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Clinical Article
Local neural activity and functional network alterations in adolescents with subclinical depression: A resting-state fMRI study
LAN Zhongli  JIANG Jinghua  ZHANG Chengfeng  GAN Jiefeng  CHEN Jun 

DOI:10.12015/issn.1674-8034.2026.02.002.


[Abstract] Objective To investigate the characteristics of brain functional abnormalities in adolescents with subclinical depression (SD) using amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) by resting-state functional magnetic resonance imaging (rs-fMRI).Materials and Methods Eighty-five adolescents were enrolled, including 62 in the SD group and 23 healthy controls (HC). Whole-brain ALFF and ReHo maps were computed and compared between groups. The overlapping regions of significant ALFF and ReHo alterations were defined as composite regions of interest for whole-brain functional connectivity (FC) analysis. Correlation analysis was performed using the Self-Rating Depression Scale (SDS) scores.Results Compared with the HC group, the SD group showed significantly decreased ALFF in the anterior cingulate cortex and subgenual anterior cingulate cortex (t = -5.456, voxel-level P < 0.005, cluster-level P < 0.05) and ReHo (t = -4.724, voxel-level P < 0.005, cluster-level P < 0.05), and significantly increased ALFF in the left anterior cerebellum (t = 4.277, voxel-level P < 0.005, cluster-level P < 0.05). FC analysis using the overlapping regions of positive ALFF and ReHo results as composite seeds revealed reduced connectivity with the medial prefrontal cortex, anterior cingulate cortex, rectus gyrus, olfactory cortex, and caudate nucleus (t = -4.099, voxel-level P < 0.005, cluster-level P < 0.05). No significant correlation was found between SDS scores and brain functional indicators (all P > 0.05).Conclusions Adolescents with SD already exhibit significant functional abnormalities in the sgACC and left anterior cerebellum, offering new neuroimaging clues for the early identification of depression risk and for understanding its underlying mechanisms.
[Keywords] subclinical depression;adolescents;resting-state functional magnetic resonance imaging;magnetic resonance imaging;amplitude of low-frequency fluctuation;regional homogeneity;functional connectivity

LAN Zhongli1   JIANG Jinghua2   ZHANG Chengfeng2   GAN Jiefeng2   CHEN Jun2, 3*  

1 The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

2 Department of Radiology, Zhuhai Hospital of Guangdong Provincial Hospital of Traditional Chinese Medicine, Zhuhai 519015, China

3 Department of Medical Imaging, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, China

Corresponding author: CHEN J, E-mail: junesums@163.com

Conflicts of interest   None.

Received  2025-10-27
Accepted  2026-01-05
DOI: 10.12015/issn.1674-8034.2026.02.002
DOI:10.12015/issn.1674-8034.2026.02.002.

