Global long non-coding RNA expression in the rostral anterior cingulate cortex of depressed suicides
Open accessAbstract
Long non-coding RNAs (lncRNAs) are an emerging class of regulatory RNA that may be implicated in psychiatric disorders. Here we performed RNA-sequencing in the rostral anterior cingulate cortex of 26 depressed suicides and 24 matched controls. We first performed differential lncRNA expression analysis, and then conducted Weighted Gene Co-expression Network Analysis (WGCNA) to identify co-expression modules associating with depression and suicide. We identified 23 differentially expressed lncRNAs (FDR < 0.1) as well as their differentially expressed overlapping and antisense protein-coding genes. Several of these overlapping or antisense genes were associated with interferon signaling, which is a component of the innate immune response. Using WGCNA, we identified modules of highly co-expressed genes associated with depression and suicide and found protein-coding genes highly connected to differentially expressed lncRNAs within these modules. These protein-coding genes were located distal to their associated lncRNAs and were found to be part of several GO terms enriched in the significant modules, which include: cytoskeleton organization, plasma membrane, cell adhesion, nucleus, DNA-binding, and regulation of dendrite development and morphology. Altogether, we report that lncRNAs are differentially expressed in the brains of depressed individuals who died by suicide and may represent regulators of important molecular functions and biological processes.
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Levels of 60% (217 out of 364) of the 364 lncRNAs expressed in the rostral cingulate cortex of normal individuals differed from those in MDD.
“Levels of 60% (217 out of 364) of the 364 lncRNAs expressed in the rostral cingulate cortex of normal individuals differed from those in MDD.310”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [310]
The Results section, under “Differential lncRNA expression analysis,” says that 364 of 2,670 analyzed lncRNAs were differentially expressed at nominal p < 0.05. The 217 of 364 figure is the number of those differentially expressed lncRNAs that were downregulated in depressed suicides—not the number that differed from controls. (LLM, conf=0.94)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredmiRNA and lncRNA levels in blood distinguish depressed patients from healthy controls.
“Because miRNA and lncRNA levels in blood distinguish depressed patients from healthy controls,243,310,387”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [310]
The Discussion section “Differential lncRNA expression in major depression and suicide” (page not supplied) reports prior findings of altered lncRNA expression in blood and PBMCs from depressed patients. It does not report that blood miRNA levels distinguish depressed patients from healthy controls, or establish that the blood lncRNA differences can distinguish individual patients from controls. This paper’s own lncRNA analysis concerns brain tissue, not blood. (LLM, conf=0.85)
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Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
WGCNA: an R package for weighted correlation network analysis
Langfelder, P., & Horvath, S. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-559 · Cited by 27,252 · see citing works
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464 · see citing works
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668 · see citing works
Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis
Gupta, R. A., Shah, N., Wang, K., Kim, J., Horlings, H. M., Wong, D. J., Tsai, M.-C., Hung, T., Argani, P., Rinn, J. L., et al. (2010) · Nature · doi:10.1038/nature08975 · Cited by 5,203 · see citing works
Self-citationLandscape of transcription in human cells
Djebali, S., Davis, C. A., Merkel, A., Dobin, A., Lassmann, T., Mortazavi, A., Tanzer, A., Lagarde, J., Lin, W., Schlesinger, F., et al. (2012) · Nature · doi:10.1038/nature11233 · Cited by 5,187 · see citing works
Derrien, T., Johnson, R., Bussotti, G., Andrea Tanzer, A., Djebali, S., Tilgner, H., Guernec, G., Martin, D., Merkel, A., Knowles, D. G., et al. (2012) · Genome Research · doi:10.1101/gr.132159.111 · Cited by 5,017 · see citing works
Molecular Mechanisms of Long Noncoding RNAs
Wang, K., & Chang, H. Y. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.08.018 · Cited by 4,390 · see citing works
Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs
Rinn, J. L., Kertesz, M., Wang, J. K., Squazzo, S. L., Xu, X. H., Brugmann, S. A., Goodnough, L. H., Helms, J. A., Farnham, P., Segal, E., et al. (2007) · Cell · doi:10.1016/j.cell.2007.05.022 · Cited by 4,246 · see citing works
