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Increased ventricular cerebrospinal fluid lactate in depressed adolescents

Published online by Cambridge University Press:  23 March 2020

K.A.L. Bradley ,
X. Mao ,
J.A.C. Case ,
G. Kang ,
D.C. Shungu  and
V. Gabbay
K.A.L. Bradley
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place New York, 10029-6574, USA
X. Mao
Affiliation:
Department of Radiology, Weill Cornell Medical College, New York, USA
J.A.C. Case
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place New York, 10029-6574, USA
G. Kang
Affiliation:
Department of Radiology, Weill Cornell Medical College, New York, USA
D.C. Shungu
Affiliation:
Department of Radiology, Weill Cornell Medical College, New York, USA
V. Gabbay*
Affiliation:
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place New York, 10029-6574, USA Nathan Kline Institute for Psychiatric Research, Orangeburg, USA
*
*Corresponding author. Tel.: +21 2659 1661; fax: +21 2659 1693. E-mail address: vilma.gabbay@mssm.edu (V. Gabbay).
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Abstract

Background

Mitochondrial dysfunction has been increasingly examined as a potential pathogenic event in psychiatric disorders, although its role early in the course of major depressive disorder (MDD) is unclear. Therefore, the purpose of this study was to investigate mitochondrial dysfunction in medication-free adolescents with MDD through in vivo measurements of neurometabolites using high-spatial resolution multislice/multivoxel proton magnetic resonance spectroscopy.

Methods

Twenty-three adolescents with MDD and 29 healthy controls, ages 12–20, were scanned at 3 T and concentrations of ventricular cerebrospinal fluid lactate, as well as N-acetyl-aspartate (NAA), total creatine (tCr), and total choline (tCho) in the bilateral caudate, putamen, and thalamus were reported.

Results

Adolescents with MDD exhibited increased ventricular lactate compared to healthy controls [F(1,41) = 6.98, P = 0.01]. However, there were no group differences in the other neurometabolites. Dimensional analyses in the depressed group showed no relation between any of the neurometabolites and symptomatology, including anhedonia and fatigue.

Conclusions

Increased ventricular lactate in depressed adolescents suggests mitochondrial dysfunction may be present early in the course of MDD; however it is still not known whether the presence of mitochondrial dysfunction is a trait vulnerability of individuals predisposed to psychopathology or a state feature of the disorder. Therefore, there is a need for larger multimodal studies to clarify these chemical findings in the context of network function.

Keywords

Proton magnetic resonance spectroscopyAdolescent depressionMitochondrial dysfunction
Type
Original article
Information
European Psychiatry , Volume 32 , February 2016 , pp. 1 - 8
Copyright
Copyright © European Psychiatric Association 2016

