475)
Bartlett EA, Klein DN, Li KQ, DeLorenzo C, Kotov R, Perlman G (2019) Depression Severity over 27 months in adolescent girls is predicted by stress-linked cortical morphology. Biol Psychiatry 86:769–778. (PMID: 31230728681452810.1016/j.biopsych.2019.04.027)
Sagrestano LM, Paikoff RL, Holmbeck GN, Fendrich M (2003) A longitudinal examination of familial risk factors for depression among inner-city African American adolescents. J Fam Psychol 17:108–120. (PMID: 1266646710.1037/0893-3200.17.1.108)
Herman KC, Ostrander R, Tucker CM (2007) Do family environments and negative cognitions of adolescents with depressive symptoms vary by ethnic group? J Fam Psychol 21:325–330. (PMID: 1760555610.1037/0893-3200.21.2.325)
Ogburn KM, Sanches M, Williamson DE, Caetano SC, Olvera RL, Pliszka S, Hatch JP, Soares JC (2010) Family environment and pediatric major depressive disorder. Psychopathology 43:312–318. (PMID: 20664307321492110.1159/000319400)
van Amelsvoort T, Stikkelbroek Y, Bodden DHM, Kleinjan M, Reijnders M, van Baar AL (2016) Adolescent depression and Negative Life Events, the Mediating role of cognitive emotion regulation. Plos One 11.
Holt RF, Beer J, Kronenberger WG, Pisoni DB (2013) Developmental effects of Family Environment on outcomes in Pediatric Cochlear Implant recipients. Otology Neurotology 34:388–395. (PMID: 23151776359439510.1097/MAO.0b013e318277a0af)
Yu Y, Yang X, Yang Y, Chen L, Qiu X, Qiao Z, Zhou J, Pan H, Ban B, Zhu X, He J, Ding Y, Bai B (2015) The role of Family Environment in depressive symptoms among University students: a large Sample Survey in China. PLoS ONE 10:e0143612. (PMID: 26629694466784410.1371/journal.pone.0143612)
Cui L, Shi G, Oei TP (2013) A study of cognitive vulnerability-stress model of depressive symptoms among Chinese adolescents. Stress Health 29:383–391. (PMID: 2338990410.1002/smi.2484)
Zou P, Sun L, Yang W, Zeng Y, Chen Q, Yang H, Zhou N, Zhang G, Liu J, Li Y, Ao L, Cao J (2018) Associations between negative life events and anxiety, depressive, and stress symptoms: a cross-sectional study among Chinese male senior college students. Psychiatry Res 270:26–33. (PMID: 3024312910.1016/j.psychres.2018.09.019)
Zheng H, Liu D, Cheng J, Wang DB, Liu Y, Wu Y (2022) Negative life events increase the risk of suicidal ideation in 6653 Chinese freshmen: from a 1-year longitudinal study. J Affect Disord 299:604–609. (PMID: 3494223110.1016/j.jad.2021.12.039)
Zhang J-Y, Liu T-H, He Y, Pan H-Q, Zhang W-H, Yin X-P, Tian X-L, Li B-M, Wang X-D, Holmes A, Yuan T-F, Pan B-X (2019) Chronic stress remodels synapses in an Amygdala circuit–specific manner. Biol Psychiatry 85:189–201. (PMID: 3006090810.1016/j.biopsych.2018.06.019)
Liu W-Z, Zhang W-H, Zheng Z-H, Zou J-X, Liu X-X, Huang S-H, You W-J, He Y, Zhang J-Y, Wang X-D, Pan B-X (2020) Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety. Nat Commun 11.
Tang S, Li H, Lu L, Wang Y, Zhang L, Hu X, Bu X, Hu X, Gao Y, Gong Q, Huang X (2019) Anomalous functional connectivity of amygdala subregional networks in major depressive disorder. Depress Anxiety 36:712–722. (PMID: 3111162910.1002/da.22901)
Price JL (2003) Comparative aspects of amygdala connectivity. Amygdala Brain Function: Bacic Clin Approaches 985:50–58.
Sah P, Faber ESL, De Armentia ML, Power J (2003) The amygdaloid complex: anatomy and physiology. Physiol Rev 83:803–834. (PMID: 1284340910.1152/physrev.00002.2003)
Chang JJ, Yu RJ (2018) Alternations in functional connectivity of amygdalar subregions under acute social stress. Neurobiol Stress 9:264–270. (PMID: 30450390623426410.1016/j.ynstr.2018.06.001)
Grant MM, Wood K, Sreenivasan K, Wheelock M, White D, Thomas J, Knight DC, Deshpande G (2015) Influence of early life stress on intra- and extra-amygdaloid causal connectivity. Neuropsychopharmacology 40:1782–1793. (PMID: 25630572491526310.1038/npp.2015.28)