[1]
MILLER L, CAMPO J V. Depression in Adolescents[J]. N Engl J Med, 2021, 385(5): 445-449. DOI: 10.1056/NEJMra2033475.
[2]
PHILIPPI C L, MOTZKIN J C, PUJARA M S, et al. Subclinical depression severity is associated with distinct patterns of functional connectivity for subregions of anterior cingulate cortex[J]. J Psychiatr Res, 2015, 71: 103-111. DOI: 10.1016/j.jpsychires.2015.10.005.
[3]
SHOREY S, NG E D, WONG C H J. Global prevalence of depression and elevated depressive symptoms among adolescents: a systematic review and meta-analysis[J]. Br J Clin Psychol, 2022, 61(2): 287-305. DOI: 10.1111/bjc.12333.
[4]
ZAHN-WAXLER C, KLIMES-DOUGAN B, SLATTERY M J. Internalizing problems of childhood and adolescence: prospects, pitfalls, and progress in understanding the development of anxiety and depression[J]. Dev Psychopathol, 2000, 12(3): 443-466. DOI: 10.1017/S0954579400003102.
[5]
GONZÁLEZ-TEJERA G, CANINO G, RAMÍREZ R, et al. Examining minor and major depression in adolescents[J]. J Child Psychol Psychiatry, 2005, 46(8): 888-899. DOI: 10.1111/j.1469-7610.2005.00370.x.
[6]
CATRAMBONE V, MESSEROTTI BENVENUTI S, GENTILI C, et al. Intensification of functional neural control on heartbeat dynamics in subclinical depression[J/OL]. Transl Psychiatry, 2021, 11(1): 221 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/33854037/. DOI: 10.1038/s41398-021-01336-4.
[7]
KWOK N T, SO S H, CHAN S S M, et al. Clinical and subthreshold depression in an epidemiologic sample of adolescents[J/OL]. J Affect Disord, 2025, 392: 120143 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/40876635/. DOI: 10.1016/j.jad.2025.120143.
[8]
ZHANG R, PENG X, SONG X, et al. The prevalence and risk of developing major depression among individuals with subthreshold depression in the general population[J]. Psychol Med, 2023, 53(8): 3611-3620. DOI: 10.1017/S0033291722000241.
[9]
JIANG L, WANG Y, ZHANG Y, et al. The reliability and validity of the Center for Epidemiologic Studies Depression Scale (CES-D) for Chinese university students[J/OL]. Front Psychiatry, 2019, 10: 315 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/31178764/. DOI: 10.3389/fpsyt.2019.00315.
[10]
MIKOLAJCZYK R T, MAXWELL A E, NAYDENOVA V, et al. Depressive symptoms and perceived burdens related to being a student: survey in three European countries[J/OL]. Clin Pract Epidemiol Ment Health, 2008, 4: 19 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/18598340/. DOI: 10.1186/1745-0179-4-19.
[11]
FOGEL J, EATON W W, FORD D E. Minor depression as a predictor of the first onset of major depressive disorder over a 15-year follow-up[J]. Acta Psychiatr Scand, 2006, 113(1): 36-43. DOI: 10.1111/j.1600-0447.2005.00654.x.
[12]
JIANG J, LI L, SUO X, et al. Temporal dynamics of intrinsic brain activity in older women with subclinical depression[J/OL]. J Gerontol A Biol Sci Med Sci, 2025, 80(6): glaf084 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/40247731/. DOI: 10.1093/gerona/glaf084.
[13]
LYU C, LYU X, GONG Q, et al. Neural activation signatures in individuals with subclinical depression: a task-fMRI meta-analysis[J]. J Affect Disord, 2024, 362: 104-113. DOI: 10.1016/j.jad.2024.06.040.
[14]
ZOU Q H, ZHU C Z, YANG Y, et al. An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF[J]. J Neurosci Methods, 2008, 172(1): 137-141. DOI: 10.1016/j.jneumeth.2008.04.012.
[15]
ZHU C Z, ZANG Y F, CAO Q J, et al. Fisher discriminative analysis of resting-state brain function for attention-deficit/hyperactivity disorder[J]. Neuroimage, 2008, 40(1): 110-120. DOI: 10.1016/j.neuroimage.2007.11.029.
