HDAC inhibitors as cognitive enhancers in fear, anxiety and trauma therapy: Where do we stand?
Open accessAbstract
A novel strategy to treat anxiety and fear-related disorders such as phobias, panic and PTSD (post-traumatic stress disorder) is combining CBT (cognitive behavioural therapy), including extinction-based exposure therapy, with cognitive enhancers. By targeting and boosting mechanisms underlying learning, drug development in this field aims at designing CBT-augmenting compounds that help to overcome extinction learning deficits, promote long-term fear inhibition and thus support relapse prevention. Progress in revealing the role of epigenetic regulation of specific genes associated with extinction memory generation has opened new avenues in this direction. The present review examines recent evidence from pre-clinical studies showing that increasing histone acetylation, either via genetic or pharmacological inhibition of HDACs (histone deacetylases) by e.g. vorinostat/SAHA (suberoylanilide hydroxamic acid), entinostat/MS-275, sodium butyrate, TSA (trichostatin A) or VPA (valproic acid), or by targeting HATs (histone acetyltransferases), augments fear extinction and, importantly, generates a long-term extinction memory that can protect from return of fear phenomena. The molecular mechanisms and pathways involved including BDNF (brain-derived neurotrophic factor) and NMDA (N-methyl-D-aspartate) receptor signalling are just beginning to be revealed. First studies in healthy humans are in support of extinction-facilitating effects of HDAC inhibitors. Very recent evidence that HDAC inhibitors can rescue deficits in extinction-memory-impaired rodents indicates a potential clinical utility of this approach also for exposure therapy-resistant patients. Important future work includes investigation of the long-term safety aspects of HDAC inhibitor treatment, as well as design of isotype(s)-specific inhibitors. Taken together, HDAC inhibitors display promising potential as pharmacological adjuncts to augment the efficacy of exposure-based approaches in anxiety and trauma therapy.
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Drugs modulating epigenetic mechanisms may lead to the development of novel treatment options such as HDAC or DNMT inhibitors, based mostly on preclinical models.
“Studies mostly in preclinical models suggest drugs modulating epigenetic mechanisms that may lead to the development of novel, innovative treatment options such as HDAC or DNMT inhibitors (cf.Whittle & Singewald, 2014).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Whittle & Singewald, 2014
The Introduction (page unavailable) says the review examines mainly preclinical rodent studies and small clinical studies of drugs that increase histone acetylation as potential aids to anxiety treatment. The Future development section discusses developing targeted HDAC inhibitors. The cited paper does not support the DNMT-inhibitor example (searched: DNMT and DNA methyltransferase inhibitors). (LLM, conf=0.86)
Experimental — accuracy not yet measuredHistone-deacetylase inhibitors may be useful in anxiety disorders by promoting relevant gene expression and targeting some common comorbidities of anxiety disorders.
“histone-deacetylase inhibitors may be useful in anxiety disorders, by promoting relevant gene expression (Sah et al., 2019;Tran, Schulkin, Ligon, & Greenwood-Van Meerveld, 2015;Whittle & Singewald, 2014) and targeting also some common comorbidities of anxiety disorders (Moloney, Stilling, Dinan, & Cryan, 2015).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Whittle & Singewald, 2014
HDACs have been implicated in a range of neuropsychiatric disorders, including depression and schizophrenia, and HDAC inhibitors could be potential cognitive enhancers in anxiety- and fear-related disorders.
