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01-07-2018 | Review

The role of suboptimal mitochondrial function in vulnerability to post-traumatic stress disorder

Published in: Journal of Inherited Metabolic Disease | Issue 4/2018

Abstract

Post-traumatic stress disorder remains the most significant psychiatric condition associated with exposure to a traumatic event, though rates of traumatic event exposure far outstrip incidence of PTSD. Mitochondrial dysfunction and suboptimal mitochondrial function have been increasingly implicated in several psychopathologies, and recent genetic studies have similarly suggested a pathogenic role of mitochondria in PTSD. Mitochondria play a central role in several physiologic processes underlying PTSD symptomatology, including abnormal fear learning, brain network activation, synaptic plasticity, steroidogenesis, and inflammation. Here we outline several potential mechanisms by which inherited (genetic) or acquired (environmental) mitochondrial dysfunction or suboptimal mitochondrial function, may contribute to PTSD symptomatology and increase susceptibility to PTSD. The proposed pathogenic role of mitochondria in the pathophysiology of PTSD has important implications for prevention and therapy, as antidepressants commonly prescribed for patients with PTSD have been shown to inhibit mitochondrial function, while alternative therapies shown to improve mitochondrial function may prove more efficacious.

Accardi MV, Daniels BA, Brown PMGE, Fritschy J-M, Tyagarajan SK, Bowie D (2014) Mitochondrial reactive oxygen species regulate the strength of inhibitory GABA-mediated synaptic transmission. Nat Commun 5:3168PubMedPubMedCentralCrossRef

Almeida OFX, Conde GI, Crochemore C, Demeneix BA, Fischer D, Hassan AHS, Meyer M, Holsboer F, Michaelidis TM (2017) Subtle shifts in the ratio between pro- and antiapoptotic molecules after activation of corticosteroid receptros decide neuronal fate. FASEB J 14(5):779–790CrossRef

Artuch R, Pavia C, Playan A (1998) Multiple endocrine involvement in two pediatric patients with Kearns-Sayre syndrome. Horm Res 50(2):99–104PubMed

Aupperle RL, Melrose AJ, Stein MB, Paulus MP (2012) Executive function and PTSD: disengaging from trauma. Neuropharmacology 62(2):686–694PubMedCrossRef

Baker DG, West SA, Nicholson WE, Ekhator NN, Kasckow JW, Hill KK, Bruce AB, Orth DN (1999) Geracioti TD Jr. serial CSF corticotropin-releasing hormone levels and adrenocortical activity in combat veterans with posttraumatic stress disorder. Am J Psychiatry 156(4):585–588PubMed

Baxter KK, Uittenbogaard M, Yoon J, Chiaramello A (2009) The neurogenic basic helix–loop–helix transcription factor neuroD6 concomitantly increases mitochondrial mass and regulates cytoskeletal organization in the early stages of neuronal differentiation. ASN NEURO 1(4):art:e00016. https://doi.org/10.1042/AN20090036 CrossRef

Benjet C, Bromet E, Karam EG et al (2016) The epidemiology of traumatic event exposure worldwide: results from the World Mental health survey consortium. Psychol Med 46(2):327–343PubMedCrossRef

Bersani FS, Morley C, Lindqvist D, Epel ES, Picard M, Yehuda R, Flory J, Bierer LM, Makotkine I, Abu-Amara D, Coy M, Reus VI, Lin J, Blackburn E, Marmar C, Wolkowitz OM, Mellon SH (2015) Mitochondrial DNA copy number is reduced in male combat veterans with PTSD. Progress Neuro-Psychoparmacol Biol Psychiatry 64:10–17CrossRef

Bezprozvanny I, Mattson MP (2008) Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease. Trends Neurosci 31(9):454–463. https://doi.org/10.1016/j.tins.2008.06.005 PubMedPubMedCentralCrossRef

Boles RG, Roe T, Senadheera D (1998) Mitochondrial DNA deletion with Kearns Sayre syndrome in a child with Addison disease. Eur J Pediatr 157(8):643–647PubMedCrossRef

Voccoli V, Colombaioni L (2009) Mitochondrial remodeling in differentiating neuroblasts. Brain Res 1252:15–29PubMedCrossRef

Brady K, Pearlstein T, Asnis GM et al (2000) Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. JAMA 283:1837–1844PubMedCrossRef

Bremner JD, Krystal JH, Southwick SM, Charney DS (1995) Functional neuroanatomical correlates of the effects of stress on memory. J Trauma Stress 8:527–553PubMedCrossRef

Broekman BFP, Olff M, Boer F (2007) The genetic background to PTSD. Neurosci Behav Rev 31:348–362CrossRef

Brown GC (2003) NO says yes to mitochondria. Science 299(5608):838–839PubMedCrossRef

Bruno C, Minetti C, Tang Y (1998) Primary adrenal insufficiency in a child with a mitochondrial DNA deletion. J Inherit Metab Dis 21(2):155–161PubMedCrossRef

Burkhalter J, Fiumelli H, Allaman I, Chatton JY, Martin JL (2003) Brain-derived neurotrophic factor stimulates energy metabolism in developing cortical neurons. J Neurosci 23(23):8212–8220PubMedCrossRef

Butler MP, O’Connor JJ, Moynagh PN (2004) Dissection of tumor-necrosis factor-alpha inhibition of long-term potentiation (LTP) reveals a p38 mitogen-activated protein kinase-dependent mechanism which maps to early-but not late-phase LTP. Neurosci 124:319–326CrossRef

