Immunological Disturbances and Neuroimaging Findings in Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) Comorbid Patients

Andriana       Kakanakova; Stefan       Popov; Michael       Maes
Abstract

Mood disorders and Major Depressive Disorder, in particular, appear to be some of the most common psychiatric disorders with a high rate of comorbidity most frequently of anxiety or substance abuse disorders (alcohol use disorder). In both cases – MDD and AUD, a number of immunological disturbances are observed, such as chronic mild inflammation response, increased level of cytokines, hypercortisolaemia, which lead to specific changes in brain neurotransmitter functions.
Some of the contemporary brain imaging techniques are functional magnetic resonance imaging (fMRI) and magnetic spectroscopy which are most commonly used to assess the brain metabolism and functional connectivity changes such as altered responses to emotional stimuli in MDD or overactivation of ventromedial prefrontal areas during delayed and underactivation of dorsolateral prefrontal regions during impulsive reward decisions in AUD and dysfunction of gamma-aminobutyric acid (GABA) and/or glutamate neurotransmitter systems, low NAA and myo-Inositol in both MDD and AUD.
Keywords: Major depressive disorder, Alcohol use disorder, Cytokines, Bacterial gut translocation, Neuroimaging, Immunological disturbances.
[1] 
Gabbay, V.; Bradley, K.A.; Mao, X.; Ostrover, R.; Kang, G.; Shungu, D.C. Anterior cingulate cortex γ-aminobutyric acid deficits in youth with depression. Transl. Psychiatry,  2017, 7(8)e1216
[http://dx.doi.org/10.1038/tp.2017.187] [PMID: 28892070] 
[2] 
Coryell, W.; Winokur, G.; Keller, M.; Scheftner, W.; Endicott, J. Alcoholism and primary major depression: a family study approach to co-existing disorders. J. Affect. Disord.,  1992, 24(2), 93-99.
[http://dx.doi.org/10.1016/0165-0327(92)90023-Y] [PMID: 1541771] 
[3] 
Sadock, B.J.; Sadock, V.A.; Ruiz, P. Kaplan & Sadock’s Synopsis of Psychiatry Behavioral Sciences/Clinical Psychiatry, 11th ed; Wolters Kluwer: Philadelphia, 2015, p. 621.
[4] 
Roomruangwong, C.; Kanchanatawan, B.; Sirivichayakul, S.; Mahieu, B.; Nowak, G.; Maes, M. Lower serum zinc and higher crp strongly predict prenatal depression and physio-somatic symptoms, which all together predict postnatal depressive symptoms. Mol. Neurobiol.,  2017, 54(2), 1500-1512.
[http://dx.doi.org/10.1007/s12035-016-9741-5] [PMID: 26846364] 
[5] 
Kessler, R.C.; McGonagle, K.A.; Zhao, S.; Nelson, C.B.; Hughes, M.; Eshleman, S.; Wittchen, H.U.; Kendler, K.S. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch. Gen. Psychiatry,  1994, 51(1), 8-19.
[http://dx.doi.org/10.1001/archpsyc.1994.03950010008002] [PMID: 8279933] 
[6] 
Sadock, B.J.; Sadock, V.A. Kaplan and Sadock’s Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 11th ed; Lippincott Williams & Wilkins: Philadelphia, 2011, p. 625.
[7] 
Yang, X.R.; Langevin, L.M.; Jaworska, N.; Kirton, A.; Lebel, R.M.; Harris, A.D.; Jasaui, Y.; Wilkes, T.C.; Sembo, M.; Swansburg, R.; MacMaster, F.P. Proton spectroscopy study of the dorsolateral prefrontal cortex in youth with familial depression. Psychiatry Clin. Neurosci.,  2016, 70(7), 269-277.
[http://dx.doi.org/10.1111/pcn.12392] [PMID: 27059533] 
[8] 
Anderson, P. WHO reports 3 million alcohol-related deaths,  in 2016.
Available from: 
                    https://www.medscape.com/viewarticle/9026142018
[9] 
Brière, F.N.; Rohde, P.; Seeley, J.R.; Klein, D.; Lewinsohn, P.M. Comorbidity between major depression and alcohol use disorder from adolescence to adulthood. Compr. Psychiatry,  2014, 55(3), 526-533.
[http://dx.doi.org/10.1016/j.comppsych.2013.10.007] [PMID: 24246605] 
[10] 
de Rezende, M.G.; Rosa, C.E.; Garcia-Leal, C.; de Figueiredo, F.P.; Cavalli, R.C.; Bettiol, H.; Salmon, C.E.G.; Barbieri, M.A.; de Castro, M.; Carlos Dos Santos, A.; Del-Ben, C.M. Correlations between changes in the hypothalamic-pituitary-adrenal axis and neurochemistry of the anterior cingulate gyrus in postpartum depression. J. Affect. Disord.,  2018, 239, 274-281.
[http://dx.doi.org/10.1016/j.jad.2018.07.028] [PMID: 30029155] 
[11] 
Sapolsky, R.M.; Krey, L.C.; McEwen, B.S. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr. Rev.,  1986, 7(3), 284-301.
[http://dx.doi.org/10.1210/edrv-7-3-284] [PMID: 3527687] 
[12] 
Sapolsky, R.M. Potential behavioral modification of glucocorticoid damage to the hippocampus. Behav. Brain Res.,  1993, 57(2), 175-182.
[http://dx.doi.org/10.1016/0166-4328(93)90133-B] [PMID: 8117422] 
[13] 
Sapolsky, R.M. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch. Gen. Psychiatry,  2000, 57(10), 925-935.
[http://dx.doi.org/10.1001/archpsyc.57.10.925] [PMID: 11015810] 
[14] 
Yang, P.; Tao, R.; He, C.; Liu, S.; Wang, Y.; Zhang, X. The risk factors of the alcohol use disorders-through review of its comorbidities. Front. Neurosci.,  2018, 12, 303.
[http://dx.doi.org/10.3389/fnins.2018.00303] 
[15] 
Goldstein, A.N.; Walker, M.P. The role of sleep in emotional brain function. Annu. Rev. Clin. Psychol.,  2014, 10, 679-708.
[http://dx.doi.org/10.1146/annurev-clinpsy-032813-153716] [PMID: 24499013] 
[16] 
Urrila, A.S.; Hakkarainen, A.; Castaneda, A.; Paunio, T.; Marttunen, M.; Lundbom, N. Frontal cortex myo-inositol is associated with sleep and depression in adolescents: a proton magnetic resonance spectroscopy study. Neuropsychobiology,  2017, 75(1), 21-31.
[http://dx.doi.org/10.1159/000478861] [PMID: 28793304] 
[17] 
Bishehsari, F.; Magno, E.; Swanson, G.; Desai, V.; Voigt, R.M.; Forsyth, C.B. Keshavarzian, a. alcohol and gut-derived inflammation. Alcohol Res.,  2017, 38(2), 163-171.
