New approaches to antidepressant drug discovery: beyond monoamines
Abstract
All available antidepressant medications are based on serendipitous discoveries of the clinical efficacy of two classes of antidepressants more than 50 years ago. These tricyclic and monoamine oxidase inhibitor antidepressants were subsequently found to promote serotonin or noradrenaline function in the brain. Newer agents are more specific but have the same core mechanisms of action in promoting these monoamine neurotransmitters. This is unfortunate, because only approximately 50% of individuals with depression show full remission in response to these mechanisms. This review summarizes the obstacles that have hindered the development of non-monoamine-based antidepressants, and provides a progress report on some of the most promising current strategies.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Chronic antidepressant treatment can reverse CSDS-induced depression-like behaviors, including social avoidance.
“Chronic antidepressant treatment can reverse CSDS-induced depression-like behaviors, including social avoidance25, 32.”
From Social stress induces neurovascular pathology promoting depression (2017) · cites this paper as [25]
In rodents, CSDS induces a depression-like phenotype (social avoidance, anhedonia) in a subset of mice termed stress-susceptible that can be reversed only by chronic, but not acute, antidepressant treatment.
“Similarly, in rodents, CSDS induces a depression-like phenotype (social avoidance, anhedonia) in a subset of mice termed stress-susceptible (SS) that can be reversed only by chronic, but not acute, antidepressant treatment25, 26.”
From Social stress induces neurovascular pathology promoting depression (2017) · cites this paper as [25]
Experimental control over the intensity of social defeat stress exposure makes it possible to examine a wide range of individual responses across molecular, cellular and behavioral endpoints.
“Experimental control over the intensity of social defeat stress exposure makes it possible to examine a wide range of individual responses across molecular, cellular and behavioral endpoints20,21.”
From A standardized protocol for repeated social defeat stress in mice (2011) · cites this paper as [20]
Social defeat stress provides a potential means to investigate components of the basic neuropathology underlying affective illnesses, which is providing fundamentally new information about the molecular basis of affective disorders to aid in the development of novel antidepressant treatment strategies.
“Thus, social defeat stress provides a potential means to investigate components of the basic neuropathology underlying affective illnesses8,33–36, which is providing fundamentally new information about the molecular basis of affective disorders to aid in the development of novel antidepressant treatment strategies20.”
From A standardized protocol for repeated social defeat stress in mice (2011) · cites this paper as [20]
Cites
A molecular and cellular theory of depression
Duman, R. S. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830190015002 · Cited by 2,129 · see citing works
The cellular neurobiology of depression
Manji, H. K., Drevets, W. C., & Charney, D. S. (2001) · Nature Medicine · doi:10.1038/87865 · Cited by 1,182 · see citing works
Korte, S. M., Koolhaas, J. M., Wingfield, J. C., & McEwen, B. S. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.08.009 · Cited by 1,097 · see citing works
New Vistas on Amygdala Networks in Conditioned Fear
Paré, D., Quirk, G. J., & Ledoux, J. E. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00153.2004 · Cited by 841 · cited 1× · see citing works
“The amygdala and BNST are implicated in the generation of anxiety-like behaviou”
BackgroundEpigenetic mechanisms in memory formation
Levenson, J. M., & Sweatt, J. D. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1604 · Cited by 767 · see citing works
Essential role of brain-derived neurotrophic factor in adult hippocampal function
Monteggia, L. M., Barrot, M., Powell, C. M., Berton, O., Galanis, V., Gemelli, T., Meuth, S., Nagy, A., Greene, R. W., & Nestler, E. J. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402141101 · Cited by 685 · see citing works
Self-citationImplication of the hypothalamic-pituitary-adrenal axis in the physiopathology of depression
Barden, N. (2004) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0421 · Cited by 416 · see citing works
