A Comprehensive Overview of the Role of Visual Cortex Malfunction in Depressive Disorders: Opportunities and Challenges

Overview

Journal Neurosci Bull

Specialty Neurology

Date 2023 Mar 30

PMID 36995569

Authors

Fangfang Wu

Qingbo Lu

Yan Kong

Zhijun Zhang

Affiliations

Soon will be listed here.

Abstract

Major depressive disorder (MDD) is a highly heterogeneous mental disorder, and its complex etiology and unclear mechanism are great obstacles to the diagnosis and treatment of the disease. Studies have shown that abnormal functions of the visual cortex have been reported in MDD patients, and the actions of several antidepressants coincide with improvements in the structure and synaptic functions of the visual cortex. In this review, we critically evaluate current evidence showing the involvement of the malfunctioning visual cortex in the pathophysiology and therapeutic process of depression. In addition, we discuss the molecular mechanisms of visual cortex dysfunction that may underlie the pathogenesis of MDD. Although the precise roles of visual cortex abnormalities in MDD remain uncertain, this undervalued brain region may become a novel area for the treatment of depressed patients.

Citing Articles

Major depressive disorder on a neuromorphic continuum.

Li J, Long Z, Ji G, Han S, Chen Y, Yao G Nat Commun. 2025; 16(1):2405.

PMID: 40069198 PMC: 11897166. DOI: 10.1038/s41467-025-57682-0.

Dissecting biological heterogeneity in major depressive disorder based on neuroimaging subtypes with multi-omics data.

Tang L, Tang R, Zheng J, Zhao P, Zhu R, Tang Y Transl Psychiatry. 2025; 15(1):72.

PMID: 40032862 PMC: 11876359. DOI: 10.1038/s41398-025-03286-7.

A visual cortical-lateral posterior thalamic nucleus circuit regulates depressive-like behaviors in male mice.

Wu F, Gu C, Xu R, Ma J, Gao L, Zhang Y Nat Commun. 2025; 16(1):1395.

PMID: 39915439 PMC: 11802872. DOI: 10.1038/s41467-024-55600-4.

Symptom-based depression subtypes: brain dynamic specificity and its association with gene expression profiles.

Liang Q, Zhou Z, Chen S, Lin S, Lin X, Li Y Transl Psychiatry. 2025; 15(1):33.

PMID: 39875399 PMC: 11775246. DOI: 10.1038/s41398-025-03238-1.

Exploring the Impact of Declarative Learning on the Consolidation of Acquired Motor Skills Under Valence Feedback.

Farrokhi A, Habibi M, Daliri M Hum Brain Mapp. 2025; 46(2):e70105.

PMID: 39835585 PMC: 11747997. DOI: 10.1002/hbm.70105.

References

Krishnan V, Nestler E . Linking molecules to mood: new insight into the biology of depression. Am J Psychiatry. 2010; 167(11):1305-20. PMC: 3031089. DOI: 10.1176/appi.ajp.2009.10030434. View

Gold P . The PPARg System in Major Depression: Pathophysiologic and Therapeutic Implications. Int J Mol Sci. 2021; 22(17). PMC: 8430913. DOI: 10.3390/ijms22179248. View

Sokolowska E, Viitanen R, Misiewicz Z, Mennesson M, Saarnio S, Kulesskaya N . The circadian gene Cryptochrome 2 influences stress-induced brain activity and depressive-like behavior in mice. Genes Brain Behav. 2020; 20(4):e12708. DOI: 10.1111/gbb.12708. View

Li Z, Ruan M, Chen J, Fang Y . Major Depressive Disorder: Advances in Neuroscience Research and Translational Applications. Neurosci Bull. 2021; 37(6):863-880. PMC: 8192601. DOI: 10.1007/s12264-021-00638-3. View

Sanacora G, Gueorguieva R, Epperson C, Wu Y, Appel M, Rothman D . Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry. 2004; 61(7):705-13. DOI: 10.1001/archpsyc.61.7.705. View

Ancelin M, Carriere I, Artero S, Maller J, Meslin C, Ritchie K . Lifetime major depression and grey-matter volume. J Psychiatry Neurosci. 2018; 44(1):45-53. PMC: 6306287. DOI: 10.1503/jpn.180026. View