[PMID: 28988571] 
[18] 
Leclercq, S.; de Timary, P.; Delzenne, N.M.; Stärkel, P. The link between inflammation, bugs, the intestine and the brain in alcohol dependence. Transl. Psychiatry,  2017, 7(2) e1048
[http://dx.doi.org/10.1038/tp.2017.15] [PMID: 28244981] 
[19] 
Prisciandaro, J.J.; Schacht, J.P.; Prescot, A.P.; Renshaw, P.F.; Brown, T.R.; Anton, R.F. Associations between recent heavy drinking and dorsal anterior cingulate n-acetylaspartate and glutamate concentrations in non-treatment-seeking individuals with alcohol dependence. Alcohol. Clin. Exp. Res.,  2016, 40(3), 491-496.
[http://dx.doi.org/10.1111/acer.12977] [PMID: 26853538] 
[20] 
Anisman, H.; Hayley, S. Inflammatory factors contribute to depression and its comorbid conditions. Sci. Signal.,  2012, 5(244), pe45.
[http://dx.doi.org/10.1126/scisignal.2003579] [PMID: 23033537] 
[21] 
Duffy, S.L.; Lagopoulos, J.; Cockayne, N.; Hermens, D.F.; Hickie, I.B.; Naismith, S.L. Oxidative stress and depressive symptoms in older adults: A magnetic resonance spectroscopy study. J. Affect. Disord.,  2015, 180(180), 29-35.
[http://dx.doi.org/10.1016/j.jad.2015.03.007] [PMID: 25881278] 
[22] 
Merikangas, K.R.; Risch, N.J.; Weissman, M.M. Comorbidity and co-transmission of alcoholism, anxiety and depression. Psychol. Med.,  1994, 24(1), 69-80.
[http://dx.doi.org/10.1017/S0033291700026842] [PMID: 8208896] 
[23] 
Meyer, J.H. Neuroprogression and immune activation in major depressive disorder. Mod. Trends Pharmacopsychiatry,  2017, 31, 27-36.
[http://dx.doi.org/10.1159/000470804] [PMID: 28738332] 
[24] 
Sacks, J.J.; Gonzales, K.R.; Bouchery, E.E.; Tomedi, L.E.; Brewer, R.D. 2010 national and state costs of excessive alcohol consumption. Am. J. Prev. Med.,  2015, 49(5), e73-e79.
[http://dx.doi.org/10.1016/j.amepre.2015.05.031] [PMID: 26477807] 
[25] 
Dowlati, Y.; Herrmann, N.; Swardfager, W.; Liu, H.; Sham, L.; Reim, E.K.; Lanctôt, K.L. A meta-analysis of cytokines in major depression. Biol. Psychiatry,  2010, 67(5), 446-457.
[http://dx.doi.org/10.1016/j.biopsych.2009.09.033] [PMID: 20015486] 
[26] 
Lichtblau, N.; Schmidt, F.M.; Schumann, R.; Kirkby, K.C.; Himmerich, H. Cytokines as biomarkers in depressive disorder: current standing and prospects. Int. Rev. Psychiatry,  2013, 25(5), 592-603.
[http://dx.doi.org/10.3109/09540261.2013.813442] [PMID: 24151804] 
[27] 
Maes, M.; Kubera, M.; Leunis, J.C.; Berk, M. Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut. J. Affect. Disord.,  2012, 141(1), 55-62.
[http://dx.doi.org/10.1016/j.jad.2012.02.023] [PMID: 22410503] 
[28] 
Bonaccorso, S.; Marino, V.; Biondi, M.; Grimaldi, F.; Ippoliti, F.; Maes, M. Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus. J. Affect. Disord.,  2002, 72(3), 237-241.
[http://dx.doi.org/10.1016/S0165-0327(02)00264-1] [PMID: 12450640] 
[29] 
Maes, M.; Kubera, M.; Leunis, J.C. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuroendocrinol. Lett.,  2008, 29(1), 117-124.
[PMID: 18283240] 
[30] 
Maes, M.; Mihaylova, I.; Kubera, M.; Leunis, J.C.; Geffard, M. IgM-mediated autoimmune responses directed against multiple neoepitopes in depression: new pathways that underpin the inflammatory and neuroprogressive pathophysiology. J. Affect. Disord.,  2011, 135(1-3), 414-418.
[http://dx.doi.org/10.1016/j.jad.2011.08.023] [PMID: 21930301] 
[31] 
Maes, M.; Kubera, M.; Mihaylova, I.; Geffard, M.; Galecki, P.; Leunis, J.C.; Berk, M. Increased autoimmune responses against auto-epitopes modified by oxidative and nitrosative damage in depression: implications for the pathways to chronic depression and neuroprogression. J. Affect. Disord.,  2013, 149(1-3), 23-29.
[http://dx.doi.org/10.1016/j.jad.2012.06.039] [PMID: 22898471] 
[32] 
Mayberg, H.S.; Liotti, M.; Brannan, S.K.; McGinnis, S.; Mahurin, R.K.; Jerabek, P.A.; Silva, J.A.; Tekell, J.L.; Martin, C.C.; Lancaster, J.L.; Fox, P.T. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am. J. Psychiatry,  1999, 156(5), 675-682.
[PMID: 10327898] 
[33] 
Maes, M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuroendocrinol. Lett.,  2008, 29(3), 287-291.
[PMID: 18580840] 
[34] 
Hillemacher, T.; Bachmann, O.; Kahl, K.G.; Frieling, H. Alcohol, microbiome, and their effect on psychiatric disorders.,  Prog.
Neuropsychopharmacol. Biol. Psychiatry, 2018, 85, 105-115.
[Review]
[http://dx.doi.org/10.1016/j.pnpbp.2018.04.015] [PMID: 29705711] 
[35] 
Maes, M.; Galecki, P.; Chang, Y.S.; Berk, M.  A review on the
oxidative and nitrosative stress (O&NS) pathways in major
depression and their possible contribution to the
(neuro)degenerative processes in that illness. Prog.
Neuropsychopharmacol. Biol. Psychiatry, 2011, 35(3), 676-692.
[Review].
[http://dx.doi.org/10.1016/j.pnpbp.2010.05.004] [PMID: 20471444] 
[36] 
Stärkel, P.; Leclercq, S.; de Timary, P.; Schnabl, B. Intestinal dysbiosis and permeability: the yin and yang in alcohol dependence and alcoholic liver disease. Clin. Sci. (Lond.),  2018, 132(2), 199-212.
[http://dx.doi.org/10.1042/CS20171055] 
[37] 
Flores-Bastías, O.; Karahanian, E. Neuroinflammation produced by heavy alcohol intake is due to loops of interactions between Toll-like 4 and TNF receptors, peroxisome proliferator-activated receptors and the central melanocortin system: A novel hypothesis and new therapeutic avenues. Neuropharmacology,  2018, 128, 401-407.
[http://dx.doi.org/10.1016/j.neuropharm.2017.11.003] [PMID: 29113896] 
[38] 
Sureshchandra, S.; Raus, A.; Jankeel, A.; Ligh, B.J.K.; Walter, N.A.R.; Newman, N.; Grant, K.A.; Messaoudi, I. Dose-dependent effects of chronic alcohol drinking on peripheral immune responses. Sci. Rep.,  2019, 9(1), 7847.