“HDACs have been implicated in a range of neuropsychiatric disorders [e.g., depression and schizophrenia (358)] and HDAC inhibitors could be potential cognitive enhancers in anxiety-and fear-related disorders (359).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [359]
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1 retracted
Bousiges, O., Neidl, R., Majchrzak, M. J., Muller, M., Barbelivien, A., de Vasconcelos, A. P., Schneider‐Anthony, A., Loeffler, J., Cassel, J., & Boutillier, A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057816 · Cited by 70 · see citing works
RetractedKessler, R. C., Chiu, W. T., Demler, O., & Walters, E. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.6.617 · Cited by 12,052 · see citing works
Jenuwein, T., & Allis, C. D. (2001) · Science · doi:10.1126/science.1063127 · Cited by 9,756 · see citing works
Crystal structure of the nucleosome core particle at 2.8 Å resolution
Luger, K., Mäder, A. W., Richmond, R. K., Sargent, D. F., & Richmond, T. J. (1997) · Nature · doi:10.1038/38444 · Cited by 9,466 · see citing works
Chen, X., Xiu, M., Xing, J., Yu, S., Min, D., & Guo, F. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479439 · Cited by 5,759 · see citing works
Memory - A century of consolidation
McGaugh, J. L. (2000) · Science · doi:10.1126/science.287.5451.248 · Cited by 4,250 · see citing works
Lysine acetylation targets protein complexes and co-regulates major cellular functions
Choudhary, C., Kumar, C., Gnad, F., Nielsen, M. L., Rehman, M., Walther, T. C., Olsen, J. V., & Mann, M. (2009) · Science · doi:10.1126/science.1175371 · Cited by 4,040 · see citing works
Histone deacetylases (HDACs): characterization of the classical HDAC family
RUIJTER, A. J. M. D., GENNIP, A. H. V., CARON, H. N., KEMP, S., & KUILENBURG, A. B. P. V. (2003) · Biochemical Journal · doi:10.1042/bj20021321 · Cited by 3,114 · see citing works
Effects of an expanding-spaced vs massed exposure schedule on fear reduction and return of fear
Rowe, M. K., & Craske, M. G. (1998) · Behaviour Research and Therapy · doi:10.1016/s0005-7967(97)10016-x · Cited by 1,778 · see citing works
HDAC2 negatively regulates memory formation and synaptic plasticity
Guan, J.-S., Haggarty, S. J., Giacometti, E., Dannenberg, J.-H., Joseph, N., Gao, J., Nieland, T. J. F., Zhou, Y., Wang, X., Mazitschek, R., et al. (2009) · Nature · doi:10.1038/nature07925 · Cited by 1,644 · see citing works
The economic cost of brain disorders in Europe
Olesen, J., Gustavsson, A., Svensson, M., Wittchen, H., & Jönsson, B. (2012) · European Journal of Neurology · doi:10.1111/j.1468-1331.2011.03590.x · Cited by 1,560 · see citing works
Fear Extinction as a Model for Translational Neuroscience: Ten Years of Progress
Milad, M. R., & Quirk, G. J. (2012) · Annual Review of Psychology · doi:10.1146/annurev.psych.121208.131631 · Cited by 1,466 · see citing works
Neurobiological Basis of Failure to Recall Extinction Memory in Posttraumatic Stress Disorder
Milad, M. R., Pitman, R. K., Ellis, C. B., Gold, A. L., Shin, L. M., Lasko, N. B., Zeidan, M. A., Handwerger, K., Orr, S. P., & Rauch, S. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.06.026 · Cited by 1,339 · see citing works
BDNF function in adult synaptic plasticity: The synaptic consolidation hypothesis
Bramham, C. R., & Messaoudi, E. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.06.003 · Cited by 1,193 · see citing works
Pape, H.-C., & Pare, D. (2010) · Physiological Reviews · doi:10.1152/physrev.00037.2009 · Cited by 994 · see citing works
Transcription Factors in Long-Term Memory and Synaptic Plasticity
Alberini, C. M. (2009) · Physiological Reviews · doi:10.1152/physrev.00017.2008 · Cited by 991 · see citing works
Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice
Peleg, S., Sananbenesi, F., Zovoilis, A., Burkhardt, S., Bahari-Javan, S., Agis-Balboa, R. C., Cota, P., Wittnam, J. L., Gogol-Doering, A., Opitz, L., et al. (2010) · Science · doi:10.1126/science.1186088 · Cited by 951 · see citing works
Behavioral and Neural Analysis of Extinction
Myers, K. M., & Davis, M. (2002) · Neuron · doi:10.1016/s0896-6273(02)01064-4 · Cited by 918 · see citing works