Widespread transcription at neuronal activity-regulated enhancers
Kim, T.-K., Hemberg, M., Gray, J. M., Costa, A. M., Bear, D. M., Wu, J., Harmin, D. A., Laptewicz, M., Barbara-Haley, K., Kuersten, S., et al. (2010) · Nature · doi:10.1038/nature09033 · Cited by 2,450 · see citing works
Long Noncoding RNAs with Enhancer-like Function in Human Cells
Ørom, U. A., Derrien, T., Beringer, M., Gumireddy, K., Gardini, A., Bussotti, G., Lai, F., Zytnicki, M., Notredame, C., Huang, Q., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.001 · Cited by 1,721 · see citing works
IRF Family of Transcription Factors as Regulators of Host Defense
Taniguchi, T., Ogasawara, K., Takaoka, A., & Tanaka, N. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.623 · Cited by 1,658 · see citing works
Pandey, R. R., Mondal, T., Mohammad, F., Enroth, S., Redrup, L., Komorowski, J., Nagano, T., Mancini‐DiNardo, D., & Kanduri, C. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.08.022 · Cited by 1,192 · see citing works
The subgenual anterior cingulate cortex in mood disorders
Drevets, W. C., Savitz, J., & Trimble, M. (2008) · CNS Spectrums · doi:10.1017/s1092852900013754 · Cited by 1,109 · see citing works
The non-coding Air RNA is required for silencing autosomal imprinted genes
Sleutels, F., Zwart, R., & Barlow, D. P. (2002) · Nature · doi:10.1038/415810a · Cited by 1,071 · see citing works
Activating RNAs associate with Mediator to enhance chromatin architecture and transcription
Lai, F., Ørom, U. A., Cesaroni, M., Beringer, M., Taatjes, D. J., Blobel, G. A., & Shiekhattar, R. (2013) · Nature · doi:10.1038/nature11884 · Cited by 857 · see citing works
Evolutionary conservation of long non-coding RNAs; sequence, structure, function
Johnsson, P., Lipovich, L., Grandér, D., & Morris, K. V. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.10.035 · Cited by 699 · see citing works
Whalen, P. J., Bush, G., McNally, R. J., Wilhelm, S., McInerney, S. C., Jenike, M. A., & Rauch, S. L. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00251-0 · Cited by 650 · see citing works
Genome-wide analysis of long noncoding RNA stabilityPreprint
Clark, M. B., Johnston, R. L., Inostroza-Ponta, M., Fox, A. H., Fortini, E., Moscato, P., Dinger, M. E., & Mattick, J. S. (2012) · Genome Research · doi:10.1101/gr.131037.111 · Cited by 589 · see citing works
Dumais, A., Lesage, A. D., Alda, M., Rouleau, G., Dumont, M., Chawky, N., Roy, M., Mann, J. J., Benkelfat, C., & Turecki, G. (2005) · American Journal of Psychiatry · doi:10.1176/appi.ajp.162.11.2116 · Cited by 583 · see citing works
Self-citationTranscriptional interference – a crash course
Shearwin, K. E., Callen, B. P., & Egan, J. B. (2005) · Trends in Genetics · doi:10.1016/j.tig.2005.04.009 · Cited by 565 · see citing works
Emerging roles of non-coding RNAs in brain evolution, development, plasticity and disease
Qureshi, I., & Mehler, M. F. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3234 · Cited by 561 · see citing works
Ravasi, T., Suzuki, H., Pang, K. C., Katayama, S., Furuno, M., Okunishi, R., Fukuda, S., Ru, K., Frith, M. C., Gongora, M., et al. (2005) · Genome Research · doi:10.1101/gr.4200206 · Cited by 522 · see citing works
Enhancer RNA Facilitates NELF Release from Immediate Early Genes
Schaukowitch, K., Joo, J., Liu, X., Watts, J. K., Martinez, C., & Kim, T.-K. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.023 · Cited by 445 · see citing works
A pseudogene long-noncoding-RNA network regulates PTEN transcription and translation in human cells
Johnsson, P., Ackley, A., Vidarsdóttir, L., Lui, W., Corcoran, M., Grandér, D., & Morris, K. V. (2013) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2516 · Cited by 437 · see citing works
Epigenetics of the depressed brain: role of histone acetylation and methylation
Sun, H., Kennedy, P. J., & Nestler, E. J. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.73 · Cited by 413 · see citing works
Cis-acting noncoding RNAs: friends and foes
Guil, S., & Esteller, M. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2428 · Cited by 369 · see citing works
Bagot, R. C., Cates, H. M., Purushothaman, I., Lorsch, Z. S., Walker, D. M., Wang, J., Huang, X., Schlüter, O. M., Maze, I., Peña, C. J., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.015 · Cited by 333 · cited 2× · see citing works
“For example, Bagot et al.61 showed that the overexpression of key network “hub genes” led to changes in the expression of a significant number of genes which were enriched with those belonging to the corresponding co-expression network that was related to depression susceptibility in mice.”