Calabresi P, Gubellini P, Picconi B, Centonze D, Pisani A, Bonsi P, Greengard P, Hipskind RA, Borrelli E, Bernardi G (2001) Inhibition of mitochondrial complex II induces a long-term potentiation of NMDA-mediated synaptic excitation in the striatum requiring endogenous dopamine. J Neurosci 21:5110–5120PubMedCrossRef

Chada SR, Hollenbeck PJ (2004) Nerve growth factor signaling regulates motility and docking of axonal mitochondria. Curr Biol 14:1272–1276PubMedCrossRef

Chan SL, Liu D, Kyriazis GA, Bagsiyao P, Ouyang X, Mattson MP (2006) Mitochondrial uncoupling protein-4 regulates calcium homeostasis and sensitivity to store depletion-induced apoptosis in neural cells. J Biol Chem 281:37391–37403PubMedCrossRef

Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59(3):527–605PubMedCrossRef

Charney DS (2004) Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress. Am J Psychiatry 161(2):195–216PubMedCrossRef

Chen GQ, Zhu J, Shi XG, Ni JH, Zhong HJ, Si GY, Jin XL, Tang W, Li XS, Xong SM, Shen XZ, Sun GL, Ma J, Zhang P, Zhang TD, Gazin C, Naoe T, Chen SJ, Wang ZY, Chen Z (1996) In vitro studies on cellular and moleular mechanisms of arsenic trioxid (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins. Blood 88(3):1052–1061PubMed

Cheng A, Hou Y, Mattson MP (2010) Mitochondria and neuroplasticity. ASN NEURO 2(5):e00045. https://doi.org/10.1042/AN20100019. PubMedPubMedCentralCrossRef

Chihara T, Luginbuhl D, Luo L (2007) Cytoplasmic and mitochondrial protein translation in axonal and dendritic terminal arborization. Nat Neurosci 10:828–837PubMedCrossRef

Chow J, Rahman J, Achermann JC, Dattani MT, Rahman S (2017) Mitochondrial disease and endocrine dysfunction. Nat Rev Endocrinol 13:92–104PubMedCrossRef

Cowell RM, Blake KR, Russell JW (2007) Localization of the transcriptional coactivator PGC-1alpha to GABAergic neurons during maturation of the rat brain. J Comp Neurol 502:1–18PubMedCrossRef

Craske MG, Stein MB, Elay TC, Milad MR, Holmes A, Rapee RM, Wittchen HU (2017) Anxiety disorders. Nat Rev Disease Primers 3:17100PubMedCrossRef

Cui H, Kong Y, Zhang H (2012) Oxidative stress, mitochondrial dysfunction, and aging. J Signal Transduct 2012:646354PubMedCrossRef

Curti C, Mingatto FE, Plizello AC, Galastri LO, Uyemura SA, Santos AC (1999) Fluoxetine interacts with the lipid bilayer of the inner membrane of isolated rat brain mitochondria, inhibiting electron transport and F1F0-ATPase activity. Mol Cell Biochem 199(1–2):103–109PubMedCrossRef

Datson NA, van der Perk J, de Kloet ER, Vreugdenhil E (2001) Identification of corticosteroid-responsive genes in rat hippocampus using serial analysis of gene expression. Eur J Neurosci 14:675–689PubMedCrossRef

de Kloet ER, Joels M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6(6):463–475PubMedCrossRef

Dedov VN, Armati PJ, Roufogalis BD (2000) Three-dimensional organisation of mitochondrial clusters in regenerating dorsal root ganglion (DRG) neurons from neonatal rats: evidence for mobile mitochondrial pools. J Peripher Nerv Syst 5(1):3–10PubMedCrossRef

Diamond DM, Bennett MC, Fleshner M, Rose GM (1992) Inverted-U relationship between the level of peripheral corticosterone and the magnitude of hippocampal primed burst potentiation. Hippocampus 2:421–430PubMedCrossRef

Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KLA (2010) Meta-analysis of cytokines in major depression. Biol Psychiatry 67(5):446–457PubMedCrossRef

Du C, Fang M, Li Y, Li L, Wang X (2000) Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102(1):33–42PubMedCrossRef

Duchen MR (2000) Mitochondria and Ca2+ in cell physiology and pathophysiology. Cell Calcium 28:339–348PubMedCrossRef

Dugan LL, Sensi SL, Canzoniero LM, Handran SD, Rothman SM, Lin TS, Goldberg MP, Choi DW (1995) Mitochondrial production of reactive oxygen species in cortical neurons following exposure to N-methyl-D-aspartate. J Neurosci 15(10):6377–6388PubMedCrossRef

Dunn AJ, Swiergiel AH, de Beaurepaire R (2005) Cytokines as mediators of dperession: what can we learn from animal studies? Neurosci Biobehav Rev 29(4–5):891–909PubMedCrossRef

Durroux T, Gallo-Payet N, Payet M (1991) Effects of adrenocorticotropin on action potential and calcium currents in cultured rat and bovine glomerulosa cells. Endocrinology 129:2139–2147PubMedCrossRef

Eluamai A, Brooks K (2013) Effect of aerobic exercise on mitochondrial DNA and aging. J Exerc Sci Fit 11(1):1–5.