[http://dx.doi.org/10.1038/s41598-019-44302-3] [PMID: 31127176] 
[39] 
Khan, A.R.; Hansen, B.; Wiborg, O.; Kroenke, C.D.; Jespersen, S.N. Diffusion MRI and MR spectroscopy reveal microstructural and metabolic brain alterations in chronic mild stress exposed rats: A CMS recovery study. Neuroimage,  2018, 167, 342-353.
[http://dx.doi.org/10.1016/j.neuroimage.2017.11.053] [PMID: 29196269] 
[40] 
Song, T.; Han, X.; Du, L.; Che, J.; Liu, J.; Shi, S.; Fu, C.; Gao, W.; Lu, J.; Ma, G. The role of neuroimaging in the diagnosis and treatment of depressive disorder: a recent review.,  Curr. Pharm.
	Des., 2018, 24(22), 2515-2523. [Review].
[http://dx.doi.org/10.2174/1381612824666180727111142] [PMID: 30051778] 
[41] 
Demenescu, L.R.; Colic, L.; Li, M.; Safron, A.; Biswal, B.; Metzger, C.D.; Li, S.; Walter, M. A spectroscopic approach toward depression diagnosis: local metabolism meets functional connectivity. Eur. Arch. Psychiatry Clin. Neurosci.,  2017, 267(2), 95-105.
[http://dx.doi.org/10.1007/s00406-016-0726-1] [PMID: 27561792] 
[42] 
Dichter, G.S.; Gibbs, D.; Smoski, M.J. A systematic review of relations between resting-state functional-MRI and treatment response in major depressive disorder. J. Affect. Disord.,  2015, 172, 8-17.
[http://dx.doi.org/10.1016/j.jad.2014.09.028] [PMID: 25451389] 
[43] 
Duan, C.; Cosgrove, J.; Deligiannidis, K.M. Understanding peripartum depression through neuroimaging: a review of structural and functional connectivity and molecular imaging research. Curr. Psychiatry Rep.,  2017, 19(10), 70.
[http://dx.doi.org/10.1007/s11920-017-0824-4] [PMID: 28823105] 
[44] 
Poznyak, V.; Rekve, D. Global status report on alcohol and health, 2018.  Available from: http://www.who.int/substance_abuse/publications/global_alcohol_report/gsr_2018/en/
[45] 
Zheng, H.; Jia, F.; Guo, G.; Quan, D.; Li, G.; Wu, H.; Zhang, B.; Fan, C.; He, X.; Huang, H. Abnormal anterior cingulate n-acetylaspartate and executive functioning in treatment-resistant depression after rTMS therapy. Int. J. Neuropsychopharmacol.,  2015, 18(11) pyv059
[http://dx.doi.org/10.1093/ijnp/pyv059] [PMID: 26025780] 
[46] 
Zhuo, C.; Zhu, J.; Wang, C.; Qu, H.; Ma, X.; Qin, W. Different spatial patterns of brain atrophy and global functional connectivity impairments in major depressive disorder. Brain Imaging Behav.,  2017, 11(6), 1678-1689.
[http://dx.doi.org/10.1007/s11682-016-9645-z] [PMID: 27766588] 
[47] 
Ambrosi, E.; Arciniegas, D.B.; Madan, A.; Curtis, K.N.; Patriquin, M.A.; Jorge, R.E.; Spalletta, G.; Fowler, J.C.; Frueh, B.C.; Salas, R. Insula and amygdala resting-state functional connectivity differentiate bipolar from unipolar depression. Acta Psychiatr. Scand.,  2017, 136(1), 129-139.
[http://dx.doi.org/10.1111/acps.12724] [PMID: 28369737] 
[48] 
Baeken, C.; Lefaucheur, J.P.; Van Schuerbeek, P. The impact of accelerated high frequency rTMS on brain neurochemicals in treatment-resistant depression: Insights from 1H MR spectroscopy. Clin. Neurophysiol.,  2017, 128(9), 1664-1672.
[http://dx.doi.org/10.1016/j.clinph.2017.06.243] [PMID: 28738276] 
[49] 
Cano, M.; Martínez-Zalacaín, I.; Bernabéu-Sanz, Á.; Contreras-Rodríguez, O.; Hernández-Ribas, R.; Via, E.; de Arriba-Arnau, A.; Gálvez, V.; Urretavizcaya, M.; Pujol, J.; Menchón, J.M.; Cardoner, N.; Soriano-Mas, C. Brain volumetric and metabolic correlates of electroconvulsive therapy for treatment-resistant depression: a longitudinal neuroimaging study. Transl. Psychiatry,  2017, 7(2)e1023
[http://dx.doi.org/10.1038/tp.2016.267] [PMID: 28170003] 
[50] 
Flores-Ramos, M.; Salinas, M.; Carvajal-Lohr, A.; Rodríguez-Bores, L. The role of gamma-aminobutyric acid in female depression. Gac. Med. Mex.,  2017, 153(4), 486-495.
[http://dx.doi.org/10.24875/GMM.17002544] [PMID: 28991279] 
[51] 
Freed, R.D.; Hollenhorst, C.N.; Weiduschat, N.; Mao, X.; Kang, G.; Shungu, D.C.; Gabbay, V. A pilot study of cortical glutathione in youth with depression. Psychiatry Res. Neuroimaging,  2017, 270, 54-60.
[http://dx.doi.org/10.1016/j.pscychresns.2017.10.001] [PMID: 29078101] 
[52] 
Knudsen, M.K.; Near, J.; Blicher, A.B.; Videbech, P.; Blicher, J.U. Magnetic resonance (MR) spectroscopic measurement of γ-aminobutyric acid (GABA) in major depression before and after electroconvulsive therapy. Acta Neuropsychiatr.,  2019, 31(1), 17-26.
[http://dx.doi.org/10.1017/neu.2018.22] [PMID: 30079857] 
[53] 
Romeo, B.; Choucha, W.; Fossati, P.; Rotge, J.Y. Meta-analysis of central and peripheral γ-aminobutyric acid levels in patients with unipolar and bipolar depression. J. Psychiatry Neurosci.,  2018, 43(1), 58-66.
[http://dx.doi.org/10.1503/jpn.160228] [PMID: 29252166] 
[54] 
Sadock, B.J.; Sadock, V.A.; Ruiz, P. Kaplan & Sadock’s Synopsis of Psychiatry Behavioral Sciences/Clinical Psychiatry, 11th ed; Wolters Kluwer: Philadelphia, 2015, pp. 348-351.
[55] 
Ernst, J.; Hock, A.; Henning, A.; Seifritz, E.; Boeker, H.; Grimm, S. Increased pregenual anterior cingulate glucose and lactate concentrations in major depressive disorder. Mol. Psychiatry,  2017, 22(1), 113-119.
[http://dx.doi.org/10.1038/mp.2016.73] [PMID: 27184123] 
[56] 
Figueroa, C.A.; Mocking, R.J.T.; van Wingen, G.; Martens, S.; Ruhé, H.G.; Schene, A.H. Aberrant default-mode network-hippocampus connectivity after sad memory-recall in remitted-depression. Soc. Cogn. Affect. Neurosci.,  2017, 12(11), 1803-1813.