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References

Barnes, J., Ridgway, G.R., Bartlett, J., Henley, S.M., Lehmann, M., Hobbs, N., et al.Head size, age and gender adjustment in MRI studies: a necessary nuisance?. Neuroimage 2010; 53(4): 1244–55. http://dx.doi.org/10.1016/j.neuroimage.2010.06.025.CrossRefGoogle ScholarPubMed
Birken, D.L., Oldendorf, W.H.N-acetyl-L-aspartic acid: a literature review of a compound prominent in 1H-NMR spectroscopic studies of brain. Neurosci Biobehav Rev 1989; 13(1): 23–31.CrossRefGoogle ScholarPubMed
Bradley, K.A., Case, J.A., Khan, O., Ricart, T., Hanna, A., Alonso, C.M., et al.The role of the kynurenine pathway in suicidality in adolescent major depressive disorder. Psychiatry Res 2015;227(2–3):206–12. http://dx.doi.org/10.1016/j.psychres.2015.03.031.CrossRefGoogle ScholarPubMed
Buck, L.T., Pamenter, M.E.Adaptive responses of vertebrate neurons to anoxia – matching supply to demand. Respir Physiol Neurobiol 2006;154(1–2):226–40. http://dx.doi.org/10.1016/j.resp.2006.03.004.CrossRefGoogle ScholarPubMed
Chu, W.J., Delbello, M.P., Jarvis, K.B., Norris, M.M., Kim, M.J., Weber, W., et al.Magnetic resonance spectroscopy imaging of lactate in patients with bipolar disorder. Psychiatry Res 2013; 213(3): 230–4. http://dx.doi.org/10.1016/j.pscychresns.2013.03.004.CrossRefGoogle ScholarPubMed
Clausen, T., Zauner, A., Levasseur, J.E., Rice, A.C., Bullock, R.Induced mitochondrial failure in the feline brain: implications for understanding acute post-traumatic metabolic events. Brain Res 2001; 908(1): 35–48.CrossRefGoogle ScholarPubMed
Domino, E.F.Tobacco smoking and MRI/MRS brain abnormalities compared to nonsmokers. Prog Neuropsychopharmacol Bol Psychiatry 2008; 32(8): 1778–81. http://dx.doi.org/10.1016/j.pnpbp.2008.09.004.CrossRefGoogle ScholarPubMed
Duyn, J.H., Gillen, J., Sobering, G., van Zijl, P.C., Moonen, C.T.Multisection proton MR spectroscopic imaging of the brain. Radiology 1993; 188(1): 277–82. http://dx.doi.org/10.1148/radiology.188.1.8511313.CrossRefGoogle ScholarPubMed
Ende, G., Walter, S., Welzel, H., Demirakca, T., Wokrina, T., Ruf, M., et al.Alcohol consumption significantly influences the MR signal of frontal choline-containing compounds. Neuroimage 2006; 32(2): 740–6. http://dx.doi.org/10.1016/j.neuroimage.2006.03.049.CrossRefGoogle ScholarPubMed
Farchione, T.R., Moore, G.J., Rosenberg, D.R.Proton magnetic resonance spectroscopic imaging in pediatric major depression. Biol Psychiatry 2002; 52(2): 86–92.CrossRefGoogle ScholarPubMed
Forbes, E.E.fMRI studies of reward processing in adolescent depression. Neuropsychopharmacology 2011; 36(1): 372–3. http://dx.doi.org/10.1038/npp.2010.164.CrossRefGoogle ScholarPubMed
Forbes, E.E., Christopher May, J., Siegle, G.J., Ladouceur, C.D., Ryan, N.D., Carter, C.S., et al.Reward-related decision-making in pediatric major depressive disorder: an fMRI study. J Child Psychol Psychiatry 2006; 47(10): 1031–40. http://dx.doi.org/10.1111/j.1469-7610.2006.01673.x.CrossRefGoogle Scholar
Forbes, E.E., Hariri, A.R., Martin, S.L., Silk, J.S., Moyles, D.L., Fisher, P.M., et al.Altered striatal activation predicting real-world positive affect in adolescent major depressive disorder. A J Psychiatry 2009; 166(1): 64–73. http://dx.doi.org/10.1176/appi.ajp.2008.07081336.CrossRefGoogle ScholarPubMed
Gabbay, V., Hess, D.A., Liu, S., Babb, J.S., Klein, R.G., Gonen, O.Lateralized caudate metabolic abnormalities in adolescent major depressive disorder: a proton MR spectroscopy study. A J Psychiatry 2007; 164(12): 1881–9. http://dx.doi.org/10.1176/appi.ajp.2007.06122032.CrossRefGoogle ScholarPubMed
