ABB  Vol.4 No.6 A , June 2013
Increased myo-inositol in the posterior cingulate cortex in first-episode major depressive patients
Abstract: Major depressive disorder (MDD) is a severe, disabling pathology characterized, in addition to affective, cognitive and motor symptoms, by self-focused attention and rumination. During recursive self-focused processes and rumination, the posterior cingulate cortex (PCC) is activated. In vivo proton magnetic resonance spectroscopy (MRS) is a noninvasive imaging technique that can directly assess living biochemistry in localized brain regions. The aim of this study, therefore, was to use 1H-MRS as a means of analyzing brain metabolites in the PCC of a group of first-episode, unmedicated MDD patients. PCC metabolite levels were analyzed at 3-T in a single voxel located bilaterally over the PCC in 7 patients diagnosed for the first time with MDD and with no previous pharmacological treatment, as well as in 9 control subjects. Differences in metabolite levels between groups were compared using independent t-tests. Myo-inositol was significantly higher, and NAA + NAAG/Cr significantly lower, in MDD patients than in controls. The other brain metabolites showed no statistical differences. The present results suggest that alterations in PCC metabolite levels are likely involved in MDD pathophysiology, and may help to improve our understanding of MDD and the role of the PCC in some symptoms of depression.
Cite this paper: Granados-Domínguez, L. , Flores-Gutiérrez, E. , Alcauter, S. , Cervantes, J. , Torres-Álvarez, M. and Corsi-Cabrera, M. (2013) Increased myo-inositol in the posterior cingulate cortex in first-episode major depressive patients. Advances in Bioscience and Biotechnology, 4, 45-52. doi: 10.4236/abb.2013.46A007.

[1]   World Health Organization (2001) The world health report.

[2]   Northoff, G. (2007) Psychopathology and pathophysiology of the self in depression—Neuropsychiatric hypothesis. Journal of Affective Disorders, 104, 1-14. doi:10.1016/j.jad.2007.02.012

[3]   Drevets, W.C., Videen, T.O., Price, J.L., Preskorn, S.H., Carmichael, S.T. and Raichle, M.E. (1992) A functional anatomical study of unipolar depression. Journal of Neuroscience, 12, 3628-3641.

[4]   Berman, M.G., Peltier, S., Nee, D.E., Kross, E., Deldin, P.J. and Jonides, J. (2011) Depression, rumination and the default network. Social Cognitive and Affective Neuroscience, 6, 548-555. doi:10.1093/scan/nsq080

[5]   Delaveau, P., Jabourian, M., Lemogne, C., Guionnet, S., Bergouignan, L. and Fossati, P. (2011) Brain effects of antidepressants in major depression: A meta-analysis of emotional processing studies. Journal of Affective Disorders, 130, 66-74. doi:10.1016/j.jad.2010.09.032

[6]   Fitzgerald, P.B., Laird, A.R., Maller, J. and Daskalakis, Z.J. (2008) A meta-analytic study of changes in brain activation in depression. Human Brain Mapping, 29, 683695. doi:10.1002/hbm.20426

[7]   Price, J.L. and Drevets, W.C. (2010) Neurocircuitry of mood disorders. Neuropsychopharmacology, 35, 192-216. doi:10.1038/npp.2009.104

[8]   Raichle, M.E. (2010) Two views of brain function. Trends in Cognitive Science, 14, 180-190. doi:10.1016/j.tics.2010.01.008

[9]   Lemogne, C., Mayberg, H., Bergouignan, L., Volle, E., Delaveau, P., Lehéricy, S. and Fossati, P. (2010) Selfreferential processing and the prefrontal cortex over the course of depression: A pilot study. Journal of Affective Disorders, 124, 196-201. doi:10.1016/j.jad.2009.11.003

[10]   Sajonz, B., Kahnt, T., Margulies, D.S., Park, S.Q., Wittmann, A., Stoy, M., Ströhle, A., Heinz, A., Northoff, G. and Bermpohl, F. (2010) Delineating self-referential processing from episodic memory retrieval: Common and dissociable networks. Neuroimage, 50, 1606-1617. doi:10.1016/j.neuroimage.2010.01.087

[11]   Kross, E., Davidson, M., Weber, J. and Ochsner, K. (2009) Coping with emotions past: The neural bases of regulating affect associated with negative autobiographical memories. Biological Psychiatry, 65, 361-366. doi:10.1016/j.biopsych.2008.10.019

[12]   Kjaer, T.W., Nowak, M., Kjaer, K.W., Lou, A.R. and Lou, H.C. (2001) Precuneus-prefrontal activity during awareness of visual verbal stimuli. Consciousness and Cognition, 10, 356-365. doi:10.1006/ccog.2001.0509

[13]   Sheline, Y.I., Barch, D.M., Price, J.L., Rundle, M.M., Vaishnavi, S.N., Snyder, A.Z., Mintun, M.A., Wang, S., Coalson, R.S. and Raichle, M.E. (2009) The default mode network and self-referential processes in depression. Proceedings of the National Academy of Sciences of the United States of America, 106, 1942-1947. doi:10.1073/pnas.0812686106