Altered patterns of sleep and behavioral adaptability in NPAS2-deficient mice
Dudley, C. A., Erbel-Sieler, C., Estill, S. J., Reick, M., Franken, P., Pitts, S., & McKnight, S. L. (2003) · Science · doi:10.1126/science.1082795 · Cited by 415 · see citing works
Glutamate and Depression: Clinical and Preclinical Studies
PAUL, I. A., & SKOLNICK, P. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1300.016 · Cited by 408 · see citing works
Boyle, M. P., Brewer, J. A., Funatsu, M., Wozniak, D. F., Tsien, J. Z., Izumi, Y., & Muglia, L. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406458102 · Cited by 378 · see citing works
Corticotropin-Releasing Factor in Brain: A Role in Activation, Arousal, and Affect Regulation
Heinrichs, S. C., & Koob, G. F. (2004) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.052092 · Cited by 353 · see citing works
Haller, J., Varga, B., Ledent, C., & Freund, T. F. (2004) · Behavioural Pharmacology · doi:10.1097/01.fbp.0000135704.56422.40 · Cited by 241 · see citing works
Clinical and Biological Effects of Mifepristone Treatment for Psychotic Depression
Flores, B. H., Kenna, H., Keller, J., Solvason, H. B., & Schatzberg, A. F. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300884 · Cited by 203 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The molecular neurobiology of depression
Krishnan, V., & Nestler, E. J. (2008) · Nature · doi:10.1038/nature07455 · Cited by 2,889 · see citing works
Self-citationAnimal models of neuropsychiatric disorders
Nestler, E. J., & Hyman, S. E. (2010) · Nature Neuroscience · doi:10.1038/nn.2647 · Cited by 2,023 · see citing works
Self-citationEnriched environments, experience-dependent plasticity and disorders of the nervous system
Nithianantharajah, J., & Hannan, A. J. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1970 · Cited by 1,771 · see citing works
Kelly, J. R., Borre, Y., O' Brien, C., Patterson, E., El Aidy, S., Deane, J., Kennedy, P. J., Beers, S., Scott, K., Moloney, G., et al. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.07.019 · Cited by 1,683 · see citing works
A standardized protocol for repeated social defeat stress in mice
Golden, S. A., Covington, H. E., Berton, O., & Russo, S. J. (2011) · Nature Protocols · doi:10.1038/nprot.2011.361 · Cited by 1,581 · see citing works
Self-citationEpigenetic regulation in psychiatric disorders
Tsankova, N., Renthal, W., Kumar, A., & Nestler, E. J. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2132 · Cited by 1,400 · see citing works
Self-citationAdult hippocampal neurogenesis in depression
Sahay, A., & Hen, R. (2007) · Nature Neuroscience · doi:10.1038/nn1969 · Cited by 1,206 · see citing works
Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons
Chaudhury, D., Walsh, J. J., Friedman, A. K., Juarez, B., Ku, S. M., Koo, J. W., Ferguson, D., Tsai, H.-C., Pomeranz, L., Christoffel, D. J., et al. (2013) · Nature · doi:10.1038/nature11713 · Cited by 1,156 · see citing works
Self-citationSocial stress induces neurovascular pathology promoting depression
Menard, C., Pfau, M. L., Hodes, G. E., Kana, V., Wang, V. X., Bouchard, S., Takahashi, A., Flanigan, M. E., Aleyasin, H., LeClair, K. B., et al. (2017) · Nature Neuroscience · doi:10.1038/s41593-017-0010-3 · Cited by 1,028 · see citing works
Bewernick, B. H., Hurlemann, R., Matusch, A., Kayser, S., Grubert, C., Hadrysiewicz, B., Axmacher, N., Lemke, M., Cooper-Mahkorn, D., Cohen, M. X., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.013 · Cited by 865 · see citing works
IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress
Koo, J. W., & Duman, R. S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708092105 · Cited by 862 · see citing works
Goshen, I., Kreisel, T., Ben-Menachem-Zidon, O., Licht, T., Weidenfeld, J., Ben-Hur, T., & Yirmiya, R. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002055 · Cited by 762 · see citing works
Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes
Rudolph, U., & Knoflach, F. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3502 · Cited by 733 · see citing works
“Although there is tremendous interest in developing antidepressant agents that utilize different mechanisms of action, the development of such agents has not yet been successfu”
BackgroundCastagné, V., Moser, P., Roux, S., & Porsolt, R. D. (2011) · Current Protocols in Neuroscience · doi:10.1002/0471142301.ns0810as55 · Cited by 702 · see citing works