BackgroundSmalheiser, N. R., Lugli, G., Rizavi, H. S., Torvik, V. I., Turecki, G., & Dwivedi, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033201 · Cited by 324 · see citing works
Self-citationWeder, N., Zhang, H., Jensen, K., Yang, B. Z., Simen, A., Jackowski, A., Lipschitz, D., Douglas-Palumberi, H., Ge, M., Perepletchikova, F., et al. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2013.12.025 · Cited by 324 · see citing works
Astrocytic abnormalities and global DNA methylation patterns in depression and suicide
Nagy, C., Suderman, M., Yang, J., Szyf, M., Mechawar, N., Ernst, C., & Turecki, G. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.21 · Cited by 301 · see citing works
Self-citationThe molecular bases of the suicidal brain
Turecki, G. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3839 · Cited by 281 · see citing works
Self-citationDuman, R. S. (2014) · Depression and Anxiety · doi:10.1002/da.22227 · Cited by 213 · see citing works
Tsukita, S., Hieda, Y., & Tsukita, S. (1989) · The Journal of Cell Biology · doi:10.1083/jcb.108.6.2369 · Cited by 207 · see citing works
Lutz, P.-E., Tanti, A., Gasecka, A., Barnett-Burns, S., Kim, J. J., Zhou, Y., Chen, G. G., Wakid, M., Shaw, M., Almeida, D., et al. (2017) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2017.16111286 · Cited by 203 · see citing works
Self-citationNeurobiological basis of depression: an update
Kalia, M. (2005) · Metabolism · doi:10.1016/j.metabol.2005.01.009 · Cited by 202 · see citing works
Mostafavi, S., Battle, A., Zhu, X., Potash, J. B., Weissman, M. M., Shi, J., Beckman, K., Haudenschild, C., McCormick, C., Mei, R., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.161 · Cited by 187 · see citing works
Neuropathology of suicide: Recent findings and future directions
Lutz, P.-E., Mechawar, N., & Turecki, G. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.141 · Cited by 158 · see citing works
Self-citationLiu, Z., Li, X., Sun, N., Xu, Y. J., Meng, Y.-Q., Yang, C., Wang, Y., & Zhang, K. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093388 · Cited by 121 · see citing works
Self-citationPolygenic associations of neurodevelopmental genes in suicide attempt
Sokolowski, M., Wasserman, J., & Wasserman, D. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.187 · Cited by 117 · see citing works
McGirr, A., Tousignant, M., Routhier, D., Pouliot, L., Chawky, N., Margolese, H. C., & Turecki, G. (2006) · Schizophrenia Research · doi:10.1016/j.schres.2006.02.025 · Cited by 110 · see citing works
Self-citationPatterns of co-morbidity in male suicide completers
KIM, C. D., LESAGE, A., SEGUIN, M., CHAWKY, N., VANIER, C., LIPP, O., & TURECKI, G. (2003) · Psychological Medicine · doi:10.1017/s0033291703008146 · Cited by 104 · see citing works
Self-citationLopez, J. P., Fiori, L. M., Gross, J. A., Labonte, B., Yerko, V., Mechawar, N., & Turecki, G. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145713000941 · Cited by 103 · see citing works
Self-citationGenome-wide differential expression of synaptic long noncoding RNAs in autism spectrum disorder
Wang, Y., Zhao, X., Ju, W., Flory, M. J., Zhong, J. L., Jiang, S., Wang, P., Dong, X., Tao, X., Chen, Q., et al. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.144 · Cited by 97 · see citing works
Self-citationThe link between long noncoding RNAs and depression
Huang, X., Luo, Y., Mao, Y.-S., & Jian-lin, J. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.06.004 · Cited by 92 · see citing works
Long Non-Coding RNA: Potential Diagnostic and Therapeutic Biomarker for Major Depressive Disorder
Cui, X., Sun, X., Niu, W., Kong, L., He, M., Zhong, A., Chen, S., Jiang, K., Zhang, L.-Y., & Cheng, Z. (2016) · Medical Science Monitor · doi:10.12659/msm.899372 · Cited by 82 · see citing works
Comprehensive prediction of lncRNA–RNA interactions in human transcriptome
Terai, G., Iwakiri, J., Kameda, T., Hamada, M., & Asai, K. (2016) · BMC Genomics · doi:10.1186/s12864-015-2307-5 · Cited by 69 · see citing works
Evidence of Altered Polyamine Concentrations in Cerebral Cortex of Suicide Completers
Chen, G. G., Fiori, L. M., Moquin, L., Gratton, A. P., Mamer, O., Mechawar, N., & Turecki, G. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.17 · Cited by 61 · see citing works
Self-citationXu, X., Qiu, C., Zhu, L., Huang, J., Li, L., Fu, W., Zhang, L., Wei, J., Wang, Y., Geng, Y., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401249 · Cited by 55 · see citing works
Self-citationAberrant Expression of Long Non-Coding RNAs in Schizophrenia Patients
Chen, S., Sun, X., Niu, W., Kong, L., He, M., Li, W., Zhong, A., Lu, J. Z., & Zhang, L.-Y. (2016) · Medical Science Monitor · doi:10.12659/msm.896927 · Cited by 50 · see citing works
Different stress-related gene expression in depression and suicide
Zhao, J., Qi, X., Gao, S., Lu, J., van Wamelen, D. J., Kamphuis, W., Bao, A., & Swaab, D. F. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.06.010 · Cited by 46 · see citing works