[16]
ZHANG B, QI S, LIU S, et al. Altered spontaneous neural activity in the precuneus, middle and superior frontal gyri, and hippocampus in college students with subclinical depression[J/OL]. BMC Psychiatry, 2021, 21(1): 280 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/34074266/. DOI: 10.1186/s12888-021-03292-1.
[17]
LUO G, ZHOU J, LIU L, et al. Abnormal ReHo and ALFF values in drug-naïve depressed patients with suicidal ideation or attempts: Evidence from the REST-meta-MDD consortium[J/OL]. Prog Neuropsychopharmacol Biol Psychiatry, 2025, 136: 111210 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/39631721/. DOI: 10.1016/j.pnpbp.2024.111210.
[18]
ZUNG W W. A self-rating depression scale[J]. Arch Gen Psychiatry, 1965, 12: 63-70. DOI: 10.1001/archpsyc.1965.01720310065008.
[19]
SHEN L L, LAO L M, JIANG S F, et al. A survey of anxiety and depression symptoms among primary-care physicians in China[J]. Int J Psychiatry Med, 2012, 44(3): 257-270. DOI: 10.2190/PM.44.3.f.
[20]
LI F, WANG J, CHEN J, et al. Mental health of junior college students in China during COVID-19 school lockdown[J/OL]. Medicine (Baltimore), 2023, 102(52): e36808 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/38206719/. DOI: 10.1097/MD.0000000000036808.
[21]
LEE H C, CHIU H F, WING Y K, et al. The Zung Self-Rating Depression Scale: screening for depression among Hong Kong Chinese elderly[J]. J Geriatr Psychiatry Neurol, 1994, 7(4): 216-220. DOI: 10.1177/089198879400700404.
[22]
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)[EB/OL]. Washington, DC: American Psychiatric Publishing, 2013 [2025-10-27]. https://psychiatryonline.org/doi/book/10.1176/appi.books.9780890425596. DOI: 10.1176/appi.books.9780890425596.
[23]
YAN C G, WANG X D, ZUO X N, et al. DPABI: data processing & analysis for (resting-state) brain imaging[J]. Neuroinformatics, 2016, 14(3): 339-351. DOI: 10.1007/s12021-016-9299-4.
[24]
MURPHY K, BODURKA J, BANDETTINI P A. How long to scan? The relationship between fMRI temporal signal to noise and necessary scan duration[J]. Neuroimage, 2007, 34(2): 565-574. DOI: 10.1016/j.neuroimage.2006.09.032.
[25]
ZANG Y, JIANG T, LU Y, et al. Regional homogeneity approach to fMRI data analysis[J]. Neuroimage, 2004, 22(1): 394-400. DOI: 10.1016/j.neuroimage.2003.12.030.
[26]
GHASEMI A, ZAHEDIASL S. Normality tests for statistical analysis: a guide for non-statisticians[J]. Int J Endocrinol Metab, 2012, 10(2): 486-489. DOI: 10.5812/ijem.3505.
[27]
BLANCA M J, ALARCÓN R, ARNAU J, et al. Non-normal data: Is ANOVA still a valid option?[J]. Psicothema, 2017, 29(4): 552-557. DOI: 10.7334/psicothema2016.383.
[28]
SCHOBER P, BOER C, SCHWARTE L A. Correlation coefficients: appropriate use and interpretation[J]. Anesth Analg, 2018, 126(5): 1763-1768. DOI: 10.1213/ANE.0000000000002864.
[29]
CHEN Y, LI H T, LUO X, et al. Polygenic risk for depression and resting-state functional connectivity of subgenual anterior cingulate cortex in young adults[J/OL]. J Psychiatry Neurosci, 2025, 50(1): E31-E44 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/39809531/. DOI: 10.1503/jpn.240087.
[30]
DREVETS W C, SAVITZ J, TRIMBLE M. The subgenual anterior cingulate cortex in mood disorders[J]. CNS Spectr, 2008, 13(8): 663-681. DOI: 10.1017/s1092852900013754.
[31]
MORRIS L S, COSTI S, TAN A, et al. Ketamine normalizes subgenual cingulate cortex hyper-activity in depression[J]. Neuropsychopharmacology, 2020, 45(6): 975-981. DOI: 10.1038/s41386-019-0591-5.