Fanselow MS, LeDoux JE (1999) Why we think plasticity underlying Pavlovian fear conditioning occurs in the basolateral amygdala. Neuron 23:229–232PubMedCrossRef

Feleder C, Tseng KY, Calhoon GG, O'Donnell P (2010) Neonatal intra-hippocampal immune challenge alters dopamine modulation of prefrontal cortical interneurons in adult rats. Biol Psychiatry 67(4):386–392PubMedCrossRef

Flaquer A, Baumbach C, Ladwig K-H et al (2015) Mitochondrial genetic variants identified to be associated with posttraumatic stress disorder. Transl Psychiatry 5(3):e524. https://doi.org/10.1038/tp.2015.18 PubMedPubMedCentralCrossRef

Flory JD, Yehuda R (2015) Comorbidity between post-traumatic stress disorder and major depressive disorder: alternative explanations and treatment considerations. Dialogues Clin Neurosci 17(2):141–150PubMedPubMedCentral

Francati V, Vermetten E, Bremner JD (2007) Functional neuroimaging studies in posttraumatic stress disorder: review of current methods and findings. Depression and anxiety. 24(3):202–218. https://doi.org/10.1002/da.20208 PubMedPubMedCentralCrossRef

Friedman JR, Nunnari J (2014) Mitochondrial form and function. Nature 505(7483):335–343PubMedPubMedCentralCrossRef

Frodl T, Amico F (2014) Is there an association between peripheral immune markers and structural/functional neuroimaging findings? Prog Neuropsychoparmacol Biol Psychiatry 48:295–303CrossRef

Gould E, Woolley CS, McEwen BS (1990) Short-term glucocorticoid manipulations affect neuronal morphology and survival in the adult rat dentate gyrus. Neuroscience 37:367–375PubMedCrossRef

Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281(5381):1309–1312PubMedCrossRef

Guidarelli A, Cerioni L, Cantoni O (2007) Inhibition of complex III promotes loss of Ca2+ dependence for mitochondrial superoxide formation and permeability transition evoked by peroxynitrite. J Cell Sci 120(Pt 11):1908–1914

Gulyas AI, Buzsaki G, Freund TF, Hirase H (2006) Populations of hippocampal inhibitory neurons express different levesl of cytochrome c. Eur J Nerosci 23:2581–2594CrossRef

Gunasekar PG, Kanthasamy AG, Borowitz JL, Isom GE (1995) NMDA receptor activation produces a concurrent generation of nitric oxide and reactive oxygen species: implication for cell death. J Neurochem 65:2016–2021PubMedCrossRef

Hakem R, Hakem A, Duncan GS, Henderson JT, Woo M, Soengas MS, Elia A, de la Pompa JL, Kagi D, Khoo W, Potter J, Yoshida R, Kaufman SA, Lowe SW, Penninger JM, Mak TW (1998) Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 94(3):339–352PubMedCrossRef

Harris JJ, Jolivet R, Attwell D (2012) Synaptic energy use and supply. Neuron 75:762–777PubMedCrossRef

Hayes JP, VanElzakker MB, Shin LM (2012) Emotion and cognition interactions in PTSD: a review of neurocognitive and neuroimaging studies. Front Integr Neurosci 6:89PubMedPubMedCentralCrossRef

Hendler T, Rotshtein P, Yeshurun Y, Weizmann T, Kahn I, Ben-Bashat D, Malach R, Bleich A (2003) Sensing the inveisible: differential sensitivity of visual cortex and amygdala to traumatic context. NeuroImage 19:587–600PubMedCrossRef

Hroudova J, Fisar Z (2010) Activities of respiratory chain complexes and citrate synthase influenced by pharmacologically different antidepressants and mood stabilizers. Neuro Endocrinol Lett 31(3):336–342PubMed

Hu Z, Yuri K, Ozawa H, Lu H, Kawata M (1997) The in vivo time course for elimination of adrenalectomy-induced apoptotic profiles from the granule cell layer fo the rat hippocampus. J Neurosci 17(11):3981–3989PubMedCrossRef

Huang YY, Kandel ER (1998) Postsynaptic induction and PKA-dependent expression of LTP in the lateral amygdala. Neuron 21(1):169–178PubMedCrossRef

Inohara N, Gourley TS, Carrio R, Muniz M, Merino J, Garcia I, Koseki T, Hu Y, Chen S, Diva NG (1998) A Bcl-2 homologue that binds directly to Apaf-1 and induces BH3-independent cell death. J Biol Chem 273:32479–32486PubMedCrossRef

Jou SH, Chiu NY, Liu CS (2009) Mitochondrial dysfunction and psychiatric disorders. Chang Gung Med J 32(4):370–379PubMed

Juo P, Kuo CJ, Yuan J, Blenis J (1998) Essential requirement for caspase-8/FLICE in the initiation of the Fas-induced apoptotic cascade. Curr Biol 8(18):1001–1008PubMedCrossRef

Kageyama GH, Won-Riley MTT (1982) Histochemical localization of cytochrome oxidase in the hippocampus: correlation with specific neuronal types and afferent pathways. Neuroscience 7:2337–2361PubMedCrossRef

Kann O, Kovacs R (2007) Mitochondria and neuronal activity. Am J Physiol Cell Physiol 292:C641–C657PubMedCrossRef

Kann O, Huchzermeyer C, Kovacs R, Wirtz S, Schuelke M (2011) Gamma oscillations in the hippocampus require high complex I gene expression and strong functional performance of mitochondria. Brain 134:345–358PubMedCrossRef