Mellon, S. H., Wolkowitz, O. M., Schonemann, M. D., Epel, E. S., Rosser, R., Burke, H. B., Mahan, L., Reus, V. I., Stamatiou, D., Liew, C. C., et al. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.79 · Cited by 45 · see citing works
Cruceanu, C., Tan, P. P. C., Rogić, S., López, J. P., Torres-Platas, S. G., Gigek, C. O., Alda, M., Rouleau, G. A., Pavlidis, P., & Turecki, G. (2015) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.14101279 · Cited by 41 · see citing works
Self-citationJungke, P., Ostrow, G., Li, J., Norton, S., Nieber, K., Kelber, O., & Butterweck, V. (2010) · Psychopharmacology · doi:10.1007/s00213-010-2032-3 · Cited by 32 · see citing works
Investigation of genes important in neurodevelopment disorders in adult human brain
Maussion, G., Diallo, A., Gigek, C. O., Chen, E., Crapper, L., Théroux, J., Chen, G. G., Vasuta, C., & Ernst, C. (2015) · Human Genetics · doi:10.1007/s00439-015-1584-z · Cited by 31 · see citing works
Belzeaux-R, R., Lin, C., Ding, Y., Bergon, A., Ibrahim, E. C., Turecki, G., Tseng, G. C., & Sibille, E. L. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.07.009 · Cited by 31 · see citing works
Self-citationZeng, Y., Navarro, P., Shirali, M., Howard, D. M., Adams, M. J., Hall, L. S., Clarke, T., Thomson, P. A., Smith, B. H., Murray, A. D., et al. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.12.012 · Cited by 31 · see citing works
Decreased expression of nociceptin/orphanin FQ in the dorsal anterior cingulate cortex of suicides
Lutz, P.-É., Zhou, Y., Labbe, A., Mechawar, N., & Turecki, G. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.08.015 · Cited by 25 · see citing works
Self-citationWu, L., Zhang, C., Zheng, X., Tian, Z., & Zhang, J. (2011) · International Immunopharmacology · doi:10.1016/j.intimp.2011.07.021 · Cited by 18 · see citing works
Radixin Knockdown by RNA Interference Suppresses Human Glioblastoma Cell Growth in Vitro and in Vivo
Qin, J.-J., Wang, J.-M., Du, J., Zeng, C., Wu, H., Li, Z.-D., Xie, J. W., & Li, G. (2014) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2014.15.22.9805 · Cited by 11 · see citing works
Flagged first, then by citations
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Yuan, M., Yang, B., Rothschild, G., Mann, J. J., Sanford, L. D., Tang, X., Huang, C., Wang, C., & Zhang, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01519-z · Cited by 246 · see citing works
“Levels of 60% (217 out of 364) of the 364 lncRNAs expressed in the rostral cingulate cortex of normal individuals differed from those in MDD.(310) Using whole-genome sequencing, a recent study found that lncRNAs accounted for 30% of the differences between patients with depression and control populations.”
ResultInfluentialSex-Specific Role for the Long Non-coding RNA LINC00473 in Depression
Issler, O., van der Zee, Y. Y., Ramakrishnan, A., Wang, J., Tan, C., Loh, Y.-H. E., Purushothaman, I., Walker, D. M., Lorsch, Z. S., Hamilton, P. J., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.03.023 · Cited by 156 · see citing works
“Descriptive studies profiling lncRNAs in humans have found differences in rACC (Zhou et al., 2018) and blood (Liu et al.”
InfluentialBecker, L. J., Fillinger, C., Waegaert, R., Journée, S. H., Hener, P., Ayazgök, B., Humo, M., Karatas, M., Thouaye, M., Gaikwad, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37878-y · Cited by 116 · see citing works
“We have now included contralateral data in the main text (see Fig.1), and rephrased the results section accordingly (see page 4-5).”
Self-citationUnraveling the epigenetic landscape of depression: focus on early life stress
Torres‐Berrío, A., Issler, O., Parise, E. M., & Nestler, E. J. (2019) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2019.21.4/enestler · Cited by 102 · see citing works
Junior, H. P. D. O. S., Bhattacharya, A., Martin, E. M., Addo, K., Psioda, M., Smeester, L., Joseph, R. M., Hooper, S. R., Frazier, J. A., Kuban, K., et al. (2019) · Epigenetics · doi:10.1080/15592294.2019.1614743 · Cited by 82 · see citing works
Non-Coding RNAs in Psychiatric Disorders and Suicidal Behavior
Yoshino, Y., & Dwivedi, Y. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.543893 · Cited by 82 · see citing works
“4) were successfully validated by qPCR (79)”
BackgroundNon-coding RNAs in depression: Promising diagnostic and therapeutic biomarkers
Shi, Y., Wang, Q., Song, R., Kong, Y., & Zhang, Z. (2021) · eBioMedicine · doi:10.1016/j.ebiom.2021.103569 · Cited by 79 · see citing works
“In the anterior cingulate cortex tissue, nine lncRNAs showed a significantly differential expression between depressed and healthy subjects [95].”
BackgroundMolecular mechanisms of psychiatric diseases
Blokhin, I. O., Khorkova, O., Saveanu, R. V., & Wahlestedt, C. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105136 · Cited by 58 · see citing works
“RNA sequencing in the anterior cingulate cortex of 26 patients with MDD who committed suicide and 24 control subjects followed by WGCNA (weighted gene coexpression network analysis) pinpointed 23 differentially expressed lncRNAs (144).”