Gabbay, V., Klein, R.G., Alonso, C.M., Babb, J.S., Nishawala, M., De Jesus, G., et al.Immune system dysregulation in adolescent major depressive disorder. J Affect Disord 2009;115(1–2):177–82. http://dx.doi.org/10.1016/j.jad.2008.07.022.CrossRefGoogle ScholarPubMed
Gabbay, V., Klein, R.G., Guttman, L.E., Babb, J.S., Alonso, C.M., Nishawala, M., et al.A preliminary study of cytokines in suicidal and nonsuicidal adolescents with major depression. J Child Adolesc Psychopharmacol 2009; 19(4): 423–30. http://dx.doi.org/10.1089/cap.2008.0140.CrossRefGoogle ScholarPubMed
Gabbay, V., Liebes, L., Katz, Y., Liu, S., Mendoza, S., Babb, J.S., et al.The kynurenine pathway in adolescent depression: preliminary findings from a proton MR spectroscopy study. Prog Neuropsychopharmacol Bol Psychiatry 2010; 34(1): 37–44. http://dx.doi.org/10.1016/j.pnpbp.2009.09.0159.CrossRefGoogle ScholarPubMed
Gabbay, V., Ely, B.A., Babb, J., Liebes, L.The possible role of the kynurenine pathway in anhedonia in adolescents. J Neural Transm 2012; 119(2): 253–60. http://dx.doi.org/10.1007/s00702-011-0685-7.CrossRefGoogle ScholarPubMed
Gabbay, V., Mao, X., Klein, R.G., Ely, B.A., Babb, J.S., Panzer, A.M., et al.Anterior cingulate cortex gamma-aminobutyric acid in depressed adolescents: relationship to anhedonia. Arch Gen Psychiatry 2012; 69(2): 139–49. http://dx.doi.org/10.1001/archgenpsychiatry.2011.131.CrossRefGoogle ScholarPubMed
Gabbay, V., Ely, B.A., Li, Q., Bangaru, S.D., Panzer, A.M., Alonso, C.M., et al.Striatum-based circuitry of adolescent depression and anhedonia. J Am Acad Child Adolesc Psychiatry 2013; 52(6) http://dx.doi.org/10.1016/j.jaac.2013.04.003. 628–41 e13.CrossRefGoogle ScholarPubMed
Gabbay, V., Johnson, A.R., Alonso, C.M., Evans, L.K., Babb, J.S., Klein, R.G.Anhedonia, but not irritability, is associated with illness severity outcomes in adolescent major depression. J Child Adolesc Psychopharmacol; 2015 http://dx.doi.org/10.1089/cap.2014.0105.CrossRefGoogle Scholar
Gardner, A., Boles, R.G.Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders. Prog Neuropsychopharmacol Bol Psychiatry 2011; 35(3): 730–43. http://dx.doi.org/10.1016/j.pnpbp.2010.07.030.CrossRefGoogle ScholarPubMed
Henderson, S.E., Johnson, A.R., Vallejo, A.I., Katz, L., Wong, E., Gabbay, V.A preliminary study of white matter in adolescent depression: relationships with illness severity, anhedonia, and irritability. Front Psychiatry 2013;4:152. http://dx.doi.org/10.3389/fpsyt.2013.00152.CrossRefGoogle ScholarPubMed
Jou, S.H., Chiu, N.Y., Liu, C.S.Mitochondrial dysfunction and psychiatric disorders. Chang Gung Med J 2009; 32(4): 370–9.Google ScholarPubMed
Kaufman, A.S., Kaufman, N.L.Manual for the Kaufman Brief Intelligence Test MN: American Guidance Service; 1990.Google Scholar
Kaufman, J., Birmaher, B., Brent, D., Rao, U., Flynn, C., Moreci, P., et al.Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 1997; 36(7): 980–8.CrossRefGoogle ScholarPubMed
Kaufmann, P., Shungu, D.C., Sano, M.C., Jhung, S., Engelstad, K., Mitsis, E., et al.Cerebral lactic acidosis correlates with neurological impairment in MELAS. Neurology 2004; 62(8): 1297–302.CrossRefGoogle ScholarPubMed
Keedwell, P.A., Andrew, C., Williams, S.C., Brammer, M.J., Phillips, M.L.The neural correlates of anhedonia in major depressive disorder. Biol Psychiatry 2005; 58(11): 843–53. http://dx.doi.org/10.1016/j.biopsych.2005.05.019.CrossRefGoogle ScholarPubMed