Kann O, Papageorgiou IE, Draguhn A (2014) Highly energized inhibitory interneurons are a central element for information processin gin cortical networks. J Cereb Blood Flow Metab 34:1270–1282PubMedPubMedCentralCrossRef

Karam EG, Friedman MJ, Hill ED et al (2014) Cumulative traumas and risk thresholds: 12-month PTSD in the WORLD MENTAL health (WMH) SURVEYS. Depression and anxiety 31(2):130–142. https://doi.org/10.1002/da.22169 PubMedCrossRef

Kepp O, Galluzzi L, Martins I, Schlemmer F, Adjemian S, Michaud M, Sukkurwala AQ, Menger L, Zitvogel L, Kroemer G (2011) Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy. Cancer Metastasis Rev 30(1):61–69PubMedCrossRef

Kessler RC, Rose S, Koenen KC et al (2014) How well can post-traumatic stress disorder be predicted from pre-trauma risk factors? An exploratory study in the WHO World Mental health Surveys. World Psychiatry 13(3):265–274PubMedPubMedCentralCrossRef

Kim JJ, Diamond DM (2002) The stressed hippocampus, synaptic plasticity and lost memories. Nat Rev Neurosci 3:453–462PubMedCrossRef

Klinedinst NJ, Regenold WTA (2015) Mitochondrial bioenergetic basis of depression. J Bioenerg Biomembr 47(1–2):155–171PubMedCrossRef

Kojima I, Kojima K, Rasmussen II (1985) Characteristics of angiotensin II, K+, and ACTH-induced calcium influx in adrenal glomerulosa cells. J Biol Chem 260:9171–9176PubMed

Krajewski S, Krajewska M, Ellerby LM, Welsh K, Xie Z, Deveraux QL, Salvesen GS, Bredesen DE, Rosenthal RE, Fiskum G (1999) Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia. Proc Natl Acad Sci U S A 96:5752–5757PubMedPubMedCentralCrossRef

Kroemer G, Reed JC (2000) Mitochondrial control of cell death. Nat Med 6:513–519PubMedCrossRef

Kuida K, Haydar TF, Kuan CY, Gu Y, Taya C, Karasuyama H, Su MS, Rakic P, Flavell RA (1998) Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 94(3):325–337PubMedCrossRef

Lanza IR, Zabielski P, Klaus KA et al (2012) Chronic caloric restriction preserves mitochondrial function in senescence without increasing mitochondrial biogenesis. Cell Metab 16(6):777–788. https://doi.org/10.1016/j.cmet.2012.11.003 PubMedPubMedCentralCrossRef

LeDoux JE (1993) Emotional memory systems in the brain. Behav Brain Res 58(1–2):69–79PubMedCrossRef

Levkovitz Y, Gil-Ad I, Zeldich E, Dayag M, Weizman A (2005) Differential induction of apoptosis by antidepressants in glioma and neuroblastoma cell lines. J Mol Neurosci 27:29–42PubMedCrossRef

Li Z, Okamoto K, Hayashi Y, Sheng M (2004) The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119:873–887PubMedCrossRef

Li Z, Jo J, Jia JM, Lo SC, Whitcomb DJ, Jiao S, Cho K, Sheng M (2010) Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization. Cell 141:859–871PubMedPubMedCentralCrossRef

Li P, Zhao Y, Wu X et al (2012) Interferon gamma (IFN-γ) disrupts energy expenditure and metabolic homeostasis by suppressing SIRT1 transcription. Nucleic Acids Res 40(4):1609–1620. https://doi.org/10.1093/nar/gkr984 PubMedCrossRef

Li H, Li X, Smerin SE et al (2014) Mitochondrial gene expression profiles and metabolic pathways in the amygdala associated with exaggerated fear in an animal model of PTSD. Front Neurol 5:164. https://doi.org/10.3389/fneur.2014.00164 PubMedPubMedCentralCrossRef

Liberzon I, Abelson JL (2016) Context processing and the neurobiology of post-traumatic stress disorder. Neuron 92(1):14–30PubMedPubMedCentralCrossRef

Liberzon I, Taylor SF, Amdur R, Jung TD, Chamberlain KR, Minoshima S, Koeppe RA, Fig LM (1999) Brain activation in PTSD in response to trauma-related stimuli. Biol Psychiatry 45:817–826PubMedCrossRef

Liu D, Chan SL, de Souza-Pinto NC, Slevin JR, Wersto RP, Zhan M, Mustafa K, de Cabo R, Mattson MP (2006) Mitochondrial UCP4 mediates an adaptive shift in energy metabolism and increases the resistance of neurons to metabolic and oxidative stress. NeuroMolecular Med 8:389–414PubMedCrossRef

Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, Jager S, Vianna CR, Reznick RM (2004) Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell 119:121–135PubMedCrossRef

Lopez-Armada MJ, Riveiro-Naveira RR, Vaamonde-Garcia C, Valcarcel-Ares MN (2013) Mitochondrial dysfunction and the inflammatory response. Mitochondrion 13(2):106–118PubMedCrossRef

Lopez-Lluch G, Hunt N, Jones B, Zhu M, Jamieson H, Hilmer S, Cascajo MV, Allard J, Ingram DK, Navas P, de Cabo R (2006) Calorie restriction induces mitochondrial biogenesis and bioenergectic efficiency. Proc Natl Acad Sci U S A 103(6):1768–1773PubMedPubMedCentralCrossRef