MethodThe long noncoding RNA FEDORA is a cell type– and sex-specific regulator of depression
Issler, O., van der Zee, Y. Y., Ramakrishnan, A., Xia, S.-H., Zinsmaier, A. K., Tan, C., Li, W., Browne, C. J., Walker, D. M., Salery, M., et al. (2022) · Science Advances · doi:10.1126/sciadv.abn9494 · Cited by 53 · see citing works
“We and others reported regulation of specific lncRNAs in postmortem brain tissue of MDD patients (17, 18) and rodent stress models (19, 20).”
BackgroundGlăvan, D., Gheorman, V., Greșiță, A., Hermann, D. M., Udriștoiu, I., & Popa‐Wagner, A. (2021) · Scientific Reports · doi:10.1038/s41598-021-98210-6 · Cited by 45 · see citing works
A new perspective on depression and neuroinflammation: Non-coding RNA
Zhou, S., Chen, R., She, Y., Liu, X., Zhao, H., Li, C., & Jia, Y. (2022) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2022.02.007 · Cited by 42 · see citing works
Wang, Q., Roy, B., & Dwivedi, Y. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0448-z · Cited by 42 · see citing works
“Another study, conducted in the anterior cingulate cortex of depressed subjects who had died by suicide, showed significant changes in the expression of a large number of lncRNAs and their possible regulatory roles in altering transcriptome dynamics implicated in various molecular pathways associated with depression s…”
BackgroundA transcriptomic analysis of neuropathic pain in the anterior cingulate cortex after nerve injury
Zhang, Y., Jiang, S., Liao, F., Huang, Z., Yang, X., Zou, Y., He, X., Guo, Q., & Huang, C. (2022) · Bioengineered · doi:10.1080/21655979.2021.2021710 · Cited by 39 · see citing works
Bekhbat, M., Goldsmith, D. R., Woolwine, B. J., Haroon, E., Miller, A. H., & Felger, J. C. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01258-z · Cited by 33 · see citing works
Afridi, R., Seol, S., Kang, H. J., & Suk, K. (2021) · Biochemical Pharmacology · doi:10.1016/j.bcp.2021.114532 · Cited by 29 · see citing works
Mirza, S. A., Docherty, A. R., Bakian, A. V., Coon, H. H., Soares, J. C., Walss‐Bass, C., & Fries, G. R. (2022) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32917 · Cited by 32 · see citing works
“We identified four genome-wide linkage studies focused on SITB (Butler et al., 2010; Dick et al., 2010; Willour et al., 2007; Zubenko et al., 2004).”
BackgroundSnelleksz, M., & Dean, B. (2021) · Psychiatry Research · doi:10.1016/j.psychres.2021.114096 · Cited by 28 · see citing works
Molecular mechanisms underlying major depressive disorder and post-stroke affective disorders
Coliță, D., Burdusel, D., Glăvan, D., Hermann, D. M., Coliță, C.-I., Coliță, E., Udriștoiu, I., & Popa‐Wagner, A. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.10.037 · Cited by 27 · see citing works
Epigenetic Mechanisms of Rapid-Acting Antidepressants
Inserra, A., Campanale, A., Rezai, T., Romualdi, P., & Rubino, T. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-03055-y · Cited by 27 · see citing works
Song, B., Qian, J., & Fu, J. (2023) · International Journal of Legal Medicine · doi:10.1007/s00414-023-03091-1 · Cited by 25 · see citing works
“By genome-wide multiplex testing correction, Zhou et al. [104] screened differentially expressed lncRNAs by RNA sequencing in the rostral anterior cingulate cortex of 26 depressed suicides and 24 healthy controls and identified a total of 23 statistically significant differentially expressed…”
Neuroepigenetics of psychiatric disorders: Focus on lncRNA
Jovčevska, I., & Paska, A. V. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.105140 · Cited by 25 · see citing works
“Using qPCR, three genes IRF2, LY6E, and HMOBX1, withstood the validation (Zhou et al., 2018).”
Deciphering Depression: Epigenetic Mechanisms and Treatment Strategies
Aljabali, A. A. A., Alkaraki, A. K., Gammoh, O., Tambuwala, M. M., Mishra, V. K., Mishra, Y., Hassan, S. S., & El‐Tanani, M. (2024) · Biology · doi:10.3390/biology13080638 · Cited by 26 · see citing works
“Behavioral response to stress, depressive behaviors, and response to antidepressants [119].”
BackgroundThe molecular basis of depression: implications of sex-related differences in epigenetic regulation
Kawatake-Kuno, A., Murai, T., & Uchida, S. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.708004 · Cited by 23 · see citing works
“expressed lncRNAs as well as their differentially expressed overlapping and antisense protein-coding genes in the rostral anterior cingulate cortex (Zhou et al., 2018).”
BackgroundHippocampal neuropathology in suicide: Gaps in our knowledge and opportunities for a breakthrough
Zhang, L., Lucassen, P. J., Salta, E., Verhaert, P. D. E. M., & Swaab, D. F. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.12.023 · Cited by 22 · see citing works
Integrative Analysis of lncRNA and mRNA and Profiles in Postoperative Delirium Patients
Song, Y., Wang, X., Hou, A., Li, H., Lou, J., Liu, Y., Cao, J., & Mi, W. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.665935 · Cited by 22 · see citing works
“, 2020), major depressive disorder, autism, and schizophrenia (Briggs et al., 2015; Parikshak et al., 2016; Liu Y. et al., 2018; Zhou et al., 2018).”