Kessler, R.C., Berglund, P., Demler, O., Jin, R., Merikangas, K.R., Walters, E.E.Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62(6): 593–602. http://dx.doi.org/10.1001/archpsyc.62.6.593.CrossRefGoogle ScholarPubMed
Klinedinst, N.J., Regenold, W.T.A mitochondrial bioenergetic basis of depression. J Bioenerg Biomembr 2015;47(1–2):155–71. http://dx.doi.org/10.1007/s10863-014-9584-6.CrossRefGoogle ScholarPubMed
Kondo, D.G., Hellem, T.L., Sung, Y.H., Kim, N., Jeong, E.K., Delmastro, K.K., et al.Review: magnetic resonance spectroscopy studies of pediatric major depressive disorder. Depress Res Treat 2011;2011:650450. http://dx.doi.org/10.1155/2011/650450.Google ScholarPubMed
Kusumakar, V., MacMaster, F.P., Gates, L., Sparkes, S.J., Khan, S.C.Left medial temporal cytosolic choline in early onset depression. Can J Psychiatry 2001; 46(10): 959–64.CrossRefGoogle ScholarPubMed
Louveau, A., Smirnov, I., Keyes, T.J., Eccles, J.D., Rouhani, S.J., Peske, J.D., et al.Structural and functional features of central nervous system lymphatic vessels. Nature 2015 http://dx.doi.org/10.1038/nature14432.CrossRefGoogle ScholarPubMed
MacMaster, F.P., Kusumakar, V.Choline in pediatric depression. Mcgill J Med 2006; 9(1): 24–7.Google ScholarPubMed
MacMaster, F.P., Moore, G.J., Russell, A., Mirza, Y., Taormina, S.P., Buhagiar, C., et al.Medial temporal N-acetyl-aspartate in pediatric major depression. Psychiatry Res 2008; 164(1): 86–9. http://dx.doi.org/10.1016/j.pscychresns.2007.12.022.CrossRefGoogle ScholarPubMed
Mathew, S.J., Mao, X., Keegan, K.A., Levine, S.M., Smith, E.L., Heier, L.A., et al.Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study. NMR Biomed 2009; 22(3): 251–8. http://dx.doi.org/10.1002/nbm.1315.CrossRefGoogle Scholar
McMakin, D.L., Olino, T.M., Porta, G., Dietz, L.J., Emslie, G., Clarke, G., et al.Anhedonia predicts poorer recovery among youth with selective serotonin reuptake inhibitor treatment-resistant depression. J Am Acad Child Adolesc Psychiatry 2012; 51(4): 404–11. http://dx.doi.org/10.1016/j.jaac.2012.01.011.CrossRefGoogle ScholarPubMed
Miller, A.H.Depression and immunity: a role for T cells?. Brain Behav Immun 2010; 24(1): 1–8. http://dx.doi.org/10.1016/j.bbi.2009.09.009.CrossRefGoogle ScholarPubMed
Moore, C.M., Christensen, J.D., Lafer, B., Fava, M., Renshaw, P.F.Lower levels of nucleoside triphosphate in the basal ganglia of depressed subjects: a phosphorous-31 magnetic resonance spectroscopy study. A J Psychiatry 1997; 154(1): 116–8.Google ScholarPubMed
Murrough, J.W., Mao, X., Collins, K.A., Kelly, C., Andrade, G., Nestadt, P., et al.Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder. NMR Biomed 2010; 23(6): 643–50. http://dx.doi.org/10.1002/nbm.1512.CrossRefGoogle Scholar
Naik, E., Dixit, V.M.Mitochondrial reactive oxygen species drive proinflammatory cytokine production. J Exp Med 2011; 208(3): 417–20. http://dx.doi.org/10.1084/jem.20110367.CrossRefGoogle ScholarPubMed
Najjar, S., Pearlman, D.M., Alper, K., Najjar, A., Devinsky, O.Neuroinflammation and psychiatric illness. J Neuroinflammation 2013;10:43. http://dx.doi.org/10.1186/1742-2094-10-43.CrossRefGoogle ScholarPubMed
Olvera, R.L., Caetano, S.C., Stanley, J.A., Chen, H.H., Nicoletti, M., Hatch, J.P., et al.Reduced medial prefrontal N-acetyl-aspartate levels in pediatric major depressive disorder: a multi-voxel in vivo(1)H spectroscopy study. Psychiatry Res 2010; 184(2): 71–6. http://dx.doi.org/10.1016/j.pscychresns.2010.07.008.CrossRefGoogle ScholarPubMed
Patel, T.B., Clark, J.B.Synthesis of N-acetyl-L-aspartate by rat brain mitochondria and its involvement in mitochondrial/cytosolic carbon transport. Biochem J 1979; 184(3): 539–46.CrossRefGoogle ScholarPubMed