[32]
DREVETS W C, PRICE J L, SIMPSON J R, et al. Subgenual prefrontal cortex abnormalities in mood disorders[J]. Nature, 1997, 386(6627): 824-827. DOI: 10.1038/386824a0.
[33]
CASEY B J, JONES R M, HARE T A. The adolescent brain[J]. Ann N Y Acad Sci, 2008, 1124: 111-126. DOI: 10.1196/annals.1440.010.
[34]
MILLER J G, HO T C, KIRSHENBAUM J S, et al. Testing a developmental model of positive parenting, amygdala-subgenual anterior cingulate cortex connectivity, and depressive symptoms in adolescents before and during the COVID-19 pandemic[J]. Biol Psychiatry Glob Open Sci, 2021, 1(4): 291-299. DOI: 10.1016/j.bpsgos.2021.07.005.
[35]
LICHENSTEIN S D, VERSTYNEN T, FORBES E E. Adolescent brain development and depression: a case for the importance of connectivity of the anterior cingulate cortex[J]. Neurosci Biobehav Rev, 2016, 70: 271-287. DOI: 10.1016/j.neubiorev.2016.07.024.
[36]
RUDOLPH K D, DAVIS M M, SKYMBA H V, et al. Social experience calibrates neural sensitivity to social feedback during adolescence: A functional connectivity approach[J/OL]. Dev Cogn Neurosci, 2021, 47: 100903 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/33370666/. DOI: 10.1016/j.dcn.2020.100903.
[37]
ZHANG L, QIN K, PAN N, et al. Shared and distinct patterns of default mode network dysfunction in major depressive disorder and bipolar disorder: A comparative meta-analysis[J]. J Affect Disord, 2025, 368: 23-32. DOI: 10.1016/j.jad.2024.09.021.
[38]
ZHANG Z, ZHANG Y, WANG H, et al. Resting-state network alterations in depression: a comprehensive meta-analysis of functional connectivity[J/OL]. Psychol Med, 2025, 55: e63 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/40008424/. DOI: 10.1017/S0033291725000303.
[39]
SHELINE Y I, PRICE J L, YAN Z, et al. Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus[J]. Proc Natl Acad Sci U S A, 2010, 107(24): 11020-11025. DOI: 10.1073/pnas.1000446107.
[40]
CHEN X, LU B, WANG Y W, et al. Subgenual anterior cingulate cortex functional connectivity abnormalities in depression: Insights from brain imaging big data and precision-guided personalized intervention via transcranial magnetic stimulation[J]. Sci Bull (Beijing), 2025, 70(16): 2676-2690. DOI: 10.1016/j.scib.2025.05.042.
[41]
RUDOLPH S, BADURA A, LUTZU S, et al. Cognitive-affective functions of the cerebellum[J]. J Neurosci, 2023, 43(45): 7554-7564. DOI: 10.1523/JNEUROSCI.1451-23.2023.
[42]
SCHMAHMANN J D, SHERMAN J C. The cerebellar cognitive affective syndrome[J]. Brain, 1998, 121(4): 561-579. DOI: 10.1016/s0074-7742(08)60363-3.
[43]
FRONTERA J L, SALA R W, GEORGESCU I A, et al. The cerebellum regulates fear extinction through thalamo-prefrontal cortex interactions in male mice[J/OL]. Nat Commun, 2023, 14(1): 1508 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/36932068/. DOI: 10.1038/s41467-023-36943-w.
[44]
COUTO-OVEJERO S, YE J, KIND P C, et al. Cerebellar contributions to fear-based emotional processing: relevance to understanding the neural circuits involved in autism[J/OL]. Front Syst Neurosci, 2023, 17: 1229627 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/38075533/. DOI: 10.3389/fnsys.2023.1229627.
[45]
LIU Z, XU C, XU Y, et al. Decreased regional homogeneity in insula and cerebellum: a resting-state fMRI study in patients with major depression and subjects at high risk for major depression[J]. Psychiatry Res Neuroimaging, 2010, 182(3): 211-215. DOI: 10.1016/j.pscychresns.2010.03.004.