Castrén, E., & Rantamäki, T. (2010) · Developmental Neurobiology · doi:10.1002/dneu.20758 · Cited by 864 · see citing works
2007 National Survey of Mental Health and Wellbeing: Methods and Key Findings
Slade, T., Johnston, A., Oakley Browne, M. A., Andrews, G., & Whiteford, H. (2009) · Australian & New Zealand Journal of Psychiatry · doi:10.1080/00048670902970882 · Cited by 832 · see citing works
Therapeutic application of histone deacetylase inhibitors for central nervous system disorders
Kazantsev, A. G., & Thompson, L. M. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2681 · Cited by 715 · see citing works
Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors
Khan, N., Jeffers, M., Kumar, S., Hackett, C., Boldog, F., Khramtsov, N., Qian, X., Mills, E., Berghs, S. C., Carey, N., et al. (2008) · Biochemical Journal · doi:10.1042/bj20070779 · Cited by 713 · see citing works
Prefrontal mechanisms in extinction of conditioned fear
Quirk, G. J., Garcia, R., & González-Lima, F. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.010 · Cited by 682 · see citing works
Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes
Bantscheff, M., Hopf, C., Savitski, M. M., Dittmann, A., Grandi, P., Michon, A.-M., Schlegl, J., Abraham, Y., Becher, I., Bergamini, G., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1759 · Cited by 659 · see citing works
CREB required for the stability of new and reactivated fear memories
Kida, S., Josselyn, S. A., de Ortı́z, S. P., Kogan, J. H., Chévere-Torres, I., Masushige, S., & Silva, A. J. (2002) · Nature Neuroscience · doi:10.1038/nn819 · Cited by 624 · see citing works
Fear extinction in rats: Implications for human brain imaging and anxiety disorders
Milad, M. R., Rauch, S. L., Pitman, R. K., & Quirk, G. J. (2006) · Biological Psychology · doi:10.1016/j.biopsycho.2006.01.008 · Cited by 597 · see citing works
A Genetic Variant BDNF Polymorphism Alters Extinction Learning in Both Mouse and Human
Soliman, F., Glatt, C. E., Bath, K. G., Levita, L., Jones, R. M., Pattwell, S. S., Jing, D., Tottenham, N., Amso, D., Somerville, L. H., et al. (2010) · Science · doi:10.1126/science.1181886 · Cited by 585 · see citing works
New insights into brain BDNF function in normal aging and Alzheimer disease
Tapia‐Arancibia, L., Aliaga, E., Silhol, M., & Arancibia, S. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.07.007 · Cited by 571 · see citing works
Bredy, T. W., Wu, H., Crego, C., Zellhoefer, J., Sun, Y. E., & Barad, M. (2007) · Learning & Memory · doi:10.1101/lm.500907 · Cited by 548 · see citing works
The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2
Krämer, O. H., Zhu, P., Ostendorff, H. P., Golebiewski, M., Tiefenbach, J., Peters, M. A., Brill, B., Groner, B., Bach, I., Heinzel, T., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg315 · Cited by 523 · see citing works
HDAC3 Is a Critical Negative Regulator of Long-Term Memory Formation
McQuown, S. C., Barrett, R. M., Matheos, D. P., Post, R. J., Rogge, G. A., Alenghat, T., Mullican, S. E., Jones, S., Rusche, J. R., Lazar, M. A., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5052-10.2011 · Cited by 507 · see citing works
Delcuve, G. P., Khan, D. H., & Davie, J. R. (2012) · Clinical Epigenetics · doi:10.1186/1868-7083-4-5 · Cited by 505 · see citing works
Neuronal circuits of fear extinction
Herry, C., Ferraguti, F., Singewald, N., Letzkus, J. J., Ehrlich, I., & Lüthi, A. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07101.x · Cited by 484 · see citing works
Self-citationInduction of Fear Extinction with Hippocampal-Infralimbic BDNF
Peters, J., Dieppa-Perea, L. M., Melendez, L. M., & Quirk, G. J. (2010) · Science · doi:10.1126/science.1186909 · Cited by 462 · see citing works
Histone Deacetylase Is a Target of Valproic Acid-Mediated Cellular Differentiation
Gurvich, N., Tsygankova, O. M., Meinkoth, J. L., & Klein, P. S. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-0799 · Cited by 460 · see citing works
Neural and cellular mechanisms of fear and extinction memory formation