BackgroundEpigenetic mechanisms in depression: Implications for pathogenesis and treatment
Chen, H.-S., Wang, F., & Chen, J. (2024) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2024.102854 · Cited by 23 · see citing works
Swieck, K., Conta, A. C., Middleton, F. A., Siebert, J. R., Osterhout, D. J., & Stelzner, D. J. (2019) · BMC Neuroscience · doi:10.1186/s12868-019-0491-y · Cited by 22 · see citing works
Emerging roles for long noncoding RNAs in learning, memory and associated disorders
Grinman, E., Espadas, I., & Puthanveettil, S. V. (2019) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2019.107034 · Cited by 20 · see citing works
Bekhbat, M., Ulukaya, G. B., Bhasin, M., Felger, J. C., & Miller, A. H. (2022) · Neurobiology of Stress · doi:10.1016/j.ynstr.2022.100462 · Cited by 21 · see citing works
“An FDR significance threshold of q < 0.1 (Storey and Tibshirani, 2003) was used herein for pathway analysis to ensure biologically meaningful pathway results (Mostafavi et al., 2014; Jansen et al., 2016; Hulsegge et al., 2009; Yang et al., 2008, 2014; de Kluiver et al., 2019; Zhou et al., 2018).”
MethodInfluentialResearch trend of epigenetics and depression: adolescents' research needs to strengthen
Yuan, D., Meng, Y., Ai, Z., & Zhou, S. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1289019 · Cited by 20 · see citing works
Figueiredo, S., & Devezas, M. (2024) · Perioperative Care and Operating Room Management · doi:10.1016/j.pcorm.2024.100401 · Cited by 18 · see citing works
LncRNAs in neuropsychiatric disorders and computational insights for their prediction
Baruah, C., Nath, P., & Barah, P. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-07819-x · Cited by 17 · see citing works
“3 is another highly differentially expressed lncRNA associated with genetic variation and is responsible for depressive characteristics in patients [38].”
BackgroundRoy, B., Verma, A. K., Funahashi, Y., & Dwivedi, Y. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70135 · Cited by 16 · see citing works
Gibbons, A. S., Sundram, S., & Dean, B. (2020) · Non-Coding RNA · doi:10.3390/ncrna6030033 · Cited by 16 · see citing works
Servaas, N. H., Mariotti, B., van der Kroef, M., Wichers, C. G. K., Pandit, A., Bazzoni, F., Radstake, T. R. D. J., & Rossato, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094365 · Cited by 16 · see citing works
Recent developments in omics studies and artificial intelligence in depression and suicide
Wang, Q., & Dwivedi, Y. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03497-y · Cited by 14 · see citing works
Suicide Is a Confounder in Postmortem Studies on Depression
Zhao, J., Lucassen, P. J., & Swaab, D. F. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.04.015 · Cited by 15 · see citing works
Bekhbat, M., Block, A. M., Dickinson, S. Y., Tharpd, G. K., Bosinger, S. E., & Felger, J. C. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.01.010 · Cited by 13 · see citing works
Sex Differences in Susceptibility to Depression: A Role for LncRNAs
Gururajan, A. (2020) · Neuron · doi:10.1016/j.neuron.2020.05.016 · Cited by 12 · see citing works
Zhong, X.-L., Du, Y., Chen, L. T., & Cheng, Y. (2023) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2023.06.017 · Cited by 12 · see citing works
Suicidal Behavior and Its Relationship with Postmortem Forensic Toxicological Findings
Collados-Ros, A., Torres-Sánchez, C., Pérez-Cárceles, M. D., Luna, A., & Legaz, I. (2022) · Toxics · doi:10.3390/toxics10060319 · Cited by 13 · see citing works
Brain and Blood Biomarkers of Major Depressive Disorder
Zallar, L. J., & Dupont, M. B. (2026) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2025.4613 · Cited by 12 · see citing works
Ghamari, M., Mohseni, M. M., Taheri, M. N., Neishabouri, S. M., & Shirvani-Farsani, Z. (2023) · Metabolic Brain Disease · doi:10.1007/s11011-023-01316-1 · Cited by 10 · see citing works
Molecular programs underlying differences in the expression of mood disorders in males and females
Mena, F., & Benoit, L. (2019) · Brain Research · doi:10.1016/j.brainres.2019.05.016 · Cited by 9 · see citing works
Depicting the molecular features of suicidal behavior: a review from an “omics” perspective
Pereira, C. A., Reis‐de‐Oliveira, G., Pierone, B. C., Martins‐de‐Souza, D., & Kaster, M. P. (2023) · Psychiatry Research · doi:10.1016/j.psychres.2023.115682 · Cited by 9 · see citing works
A meta-study on transcription factor networks in the suicidal brain
Cabrera‐Mendoza, B., de Anda‐Jáuregui, G., Nicolini, H., & Fresno, C. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.01.037 · Cited by 9 · see citing works
The Roles of Long Noncoding RNA in Depression
Wang, S., Tang, L., Huang, N., & Wang, H. (2023) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2811321 · Cited by 8 · see citing works
“[ 94].”
