lab member bolded, * shared authorship, # corresponding
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TWAS of PTSD
Huckins LM, Chatzinakos C, Breen MS, Hartmann J, โฆ, Sklar P, Ressler KJ, Stahl EA, Daskalakis NP# (2020). Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts. Cell Reports 31(9): 107716|10.1016/j.celrep.2020.107716
Findings from an Int’l PGC-๐ฃ๐ง๐ฆ๐ study led by our ๐ต๐ฎ.๐ป๐ฉ๐ณ lab investigating gene expression underpinnings of PTSD. Findings were validated (i.e., correlation btw predicted and observed) using blood collected before and after combat-related #trauma (๐ ๐ฎ๐ฟ๐ถ๐ป๐ฒ ๐ฅ๐ฒ๐๐ถ๐น๐ถ๐ฒ๐ป๐ฐ๐ ๐ฆ๐๐๐ฑ๐), where we additionally observed deployment stress effects on the identified genes. In cell culture, we validated the function of SNRNP35 on ๐จ๐ญ๐ฎ ๐๐ฝ๐น๐ถ๐ฐ๐ถ๐ป๐ด, and in mouse brains, we validated the effects of stress hormones (glucocorticoids) on this gene.
Selected
Systems Biology & Transcriptomics
Dalvie S, Chatzinakos C, Al Zoubi O, Georgiadis F; PGC-PTSD Systems Biology workgroup, Lancashire L, Daskalakis NP. From genetics to systems biology of stress-related mental disorders. Neurobiology of Stress. 2021 Sep 12;15:100393. doi: 10.1016/j.ynstr.2021.100393 [review]
Chatzinakos C, Georgiadis F, Daskalakis NP. GWAS meets transcriptomics: from genetic letters to transcriptomic words of neuropsychiatric risk. Neuropsychopharmacology. 2021 Jan;46(1):255-256. doi: 10.1038/s41386-020-00835-0
Chatzinakos C, Lee D, Cai N, Vladimirov VI, Docherty A, Webb BT, Riley BP, Flint J, Kendler KS, Daskalakis NP, Bacanu SA. TWAS pathway method greatly enhances the number of leads for uncovering the molecular underpinnings of psychiatric disorders. Am J Med Genet B Neuropsychiatr Genet. 2020 Dec;183(8):454-463. doi: 10.1002/ajmg.b.32823
Huckins LM, Chatzinakos C, Breen MS, Hartmann J, โฆ, Sklar P, Ressler KJ, Stahl EA, Daskalakis NP# (2020). Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts. Cell Reports 31(9). doi: 10.1016/j.celrep.2020.107716
Daskalakis NP#, Provost AC, Hunter RG, Guffanti G (2018). Noncoding RNAs: Stress, Glucocorticoids and PTSD. Biological Psychiatry. 15;83(10):849-865. PMID: 29559087| 10.1016/j.biopsych.2018.01.009 [review]
Genetic and epigenetic epidemiology: GWAS/EWAS
Chatzinakos C#, Lee D, Cai N, Vladimirov VI, Webb BT, Riley BP, Flint J, Kendler KS, Ressler KJ, Daskalakis NP, Bacanu SA. Increasing the resolution and precision of psychiatric GWAS by re-imputing summary statistics using a large, diverse reference panel. Am J Med Genet B Neuropsychiatr Genet. 2021 Jan;186(1):16-27. doi: 10.1002/ajmg.b.32834
Smith, AK, Ratanatharathorn, A, Maihofer AX, Naviaux RK,…Daskalakis NP… & Uddin M, Nievergelt CM (2020). Epigenome-wide meta-analysis of PTSD across 10 military and civilian cohorts identifies methylation changes in AHRR. Nature communications, 11(1), 1-9.