[http://dx.doi.org/10.1093/scan/nsx108] [PMID: 28981917] 
[57] 
Hamilton, J.P.; Farmer, M.; Fogelman, P.; Gotlib, I.H. Depressive rumination, the default-mode network, and the dark matter of clinical neuroscience. Biol. Psychiatry,  2015, 78(4), 224-230.
[http://dx.doi.org/10.1016/j.biopsych.2015.02.020] [PMID: 25861700] 
[58] 
Kang, S.G.; Na, K.S.; Choi, J.W.; Kim, J.H.; Son, Y.D.; Lee, Y.J. Resting-state functional connectivity of the amygdala in suicide attempters with major depressive disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2017, 77, 222-227.
[http://dx.doi.org/10.1016/j.pnpbp.2017.04.029] [PMID: 28445688] 
[59] 
Kessler, R.C.; Price, R.H. Primary prevention of secondary disorders: a proposal and agenda. Am. J. Community Psychol.,  1993, 21(5), 607-633.
[http://dx.doi.org/10.1007/BF00942174] [PMID: 8192124] 
[60] 
Lee, T.S.; Quek, S.Y.; Krishnan, K.R. Molecular imaging for depressive disorders. AJNR Am. J. Neuroradiol.,  2014, 35(6)(Suppl.), S44-S54.
[http://dx.doi.org/10.3174/ajnr.A3965] 
[61] 
Mannie, Z.N.; Filippini, N.; Williams, C.; Near, J.; Mackay, C.E.; Cowen, P.J. Structural and functional imaging of the hippocampus in young people at familial risk of depression. Psychol. Med.,  2014, 44(14), 2939-2948.
[http://dx.doi.org/10.1017/S0033291714000580] [PMID: 25066547] 
[62] 
Sambataro, F.; Visintin, E.; Doerig, N.; Brakowski, J.; Holtforth, M.G.; Seifritz, E.; Spinelli, S. Altered dynamics of brain connectivity in major depressive disorder at-rest and during task performance. Psychiatry Res. Neuroimaging,  2017, 259, 1-9.
[http://dx.doi.org/10.1016/j.pscychresns.2016.11.001] [PMID: 27918910] 
[63] 
Wang, Y.; Chen, G.; Zhong, S.; Jia, Y.; Xia, L.; Lai, S.; Zhao, L.; Huang, L.; Liu, T. Association between resting-state brain functional connectivity and cortisol levels in unmedicated major depressive disorder. J. Psychiatr. Res.,  2018, 105, 55-62.
[http://dx.doi.org/10.1016/j.jpsychires.2018.08.025] [PMID: 30189325] 
[64] 
Li, Y.; Yan, J.; Wang, D.; Sun, M.; Zhu, Y.; Zhu, X.; Jiang, P.; Yin, R.; Zhao, L. Magnetic resonance study of the structure and function of the hippocampus and amygdala in patients with depression. Chin. Med. J. (Engl.),  2014, 127(20), 3610-3615.
[PMID: 25316238] 
[65] 
Shen, Z.; Jiang, L.; Yang, S.; Ye, J.; Dai, N.; Liu, X.; Li, N.; Lu, J.; Liu, F.; Lu, Y.; Sun, X. X. Identify changes of brain regional homogeneity in early and later adult onset patients with first-episode depression using resting-state fMRI. PLoS One,  2017, 12(9) e0184712
[66] 
Shirayama, Y.; Takahashi, M.; Osone, F.; Hara, A.; Okubo, T. Myo-inositol, glutamate, and glutamine in the prefrontal cortex, hippocampus, and amygdala in major depression. Biol. Psychiatry Cogn. Neurosci. Neuroimaging,  2017, 2(2), 196-204.
[http://dx.doi.org/10.1016/j.bpsc.2016.11.006] [PMID: 29560915] 
[67] 
Yang, Y.; Zhong, N.; Imamura, K.; Lu, S.; Li, M.; Zhou, H.; Li, H.;
Yang, X.; Wan, Z.; Wang, G.; Hu, B.; Li, K Gender differences in brain activity and the relationship between brain activity and differences in prevalence rates between male and female major depressive disorder patients: a resting-state fMRI study. Clin. Neurophysiol.,  2014, 125(11), 2232-2239.
[68] 
Yao, Z.; Yan, R.; Wei, M.; Tang, H.; Qin, J.; Lu, Q. Gender differences in brain activity and the relationship between brain activity and differences in prevalence rates between male and female major depressive disorder patients: a resting-state fMRI study. Clin. Neurophysiol.,  2014, 125(11), 2232-2239.
[http://dx.doi.org/10.1016/j.clinph.2014.03.006] [PMID: 24746685] 
[69] 
Young, K.D.; Bodurka, J.; Drevets, W.C. Functional neuroimaging of sex differences in autobiographical memory recall in depression. Psychol. Med.,  2017, 47(15), 2640-2652.
[http://dx.doi.org/10.1017/S003329171700112X] [PMID: 28446254] 
[70] 
Yüksel, D.; Dietsche, B.; Konrad, C.; Dannlowski, U.; Kircher, T.; Krug, A. Neural correlates of working memory in first episode and
	recurrent depression: An fMRI study. Prog.
		Neuropsychopharmacol. Biol. Psychiatry., 2018, 84(Pt A), 39-49. 
[71] 
Gazdzinski, S.; Durazzo, T.C.; Mon, A.; Meyerhoff, D.J. Body mass index is associated with brain metabolite levels in alcohol dependence--a multimodal magnetic resonance study. Alcohol. Clin. Exp. Res.,  2010, 34(12), 2089-2096.
[http://dx.doi.org/10.1111/j.1530-0277.2010.01305.x] [PMID: 21087290] 
[72] 
Harrison, N.A.; Brydon, L.; Walker, C.; Gray, M.A.; Steptoe, A.; Critchley, H.D. Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol. Psychiatry,  2009, 66(5), 407-414.
[http://dx.doi.org/10.1016/j.biopsych.2009.03.015] [PMID: 19423079] 
[73] 
Rae, C.D.; Williams, S.R. Glutathione in the human brain: Review of its roles and measurement by magnetic resonance spectroscopy. Anal. Biochem.,  2017, 529, 127-143.
[http://dx.doi.org/10.1016/j.ab.2016.12.022] [PMID: 28034792] 
[74] 
Riley, C.A.; Renshaw, P.F. Brain choline in major depression: A review of the literature. Psychiatry Res. Neuroimaging,  2018, 271, 142-153.
[http://dx.doi.org/10.1016/j.pscychresns.2017.11.009] [PMID: 29174766] 
[75] 
Rosenbaum, D.; Haipt, A.; Fuhr, K.; Haeussinger, F.B.; Metzger, F.G.; Nuerk, H.C.; Fallgatter, A.J.; Batra, A.; Ehlis, A.C. Aberrant functional connectivity in depression as an index of state and trait rumination. Sci. Rep.,  2017, 7(1), 2174.