BackgroundCabrera-Mendoza, B., Martínez-Magaña, J., Monroy-Jaramillo, N., Genis-Mendoza, A., Fresno, C., Fries, G., Walss-Bass, C., López-Armenta, M., García-Dolores, F., Díaz-Otañez, C., et al. (2021) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32830 · Cited by 8 · see citing works
Wang, Q., Wang, H., & Dwivedi, Y. (2024) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2024.100365 · Cited by 6 · see citing works
“Zhou et al. (25) identi fi ed 23 signi fi cantly dysregulated lncRNAs through differential expression and weighted coexpression network analyses.”
InfluentialDwivedi, Y., & Roy, B. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03396-0 · Cited by 5 · see citing works
Epigenetic marks in suicide: a review
Ramos-Rosales, D. F., Vázquez-Alaníz, F., Urtiz-Estrada, N., Ramirez-Valles, E. G., Méndez-Hernández, E. M., Salas-Leal, A. C., & Barraza-Salas, M. (2021) · Psychiatric Genetics · doi:10.1097/ypg.0000000000000297 · Cited by 4 · see citing works
“…who died by suicide showed differentially expressed lncRNAs; target genes are involved in neuronal remodeling (PPFIA1, SNCB and GRIN1) and cytoskeletal or membrane regulation (TCF12 and FNBP1) (Zhou et al., 2018) providing a novel molecular strategy to study potential therapeutic targets.”
BackgroundPlasil, S. L., Collins, V. J., Baratta, A. M., Farris, S. P., & Homanics, G. E. (2022) · Advances in Drug and Alcohol Research · doi:10.3389/adar.2022.10831 · Cited by 4 · see citing works
“The dysregulation of lncRNAs has been linked to the pathophysiology of several disease states (7, 8, 41, 44, 53, 60–66) including AUD (41, 67, 68), drug addiction (63, 69–71), psychiatric disorders (72, 73), and stress responses (74, 75).”
BackgroundRepeated social defeat stress leads to immunometabolic shifts in innate immune cells of the spleen
Bekhbat, M., Drake, J. W., Reed, E. C., Lauten, T. H., Natour, T., Vladimirov, V. I., & Case, A. J. (2023) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2023.100690 · Cited by 5 · see citing works
Epigenetics and immunology: Under-recognized aspects of suicidality
Kouter, K., Šmon, J., & Paska, A. V. (2025) · World Journal of Psychiatry · doi:10.5498/wjp.v15.i9.107726 · Cited by 3 · see citing works
Small Nucleolar RNAs and the Brain: Growing Evidence Supporting Their Role in Psychiatric Disorders
Salles, J., Lin, R., & Turecki, G. (2024) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2024.100415 · Cited by 3 · see citing works
Self-citationCircular RNA expression profiles in human bronchial epithelial cells treated with beryllium sulfate
Liu, Y.-P., Cai, Y., Lei, Y., Yuan, X., Wang, Y., Yi, S., Li, X., Huang, L., Long, D., & Zhang, Z. (2021) · Toxicology Research · doi:10.1093/toxres/tfab086 · Cited by 3 · see citing works
Self-citationArasappan, D., Spears, A., Shah, S., Mayfield, R. D., Akula, N., McMahon, F. J., & Jabbi, M. (2025) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2025.101051 · Cited by 3 · see citing works
“…responses (McGrath et al., 2013; Riva-Posse et al., 2018), and transcriptome studies of this brain network revealed molecular abnormalities related to mood disorders and suicide phenotypes (Jabbi et al., 2020a; Galvalvy et al., 2013; Orozco-Solis et al., 2017; Lutz et al., 2017; Zhou et al., 2018).”
Zhang, L., Tian, Q., & Chunming, X. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.09.029 · Cited by 2 · see citing works
Matsushima, T., Toji, N., Wada, K., Shikanai, H., & Izumi, T. (2025) · Cerebral Cortex · doi:10.1093/cercor/bhaf044 · Cited by 2 · see citing works
Becker, L. J., Fillinger, C., Waegaert, R., Hener, P., Ayazgök, B., Humo, M., Journée, S. H., Karatas, M., Degiorgis, L., Santin, M. D. N., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.08.09.503276 · Cited by 2 · see citing works
Self-citationBu, T., Yang, J., Zhou, J., Liu, Y., Qiao, K., Wang, Y., Zhang, J., Zhao, E., Owura, B. K., Qiu, X., et al. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1241089 · Cited by 1 · see citing works
“Zhou et al. showed that the regulatory in fl uence of lncRNAs on gene expression was stronger in women than men (33).”