Lu B, Wang KH, Nose A (2009) Molecular mechanisms underlying neural circuit formation. Curr Opin Neurobiol 19:162–167PubMedPubMedCentralCrossRef

Lüscher C, Malenka RC (2012) NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). Cold Spring Harb Perspect Biol 4(6):a005710. https://doi.org/10.1101/cshperspect.a005710 PubMedPubMedCentralCrossRef

Maalouf MA, Rho JM, Mattson MP (2009) The neuroprotective properties of calorei restriction, the ketogenic diet, and ketone bodies. Brain Res Rev 59(2):293–315PubMedCrossRef

MacGibbon GA, Lawlor PA, Sirimanne ES, Walton MR, Connor B, Young D, Williams C, Gluckman P, Faull RL, Hughes P, Dragunow M (1997) Bax expression in mammalian neurons undergoing apoptosis, and in Alzheimer's disease hippocampus. Brain Res 750(1–2):223–234PubMedCrossRef

Mancini M, Nicholson DW, Roy S, Thornberry NA, Peterson EP, Casciola-Rosen LA, Rosen A (1998) The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling. J Cell Biol 140:1485–1495PubMedPubMedCentralCrossRef

Marchi S, Giorgi C, Suski JM, Agnoletto C, Bononi A, Bonora M, De Marchi E, Missiroli S, Patergnani S, Poletti F, Rimessi A, Duszynski J, Wiechowski MR, Pinton P (2012) Mitochondria-Ros crosstalk in the control of cell death and aging. J Signal Transduct. 2012:329635PubMedCrossRef

Markham A, Cameron I, Franklin P, Spedding MBDNF (2004) Increases rat brain mitochondrial respiratory coupling at complex I, but not complex II. Eur J Neurosci 20(5):1189–1196PubMedCrossRef

Marshall RD, Beebe KL, Oldham M et al (2001) Efficacy and safety of paroxetine treatment for chronic PTSD: a fixed-dose, placebo-controlled study. Am J Psychiatry 158:1982–1988PubMedCrossRef

Martin J-L, Finsterwald C (2011) Cooperation between BDNF and glutamate in the regulation of synaptic transmission and neuronal development. Commun Integrat Biol 4(1):14–16. https://doi.org/10.4161/cib.4.1.13761 CrossRef

Mathew A, Lindsley TA, Sheridan A, Bhoiwala DL, Hushmendy SF, Yager EJ, Ruggiero EA, Crawford DR (2012) Degraded mitochondrial DNA Isa a newly identified subtype of the damage associated molecular pattern (DAMP) family and possible trigger of neurodegeneration. J Alzheimers Dis 30(3):617–627PubMedCrossRef

Mattson MP, Liu D (2003) Mitochondrial potassium channels and uncoupling proteins in synaptic plasticity and neuronal cell death. Biochem Biophys Res Commun 304:539–549. https://doi.org/10.1016/S0006-291X(03)00627-2 PubMedCrossRef

Mattson MP, Partin J (1999) Evidence for mitochondrial control of neuronal polarity. J Neurosci Res 56:8–20PubMedCrossRef

McEwen BS, Wingfield JC (2003) The concept of allostasis in biology and biomedicine. Horm Behav 43(1):2–15PubMedCrossRef

Menshikova EV, Ritov VB, Fairfull L, Ferrell RE, Kelley DE, Goodpaster BH (2006) Effects of exercise on mitochondrial content and function in aging human skeletal muscle. J Gerontol A Biol Sci Med Sci 61(6):534–540PubMedPubMedCentralCrossRef

Michopoulos V, Rothbaum AO, Jovanovic T et al (2015) CRP genetic variation and CRP levels are associated with increased PTSD symptoms and physiological responses in a highly traumatized civilian population. Am J Psychiatry 172(4):353–362. https://doi.org/10.1176/appi.ajp.2014.14020263. PubMedCrossRef

Middleton G, Nunez G, Davies AM (1996) Bax promotes neuronal survival and antagonises the survival effects of neurotrophic factors. Development 122(2):695–701PubMed

Milgram NW, Siwak-Tapp CT, Araujo J, Head E (2006) Neuroprotective effects of cognitive enrichment. Agein Res Rev 5(3):354–369CrossRef

Miller WL (2013) Steroid hormone synthesis in mitochondria. Mol Cell Endocrinol 379(1–2):62–73PubMedCrossRef

Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417(Pt 1):1–13PubMedCrossRef

Myers KM, Davis M (2007) Mechanisms of fear extinction. Mol Psychiatry 12(2):120–150PubMedCrossRef

Nair SM, Karst H, Dumas T, Phillips R, Sapolsky RM, Rumpff-van Essen L, Maslam S, Lucassen PJ, Joels M (2004) Gene expression profiles associated with survival of individual rat dentat cells after endogenous corticosteroid deprivation. Eur J Neurosci 20(12):3233–3243PubMedCrossRef

Nakahira K, Haspel JA, Rathinam VA et al (2011) Autophagy proteins regulate innate immune response by inhibiting NALP3 inflammasome-mediated mitochondrial DNA release. Nat Immunol 12(3):222–230. https://doi.org/10.1038/ni.1980. PubMedCrossRef

Nicholls DG, Budd SL (2000) Mitochondria and neuronal survival. Physiol Rev 80:315–360PubMedCrossRef