Rosso IM, Cintron CM, Steingard RJ, Renshaw PF, Young AD, Yurgelun-Todd DA (2005) Amygdala and hippocampus volumes in pediatric major depression. Biol Psychiatry 57:21–26. (PMID: 1560729610.1016/j.biopsych.2004.10.027)
Gifuni AJ, Chakravarty MM, Lepage M, Ho TC, Geoffroy M-C, Lacourse E, Gotlib IH, Turecki G, Renaud J, Jollant F (2021) Brain cortical and subcortical morphology in adolescents with depression and a history of suicide attempt. J Psychiatry Neurosci 46:E347–E357. (PMID: 33961355832798010.1503/jpn.200198)
Tang S, Lu L, Zhang L, Hu X, Bu X, Li H, Hu X, Gao Y, Zeng Z, Gong Q, Huang X (2018) Abnormal amygdala resting-state functional connectivity in adults and adolescents with major depressive disorder: a comparative meta-analysis. EBioMedicine 36:436–445. (PMID: 30316866619779810.1016/j.ebiom.2018.09.010)
Li YY, Ni XK, You YF, Qing YH, Wang PR, Yao JS, Ren KM, Zhang L, Liu ZW, Song TJ, Wang J, Zang YF, Shen YD, Chen W (2021) Common and specific alterations of Amygdala subregions in Major Depressive Disorder with and without anxiety: a combined structural and resting-state functional MRI study. Front Hum Neurosci 15:634113. (PMID: 33658914791718610.3389/fnhum.2021.634113)
Zhang S, Cui J, Zhang Z, Wang Y, Liu R, Chen X, Feng Y, Zhou J, Zhou Y, Wang G (2022) Functional connectivity of amygdala subregions predicts vulnerability to depression following the COVID-19 pandemic. J Affect Disord 297:421–429. (PMID: 3460681410.1016/j.jad.2021.09.107)
Zu MD, Wang AZ, Bai TJ, Xie W, Guan JJ, Tian YH, Wang K (2019) Resting-state functional connectivity between Centromedial Amygdala and Insula as related to somatic symptoms in depressed patients: a preliminary study. Psychosom Med 81:434–440. (PMID: 3100890310.1097/PSY.0000000000000697)
Wang XD, Wang XL, Ma H (1999) Rating scales for Mental Health. Chinese Mental Health Journal, Beijing.
Liu XC, Liu LQ, Yang J, Chai FX, Sun LM (1997) Development and psychometric reliability and validity of adolescent self-rating life events checklist (Chinese). Shandong Arch Psychiatry 10:15–19.
Yan CG, Cheung B, Kelly C, Colcombe S, Craddock RC, Di Martino A, Li Q, Zuo XN, Castellanos FX, Milham MP (2013) A comprehensive assessment of regional variation in the impact of head micromovements on functional connectomics. NeuroImage 76:183–201. (PMID: 2349979210.1016/j.neuroimage.2013.03.004)
Eickhoff SB, Stephan KE, Mohlberg H, Grefkes C, Fink GR, Amunts K, Zilles K (2005) A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data. NeuroImage 25:1325–1335. (PMID: 1585074910.1016/j.neuroimage.2004.12.034)
Hashimoto K, Tsujii N, Mikawa W, Tsujimoto E, Adachi T, Niwa A, Ono H, Shirakawa O (2017) Reduced left precentral regional responses in patients with major depressive disorder and history of suicide attempts. Plos One 12.
Yu H, Li M-L, Li Y-F, Li X-J, Meng Y, Liang S, Li Z, Guo W, Wang Q, Deng W, Ma X, Coid J, Li DT (2020) Anterior cingulate cortex, insula and amygdala seed-based whole brain resting-state functional connectivity differentiates bipolar from unipolar depression. J Affect Disord 274:38–47. (PMID: 3246983010.1016/j.jad.2020.05.005)
Li W, Wang C, Lan X, Fu L, Zhang F, Ye Y, Liu H, Zhou Y, Ning Y (2022) Resting-state functional connectivity of the amygdala in major depressive disorder with suicidal ideation. J Psychiatr Res 153:189–196. (PMID: 3583966010.1016/j.jpsychires.2022.07.001)
Zhang X, Zhang R, Lv L, Qi X, Shi J, Xie S (2022) Correlation between cognitive deficits and dorsolateral prefrontal cortex functional connectivity in first-episode depression. J Affect Disord 312:152–158. (PMID: 3575221710.1016/j.jad.2022.06.024)
Ye T, Peng J, Nie B, Gao J, Liu J, Li Y, Wang G, Ma X, Li K, Shan B (2012) Altered functional connectivity of the dorsolateral prefrontal cortex in first-episode patients with major depressive disorder. Eur J Radiol 81:4035–4040. (PMID: 2293936710.1016/j.ejrad.2011.04.058)