[http://dx.doi.org/10.1038/s41598-017-02277-z] [PMID: 28526867] 
[76] 
Takamura, M.; Okamoto, Y.; Okada, G.; Toki, S.; Yamamoto, T.; Yamamoto, O.; Jitsuiki, H.; Yokota, N.; Tamura, T.; Kurata, A.; Kaichi, Y.; Akiyama, Y.; Awai, K.; Yamawaki, S. Disrupted brain activation and deactivation pattern during semantic verbal fluency task in patients with major depression. Neuropsychobiology,  2016, 74(2), 69-77.
[http://dx.doi.org/10.1159/000453399] [PMID: 28052303] 
[77] 
Godlewska, B.R.; Near, J.; Cowen, P.J. Neurochemistry of major depression: a study using magnetic resonance spectroscopy. Psychopharmacology (Berl.),  2015, 232(3), 501-507.
[http://dx.doi.org/10.1007/s00213-014-3687-y] [PMID: 25074444] 
[78] 
Gong, L.; Yin, Y.; He, C.; Ye, Q.; Bai, F.; Yuan, Y.; Zhang, H.; Lv, L.; Zhang, H.; Xie, C.; Zhang, Z. Disrupted reward circuits is associated with cognitive deficits and depression severity in major depressive disorder. J. Psychiatr. Res.,  2017, 84, 9-17.
[http://dx.doi.org/10.1016/j.jpsychires.2016.09.016] [PMID: 27673704] 
[79] 
Jenkins, L.M.; Kendall, A.D.; Kassel, M.T.; Patrón, V.G.; Gowins, J.R.; Dion, C.; Shankman, S.A.; Weisenbach, S.L.; Maki, P.; Langenecker, S.A. Considering sex differences clarifies the effects of depression on facial emotion processing during fMRI. J. Affect. Disord.,  2018, 225, 129-136.
[http://dx.doi.org/10.1016/j.jad.2017.08.027] [PMID: 28826089] 
[80] 
Kang, L.; Zhang, A.; Sun, N.; Liu, P.; Yang, C.; Li, G.; Liu, Z.; Wang, Y.; Zhang, K. Functional connectivity between the thalamus and the primary somatosensory cortex in major depressive disorder: a resting-state fMRI study. BMC Psychiatry,  2018, 18(1), 339.
[http://dx.doi.org/10.1186/s12888-018-1913-6] [PMID: 30340472] 
[81] 
Stoyanov, D.; Kandilarova, S.; Borgwardt, S.; Stieglitz, R.D.; Hugdahl, K.; Kostianev, S. Psychopathology assessment Methods revisited: On Translational cross-Validation of clinical self-evaluation scale and fMri. Front. Psychiatry,  2018, 9, 21.
[http://dx.doi.org/10.3389/fpsyt.2018.00021] 
[82] 
Le, T.M.; Borghi, J.A.; Kujawa, A.J.; Klein, D.N.; Leung, H.C. Alterations in visual cortical activation and connectivity with prefrontal cortex during working memory updating in major depressive disorder. Neuroimage Clin.,  2017, 14, 43-53.
[http://dx.doi.org/10.1016/j.nicl.2017.01.004] 
[83] 
Knyazev, G.G.; Savostyanov, A.N.; Bocharov, A.V.; Brak, I.V.; Osipov, E.A.; Filimonova, E.A.; Saprigyn, A.E.; Aftanas, L.I. Task-positive and task-negative networks in major depressive disorder: A combined fMRI and EEG study. J. Affect. Disord.,  2018, 235, 211-219.
[http://dx.doi.org/10.1016/j.jad.2018.04.003] [PMID: 29656269] 
[84] 
Miller, J.M.; Schneck, N.; Siegle, G.J.; Chen, Y.; Ogden, R.T.; Kikuchi, T.; Oquendo, M.A.; Mann, J.J.; Parsey, R.V. fMRI response to negative words and SSRI treatment outcome in major depressive disorder: a preliminary study. Psychiatry Res.,  2013, 214(3), 296-305.
[http://dx.doi.org/10.1016/j.pscychresns.2013.08.001] [PMID: 24446548] 
[85] 
Biedermann, S.V.; Weber-Fahr, W.; Demirakca, T.; Tunc-Skarka, N.; Hoerst, M.; Henn, F.; Sartorius, A.; Ende, G. 31P RINEPT MRSI and VBM reveal alterations in brain aging associated with major depression. Magn. Reson. Med.,  2015, 73(4), 1390-1400.
[http://dx.doi.org/10.1002/mrm.25278] [PMID: 24798730] 
[86] 
Brennan, B.P.; Admon, R.; Perriello, C.; LaFlamme, E.M.; Athey, A.J.; Pizzagalli, D.A.; Hudson, J.I.; Pope, H.G., Jr; Jensen, J.E. Acute change in anterior cingulate cortex GABA, but not glutamine/glutamate, mediates antidepressant response to citalopram. Psychiatry Res. Neuroimaging,  2017, 269, 9-16.
[http://dx.doi.org/10.1016/j.pscychresns.2017.08.009] [PMID: 28892734] 
[87] 
Henriques, J.F.; Portugal, C.C.; Canedo, T.; Relvas, J.B.; Summavielle, T.; Socodato, R. Microglia and alcohol meet at the
crossroads: Microglia as critical modulators of alcohol
	neurotoxicity. Toxicol. Lett., 2018, 283, 21-31. [Review]. 
[http://dx.doi.org/10.1016/j.toxlet.2017.11.002] [PMID: 29129797] 
[88] 
Harper, D.G.; Joe, E.B.; Jensen, J.E.; Ravichandran, C.; Forester, B.P. Brain levels of high-energy phosphate metabolites and executive function in geriatric depression. Int. J. Geriatr. Psychiatry,  2016, 31(11), 1241-1249.
[http://dx.doi.org/10.1002/gps.4439] [PMID: 26891040] 
[89] 
Jayaweera, H.K.; Lagopoulos, J.; Duffy, S.L.; Lewis, S.J.; Hermens, D.F.; Norrie, L.; Hickie, I.B.; Naismith, S.L. Spectroscopic markers of memory impairment, symptom severity and age of onset in older people with lifetime depression: Discrete roles of N-acetyl aspartate and glutamate. J. Affect. Disord.,  2015, 183, 31-38.
[http://dx.doi.org/10.1016/j.jad.2015.04.023] [PMID: 26000754] 
[90] 
Liu, C.H.; Ma, X.; Yuan, Z.; Song, L.P.; Jing, B.; Lu, H.Y.; Tang, L.R.; Fan, J.; Walter, M.; Liu, C.Z.; Wang, L.; Wang, C.Y. Decreased resting-state activity in the precuneus is associated with depressive episodes in recurrent depression. J. Clin. Psychiatry,  2017, 78(4), e372-e382.
[http://dx.doi.org/10.4088/JCP.15m10022] [PMID: 28297595] 
[91] 
Frischknecht, U.; Hermann, D.; Tunc-Skarka, N.; Wang, G.Y.; Sack, M.; van Eijk, J.; Demirakca, T.; Falfan-Melgoza, C.; Krumm, B.; Dieter, S.; Spanagel, R.; Kiefer, F.; Mann, K.F.; Sommer, W.H.; Ende, G.; Weber-Fahr, W. Negative association between mr-spectroscopic glutamate markers and gray matter volume after alcohol withdrawal in the hippocampus: a translational study in humans and rats. Alcohol. Clin. Exp. Res.,  2017, 41(2), 323-333.