Synaptic potentiation onto habenula neurons in the learned helplessness model of depression
Li, B., Piriz, J., Mirrione, M., Chung, C., Proulx, C. D., Schulz, D., Henn, F., & Malinow, R. (2011) · Nature · doi:10.1038/nature09742 · Cited by 634 · see citing works
Antidepressant Actions of Histone Deacetylase Inhibitors
Covington, H. E., Maze, I., LaPlant, Q. C., Vialou, V. F., Ohnishi, Y. N., Berton, O., Fass, D. M., Renthal, W., Rush, A. J., Wu, E. Y., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1758-09.2009 · Cited by 624 · see citing works
Self-citationBessa, J. M., Ferreira, D., Melo, I., Marques, F., Cerqueira, J. J., Palha, J. A., Almeida, O. F. X., & Sousa, N. (2009) · Molecular Psychiatry · doi:10.1038/mp.2008.119 · Cited by 598 · see citing works
The Effects of Psychological Stress on Depression
Yang, L., Zhao, Y., Wang, Y., Liu, L., Zhang, X., Li, B., & Cui, R. (2015) · Current Neuropharmacology · doi:10.2174/1570159x1304150831150507 · Cited by 589 · see citing works
Pathogenesis of depression: Insights from human and rodent studies
Ménard, C., Hodes, G. E., & Russo, S. J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.053 · Cited by 593 · see citing works
Antidepressant-Like Effects of the Histone Deacetylase Inhibitor, Sodium Butyrate, in the Mouse
Schroeder, F. A., Lin, C. L., Crusio, W. E., & Akbarian, S. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.06.036 · Cited by 541 · see citing works
Animal Models of Depression: Molecular Perspectives
Krishnan, V., & Nestler, E. J. (2011) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2010_108 · Cited by 528 · see citing works
Self-citationA Meta-analysis of oxidative stress markers in depression
Liu, T., Zhong, S., Liao, X., Chen, J., He, T., Lai, S., & Jia, Y. (2015) · PLOS ONE · doi:10.1371/journal.pone.0138904 · Cited by 485 · see citing works
MiR-16 Targets the Serotonin Transporter: A New Facet for Adaptive Responses to Antidepressants
Baudry, A., Mouillet-Richard, S., Schneider, B., Launay, J.-M., & Kellermann, O. (2010) · Science · doi:10.1126/science.1193692 · Cited by 480 · see citing works
Mapping anhedonia onto reinforcement learning: a behavioural meta-analysis
Huys, Q. J., Pizzagalli, D. A., Bogdan, R., & Dayan, P. (2013) · Biology of Mood & Anxiety Disorders · doi:10.1186/2045-5380-3-12 · Cited by 480 · see citing works
Molendijk, M. L., Bus, B. A. A., Spinhoven, P., Penninx, B. W. J. H., Kenis, G., Prickaerts, J., Voshaar, R. O., & Elzinga, B. M. (2011) · Molecular Psychiatry · doi:10.1038/mp.2010.98 · Cited by 437 · see citing works
Sharma, S., & Fulton, S. (2013) · International Journal of Obesity · doi:10.1038/ijo.2012.48 · Cited by 424 · see citing works
Cao, J.-L., Covington, H. E., Friedman, A. K., Wilkinson, M. B., Walsh, J. J., Cooper, D. C., Nestler, E. J., & Han, M.-H. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3177-10.2010 · Cited by 402 · see citing works
Self-citationMicroRNAs in neuronal function and dysfunction
Im, H.-I., & Kenny, P. J. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.01.004 · Cited by 399 · see citing works
Role of GSK3β in behavioral abnormalities induced by serotonin deficiency
Beaulieu, J.-M., Zhang, X., Rodriguiz, R. M., Sotnikova, T. D., Cools, M. J., Wetsel, W. C., Gainetdinov, R. R., & Caron, M. G. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711496105 · Cited by 368 · see citing works
Chen, C.-H., Ridler, K., Suckling, J., Williams, S., Fu, C. H. Y., Merlo-Pich, E., & Bullmore, E. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.09.018 · Cited by 354 · see citing works
Wallace, D. L., Han, M.-H., Graham, D. L., Green, T. A., Vialou, V., Iñiguez, S. D., Cao, J.-L., Kirk, A., Chakravarty, S., Kumar, A., et al. (2009) · Nature Neuroscience · doi:10.1038/nn.2257 · Cited by 342 · see citing works
Self-citationThe Role of BDNF in Depression on the Basis of Its Location in the Neural Circuitry
Yu, H., & Chen, Z.-Y. (2011) · Acta Pharmacologica Sinica · doi:10.1038/aps.2010.184 · Cited by 343 · see citing works
The subjective effects of psychedelics may not be necessary for their enduring therapeutic effects
Olson, D. E. (2021) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.0c00192 · Cited by 329 · see citing works
Issler, O., Haramati, S., Paul, E. D., Maeno, H., Navon, I., Zwang, R., Gil, S., Mayberg, H. S., Dunlop, B. W., Menke, A., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.042 · Cited by 318 · see citing works