Orsini, C. A., & Maren, S. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.12.014 · Cited by 429 · see citing works
Modulation of long-term memory for object recognition via HDAC inhibition
Stefanko, D. P., Barrett, R. M., Ly, A. R., Reolon, G. K., & Wood, M. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903964106 · Cited by 402 · see citing works
Fear erasure in mice requires synergy between antidepressant drugs and extinction training
Karpova, N. N., Pickenhagen, A., Lindholm, J., Tiraboschi, E., Kulesskaya, N., Ágústsdóttir, A., Antila, H., Popova, D., Akamine, Y., Sullivan, R., et al. (2011) · Science · doi:10.1126/science.1214592 · Cited by 382 · see citing works
Yasuda, S., Liang, M.-H., Marinova, Z., Yahyavi, A., & Chuang, D.-M. (2009) · Molecular Psychiatry · doi:10.1038/sj.mp.4002099 · Cited by 358 · see citing works
Epigenetic Priming of Memory Updating during Reconsolidation to Attenuate Remote Fear Memories
Gräff, J., Joseph, N. F., Horn, M. E., Samiei, A., Meng, J., Seo, J., Rei, D., Bero, A. W., Phan, T. X., Wagner, F., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.020 · Cited by 357 · see citing works
Targeting the correct HDAC(s) to treat cognitive disorders
Fischer, A., Sananbenesi, F., Mungenast, A. E., & Tsai, L. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.09.003 · Cited by 355 · see citing works
Gunduz-Cinar, O., MacPherson, K. P., Cinar, R., Gamble-George, J., Sugden, K., Williams, B., Godlewski, G., Ramikie, T. S., Gorka, A. X., Alapafuja, S. O., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.72 · Cited by 307 · see citing works
The Potential of HDAC Inhibitors as Cognitive Enhancers
Gräff, J., & Tsai, L. (2013) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140216 · Cited by 297 · see citing works
Histone deacetylase inhibitors (HDACIs): multitargeted anticancer agents
Licciardi, P. V., Ververis, Hiong, & Karagiannis, T. C. (2013) · Biologics · doi:10.2147/btt.s29965 · Cited by 278 · see citing works
Predicting treatment response in social anxiety disorder from functional magnetic resonance imaging.
Doehrmann, O., Ghosh, S. S., Polli, F. E., Reynolds, G. O., Horn, F., Keshavan, A., Triantafyllou, C., Saygin, Z. M., Whitfield-Gabrieli, S., Hofmann, S. G., et al. (2013) · JAMA Psychiatry · doi:10.1001/2013.jamapsychiatry.5 · Cited by 262 · see citing works
Bredy, T. W., & Barad, M. (2008) · Learning & Memory · doi:10.1101/lm.801108 · Cited by 248 · see citing works
Hefner, K. R., Whittle, N., Juhasz, J., Norcross, M. A., Karlsson, R., Saksida, L. M., Bussey, T. J., Singewald, N., & Holmes, A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4904-07.2008 · Cited by 248 · see citing works
Self-citationSystemic or intrahippocampal delivery of histone deacetylase inhibitors facilitates fear extinction.
Lattal, K. M., Barrett, R. M., & Wood, M. A. (2007) · Behavioral Neuroscience · doi:10.1037/0735-7044.121.5.1125 · Cited by 236 · see citing works
An Essential Role for Histone Deacetylase 4 in Synaptic Plasticity and Memory Formation
Kim, M.-S., Akhtar, M. W., Adachi, M., Mahgoub, M., Bassel-Duby, R., Kavalali, E. T., Olson, E. N., & Monteggia, L. M. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.2089-12.2012 · Cited by 235 · see citing works
Yamamoto, S., Morinobu, S., Fuchikami, M., Kurata, A., Kozuru, T., & Yamawaki, S. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301605 · Cited by 224 · see citing works
Chhatwal, J. P., Myers, K. M., Ressler, K. J., & Davis, M. E. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3301-04.2005 · Cited by 214 · see citing works
Otto, M. W., Smits, J. A. J., & Reese, H. E. (2005) · Clinical Psychology Science and Practice · doi:10.1093/clipsy.bpi009 · Cited by 204 · see citing works
Effects of varied-stimulus exposure training on fear reduction and return of fear
Rowe, M. K., & Craske, M. G. (1998) · Behaviour Research and Therapy · doi:10.1016/s0005-7967(97)10017-1 · Cited by 202 · see citing works
Litz, B. T., Salters-Pedneault, K., Steenkamp, M. M., Hermos, J. A., Bryant, R. A., Otto, M. W., & Hofmann, S. G. (2012) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.05.006 · Cited by 196 · see citing works