Nicolino M, Ferlin T, Forest M (1997) Identification of a large-scale mitochondrial deoxyribonucleic acid deletion in endocrinopathies and deafness: report of two unrelated cases with diabetes mellitus and adrenal insufficiency, respectively. J Clin Endocrinol Metab 82(9):3063–3067PubMed

North K, Korson MS, Krawiecki N (1996) Oxidative phosphorylation defect associated with primary adrenal insufficiency. J Pediatr 128(5 Pt 1):688–692PubMedCrossRef

Nutt DH, Malizia AL (2004) Structural and functional brain changes in postraumatic stress diosrder. J Clin Psychiatry 65(Suppl 1):11–17PubMed

Olff M, Polak AR, Witteveen AB, Denys D (2014) Executive function in posttaumatic stress disorder (PTSD) and the influence of comorbid depression. Neurobiol Learn Mem 112:114–121PubMedCrossRef

Overly CC, Rieff HI, Hollenbeck PJ (1996) Organelle motility and metabolism in axons vs dendrites of cultured hippocampal neurons. J Cell Sci 109:971–980PubMed

Ozer EJ, Best SR, Lipsey TL, Weiss DS (2003) Predictors of posttraumatic stress disorder and symptoms in adults: a meta-analysis. Psychol Bull 129(1):52–73PubMedCrossRef

Parr RL, Martin LH (2012) Mitochondrial and nuclear genomics and the emergence of personalized medicine. Human Genomics 6(1):3. https://doi.org/10.1186/1479-7364-6-3 PubMedPubMedCentralCrossRef

Pavlides C, Watanabe Y, McEwen BS (1993) Effects of glucocorticoids on hippocampal long-term potentiation. Hippocampus 3:183–19210PubMedCrossRef

Peng TI, Jou MJ, Sheu SS, Greenamyre JT (1998) Visualization of NMDA receptor-induced mitochondrial calcium accumluation in striatal neurons. Exp Neurol 149(1):1–12PubMedCrossRef

Pervanidou P, Kolaitis G, Charitaki S, Lazaropoulou C, Papassotiriou I, Hindmarsh P, Bakoula C, Tsiantis J, Chrousos GP (2007) The natural history of neuroendocrine changes in pediatric posttraumatic stress disorder (PTSD) after motor vehicle accidents: progressive divergence of noradrenaline and cortisol concentrations over time. Biol Psychiatry 62(10):1095–1102. https://doi.org/10.1016/j.biopsych.2007.02.008

Picard M, Juster RP, McEwen BS (2014) Mitochondrial allostatic load puts the "gluc" back in glucocorticoids. Nat Rev Endocrinol 10:303–310PubMedCrossRef

Pissiota A, Frans O, Fernandez M, von Knorring L, Fisher H, Fredrikson M (2002) Neurofunctional correlates of posttraumatic stress disorder; a PET symptom provocation study. Eur Arch Psychiatry Clin Neurosci 252:68–75PubMedCrossRef

Polak AR, Witteveen AB, Reitsma JB, Olff M (2012) The role of executive funciton in posttraumatic stress disorder: a systematic review. J Affect Disord 141(1):11–21PubMedCrossRef

Prigione A, Fauler B, Lurz R, Lehrach H, Adjaye J (2010) The senescence-related mitochondrial/oxidative stress pathway is repressed in human induced pluripotent stem cells. Stem Cells 28:721–733PubMedCrossRef

Quirk GJ, Mueller D (2007) Neural mechanisms of extinction learning and retreival. Neuropsychopharmacology 33(1):56–72PubMedPubMedCentralCrossRef

Rajasekaran A, Venkatasubramanian G, Berk M, Debnath M (2015) Mitochondrial dysfunction in schizophrenia: pathways, mechanisms and implications. Neurosci Biobehav Rev 48:10–21PubMedCrossRef

Reed JC (1997) Bcl-2 family proteins: regulators of apoptosis and chemoresistance in hematologic malignancies. Semin Hematol 34(4 Suppl 5):9–19PubMed

Reynolds IJ, Hastings TG (1995) Glutamate induces the production of reactive oxygen species in culture forebrain nerons following nmda receptor activation. J Neurosci 15(5 Pt 1):3318–3327PubMedCrossRef

Rizzuto R, De Stefani D, Raffaello A, Mammucari C (2012) Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol 13:566–578PubMedCrossRef

Roberts AL, Gilman SE, Breslau J, Breslau N, Koenen KC (2011) Race/ethnic differences in exposure to traumatic events, development of post-traumatic stress disorder, and treatment-seeking for post-traumatic stress disorder in the United States. Psychol Med 41:71–83PubMedCrossRef

Rubin DC, Feeling N (2013) Measuring the severity of negative and traumatic events. Clin Psychol Sci 1(4):375–389PubMedPubMedCentralCrossRef

Ruthel G, Hollenbeck PJ (2003) Response of mitochondrial traffic to axon determination and differential branch growth. J Neurosci 23:8618–8624PubMedCrossRef

Shalev A, Liverzon I, Marmar C (2017) Post-traumatic stress disorder. N Engl J Med 376:2459–2469PubMedCrossRef

Shin LM, Kozzlyn SM, McNally RJ, Alpert NM, Thmopson WL, Rauch SL, Macklin ML, Pitman RK (1997) Visual imagery and perception in posttraumatic stress disorder a positron emission tomographic investigation. Arch Gen Psychiatry 54:233–241PubMedCrossRef