Serotonin receptors involved in antidepressant effects
Artigas, F. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.09.006 · Cited by 311 · see citing works
A Role for Repressive Histone Methylation in Cocaine-Induced Vulnerability to Stress
Covington, H. E., Maze, I., Sun, H., Bomze, H. M., DeMaio, K. D., Wu, E. Y., Dietz, D. M., Lobo, M. K., Ghose, S., Mouzon, E., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.007 · Cited by 289 · see citing works
Self-citationIκB Kinase Regulates Social Defeat Stress-Induced Synaptic and Behavioral Plasticity
Christoffel, D. J., Golden, S. A., Dumitriu, D., Robison, A. J., Janssen, W. G., Ahn, H. F., Krishnan, V., Reyes, C. M., Han, M.-H., Ables, J. L., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4763-10.2011 · Cited by 267 · see citing works
Neuropsychological mechanism underlying antidepressant effect: a systematic meta-analysis
Ma, Y. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.24 · Cited by 270 · see citing works
Liu, R.-J., Fuchikami, M., Dwyer, J. M., Lepack, A. E., Duman, R. S., & Aghajanian, G. K. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.128 · Cited by 256 · see citing works
Gut microbiota–brain axis in depression: the role of neuroinflammation
Carlessi, A. S., Borba, L. A., Zugno, A. I., Quevedo, J., & Réus, G. Z. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14631 · Cited by 243 · see citing works
How can drug discovery for psychiatric disorders be improved?
Agid, Y., Buzsáki, G., Diamond, D. M., Frackowiak, R., Giedd, J., Girault, J.-A., Grace, A., Lambert, J. J., Manji, H., Mayberg, H., et al. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2217 · Cited by 240 · see citing works
An astroglial basis of major depressive disorder? An overview
Wang, Q., Jie, W., Liu, J., Yang, J., & Gao, T. (2017) · Glia · doi:10.1002/glia.23143 · Cited by 222 · see citing works
Reinforcement learning in depression: a review of computational research
Chen, C., Takahashi, T., Nakagawa, S., Inoue, T., & Kusumi, I. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.005 · Cited by 233 · see citing works
Mozhui, K., Karlsson, R.-M., Kash, T. L., Ihne, J., Norcross, M., Patel, S., Farrell, M. R., Hill, E. E., Graybeal, C., Martin, K. P., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5017-09.2010 · Cited by 226 · see citing works
Ruhé, H. G., Huyser, J., Swinkels, J. A., & Schene, A. H. (2006) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v67n1203 · Cited by 230 · see citing works
Raineki, C., Cortés, M. R., Belnoue, L., & Sullivan, R. M. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5843-11.2012 · Cited by 217 · see citing works
Réus, G. Z., Jansen, K., Titus, S., Carvalho, A. F., Gabbay, V., & Quevedo, J. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.05.007 · Cited by 221 · see citing works
Cerniauskas, I., Winterer, J., de Jong, J. W., Lukacsovich, D., Yang, H., Khan, F., Peck, J. R., Obayashi, S. K., Lilascharoen, V., Lim, B. K., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.09.005 · Cited by 187 · see citing works
Role of microglial m1/m2 polarization in relapse and remission of psychiatric disorders and diseases
Nakagawa, Y., & Chiba, K. (2014) · Pharmaceuticals · doi:10.3390/ph7121028 · Cited by 215 · see citing works
Yamawaki, Y., Yoshioka, N., Nozaki, K., Ito, H., Oda, K., Harada, K., Shirawachi, S., Asano, S., Aizawa, H., Yamawaki, S., et al. (2018) · Brain Research · doi:10.1016/j.brainres.2017.12.004 · Cited by 204 · see citing works
Lopez, J. P., Fiori, L. M., Cruceanu, C., Lin, R., Labonte, B., Cates, H. M., Heller, E. A., Vialou, V., Ku, S. M., Gerald, C., et al. (2017) · Nature Communications · doi:10.1038/ncomms15497 · Cited by 201 · see citing works
Self-citationDescalzi, G., Mitsi, V., Purushothaman, I., Gaspari, S., Avrampou, K., Loh, Y.-H. E., Shen, L., & Zachariou, V. (2017) · Science Signaling · doi:10.1126/scisignal.aaj1549 · Cited by 188 · see citing works
Neuronal network plasticity and recovery from depression
Castrén, E. (2013) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2013.1 · Cited by 190 · see citing works
The role of serotonin in adult hippocampal neurogenesis
Alenina, N., & Klempin, F. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.07.038 · Cited by 195 · see citing works
Cellular and molecular mechanisms in the long-term action of antidepressants.