[http://dx.doi.org/10.1111/acer.13308] [PMID: 28098946] 
[92] 
Godfrey, K.E.M.; Gardner, A.C.; Kwon, S.; Chea, W.; Muthukumaraswamy, S.D. Differences in excitatory and inhibitory neurotransmitter levels between depressed patients and healthy controls: A systematic review and meta-analysis. J. Psychiatr. Res.,  2018, 105, 33-44.
[http://dx.doi.org/10.1016/j.jpsychires.2018.08.015] [PMID: 30144668] 
[93] 
Haroon, E.; Chen, X.; Li, Z.; Patel, T.; Woolwine, B.J.; Hu, X.P.; Felger, J.C.; Miller, A.H. Increased inflammation and brain glutamate define a subtype of depression with decreased regional homogeneity, impaired network integrity, and anhedonia. Transl. Psychiatry,  2018, 8(1), 189.
[http://dx.doi.org/10.1038/s41398-018-0241-4] [PMID: 30202011] 
[94] 
Haroon, E.; Miller, A.H. Inflammation effects on brain glutamate in depression: mechanistic considerations and treatment implications.,  Curr. Top. Behav. Neurosci., 2017, 31, 173-198. [Review].
[http://dx.doi.org/10.1007/7854_2016_40 ] [PMID: 27830574 ] 
[95] 
Mikkelsen, M.; Barker, P.B.; Bhattacharyya, P.K.; Brix, M.K.; Buur, P.F.; Cecil, K.M.; Chan, K.L.; Chen, D.Y.; Craven, A.R.; Cuypers, K.; Dacko, M.; Duncan, N.W.; Dydak, U.; Edmondson, D.A.; Ende, G.; Ersland, L.; Gao, F.; Greenhouse, I.; Harris, A.D.; He, N.; Heba, S.; Hoggard, N.; Hsu, T.W.; Jansen, J.F.A.; Kangarlu, A.; Lange, T.; Lebel, R.M.; Li, Y.; Lin, C.E.; Liou, J.K.; Lirng, J.F.; Liu, F.; Ma, R.; Maes, C.; Moreno-Ortega, M.; Murray, S.O.; Noah, S.; Noeske, R.; Nosworthy, M.D.; Oeltzschner, G.; Prisciandaro, J.J.; Puts, N.A.J.; Roberts, T.P.L.; Sack, M.; Sailasuta, N.; Saleh, M.G.; Schallmo, M.P.; Simard, N.; Swinnen, S.P.; Tegenthoff, M.; Truong, P.; Wang, G.; Wilkinson, I.D.; Wittsack, H.J.; Xu, H.; Yan, F.; Zhang, C.; Zipunnikov, V.; Zöllner, H.J.; Edden, R.A.E.  .Big
	GABA: Edited MR spectroscopy at 24 research sites. Neuroimage,
	2017, 159, 32-45.
[96] 
Bühler, M.; Mann, K. Alcohol and the human brain: a systematic review of different neuroimaging methods. Alcohol. Clin. Exp. Res.,  2011, 35(10), 1771-1793.
[http://dx.doi.org/10.1111/j.1530-0277.2011.01540.x] [PMID: 21777260] 
[97] 
Harper, C.; Matsumoto, I. Ethanol and brain damage.,   Curr. Opin.
	Pharmacol., 2005, 5(1), 73-78. [Review].
[http://dx.doi.org/10.1016/j.coph.2004.06.011] [PMID: 15661629] 
[98] 
Nagel, B.J.; Kroenke, C.D. The use of magnetic resonance spectroscopy and magnetic resonance imaging in alcohol research.,  Alcohol Res. Health, 2008, 31(3), 243-246. [Review].
[PMID: 23584867] 
[99] 
O’Neill, J.; Cardenas, V.A.; Meyerhoff, D.J. Effects of abstinence on the brain: quantitative magnetic resonance imaging and magnetic resonance spectroscopic imaging in chronic alcohol abuse. Alcohol. Clin. Exp. Res.,  2001, 25(11), 1673-1682.
[http://dx.doi.org/10.1111/j.1530-0277.2001.tb02174.x] [PMID: 11707642] 
[100] 
Thayer, R.E.; YorkWilliams, S.; Karoly, H.C.; Sabbineni, A.; Ewing, S.F.; Bryan, A.D.; Hutchison, K.E. Structural neuroimaging correlates of alcohol and cannabis use in adolescents and adults. Addiction,  2017, 112(12), 2144-2154.
[http://dx.doi.org/10.1111/add.13923] [PMID: 28646566] 
[101] 
Watson, S.; Mackin, P. HPA axis function in mood disorders. Elsevier Psychiatry,  2006, 5(5), 166-170.
[http://dx.doi.org/10.1383/psyt.2006.5.5.166] 
[102] 
Zahr, N.M.; Carr, R.A.; Rohlfing, T.; Mayer, D.; Sullivan, E.V.; Colrain, I.M.; Pfefferbaum, A. Brain metabolite levels in recently sober individuals with alcohol use disorder: Relation to drinking variables and relapse. Psychiatry Res. Neuroimaging,  2016, 250, 42-49.
[http://dx.doi.org/10.1016/j.pscychresns.2016.01.015] [PMID: 27035062] 
[103] 
Zakiniaeiz, Y.; Scheinost, D.; Seo, D.; Sinha, R.; Constable, R.T. Cingulate cortex functional connectivity predicts future relapse in alcohol dependent individuals. Neuroimage Clin.,  2016, 13, 181-187.
[104] 
Zhu, X.; Cortes, C.R.; Mathur, K.; Tomasi, D.; Momenan, R. Model-free functional connectivity and impulsivity correlates of alcohol dependence: a resting-state study. Addict. Biol.,  2017, 22(1), 206-217.
[http://dx.doi.org/10.1111/adb.12272] [PMID: 26040546] 
[105] 
Zhu, X.; Dutta, N.; Helton, S.G.; Schwandt, M.; Yan, J.; Hodgkinson, C.A.; Cortes, C.R.; Kerich, M.; Hall, S.; Sun, H.; Phillips, M.; Momenan, R.; Lohoff, F.W. Resting-state functional connectivity and presynaptic monoamine signaling in Alcohol Dependence. Hum. Brain Mapp.,  2015, 36(12), 4808-4818.
[http://dx.doi.org/10.1002/hbm.22951] [PMID: 26368063] 
[106] 
Bagga, D.; Singh, N.; Singh, S.; Modi, S.; Kumar, P.; Bhattacharya, D.; Garg, M.L.; Khushu, S. Assessment of abstract reasoning abilities in alcohol-dependent subjects: an fMRI study. Neuroradiology,  2014, 56(1), 69-77.