Shin LM, Orr SP, Carson MA, Rauch SL, Macklin ML, Lasko NB, Peters PM, Metzger LJ, Dougherty DD, Cannistraro PA, Alpert M, Fischman AJ, Pitman RK (2004) Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam beterans with PTSD. Arch Gen Psychiatry 61:168–176PubMedCrossRef

Shokolenko I, Venediktova N, Bochkareva A, Wilson BL, Alexeyev MF (2009) Oxidative stress induces degradation of mitochondrial DNA. Nucleic Acids Res 37(8):2539–2548PubMedPubMedCentralCrossRef

Shuttleworth CW, Brennan AM, Connor JA (2003) NAD(P)H fluorescence imaging of postsynaptic neuronal activation in murine hippocampal slices. J Neurosci 23:3196–3208PubMedCrossRef

Simpson ER, Waterman MR (1988) Regulation of the synthesis of steroidogenic enzymes in adrenal cortical cells by ACTH. Annu Rev Physiol 50:427–424

Sloviter RS, Valiquette G, Abrams GM, Ronk EC, Sollas AI, Paul LA, Neubort SL (1989) Selective loss of hippocampal granule cells in the mature rat brain after adrenalectomy. Science 243:535–538PubMedCrossRef

Smith SM, Vale WW (2006) The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci 8(4):383–395PubMedPubMedCentral

Smorodchenko A, Rupprecht A, Sarilova I, Ninnemann O, Bräuer AU, Franke K, Schumacher S, Techritz S, Nitsch R, Schuelke M, Pohl EE (2009) Comparative analysis of uncoupling protein 4 distribution in various tissues under physiological conditions and during development. Biochim Biophys Acta 1788:2309–2319PubMedCrossRef

Song Q, Kuang Y, Dixit VM, Vincenz C (1999) Boo, a novel negative regulator of cell death, interacts with Apaf-1. EMBO J 18:167–178

Souza MEJ, Polizello ACM, Uyemur SA, Curti C (1994) Effect of fluoxetine on rat liver mitochondria. Biochem Pharmacol 48(3):535–541PubMedCrossRef

Spoont MR, Williams JW, Kehle-Forbes S, Nieuwsma JA, Mann-Wrobel MC, Gross R (2015) Does this patient have posttraumatic stress disorder? Rational clinical examination systematic review. JAMA 314(5):501–510. https://doi.org/10.1001/jama.2015.7877 PubMedCrossRef

Stress MEBS (1998) Adaptation, and disease: Allostasis and allostatic load. Ann N Y Acad Sci 840:33–44CrossRef

Strohle A (2009) Physical activity, exercise, depression and anxiety disorders. J Neural Transm 116:777–784PubMedCrossRef

Strowig T, Henao-Mejia J, Elinav E, Flavell R (2012) Inflammasomes in health and disease. Nature 481(7381):278–286PubMedCrossRef

Su YA, Wu J, Zhang L et al (2008) Dysregulated mitochondrial genes and networks with drug targets in postmortem brain of patients with posttraumatic stress disorder (PTSD) revealed by human mitochondria-focused cDNA microarrays. Int J Biol Sci 4(4):223–235PubMedPubMedCentralCrossRef

Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, Mangion J, Jacotot E, Constantini P, Loeffler M, Larochette N, Goodlett DR, Aebersold R, Siderovski DP, Penninger JM, Kroemer G (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397(6718):441–446PubMedCrossRef

Taanman J-W (1999) The mitochondrial genome: structure, transcription, translation, replication. Biochim Biophys Acta 1410(2):103–123PubMedCrossRef

Tan S, Sagara Y, Liu Y, Maher P, Schubert D (1998) The regulation of reactive oxygen species production during programmed cell death. J Cell Biol 141(6):1423PubMedPubMedCentralCrossRef

Tatton WG, Olanow CW (1999) Apoptosis in neurodegenerative diseases: the role of mitochondria. Biochim Biophys Acta 1410(2):195–213PubMedCrossRef

Telch MJ, Bruchey AK, Rosenfield D et al (2014) Post-session administration of USP methylene blue facilitates the retention of pathological fear extinction and contextual memory in phobic adults. Am J Psychiatry 171(10):1091–1098. https://doi.org/10.1176/appi.ajp.2014.13101407. PubMedPubMedCentralCrossRef

Thompson Legault J, Strittmatter L, Tardif J et al (2015) A metabolic signature of mitochondrial dysfunction revealed through a monogenic form of Leigh syndrome. Cell Rep 13(5):981–989. https://doi.org/10.1016/j.celrep.2015.09.054 PubMedPubMedCentralCrossRef

Toescu EC (2000) Mitochondria and Ca2+ signaling. J Cell Mol Med 4:164–175PubMedCrossRef

Toresson H, Grant SG (2005) Dynamic distribution of endoplasmic reticulum in hippocampal neuron dendritic spines. Eur J Neurosci 22:1793–1798PubMedCrossRef

Tursich M, Neufeld RW, Frewen PA, Harricharan S, Kibler JL, Rhind SG et al (2014) Association of trauma exposure with proinflammatory activity: a transdiagnostic meta-analysis. Transl Psychiatry 4:e413. https://doi.org/10.1038/tp.2014.56 PubMedPubMedCentralCrossRef