HDAC1 Regulates Fear Extinction in Mice
Bahari‐Javan, S., Maddalena, A., Kerimoglu, C., Wittnam, J. L., Held, T., Bähr, M., Burkhardt, S., Delalle, I., Kügler, S., Fischer, A., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0079-12.2012 · Cited by 186 · see citing works
Epigenetic Mechanisms in Learned Fear: Implications for PTSD
Zovkic, I. B., & Sweatt, J. D. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.79 · Cited by 186 · see citing works
Glutamate receptors in extinction and extinction-based therapies for psychiatric illness
Myers, K. M., Carlezon, W., & Davis, M. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.88 · Cited by 175 · see citing works
Malvaez, M., Sanchis‐Segura, C., Vo, D., Lattal, K. M., & Wood, M. A. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.07.032 · Cited by 172 · see citing works
Chatterjee, S., Mizar, P., Cassel, R., Neidl, R., Selvi, B. R., Mohankrishna, D. V., Vedamurthy, B. M., Schneider‐Anthony, A., Bousiges, O., Mathis, C., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.5772-12.2013 · Cited by 170 · see citing works
Haaker, J., Gaburro, S., Sah, A., Gartmann, N., Lonsdorf, T. B., Meier, K., Singewald, N., Pape, H.-C., Morellini, F., & Kalisch, R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303061110 · Cited by 166 · see citing works
Self-citationPhysiological Roles of Class I HDAC Complex and Histone Demethylase
Hayakawa, T., & Nakayama, J. (2010) · BioMed Research International · doi:10.1155/2011/129383 · Cited by 165 · see citing works
Evidence that GABA transmission mediates context-specific extinction of learned fear
Harris, J. A., & Westbrook, R. F. (1998) · Psychopharmacology · doi:10.1007/s002130050745 · Cited by 164 · see citing works
Loss of Histone Deacetylase 2 Improves Working Memory and Accelerates Extinction Learning
Morris, M. J., Mahgoub, M., Na, E. S., Pranav, H., & Monteggia, L. M. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.1001-12.2013 · Cited by 162 · see citing works
Increasing Histone Acetylation in the Hippocampus-Infralimbic Network Enhances Fear Extinction
Stafford, J. M., Raybuck, J. D., Ryabinin, A. E., & Lattal, K. M. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.12.012 · Cited by 157 · see citing works
Remission from post-traumatic stress disorder in the general population
Chapman, C., Mills, K. L., Slade, T. N., McFARLANE, A. C., Bryant, R. A., Creamer, M., Silove, D. M., & Teesson, M. (2011) · Psychological Medicine · doi:10.1017/s0033291711002856 · Cited by 157 · see citing works
Evidence for recovery of fear following immediate extinction in rats and humansPreprint
Schiller, D., Cain, C. K., Curley, N. G., Schwartz, J. S., Stern, S. A., LeDoux, J. E., & Phelps, E. A. (2008) · Learning & Memory · doi:10.1101/lm.909208 · Cited by 150 · see citing works
Dalton, G. L., Wu, D. C., Wang, Y. T., Floresco, S. B., & Phillips, A. G. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.09.001 · Cited by 144 · see citing works
Smits, J. A. J., Rosenfield, D., Otto, M. W., Powers, M. B., Hofmann, S. G., Telch, M. J., Pollack, M. H., & Tart, C. D. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.12.009 · Cited by 142 · see citing works
Individual differences in recovery from traumatic fear
Holmes, A., & Singewald, N. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2012.11.003 · Cited by 141 · see citing works
Self-citationTabuchi, A., Nakaoka, R., Amano, K., Yukimine, M., Andoh, T., Kuraishi, Y., & Tsuda, M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m909538199 · Cited by 138 · see citing works
mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity
Fendt, M., Schmid, S., Thakker, D. R., Jacobson, L. H., Yamamoto, R., Mitsukawa, K., Maier, R., Natt, F., Hüsken, D., Kelly, P. H., et al. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002073 · Cited by 135 · see citing works
Enhancing exposure-based therapy from a translational research perspective
Hofmann, S. G. (2007) · Behaviour Research and Therapy · doi:10.1016/j.brat.2007.06.006 · Cited by 133 · see citing works
Contextual control of human fear associations in a renewal paradigm