[46]
LIU J, REN L, WOMER F Y, et al. Alterations in amplitude of low frequency fluctuation in treatment-naïve major depressive disorder measured with resting-state fMRI[J]. Hum Brain Mapp, 2014, 35(10): 4979-4988. DOI: 10.1002/hbm.22526.
[47]
NOLEN-HOEKSEMA S. The role of rumination in depressive disorders and mixed anxiety/depressive symptoms[J]. J Abnorm Psychol, 2000, 109(3): 504-511. DOI: 10.1037/0021-843X.109.3.504.
[48]
FENG L, WU D, MA S, et al. Resting-state functional connectivity of the cerebellum-cerebrum in older women with depressive symptoms[J/OL]. BMC Psychiatry, 2023, 23(1): 732 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/37817133/. DOI: 10.1186/s12888-023-05232-7.
[49]
HWANG J W, XIN S C, OU Y M, et al. Enhanced default mode network connectivity with ventral striatum in subthreshold depression individuals[J]. J Psychiatr Res, 2016, 76: 111-120. DOI: 10.1016/j.jpsychires.2016.02.005.
[50]
ZHANG B, LIU S, LIU X, et al. Discriminating subclinical depression from major depression using multi-scale brain functional features: a radiomics analysis[J]. J Affect Disord, 2022, 297: 542-552. DOI: 10.1016/j.jad.2021.10.122.
[51]
DOW-EDWARDS D, MACMASTER F P, PETERSON B S, et al. Experience during adolescence shapes brain development: from synapses and networks to normal and pathological behavior[J/OL]. Neurotoxicol Teratol, 2019, 76: 106834 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/31505230/. DOI: 10.1016/j.ntt.2019.106834.
[52]
KONRAD K, FIRK C, UHLHAAS P J. Brain development during adolescence[J]. Dtsch Arztebl Int, 2013, 110(25): 425-431. DOI: 10.3238/arztebl.2013.0425.
[53]
SPEAR L P. Adolescent neurodevelopment[J]. J Adolesc Health, 2013, 52(2Suppl): S7-S13. DOI: 10.1016/j.jadohealth.2012.05.006.
[54]
PEPER J S, DAHL R E. Surging hormones: brain-behavior interactions during puberty[J]. Curr Dir Psychol Sci, 2013, 22(2): 134-139. DOI: 10.1177/0963721412473755.
[55]
VIJAYAKUMAR N, DE MACKS Z OP, SHIRTCLIFF E A, et al. Puberty and the human brain: Insights into adolescent development[J]. Neurosci Biobehav Rev, 2018, 92: 417-436. DOI: 10.1016/j.neubiorev.2018.06.004.
[56]
OJHA A, PARR A C, FORAN W, et al. Puberty contributes to adolescent development of fronto-striatal functional connectivity supporting inhibitory control[J/OL]. Dev Cogn Neurosci, 2022, 58: 101183 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/36495791/. DOI: 10.1016/j.dcn.2022.101183.
[57]
SHEN W, WANG X, LI Q, et al. Research on adults with subthreshold depression after aerobic exercise: A resting-state fMRI study based on regional homogeneity (ReHo)[J/OL]. Front Neurosci, 2024, 18: 1231883 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/38533447/. DOI: 10.3389/fnins.2024.1231883.
[58]
HUANG L, HUANG G, DING Q, et al. Amplitude of low-frequency fluctuation (ALFF) alterations in adults with subthreshold depression after physical exercise: A resting-state fMRI study[J]. J Affect Disord, 2021, 295: 1057-1065. DOI: 10.1016/j.jad.2021.08.094.
[59]
GRACIA-TABUENCA Z, BARBEAU E B, XIA Y, et al. Predicting depression risk in early adolescence via multimodal brain imaging[J/OL]. Neuroimage Clin, 2024, 42: 103604 [2025-10-27]. https://pubmed.ncbi.nlm.nih.gov/38603863/. DOI: 10.1016/j.nicl.2024.103604.
[60]
CHAI Y, SHELINE Y I, OATHES D J, et al. Functional connectomics in depression: insights into therapies[J]. Trends Cogn Sci, 2023, 27(9): 814-832. DOI: 10.1016/j.tics.2023.05.006.

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