Racagni, G., & Popoli, M. (2008) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2008.10.4/gracagni · Cited by 192 · see citing works
A BDNF infusion into the medial prefrontal cortex suppresses cocaine seeking in rats
Berglind, W. J., See, R. E., Fuchs, R. A., Ghee, S. M., Whitfield, T. W., Miller, S. W., & McGinty, J. F. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05692.x · Cited by 187 · see citing works
Altered gene expression of histone deacetylases in mood disorder patients
Hobara, T., Uchida, S., Otsuki, K., Matsubara, T., Funato, H., Matsuo, K., Suetsugi, M., & Watanabe, Y. (2010) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2009.08.015 · Cited by 185 · see citing works
Epigenetic mechanisms of major depression: Targeting neuronal plasticity
Uchida, S., Yamagata, H., Seki, T., & Watanabe, Y. (2018) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12621 · Cited by 181 · see citing works
Brain-derived neurotrophic factor and neuroplasticity in bipolar disorder
Kapczinski, F., Frey, B. N., Kauer-Sant’Anna, M., & Grassi-Oliveira, R. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.8.7.1101 · Cited by 181 · see citing works
How can we realize the promise of personalized antidepressant medicines?
Holsboer, F. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2453 · Cited by 177 · see citing works
The serotonin-BDNF duo: developmental implications for the vulnerability to psychopathology
Homberg, J. R., Molteni, R., Calabrese, F., & Riva, M. A. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.03.012 · Cited by 177 · see citing works
Krishnan, V., Han, M.-H., Mazei-Robison, M., Iñiguez, S. D., Ables, J. L., Vialou, V., Berton, O., Ghose, S., Covington, H. E., Wiley, M. D., et al. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.06.003 · Cited by 176 · see citing works
Self-citationLaske, C., Banschbach, S., Stransky, E., Bosch, S., Straten, G., Machann, J., Fritsche, A., Hipp, A., Niess, A., & Eschweiler, G. W. (2010) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145709991234 · Cited by 171 · see citing works
Antidepressant treatment for postnatal depression
Molyneaux, E., Howard, L. M., McGeown, H. R., Karia, A. M., & Trevillion, K. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002018.pub2 · Cited by 171 · see citing works
Goeldner, C., Lutz, P.-E., Darcq, E., Halter, T., Clesse, D., Ouagazzal, A.-M., & Kieffer, B. L. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.08.021 · Cited by 163 · see citing works
Schlaepfer, T. E., Bewernick, B. H., Kayser, S., Hurlemann, R., & Coenen, V. A. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.28 · Cited by 160 · see citing works
Minocycline alters behavior, microglia and the gut microbiome in a trait-anxiety-dependent manner
Schmidtner, A. K., Slattery, D. A., Gläsner, J., Hiergeist, A., Gryksa, K., Malik, V. A., Hellmann-Regen, J., Heuser, I., Baghai, T. C., Gessner, A., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0556-9 · Cited by 153 · see citing works
Trainor, B. C., Pride, M. C., Villalon Landeros, R., Knoblauch, N. W., Takahashi, E. Y., Silva, A. L., & Crean, K. K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017405 · Cited by 157 · see citing works
Inflammation and neuronal plasticity: a link between childhood trauma and depression pathogenesis
Cattaneo, A., Macchi, F., Plazzotta, G., Veronica, B., Bocchio-Chiavetto, L., Riva, M. A., & Pariante, C. M. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00040 · Cited by 152 · see citing works
Wei, C.-L., Wang, S., Yen, J.-T., Cheng, Y.-F., Liao, C.-L., Hsu, C.-C., Wu, C.-C., & Tsai, Y.-C. (2019) · Brain Research · doi:10.1016/j.brainres.2019.01.025 · Cited by 150 · see citing works