Self-citationBu, C., Ren, Y., Chen, Y., & Zheng, X. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-10541-z · Cited by 1 · see citing works
Zhang, G., Xu, D., Bu, S., Li, L., Jiao, J., Shi, Y., Xu, Y., Kong, Y., & Zhang, Z. (2025) · NeuroMarkers. · doi:10.1016/j.neumar.2025.100114 · Cited by 1 · see citing works
Peripheral NORAD lncRNA and MARCKS mRNA expression in suicidal adolescents: a case-control study
Saygılı, G. Y., Karadağ, M., Şahın, E., & Çalışgan, B. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-10982-6 · Cited by 1 · see citing works
Sun, S., Dochtermann, D. R., Wang, Z., Pyarajan, S., Program, V. M. V., Galfalvy, H., & Haghighi, F. G. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03332-2 · Cited by 2 · see citing works
The role of ncRNAs in depression
Luan, X., Xing, H., Guo, F., Liu, W., Jiao, Y., Liu, Z., Wang, X., & Gao, S. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e27307 · Cited by 1 · see citing works
“Issler et al. found that, as a diagnostic biomarker, LINC00473 up-regulation in adult mouse medial prefrontal cortex (mPFC) neurons only benefits females, and it may be a biomarker for females who struggle with depression [101,102].”
BackgroundRNA Sequencing of Neuropathic Pain in the Anterior Cingulate Cortex after Nerve InjuryPreprint
zhang, Y., Jiang, S., Liao, F., Huang, Z., Yang, X., Zou, Y., He, X., Guo, Q., & Huang, C. (2021) · Research Square · doi:10.21203/rs.3.rs-861152/v1
Unveiling the two faces of immune dysregulation in Systemic Sclerosis
Servaas, N. H. (2021) · doi:10.33540/93
Functional characterization of disease/comorbidity‐associated lncRNA
Tang, J., Wang, Y., Fu, J., Wu, X., Han, Z., Wang, C., Guo, M., Wang, Y., Ding, Y., Yang, B., et al. (2021) · Quantitative Biology · doi:10.15302/j-qb-021-0247
Self-citationLi, Y., Wang, Y., Tang, X., Liang, P., Chen, J., Jiang, F. X., Yang, Q., & Liang, Y. (2023) · World Journal of Psychiatry · doi:10.5498/wjp.v13.i12.1005
Self-citationRole of long non-coding RNAs in depression: Mechanisms and potential therapeutic targets
Ding, Z., Shen, J., Wei, C., Liu, Z., Huang, L., & Zhou, S. (2024) · Journal of Neurorestoratology · doi:10.1016/j.jnrt.2024.100142
Rasaei, N., Esmaeili, F., Khadem, A., Yekaninejad, M. S., & Mirzaei, K. (2024) · BMC Medical Genomics · doi:10.1186/s12920-024-01976-7
“These processes encompassed the organization of the cytoskeleton, plasma membrane function, cell adhesion, regulation of nucleus, DNA-binding, and the modulation of dendrite morphology and development [46].”
BackgroundMatsushima, T., Toji, N., Wada, K., Shikanai, H., & Izumi, T. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.15.613159
Francis, A., & Dwivedi, Y. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.16.682876
Dwivedi, Y., & Roy, B. (2025) · Biological Psychiatry · doi:10.1016/j.biopsych.2025.10.025
Dysregulation of inflammation-related long non-coding RNAs in autistic children
Mohseni, M. M., Momeni, M., Shirvani-Farsani, Z., & Ghafouri‐Fard, S. (2026) · Biomarkers in Neuropsychiatry · doi:10.1016/j.bionps.2026.100138
- Authors
- Zhou, Y., Lutz, P.-E., Wang, Y. C., Ragoussis, J., & Turecki, G.
- Affiliations
- McGill University (CA)
- McGill University and Génome Québec Innovation Centre (CA)
- Corresponding author
- Turecki, Gustavo
- Venue
- Translational Psychiatry
- Published
- 2018-10-18
- Volume
- 8
- Issue
- 1
- Pages
- 224-224
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC6193959
- OpenAlex
- W2897445681
- Cited by
- 77
- References
- 60
- Citations by year
- 2026: 2 · 2025: 14 · 2024: 12 · 2023: 11 · 2022: 9 · 2021: 17 · 2020: 5 · 2019: 7
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Pfizer
- Genome Canada
- National Alliance for Research on Schizophrenia and Depression
- Fondation pour la Recherche Médicale
- National Institutes of Health
- Canadian Institutes of Health Research (MOP119430, MOP11260, MOP93775, MOP119429, MOP93775, MOP11260, MOP119429, and MOP119430, FDN148374)
- Fonds de Recherche du Québec - Santé
- National Institute on Drug Abuse (R01DA033684)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Keywords
- long non-coding RNA, depression, suicide, rostral anterior cingulate cortex, lncRNA expression, interferon signaling, innate immune response, gene co-expression modules, antisense gene, dendrite formation, mental illness
- MeSH terms
- Major Depressive Disorder, Female, Gene Expression Regulation, Gyrus Cinguli, Humans, Male, Suicide, Sequence Analysis, RNA, Transcriptome, RNA, Long Noncoding
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