Logue MW, Miller MW, …Daskalakis NP…, McGlinchey RE, Milberg WP, Hayes JP, Verfaellie M. An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci. Clin Epigenetics. 2020 Mar 14;12(1):46. doi: 10.1186/s13148-020-0820-0
Nievergelt CM, Maihofer AX, โฆDaskalakis NPโฆ, Ressler KJ, Haas M, Koenen K. Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways. Nat Commun. 2019 Oct 8;10(1):4558. doi: 10.1038/s41467-019-12576-w. PMID: 31594949| 10.1038/s41467-019-12576-w
Daskalakis NP#, Rijal CM, King C, Huckins LM, Ressler KJ (2018). Recent Genetics and Epigenetics Approaches to PTSD. Current Psychiatry Reports, 20(5):30. PMID: 29623448| 10.1007/s11920-018-0898-7 [review]
Blood Endocrine and Molecular Biomarkers
Daskalakis NP#, Provost AC, Lori A, Schultebraucks K, Galatzer-Levy I, Daskalakis NP, Katrinli S, Smith AK, Myers AJ, Richholt R, Huentelman M, Guffanti G, Wuchty S, Gould F, Harvey PD, Nemeroff CB, Jovanovic T, Gerasimov ES, Maples-Keller JL, Stevens JS, Michopoulos V, Rothbaum BO, Wingo AP, Ressler KJ. Neuropsychopharmacology. 2021 Sep;46(10):1811-1820. doi: http://10.1038/s41386-021-01073-8
Daskalakis NP#, Cohen H, Nievergelt CM, Baker DG, Buxbaum JD, Russo SJ, Yehuda R (2016). New translational perspectives for blood-based biomarkers of PTSD: From glucocorticoid to immune mediators of stress susceptibility. Experimental Neurology, 284(Pt B),133-140. PMID: 27481726 | 10.1016/j.expneurol.2016.07.024 [perspective]
Yehuda R, Flory JD, Bierer LM, Henn-Haase C, Lehrner A, Desarnaud F, Makotkine I, Daskalakis NP, Marmar CR, Meaney MJ. Lower methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of veterans with posttraumatic stress disorder. Biol Psychiatry. 2015 Feb 15;77(4):356-64. PMID: 24661442| 10.1016/j.biopsych.2014.02.006
Yehuda R, Daskalakis NP, Desarnaud F, Makotkine I, โฆ, Buxbaum JD, Meaney MJ, Bierer LM (2013). Epigenetic Biomarkers as Predictors and Correlates of Symptom Improvement Following Psychotherapy in Combat Veterans with PTSD. Frontiers in Psychiatry, 4, 118. PMID: 24098286; PMCID: PMC3784793| 10.3389/fpsyt.2013.00118
Daskalakis NP#, Lehrner A, Yehuda R. Endocrine aspects of post-traumatic stress disorder and implications for diagnosis and treatment. Endocrinol Metab Clin North Am. 42(3):503-13. PMID: 24011883| 10.1016/j.ecl.2013.05.004
Animal models of adult stress and fear
McCullough KM, Chatzinakos C, Hartmann J, Missig G, Neve RL, Fenster RJ, Carlezon WA Jr, Daskalakis NP, Ressler KJ. Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning. Nat Commun. 2020 Oct 14;11(1):5180| 10.1038/s41467-020-18985-6
McCullough KM, Daskalakis NP, Gafford G, Morrison FG, Ressler KJ. (2018) Cell-type-specific interrogation of CeA Drd2 neurons to identify targets for pharmacological modulation of fear extinction. Transl Psychiatry. 8(1):164. PMID: 30135420| 10.1038/s41398-018-0190
Daskalakis NP#, Cohen H, Cai G, Buxbaum JD, Yehuda R. (2014) Expression profiling associates blood and brain glucocorticoid receptor signaling with trauma-related individual differences in both sexes. Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):13529-34. PMID: 25114262| 10.1073/pnas.1401660111
Daskalakis NP#, Yehuda R. (2014) Principles for developing animal models of military PTSD. Eur J Psychotraumatol. 2014 Aug 14;5. PMID: 25206946| 10.3402/ejpt.v5.23825 [review]
Daskalakis NP#, Diamantopoulou A, Claessens SEF, Remmers E, Tjรคlve M, Oitzl MS, Champagne DL, de Kloet ER. (2014) Early experience of a novel-environment in isolation primes a fearful phenotype characterized by persistent amygdala activation. Psychoneuroendocrinology. 39:39-57 PMID: 24275003| 10.1016/j.psyneuen.2013.09.021