[14]   Sheline, Y.I., Price, J.L., Yan, Z. and Mintun, M.A. (2010) Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proceedings of the National Academy of Sciences of the United States of America, 107, 11020-11025. doi:10.1073/pnas.1000446107

[15]   Grimm, S., Boesiger, P., Beck, J., Schuepbach, D., Bermpohl, F., Walter, M., Ernst, J., Hell, D., Boeker, H. and Northoff, G. (2009) Altered negative BOLD responses in the default-mode network during emotion processing in depressed subjects. Neuropsychofarmacology, 34, 932-943. doi:10.1038/npp.2008.81

[16]   Skinner, E.I. and Fernandes, M.A. (2007) Neural correlates of recollection and familiarity: A review of neuroimaging and patient data. Neuropsychologia, 45, 21632179. doi:10.1016/j.neuropsychologia.2007.03.007

[17]   Svoboda, E., McKinnon, M.C. and Levine, B. (2006) The functional neuroanatomy of autobiographical memory: A meta-analysis. Neuropsychologia, 44, 2189-2208. doi:10.1016/j.neuropsychologia.2006.05.023

[18]   Northoff, G. and Bermpohl, F. (2004) Cortical midline structures and the self. Trends in Cognitive Science, 8, 102-107. doi:10.1016/j.tics.2004.01.004

[19]   Lemogne, C., Gorwood, P., Bergouignan, L., Pélissolo, A., Lehéricy, S. and Fossati, P. (2011) Negative affectivity, self referential processing and the cortical midline structures. Social Cognitive and Affective Neuroscience, 6, 426-433. doi:10.1093/scan/nsq049

[20]   Cooney, R.E., Joormann, J., Eugène, F., Dennis, E.L. and Gotlib, I.H. (2010) Neural correlates of rumination in depression. Cognitive, Affective and Behavioral Neuroscience, 10, 470-478. doi:10.3758/CABN.10.4.470

[21]   Järnum, H., Eskildsen, S.F., Steffensen, E.G., LundbyeChristensen, S., Simonsen, C.W., Thomsen, I.S., Fründ, E.T., Théberge, J. and Larsson, E.M. (2011) Longitudinal MRI study of cortical thickness, perfusion, and metabolite levels in major depressive disorder. Acta Psychiatrica Scandinavica, 124, 435-446. doi:10.1111/j.1600-0447.2011.01766.x

[22]   Lai, C.H., Hsu, Y.Y. and Wu, Y.T. (2010) First episode drug-naïve major depressive disorder with panic disorder: Gray matter deficits in limbic and default network structures. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 20, 676-682. doi:10.1016/j.euroneuro.2010.06.002

[23]   Bai, Y., Du, L., Shen, L., Zhang, Y. and Zhang, L. (2009) GPR56 is highly expressed in neural stem cells but downregulated during differentiation. Neuroreport, 20, 918-922. doi:10.1097/WNR.0b013e32832c92d7

[24]   Pizzagalli, D.A., Nitschke, J.B., Oakes, T.R., Hendrick, A.M., Horras, K.A., Larson, C.L., Abercrombie, H.C., Schaefer, J.V., Benca, R.M., Pascual-Marqui, R.D. and Davidson R.J. (2002) Brain electrical tomography in depression: The importance of symptom severity, anxiety and melancholic features. Biological Psychiatry, 52, 7385. doi:10.1016/S0006-3223(02)01313-6

[25]   Bremner, J.D., Vythilingam, M., Vermetten, E. and Charney, D.S. (2007) Effects of antidepressant treatment on neural correlates of emotional and neutral declarative verbal memory in depression. Journal of Affective Disorders, 101, 99-111. doi:10.1016/j.jad.2006.10.028

[26]   Fu, C.H., Williams, S.C., Cleare, A.J., Brammer, M.J., Walsh, N.D., Kim, J., Andrew, C.M., Pich, E.M., Williams, P.M., Reed, L.J., Mitterschiffthaler, M.T., Suckling, J. and Bullmore, E.T. (2004) Attenuation of the neural response to sad faces in major depression by antidepressant treatment. Archives of General Psychiatry, 61, 877-889. doi:10.1001/archpsyc.61.9.877

[27]   Yildiz-Yesiloglu, A. and Ankerst, D.P. (2006) Review of 1H magnetic resonance spectroscopy findings in major depressive disorder: A meta-analysis. Psychiatry Research, 147, 1-25. doi:10.1016/j.pscychresns.2005.12.004

[28]   Dager, S.R., Oskin, N.M., Richards, T.L. and Posse, S. (2008) Research applications of magnetic resonance spectroscopy (MRS) to investigate psychiatric disorders. Topics in Magnetic Resonance Imaging, 19, 81-96. doi:10.1097/RMR.0b013e318181e0be