[http://dx.doi.org/10.1007/s00234-013-1281-3] [PMID: 24221533] 
[107] 
Cardenas, V.A.; Price, M.; Fein, G. EEG coherence related to fMRI resting state synchrony in long-term abstinent alcoholics. Neuroimage Clin.,  2017, 17, 481-490.
[108] 
Cohen-Gilbert, J.E.; Jensen, J.E.; Silveri, M.M. Contributions of magnetic resonance spectroscopy to understanding development: potential applications in the study of adolescent alcohol use and abuse. Dev. Psychopathol.,  2014, 26(2), 405-423.
[http://dx.doi.org/10.1017/S0954579414000030] 
[109] 
Courtney, K.E.; Ghahremani, D.G.; Ray, L.A. The effect of alcohol priming on neural markers of alcohol cue-reactivity. Am. J. Drug Alcohol Abuse,  2015, 41(4), 300-308.
[http://dx.doi.org/10.3109/00952990.2015.1044608] [PMID: 26125586] 
[110] 
Frye, M.A.; Hinton, D.J.; Karpyak, V.M.; Biernacka, J.M.; Gunderson, L.J.; Geske, J.; Feeder, S.E.; Choi, D.S.; Port, J.D. Elevated glutamate levels in the left dorsolateral prefrontal cortex are associated with higher cravings for alcohol. Alcohol. Clin. Exp. Res.,  2016, 40(8), 1609-1616.
[http://dx.doi.org/10.1111/acer.13131] [PMID: 27439218] 
[111] 
Herremans, S.C.; Van Schuerbeek, P.; De Raedt, R.; Matthys, F.; Buyl, R.; De Mey, J.; Baeken, C. The impact of accelerated right prefrontal high-frequency repetitive transcranial magnetic stimulation (rTMS) on cue-reactivity: an fmri study on craving in recently detoxified alcohol-dependent patients. PLoS One,  2015, 10(8) e0136182
[112] 
Kim, S.M.; Han, D.H.; Min, K.J.; Kim, B.N.; Cheong, J.H. Brain activation in response to craving- and aversion-inducing cues related to alcohol in patients with alcohol dependence. Drug Alcohol Depend.,  2014, 141, 124-131.
[http://dx.doi.org/10.1016/j.drugalcdep.2014.05.017] [PMID: 24939441] 
[113] 
Sjoerds, Z.; van den Brink, W.; Beekman, A.T.; Penninx, B.W.; Veltman, D.J. Cue reactivity is associated with duration and severity of alcohol dependence: an FMRI study. PLoS One,  9(1) e84560
[http://dx.doi.org/10.1371/journal.pone.0084560] 
[114] 
Wrase, J.; Grüsser, S.M.; Klein, S.; Diener, C.; Hermann, D.; Flor, H.; Mann, K.; Braus, D.F.; Heinz, A. Development of alcohol-associated cues and cue-induced brain activation in alcoholics. Eur. Psychiatry,  2002, 17(5), 287-291.
[http://dx.doi.org/10.1016/S0924-9338(02)00676-4] [PMID: 12381499] 
[115] 
Cyders, M.A.; Dzemidzic, M.; Eiler, W.J.; Coskunpinar, A.; Karyadi, K.; Kareken, D.A. Negative urgency and ventromedial prefrontal cortex responses to alcohol cues: FMRI evidence of emotion-based impulsivity. Alcohol. Clin. Exp. Res.,  2014, 38(2), 409-417.
[http://dx.doi.org/10.1111/acer.12266] [PMID: 24164291] 
[116] 
Czapla, M.; Baeuchl, C.; Simon, J.J.; Richter, B.; Kluge, M.; Friederich, H.C.; Mann, K.; Herpertz, S.C.; Loeber, S. Do alcohol-dependent patients show different neural activation during response inhibition than healthy controls in an alcohol-related fMRI go/no-go-task? Psychopharmacology (Berl.),  2017, 234(6), 1001-1015.
[http://dx.doi.org/10.1007/s00213-017-4541-9] [PMID: 28161772] 
[117] 
Dupuy, M.; Chanraud, S. Imaging the addicted brain: alcohol. Int. Rev. Neurobiol.,  2016, 129, 1-31.
[http://dx.doi.org/10.1016/bs.irn.2016.04.003] [PMID: 27503446] 
[118] 
Ende, G.; Hermann, D.; Demirakca, T.; Hoerst, M.; Tunc-Skarka, N.; Weber-Fahr, W.; Wichert, S.; Rabinstein, J.; Frischknecht, U.; Mann, K.; Vollstädt-Klein, S. Loss of control of alcohol use and severity of alcohol dependence in non-treatment-seeking heavy drinkers are related to lower glutamate in frontal white matter. Alcohol. Clin. Exp. Res.,  2013, 37(10), 1643-1649.
[http://dx.doi.org/10.1111/acer.12149] [PMID: 23800328] 
[119] 
Hillmer, A.T.; Mason, G.F.; Fucito, L.M.; O’Malley, S.S.; Cosgrove, K.P. How imaging glutamate, γ-aminobutyric acid, and dopamine can inform the clinical treatment of alcohol dependence and withdrawal. Alcohol. Clin. Exp. Res.,  2015, 39(12), 2268-2282.
[http://dx.doi.org/10.1111/acer.12893] [PMID: 26510169] 
[120] 
Hu, S.; Ide, J.S.; Chao, H.H.; Zhornitsky, S.; Fischer, K.A.; Wang, W.; Zhang, S.; Li, C.R. Resting state functional connectivity of the amygdala and problem drinking in non-dependent alcohol drinkers. Drug Alcohol Depend.,  2018, 185, 173-180.
[http://dx.doi.org/10.1016/j.drugalcdep.2017.11.026] [PMID: 29454928] 
[121] 
Jansen, J.M.; van Holst, R.J.; van den Brink, W.; Veltman, D.J.; Caan, M.W.; Goudriaan, A.E. Brain function during cognitive flexibility and white matter integrity in alcohol-dependent patients, problematic drinkers and healthy controls. Addict. Biol.,  2015, 20(5), 979-989.
[http://dx.doi.org/10.1111/adb.12199] [PMID: 25477246] 
[122] 
Jiang, L.; Gulanski, B.I.; De Feyter, H.M.; Weinzimer, S.A.; Pittman, B.; Guidone, E.; Koretski, J.; Harman, S.; Petrakis, I.L.; Krystal, J.H.; Mason, G.F. Increased brain uptake and oxidation of acetate in heavy drinkers. J. Clin. Invest.,  2013, 123(4), 1605-1614.
[http://dx.doi.org/10.1172/JCI65153] [PMID: 23478412] 
[123] 
Mon, A.; Durazzo, T.C.; Meyerhoff, D.J. Glutamate, GABA, and other cortical metabolite concentrations during early abstinence from alcohol and their associations with neurocognitive changes. Drug Alcohol Depend.,  2012, 125(1-2), 27-36.
[http://dx.doi.org/10.1016/j.drugalcdep.2012.03.012] [PMID: 22503310] 
[124] 
Schacht, J.P.; Anton, R.F.; Randall, P.K.; Li, X.; Henderson, S.; Myrick, H. Stability of fMRI striatal response to alcohol cues: a hierarchical linear modeling approach. Neuroimage,  2011, 56(1), 61-68.