Effting, M., & Kindt, M. (2007) · Behaviour Research and Therapy · doi:10.1016/j.brat.2007.02.011 · Cited by 128 · see citing works
Loss of HDAC5 Impairs Memory Function: Implications for Alzheimer's Disease
Agís‐Balboa, R. C., Pavelka, Z., Kerimoglu, C., & Fischer, A. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-121009 · Cited by 123 · see citing works
HDAC3 and the molecular brake pad hypothesis
McQuown, S. C., & Wood, M. A. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.04.005 · Cited by 122 · see citing works
Hofmann, S. G., Smits, J. A. J., Rosenfield, D., Simon, N., Otto, M. W., Meuret, A. E., Marques, L., Fang, A., Tart, C., & Pollack, M. H. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.12070974 · Cited by 121 · see citing works
Valproate: a simple chemical with so much to offer
Peterson, G. M., & Naunton, M. (2005) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1111/j.1365-2710.2005.00671.x · Cited by 117 · see citing works
Neuronal apoptosis induced by histone deacetylase inhibitors
Salminen, A., Tapiola, T., Korhonen, P., & Suuronen, T. (1998) · Molecular Brain Research · doi:10.1016/s0169-328x(98)00210-1 · Cited by 109 · see citing works
Activation of BDNF signaling prevents the return of fear in female micePreprint
Baker‐Andresen, D., Flavell, C. R., Li, X., & Bredy, T. W. (2013) · Learning & Memory · doi:10.1101/lm.029520.112 · Cited by 106 · see citing works
Camp, M., MacPherson, K. P., Lederle, L. I., Graybeal, C., Gaburro, S., DeBrouse, L., Ihne, J. L., Bravo, J. A., O’Connor, R. M., Ciocchi, S., et al. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.340 · Cited by 101 · see citing works
Self-citationProbing the role of HDACs and mechanisms of chromatin-mediated neuroplasticity
Haggarty, S. J., & Tsai, L. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.04.009 · Cited by 99 · see citing works
p300/CBP-Associated Factor Selectively Regulates the Extinction of Conditioned Fear
Wei, W., Coelho, C. M., Li, X., Marek, R., Yan, S., Anderson, S., Meyers, D., Mukherjee, C., Sbardella, G., Castellano, S., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0178-12.2012 · Cited by 93 · see citing works
Morris, M. J., Karra, A. S., & Monteggia, L. M. (2010) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e32833c20c0 · Cited by 82 · see citing works
Whittle, N., Hauschild, M., Lübec, G., Holmes, A., & Singewald, N. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0849-10.2010 · Cited by 81 · see citing works
Self-citationWang, W., Kang, S., Liu, W., Li, M., Liu, Y., Yu, C. F., Chen, J., Chi, Z., He, L., & Liu, J. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1991-12.2012 · Cited by 80 · see citing works
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Self-citation
- Authors
- Whittle, N., & Singewald, N.
- Affiliations
- Universität Innsbruck (AT)
- Corresponding author
- Whittle, Nigel
- Singewald, Nicolas
- Venue
- Biochemical Society Transactions
- Publisher
- Portland Press Ltd.
- Published
- 2014-03-20
- Volume
- 42
- Issue
- 2
- Pages
- 569-581
- ISSN
- 0300-5127 (ISSN-L)
- 1470-8752
- PMC
- PMC3961057
- OpenAlex
- W2046101640
- Cited by
- 117
- References
- 106
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 6 · 2023: 10 · 2022: 10 · 2021: 9 · 2020: 12 · 2019: 10 · 2018: 12 · 2017: 8 · 2016: 11 · 2015: 12 · 2014: 6
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Biochemical Society Transactions (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund (F4410, P 25375, SFB F4410)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- histone deacetylase inhibitors, nootropic drugs, fear extinction, post-traumatic stress disorder, anxiety disorders, phobia, panic disorder, exposure therapy, cognitive behavioral therapy, epigenetic regulation, histone acetylation, histone acetyltransferase, memory extinction, brain-derived neurotrophic factor, NMDA receptor signalling, vorinostat, entinostat, trichostatin A, valproic acid, sodium butyrate, relapse prevention, drug augmentation
- MeSH terms
- Anxiety, Fear, Humans, Wounds and Injuries, Nootropic Agents, Histone Deacetylase Inhibitors
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