[29]   Frey, R., Metzler, D., Fischer, P., Heiden, A., Scharfetter, J., Moser, E. and Kasper, S. (1998) Myo-inositol in depressive and healthy subjects determined by frontal 1H-magnetic resonance spectroscopy al 1.5 tesla. Journal of Psychiatric Research, 32, 411-420. doi:10.1016/S0022-3956(98)00033-8

[30]   Gruber, S., Frey, R., Mlynárik, V., Stadlbauer, A., Heiden, A., Kasper, S., Kemp, G.J. and Moser, E. (2003) Quantification of metabolic differences in the frontal brain of depressive patients and controls obtained by 1H-MRS at 3 tesla. Investigative Radiology, 38, 403-408. doi:10.1097/01.rli.0000073446.43445.20

[31]   Coupland, N.J., Ogilvie, C.J., Hegadoren, K.M., Seres, P., Hanstock, C.C. and Allen, P.S. (2005) Decreased prefrontal myo-inositol in major depressive disorder. Biological Psychiatry, 57, 1526-1534. doi:10.1016/j.biopsych.2005.02.027

[32]   Taylor, M.J., Selvaraj, S., Norbury, R., Jezzard, P. and Cowen, P.J. (2009) Normal glutamate but elevated myoinositol in anterior cingulate cortex in recovered depressed patients. Journal of Affective Disorders, 119, 186-189. doi:10.1016/j.jad.2009.02.022

[33]   Kaymak, S.U., Demir, B., Oguz, K.K., Sentürk, S. and Ulug, B. (2009) Antidepressant effect detected on proton magnetic resonance spectroscopy in drug-naive female patients with first-episode major depression. Psychiatry and Clinical Neurosciences, 63, 350-356. doi:10.1111/j.1440-1819.2009.01951.x

[34]   Wang, Y., Jia, Y., Xu, G., Ling, X., Liu, S. and Huang, L. (2012) Frontal white matter biochemical abnormalities in first-episode, treatment-naive patients with major depressive disorder: A proton magnetic resonance spectroscopy study. Journal of Affective Disorders, 136, 620-626. doi:10.1016/j.jad.2011.10.020

[35]   Portella, M.J., de Diego-Adelino, J., Gómez-Ansón, B., Morgan-Ferrando, R., Vives, Y., Puigdemont, D., PérezEgea, R., Ruscalleda, J., álvarez, E. and Pérez, V. (2011) Ventromedial prefrontal spectroscopic abnormalities over the course of depression: A comparison among first episode, remitted recurrent and chronic patients. Journal of Psychiatric Research, 45, 427-34. doi:10.1016/j.jpsychires.2010.08.010

[36]   Hasler, G., van der Veen, J.W., Tumonis, T., Meyers, N., Shen, J. and Drevets, W.C. (2007) Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Archives of General Psychiatry, 64, 193-200. doi:10.1001/archpsyc.64.2.193

[37]   Horn, D.I., Yu, C., Steiner, J., Buchmann, J., Kaufmann, J., Osoba, A., Eckert, U., Zierhut, K.C., Schiltz, K., He, H., Biswal, B., Bogerts, B. and Walter, M. (2010) Glutamatergic and resting-state functional connectivity correlates of severity in major depression—The role of pregenual anterior cingulate cortex and anterior insula. Frontiers in System Neuroscience, 4, 1-10.

[38]   American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders. American Psychiatric Press, Arlington.

[39]   Derogatis, L.R. (1997) SCL-90R: Administration, scoring and procedures manual for the revised version. John Hopkins University, Baltimore.

[40]   Hamilton, M. (1967) Development of a rating scale for primary depressive illness. The British Journal of Social and Clinical Psychology, 6, 278-96. doi:10.1111/j.2044-8260.1967.tb00530.x

[41]   Beck, A.T., Ward, C.H., Mendelson, M., Mock, J. and Erbaugh J. (1961) An inventory for measuring depression. Archives of General Psychiatry, 4, 561571. doi:10.1001/archpsyc.1961.01710120031004

[42]   Provencher, S. (2009) LCModel and LCMgui User’s Manual.

[43]   Zhu, X., Wang, X., Xiao, J., Liao, J., Zhong, M., Wang, W. and Yao, S. (2012) Evidence of a dissociation pattern in resting-state default mode network connectivity in first-episode, treatment-naive major depression patients. Biological Psychiatry, 71, 611-617. doi:10.1016/j.biopsych.2011.10.035

[44]   Davanzo, P., Yue, K., Thomas, M.A., Belin, T., Mintz, J., Venkatraman, T.N., Santoro, E., Barnett, A. and McCracken, J. (2003) Proton magnetic resonance spectroscopy of bipolar disorder versus intermittent explosive disorder in children and adolescents. American Journal of Psychiatry, 160, 1442-1452. doi:10.1176/appi.ajp.160.8.1442