Kenny ER, O’Brien JT, Cousins DA, Richardson J, Thomas AJ, Firbank MJ, Blamire AM (2010) Functional connectivity in late-life depression using resting-state functional magnetic resonance imaging. Am J Geriatr Psychiatry 18:643–651. (PMID: 2022059110.1097/JGP.0b013e3181cabd0e)
Qiao J, Tao S, Wang X, Shi J, Chen Y, Tian S, Yao Z, Lu Q (2020) Brain functional abnormalities in the amygdala subregions is associated with anxious depression. J Affect Disord 276:653–659. (PMID: 3287169710.1016/j.jad.2020.06.077)
Hwang JP, Lee TW, Tsai SJ, Chen TJ, Yang CH, Lirng JF, Tsai CF (2010) Cortical and subcortical abnormalities in late-onset depression with history of suicide attempts investigated with MRI and voxel-based morphometry. J Geriatr Psychiatry Neurol 23:171–184. (PMID: 2043097610.1177/0891988710363713)
Sublette ME, Milak MS, Galfalvy HC, Oquendo MA, Malone KM, Mann JJ (2013) Regional brain glucose uptake distinguishes suicide attempters from non-attempters in major depression. Arch Suicide Res 17:434–447. (PMID: 2422467610.1080/13811118.2013.801813)
Maggioni E, Delvecchio G, Grottaroli M, Garzitto M, Piccin S, Bonivento C, Maieron M, D’Agostini S, Perna G, Balestrieri M, Brambilla P (2019) Common and different neural markers in major depression and anxiety disorders: a pilot structural magnetic resonance imaging study. Psychiatry Research: Neuroimaging 290:42–50. (PMID: 3127995410.1016/j.pscychresns.2019.06.006)
Wang L, Feng Z, Yang G, Yang Y, Wang K, Dai Q, Zhao M, Hu C, Zhang R, Liu K, Guang Y, Xia F (2016) Depressive symptoms among children and adolescents in western China: an epidemiological survey of prevalence and correlates. Psychiatry Res 246:267–274. (PMID: 2774147910.1016/j.psychres.2016.09.050)
Park M, Unutzer J, Grembowski D (2014) Ethnic and gender variations in the associations between family cohesion, family conflict, and depression in older Asian and latino adults. J Immigr Minor Health 16:1103–1110. (PMID: 24129849461870110.1007/s10903-013-9926-1)
McEwen BS (2003) Early life influences on life-long patterns of behavior and health. Ment Retard Dev Disabil Res Rev 9:149–154. (PMID: 1295329310.1002/mrdd.10074)
Mi Kim S, Park SY, Kim YI, Son YD, Chung U-S, Min KJ, Han DH (2015) Affective network and default mode network in depressive adolescents with disruptive behaviors. Neuropsychiatric Disease and Treatment.
Leech R, Sharp DJ (2014) The role of the posterior cingulate cortex in cognition and disease. Brain 137:12–32. (PMID: 2386910610.1093/brain/awt162)
Zhu Z, Wang Y, Lau WKW, Wei X, Liu Y, Huang R, Zhang R (2022) Hyperconnectivity between the posterior cingulate and middle frontal and temporal gyrus in depression: based on functional connectivity meta-analyses. Brain Imaging Behav 16:1538–1551. (PMID: 3508835410.1007/s11682-022-00628-7)
Cullen KR, Westlund MK, Klimes-Dougan B, Mueller BA, Houri A, Eberly LE, Lim KO (2014) Abnormal amygdala resting-state functional connectivity in adolescent depression. JAMA Psychiatry 71.
Messina I, Bianco F, Cusinato M, Calvo V, Sambin M (2016) Abnormal default System Functioning in Depression: implications for emotion regulation. Front Psychol 7:858. (PMID: 27375536490107610.3389/fpsyg.2016.00858)
Hakamata Y, Mizukami S, Izawa S, Okamura H, Mihara K, Marusak H, Moriguchi Y, Hori H, Hanakawa T, Inoue Y, Tagaya H (2022) Implicit and explicit emotional memory recall in anxiety and depression: role of basolateral amygdala and cortisol-norepinephrine interaction. Psychoneuroendocrinology 136.
Mulders PC, van Eijndhoven PF, Schene AH, Beckmann CF, Tendolkar I (2015) Resting-state functional connectivity in major depressive disorder: a review. Neurosci Biobehavioral Reviews 56:330–344. (PMID: 10.1016/j.neubiorev.2015.07.014)

82372080 National Natural Science Foundation of China; 2022NSFSC0052 Natural Science Foundation of Sichuan Province

Keywords: Adolescent; Amygdala subregions; Depression; Functional connectivity; Stress

Date Created: 20240514 Date Completed: 20241204 Latest Revision: 20241204

20241204

10.1007/s00787-024-02456-0

38743107