The importance of n-6/n-3 fatty acids ratio in the major depressive disorder
Husted, K. S., & Bouzinova, E. V. (2016) · Medicina · doi:10.1016/j.medici.2016.05.003 · Cited by 142 · see citing works
Dysfunctional hippocampal activity affects emotion and cognition in mood disorders
Femenía, T., Gómez-Galán, M., Lindskog, M., & Magara, S. (2012) · Brain Research · doi:10.1016/j.brainres.2012.03.053 · Cited by 143 · see citing works
Hammack, S. E., Cooper, M. A., & Lezak, K. R. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.02.024 · Cited by 142 · see citing works
Glial Dysfunction in the Mouse Habenula Causes Depressive-Like Behaviors and Sleep Disturbance
Cui, W., Mizukami, H., Yanagisawa, M., Aida, T., Nomura, M., Isomura, Y., Takayanagi, R., Ozawa, K., Tanaka, K., & Aizawa, H. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1465-14.2014 · Cited by 139 · see citing works
Neuropeptide and small transmitter coexistence: Fundamental studies and relevance to mental illness
Hökfelt, T., Barde, S., Xu, Z.-Q. D., Kuteeva, E., Rüegg, J., Le Maitre, E., Risling, M., Kehr, J., Ihnatko, R., Theodorsson, E., et al. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00106 · Cited by 139 · see citing works
Dhir, A., & Kulkarni, S. K. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.04.028 · Cited by 133 · see citing works
A neural pathway controlling motivation to exert effort
Proulx, C. D., Aronson, S., Milivojevic, D., Molina, C., Loi, A., Monk, B., Shabel, S. J., & Malinow, R. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1801837115 · Cited by 119 · see citing works
The molecular pathophysiology of depression and the new therapeutics
Tian, H., Hu, Z., Xu, J., & Wang, C. (2022) · MedComm · doi:10.1002/mco2.156 · Cited by 122 · see citing works
Jiang, Y., Jakovcevski, M., Bharadwaj, R., Connor, C., Schroeder, F. A., Lin, C. L., Straubhaar, J., Martin, G., & Akbarian, S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1314-10.2010 · Cited by 118 · see citing works
Passie, T., Emrich, H. M., Karst, M., Brandt, S. D., & Halpern, J. H. (2012) · Drug Testing and Analysis · doi:10.1002/dta.1377 · Cited by 117 · see citing works
Yamawaki, Y., Fuchikami, M., Morinobu, S., Segawa, M., Matsumoto, T., & Yamawaki, S. (2012) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2011.585663 · Cited by 117 · see citing works
Role of Mesolimbic Brain-Derived Neurotrophic Factor in Depression
Koo, J. W., Chaudhury, D., Han, M.-H., & Nestler, E. J. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.020 · Cited by 112 · see citing works
Self-citationRong, C., Park, C., Rosenblat, J. D., Subramaniapillai, M., Zuckerman, H., Fus, D., Lee, Y. L., Pan, Z., Brietzke, E., Mansur, R. B., et al. (2018) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph15040771 · Cited by 114 · see citing works
Zellner, M. R., Watt, D. F., Solms, M., & Panksepp, J. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.01.003 · Cited by 112 · see citing works
Cholinergic modulation of multivesicular release regulates striatal synaptic potency and integration
Higley, M. J., Soler-Llavina, G. J., & Sabatini, B. L. (2009) · Nature Neuroscience · doi:10.1038/nn.2368 · Cited by 110 · see citing works
Stress and Depression: Preclinical Research and Clinical Implications
Bartolomucci, A., & Leopardi, R. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004265 · Cited by 111 · see citing works
Harmine and Imipramine Promote Antioxidant Activities in Prefrontal Cortex and Hippocampus
Réus, G. Z., Stringari, R. B., de Souza, B., Petronilho, F., Dal-Pizzol, F., Hallak, J. E., Zuardi, A. W., Crippa, J. A., & Quevedo, J. (2010) · Oxidative Medicine and Cellular Longevity · doi:10.4161/oxim.3.5.13109 · Cited by 110 · see citing works