Perou, R., Bitsko, R.H., Blumberg, S.J., Pastor, P., Ghandour, R.M., Gfroerer, J.C., et al.Mental health surveillance among children – United States, 2005–2011. MMWR Surveill Summ 2013;62(Suppl. 2):1–35.Google ScholarPubMed
Raza, H., John, A., Howarth, F.C.Increased oxidative stress and mitochondrial dysfunction in zucker diabetic rat liver and brain. Cell Physiol Biochem 2015; 35(3): 1241–51. http://dx.doi.org/10.1159/000373947.CrossRefGoogle ScholarPubMed
Regenold, W.T., Phatak, P., Marano, C.M., Sassan, A., Conley, R.R., Kling, M.A.Elevated cerebrospinal fluid lactate concentrations in patients with bipolar disorder and schizophrenia: implications for the mitochondrial dysfunction hypothesis. Biol Psychiatry 2009; 65(6): 489–94. http://dx.doi.org/10.1016/j.biopsych.2008.11.010.CrossRefGoogle ScholarPubMed
Rippon, G., Jordan-Young, R., Kaiser, A., Fine, C.Recommendations for sex/gender neuroimaging research: key principles and implications for research design, analysis, and interpretation. Front Hum Neurosci 2014;8. http://dx.doi.org/10.3389/fnhum.2014.00650.Google ScholarPubMed
Scaglia, F.The role of mitochondrial dysfunction in psychiatric disease. Dev Disabil Res Rev 2010; 16(2): 136–43. http://dx.doi.org/10.1002/ddrr.115.CrossRefGoogle ScholarPubMed
Shungu, D.C., Weiduschat, N., Murrough, J.W., Mao, X., Pillemer, S., Dyke, J.P., et al.Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology. NMR Biomed 2012; 25(9): 1073–87. http://dx.doi.org/10.1002/nbm.2772.CrossRefGoogle ScholarPubMed
Sprague, A.H., Khalil, R.A.Inflammatory cytokines in vascular dysfunction and vascular disease. Biochem Pharmacol 2009; 78(6): 539–52. http://dx.doi.org/10.1016/j.bcp.2009.04.029.CrossRefGoogle ScholarPubMed
Steingard, R.J., Yurgelun-Todd, D.A., Hennen, J., Moore, J.C., Moore, C.M., Vakili, K., et al.Increased orbitofrontal cortex levels of choline in depressed adolescents as detected by in vivo proton magnetic resonance spectroscopy. Biol Psychiatry 2000; 48(11): 1053–61.CrossRefGoogle ScholarPubMed
Stork, C., Renshaw, P.F.Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research. Mol Psychiatry 2005; 10(10): 900–19. http://dx.doi.org/10.1038/sj.mp.4001711.CrossRefGoogle ScholarPubMed
Tobe, E.H.Mitochondrial dysfunction, oxidative stress, and major depressive disorder. Neuropsychiatr Dis Treat 2013; 9: 567–73. http://dx.doi.org/10.2147/ndt.s44282.CrossRefGoogle ScholarPubMed
Truckenmiller, M.E., Namboodiri, M.A., Brownstein, M.J., Neale, J.H.N-Acetylation of L-aspartate in the nervous system: differential distribution of a specific enzyme. J Neurochem 1985; 45(5): 1658–62.CrossRefGoogle ScholarPubMed
Wang, Y., Li, S.J.Differentiation of metabolic concentrations between gray matter and white matter of human brain by in vivo 1H magnetic resonance spectroscopy. Magn Reson Med 1998; 39(1): 28–33.CrossRefGoogle ScholarPubMed
Weiduschat, N., Kaufmann, P., Mao, X., Engelstad, K.M., Hinton, V., DiMauro, S., et al.Cerebral metabolic abnormalities in A3243G mitochondrial DNA mutation carriers. Neurology 2014; 82(9): 798–805. http://dx.doi.org/10.1212/wnl.0000000000000169.CrossRefGoogle ScholarPubMed
Wilson, S., Hicks, B.M., Foster, K.T., McGue, M., Iacono, W.G.Age of onset and course of major depressive disorder: associations with psychosocial functioning outcomes in adulthood. Psychol Med 2014;1–10. http://dx.doi.org/10.1017/s0033291714001640.Google ScholarPubMed
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