Rubin-Falcone H, Zanderigo F, Thapa-Chhetry B, Lan M, Miller J, Sublette M . Pattern recognition of magnetic resonance imaging-based gray matter volume measurements classifies bipolar disorder and major depressive disorder. J Affect Disord. 2017; 227:498-505. PMC: 5805651. DOI: 10.1016/j.jad.2017.11.043. View

Tomoda A, Polcari A, Anderson C, Teicher M . Reduced visual cortex gray matter volume and thickness in young adults who witnessed domestic violence during childhood. PLoS One. 2013; 7(12):e52528. PMC: 3530484. DOI: 10.1371/journal.pone.0052528. View

Dixson L, Ridler K, Nichols T, Saemann P, Auer D, Holsboer F . Thyroid hormone transporter genes and grey matter changes in patients with major depressive disorder and healthy controls. Psychoneuroendocrinology. 2011; 36(6):929-34. DOI: 10.1016/j.psyneuen.2010.12.002. View

10.

Zhou R, Wang F, Zhao G, Xia W, Peng D, Mao R . Effects of tumor necrosis factor-α polymorphism on the brain structural changes of the patients with major depressive disorder. Transl Psychiatry. 2018; 8(1):217. PMC: 6181976. DOI: 10.1038/s41398-018-0256-x. View

11.

Miles A, Dos Santos F, Byrne E, Renteria M, McIntosh A, Adams M . Transcriptome-based polygenic score links depression-related corticolimbic gene expression changes to sex-specific brain morphology and depression risk. Neuropsychopharmacology. 2021; 46(13):2304-2311. PMC: 8580972. DOI: 10.1038/s41386-021-01189-x. View

12.

Fullard K, Maller J, Welton T, Lyon M, Gordon E, Koslow S . Is occipital bending a structural biomarker of risk for depression and sensitivity to treatment?. J Clin Neurosci. 2019; 63:55-61. DOI: 10.1016/j.jocn.2019.02.007. View

13.

Ries A, Hollander M, Glim S, Meng C, Sorg C, Wohlschlager A . Frequency-Dependent Spatial Distribution of Functional Hubs in the Human Brain and Alterations in Major Depressive Disorder. Front Hum Neurosci. 2019; 13:146. PMC: 6527901. DOI: 10.3389/fnhum.2019.00146. View

14.

de Haan E, Cowey A . On the usefulness of 'what' and 'where' pathways in vision. Trends Cogn Sci. 2011; 15(10):460-6. DOI: 10.1016/j.tics.2011.08.005. View

15.

Poeppl T, Muller V, Hoffstaedter F, Bzdok D, Laird A, Fox P . Imbalance in subregional connectivity of the right temporoparietal junction in major depression. Hum Brain Mapp. 2016; 37(8):2931-42. PMC: 6867503. DOI: 10.1002/hbm.23217. View

16.

Chen H, Liu K, Zhang B, Zhang J, Xue X, Lin Y . More optimal but less regulated dorsal and ventral visual networks in patients with major depressive disorder. J Psychiatr Res. 2019; 110:172-178. DOI: 10.1016/j.jpsychires.2019.01.005. View

17.

Lu F, Cui Q, Huang X, Li L, Duan X, Chen H . Anomalous intrinsic connectivity within and between visual and auditory networks in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2020; 100:109889. DOI: 10.1016/j.pnpbp.2020.109889. View

18.

Grayson L, Thomas A . A systematic review comparing clinical features in early age at onset and late age at onset late-life depression. J Affect Disord. 2013; 150(2):161-70. DOI: 10.1016/j.jad.2013.03.021. View

19.

Mai N, Wu Y, Zhong X, Chen B, Zhang M, Peng Q . Different Modular Organization Between Early Onset and Late Onset Depression: A Study Base on Granger Causality Analysis. Front Aging Neurosci. 2021; 13:625175. PMC: 7900556. DOI: 10.3389/fnagi.2021.625175. View

20.

Zhang F, Rao S, Cao H, Zhang X, Wang Q, Xu Y . Genetic evidence suggests posttraumatic stress disorder as a subtype of major depressive disorder. J Clin Invest. 2021; 132(3). PMC: 8803333. DOI: 10.1172/JCI145942. View