Daskalakis NP, Yehuda R, Diamond DM. Animal models in translational studies of PTSD. Psychoneuroendocrinology. 2013 Sep;38(9):1895-911. PMID: 23845512| 10.1016/j.psyneuen.2013.06.006 [review]
Brain programming by early life stress
Daskalakis NP#, Bagot RC, Parker KJ, Vinkers CH, de Kloet ER (2013). The three-hit concept of vulnerability and resilience: towards understanding adaptation to early-life adversity outcome. Psychoneuroendocrinology, 38(9), 1858-73. PMID: 23838101; PMCID: PMC3773020| 10.1016/j.psyneuen.2013.06.008 [review]
Daskalakis NP#, Oitzl MS, Schรคchinger H, Champagne DL, de Kloet ER (2012). Testing the cumulative stress and mismatch hypotheses of psychopathology in a rat model of early-life adversity. Physiology & Behavior, 106(5), 707-721. PMID: 22306534| 10.1016/j.physbeh.2012.01.015
Daskalakis NP, Claessens SE, Laboyrie JJ, Enthoven L, Oitzl MS, Champagne DL, de Kloet ER. The newborn rat’s stress system readily habituates to repeated and prolonged maternal separation, while continuing to respond to stressors in context dependent fashion. Horm Behav. 2011 Jul;60(2):165-76. PMID: 21570400 | 10.1016/j.yhbeh.2011.04.003
Claessens SE, Daskalakis NP, van der Veen R, Oitzl MS, de Kloet ER, Champagne DL. Development of individual differences in stress responsiveness: an overview of factors mediating the outcome of early life experiences. Psychopharmacology (Berl). 214(1):141-54. PMID: 21165737| 10.1007/s00213-010-2118-y
Daskalakis NP#, Kaperoni M, Koros C, de Kloet ER, Kitraki E. Environmental and tactile stimulation modulates the neonatal handling effect on adult rat spatial memory. Int J Dev Neurosci. 27(8):747-55. PMID: 19720127| 10.1016/j.ijdevneu.2009.08.013
Intergenerational transmission of stress effects
Daskalakis NP, Xu C, Bader HN, Chatzinakos C, Weber P, Makotkine I, Lehrner A, Bierer LM, Binder EB, Yehuda R. Intergenerational trauma is associated with expression alterations in glucocorticoid- and immune-related genesNeuropsychopharmacology. 2021 Mar;46(4):763-773| 10.1038/s41386-020-00900-8.
Bierer LM, Bader HN, Daskalakis NP, Lehrner A, Provenรงal N, Wiechmann T, Klengel T, Makotkine I, Binder EB, Yehuda R. (2020). Intergenerational Effects of Maternal Holocaust Exposure on FKBP5 Methylation. Am J Psychiatry. 2020 Apr 21: appiajp201919060618. doi: 10.1176/appi.ajp.2019.19060618. Online ahead of print. PMID: 32312110| 10.1176/appi.ajp.2019.19060618
Yehuda R, Daskalakis NP, Bierer LM, Bader HN, Klengel T, Holsboer F, Binder EB. (2016). Holocaust exposure induced intergenerational effects on FKBP5 methylation. Biological Psychiatry; 80(5):372-80. PMID: 26410355| 10.1016/j.biopsych.2015.08.005
Yehuda R*, Daskalakis NP*, Lehrner A*, Desarnaud F, Bader HN, Makotkine I, Flory JD, Bierer LM, Meaney MJ. (2014). Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring. American Journal of Psychiatry, 171(8), 872-80. PMID: 24832930; PMCID: PMC4127390|10.1176/appi.ajp.2014.13121571
Bader HN, Bierer LM, Lehrner A, Makotkine I, Daskalakis NP, Yehuda R. Maternal Age at Holocaust Exposure and Maternal PTSD Independently Influence Urinary Cortisol Levels in Adult Offspring. Front Endocrinol (Lausanne). 2014 Jul 4;5:103. PMID: 25071719| 10.3389/fendo.2014.00103
Bierer LM, Bader HN, Daskalakis NP, Lehrner AL, Makotkine I, Seckl JR, Yehuda R. (2014) Elevation of 11ฮฒ-hydroxysteroid dehydrogenase type 2 activity in Holocaust survivor offspring: evidence for an intergenerational effect of maternal trauma exposure. Psychoneuroendocrinology. 48:1-10. PMID: 24971590| 10.1016/j.psyneuen.2014.06.001