Andrews, P. W., Kornstein, S. G., Halberstadt, L. J., Gardner, C. O., & Neale, M. C. (2011) · Frontiers in Psychology · doi:10.3389/fpsyg.2011.00159 · Cited by 107 · see citing works
Role of the Brain's Reward Circuitry in Depression
Nestler, E. J. (2015) · International review of neurobiology · doi:10.1016/bs.irn.2015.07.003 · Cited by 108 · see citing works
Self-citationIñiguez, S. D., Aubry, A., Riggs, L. M., Alipio, J. B., Zanca, R. M., Flores-Ramirez, F. J., Hernandez, M. A., Nieto, S. J., Musheyev, D., & Serrano, P. A. (2016) · Neurobiology of Stress · doi:10.1016/j.ynstr.2016.07.001 · Cited by 105 · see citing works
Altered HDAC5 and CREB mRNA expressions in the peripheral leukocytes of major depression
Iga, J.-I., Ueno, S.-I., Yamauchi, K., Numata, S., Kinouchi, S., Tayoshi-Shibuya, S., Song, H., & Ohmori, T. (2007) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2006.12.014 · Cited by 105 · see citing works
Duclot, F., & Kabbaj, M. (2015) · Journal of Experimental Biology · doi:10.1242/jeb.107086 · Cited by 103 · see citing works
Son, H., Banasr, M., Choi, M., Chae, S. Y., Licznerski, P., Lee, B., Voleti, B., Li, N., Lepack, A., Fournier, N. M., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1201191109 · Cited by 103 · see citing works
Alme, M. N., Wibrand, K., Dagestad, G., & Bramham, C. R. (2007) · Neural Plasticity · doi:10.1155/2007/26496 · Cited by 103 · see citing works
Malberg, J. E., Platt, B., Rizzo, S. J. S., Ring, R. H., Lucki, I., Schechter, L. E., & Rosenzweig-Lipson, S. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301358 · Cited by 101 · see citing works
Sarter, M., Bruno, J. P., & Parikh, V. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301285 · Cited by 100 · see citing works
Lin, Y., Ter Horst, G. J., Wichmann, R., Bakker, P., Liu, A., Li, X., & Westenbroek, C. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhn225 · Cited by 100 · see citing works
Ketamine and other glutamate receptor modulators for depression in bipolar disorder in adults
McCloud, T. L., Caddy, C., Jochim, J., Rendell, J. M., Diamond, P. R., Shuttleworth, C., Brett, D., Amit, B. H., McShane, R., Hamadi, L., et al. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011611.pub2 · Cited by 102 · see citing works
Involvement of Sigma-1 Receptors in the Antidepressant-like Effects of Dextromethorphan
Nguyen, L., Robson, M. J., Healy, J. R., Scandinaro, A. L., & Matsumoto, R. R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089985 · Cited by 99 · see citing works
From synapse to nucleus: Novel targets for treating depression
Covington, H. E., Vialou, V., & Nestler, E. J. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2009.12.004 · Cited by 98 · see citing works
Self-citation
- Authors
- Berton, O., & Nestler, E. J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Nestler, Eric J.
- ORCID
- Nestler, Eric J.
- Venue
- Nature Reviews Neuroscience
- Published
- 2006-02
- Volume
- 7
- Issue
- 2
- Pages
- 137-151
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2035421865
- Cited by
- 1,589
- References
- 13
- Citations by year
- 2026: 23 · 2025: 45 · 2024: 50 · 2023: 44 · 2022: 61 · 2021: 78 · 2020: 70 · 2019: 79 · 2018: 76 · 2017: 103 · 2016: 92 · 2015: 88 · 2014: 107 · 2013: 90 · 2012: 115
- FWCI
- 9.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- antidepressant drug discovery, depression, monoamines, serotonin, norepinephrine, tricyclic antidepressants, monoamine oxidase inhibitors, antidepressant resistance
- MeSH terms
- Animals, Antidepressive Agents, Brain Chemistry, Depressive Disorder, Disease Models, Animal, Humans, Hypothalamo-Hypophyseal System, Models, Neurological, Biogenic Monoamines
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