Valcarcel-Ares MN, Riveiro-Naveira RR, Vaamonde-Garcia C, Lureiro J, Hermida-Carballo L, Blanco FJ, Lopez-Armada MJ (2014) Mitochondrial dysfunction promotes and aggravates the inflammatory response in normal human synoviocytes. Rheumatology 53:1332–1343PubMedCrossRef

VanElzakker MB, Dahlgren MK, Davis FC, Dubois S, Shin LM (2014) From Pavlov to PTSD: the extinction of conditioned fear in rodents, humans, and in anxiety disorders. Neurobiol Learn Mem 113:3–18PubMedCrossRef

Varfolomeev EE, Schuchmann M, Luria V, Chiannilkulchai N, Beckmann JS, Mett IL, Rebrikov D, Brodianski VM, Kemper OC, Kollet O, Lapidot T, Soffer D, Sobe T, Avraham KB, Goncharov T, Holtmann H, Lonai P, Wallach D (1998) Targeted disruption of the mouse caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity 9(2):267–276PubMedCrossRef

Verburg J, Hollenbeck PJ (2008) Mitochondrial membrane potential in axons increases with local nerve growth factor or semaphorin signaling. J Neurosci 28:8306–8315PubMedPubMedCentralCrossRef

Verhagen AM, Ekert PG, Pakush M, Silke J, Connolly LM, Reid GE, Moritz RL, Simpson RJ, Vaux DL (2000) Indentification of DIABLO, a mammalian protein that promotes apoptosis by binding to an d antagonizing IAP proteins. Cell 102(1):43–53PubMedCrossRef

von Kanel R, Hepp U, Kraemer B, Traber R, Keel M, Mica L, Schnyder U (2007) Evidence for low grade systemic proinflammatory activity in patients with posttraumatic stress disorder. J Psychatric Res 41(9):744–752CrossRef

Wanders RJA, Ruiter JPN, IJLst L, Waterham HR, Houten SM (2010) The enzymology of mitochondrial fatty acid beta-oxidation and its application to followup analysis of positive neonatal screening results. J Inherit Metab Dis 33(5):479–494PubMedPubMedCentralCrossRef

Wang L (2016) Mitochondrial purine and pyrimidine metabolism and beyond. Nucelosides Nucleotides Nucleic Acids 35(10–12):578–594CrossRef

Wang C, Youle RJ (2016) The role of mitochondria in apoptosis. Annu Rev Genet 43:95–118CrossRef

Wang C-U, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS Jr (1998) NF-kB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 281(5383):1680–1683PubMedCrossRef

Whittaker RG, Turnbull DM, Whittington MA, Cunningham MO (2011) Impaired mitochondrial function abolishes gamma oscillations in the hippocampus through an effect on fast-spiking interneurons. Brain 134:e180PubMedPubMedCentralCrossRef

Williams JM, Thompson VL, Mason-Parker SE, Abraham WC, Tate WP (1998) Synaptic activity-dependent modulation of mitochondrial gene expression in the rat hippocampus. Mol Brain Res 60:50–56PubMedCrossRef

Wossink J, Karst H, Mayboroda O, Morphological JM (2001) Functional properties of rat dentate granule cells after adrenalectomy. Neuroscience 108(2):263–272PubMedCrossRef

Xavier JM, Rodrigues CMP, Mitochondria SS (2015) Major regulators of neural development. Neuroscientist 22(4):346–358PubMedCrossRef

Xu L, Anwyl R, Rowan MJ (1997) Behavioural stress facilitates the induction of long-term depression in the hippocampus. Nature 387:497–500PubMedCrossRef

Yamazaki T, Kimoto T, Higuchi K, Ohta Y, Kawato S, Kominami S (1998) Calcium ion as a second messenger for o-nitrophenylsulfenyl-adrenocorticotropin (NPS-ACTH) and ACTH in bovine adrenal steroidogenesis. Endocrinology 139(2):4765–4771PubMedCrossRef

Yang P, Wu MT, Hsu CC, Ker JH (2004) Evidence of early neurobiological alternations in adolescents with posttraumatic stress disorder: a functional MRI study. Neurosci Lett 370:13–18PubMedCrossRef

Yi PL, Tsai CH, Lu MK, Liu HJ, Chen YC, Chang FC (2007) Interleukin-1beta mediates sleep alteration in rats with rotenone-induced parkinsonism. Sleep 30(4):413–425PubMedCrossRef

Ying SW, Futter M, Rosenblum K, Webber MJ, Hunt SP, Bliss TV, Bramham CR (2002) Brain-derived neurotrophic factor induces long-term potentiation in intact adult hippocampus: requirement for ERK activation coupled to CREB and upregulation of arc synthesis. J Neurosci 22(5):1532–1540PubMedCrossRef

Zhang L, Li H, Hu X et al (2015) Mitochondria-focused gene expression profile reveals common pathways and CPT1B dysregulation in both rodent stress model and human subjects with PTSD. Transl Psychiatry 5(6):e580. https://doi.org/10.1038/tp.2015.65 PubMedPubMedCentralCrossRef

Zigmond MJ, Smeyne RJ (2014) Exercise: is it neuroprotective and if so, how does it work? Parkinsonism Relat Disord 20(Suppl 1):S123–S127PubMedCrossRef

Title: The role of suboptimal mitochondrial function in vulnerability to post-traumatic stress disorder
Publication date: 01-07-2018
Published in: Journal of Inherited Metabolic Disease / Issue 4/2018
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-018-0168-1

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