[http://dx.doi.org/10.1016/j.neuroimage.2011.02.004] [PMID: 21316465] 
[125] 
Schuckit, M.A.; Smith, T.L.; Paulus, M.P.; Tapert, S.F.; Simmons, A.N.; Tolentino, N.J.; Shafir, A. The ability of functional magnetic resonance imaging to predict heavy drinking and alcohol problems 5 years later. Alcohol. Clin. Exp. Res.,  2016, 40(1), 206-213.
[http://dx.doi.org/10.1111/acer.12935] [PMID: 26727535] 
[126] 
Schweinsburg, B.C.; Taylor, M.J.; Videen, J.S.; Alhassoon, O.M.; Patterson, T.L.; Grant, I. Elevated myo-inositol in gray matter of recently detoxified but not long-term abstinent alcoholics: a preliminary MR spectroscopy study. Alcohol. Clin. Exp. Res.,  2000, 24(5), 699-705.
[http://dx.doi.org/10.1111/j.1530-0277.2000.tb02042.x] [PMID: 10832912] 
[127] 
Seo, S.; Mohr, J.; Beck, A.; Wüstenberg, T.; Heinz, A.; Obermayer, K. Predicting the future relapse of alcohol-dependent patients from structural and functional brain images. Addict. Biol.,  2015, 20(6), 1042-1055.
[http://dx.doi.org/10.1111/adb.12302] [PMID: 26435383] 
[128] 
Vergara, V.M.; Liu, J.; Claus, E.D.; Hutchison, K.; Calhoun, V. Alterations of resting state functional network connectivity in the brain of nicotine and alcohol users. Neuroimage,  2017, 151, 45-54.
[http://dx.doi.org/10.1016/j.neuroimage.2016.11.012] [PMID: 27864080] 
[129] 
Galanter, M.; Josipovic, Z.; Dermatis, H.; Weber, J.; Millard, M.A. An initial fMRI study on neural correlates of prayer in members of alcoholics anonymous. Am. J. Drug Alcohol Abuse,  2017, 43(1), 44-54.
[http://dx.doi.org/10.3109/00952990.2016.1141912] [PMID: 27015258] 
[130] 
Walter, M.; Henning, A.; Grimm, S.; Schulte, R.F.; Beck, J.; Dydak, U.; Schnepf, B.; Boeker, H.; Boesiger, P.; Northoff, G. The relationship between aberrant neuronal activation in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in major depression. Arch. Gen. Psychiatry,  2009, 66(5), 478-486.
[http://dx.doi.org/10.1001/archgenpsychiatry.2009.39] [PMID: 19414707] 
[131] 
Wang, J.; Fan, Y.; Dong, Y.; Ma, M.; Ma, Y.; Dong, Y.; Niu, Y.; Jiang, Y.; Wang, H.; Wang, Z.; Wu, L.; Sun, H.; Cui, C. Alterations in brain structure and functional connectivity in alcohol dependent patients and possible association with impulsivity. PLoS One,  2016, 11(8)e0161956
[http://dx.doi.org/10.1371/journal.pone.0161956] 
[132] 
Fein, G.; Camchong, J.; Cardenas, V.A.; Stenger, A. Resting state synchrony in long-term abstinent alcoholics: Effects of a current major depressive disorder diagnosis. Alcohol,  2017, 59, 17-25.
[http://dx.doi.org/10.1016/j.alcohol.2016.11.008] [PMID: 28262184] 
[133] 
Lim, A.C.; Cservenka, A.; Ray, L.A. Effects of alcohol dependence severity on neural correlates of delay discounting. Alcohol Alcohol.,  2017, 52(4), 506-515.
[http://dx.doi.org/10.1093/alcalc/agx015] [PMID: 28340213] 
[134] 
Cheng, H.; Kellar, D.; Lake, A.; Finn, P.; Rebec, G.V.; Dharmadhikari, S.; Dydak, U.; Newman, S. Effects of alcohol cues on MRS glutamate levels in the anterior cingulate. Alcohol Alcohol.,  2018, 53(3), 209-215.
[http://dx.doi.org/10.1093/alcalc/agx119] [PMID: 29329417] 
[135] 
Hermens, D.F.; Chitty, K.M.; Lee, R.S.; Tickell, A.; Haber, P.S.; Naismith, S.L.; Hickie, I.B.; Lagopoulos, J. Hippocampal glutamate is increased and associated with risky drinking in young adults with major depression. J. Affect. Disord.,  2015, 186, 95-98.
[http://dx.doi.org/10.1016/j.jad.2015.07.009] [PMID: 26233319] 
[136] 
Hermens, D.F.; Lagopoulos, J. Binge drinking and the young brain: a mini review of the neurobiological underpinnings of alcohol-induced blackout. Front. Psychol.,  2018, 9, 12.
[http://dx.doi.org/10.3389/fpsyg.2018.00012] [PMID: 29403418] 
[137] 
Hermens, D.F.; Scott, E.M.; White, D.; Lynch, M.; Lagopoulos, J.; Whitwell, B.G.; Naismith, S.L.; Hickie, I.B. Frequent alcohol, nicotine or cannabis use is common in young persons presenting for mental healthcare: a cross-sectional study. BMJ Open,  2013, 3(2)e002229
[http://dx.doi.org/10.1136/bmjopen-2012-002229] [PMID: 23381649] 
[138] 
Grodin, E.N.; Steckler, L.E.; Momenan, R. Altered striatal response during effort-based valuation and motivation in alcohol-dependent individuals. Alcohol Alcohol.,  2016, 51(6), 638-646.
[http://dx.doi.org/10.1093/alcalc/agw003] [PMID: 26893259] 
[139] 
Hardee, J.E.; Cope, L.M.; Munier, E.C.; Welsh, R.C.; Zucker, R.A.; Heitzeg, M.M. Sex differences in the development of emotion circuitry in adolescents at risk for substance abuse: a longitudinal fMRI study. Soc. Cogn. Affect. Neurosci.,  2017, 12(6), 965-975.
[http://dx.doi.org/10.1093/scan/nsx021] [PMID: 28338724] 
[140] 
Haroon, E.; Fleischer, C.C.; Felger, J.C.; Chen, X.; Woolwine, B.J.; Patel, T.; Hu, X.P.; Miller, A.H. Conceptual convergence: increased inflammation is associated with increased basal ganglia glutamate in patients with major depression. Mol. Psychiatry,  2016, 21(10), 1351-1357.
[http://dx.doi.org/10.1038/mp.2015.206] [PMID: 26754953] 
[141] 
Lukas, S.E.; Lowen, S.B.; Lindsey, K.P.; Conn, N.; Tartarini, W.; Rodolico, J.; Mallya, G.; Palmer, C.; Penetar, D.M. Extended-release naltrexone (XR-NTX) attenuates brain responses to alcohol cues in alcohol-dependent volunteers: a bold FMRI study. Neuroimage,  2013, 78, 176-185.
[http://dx.doi.org/10.1016/j.neuroimage.2013.03.055] [PMID: 23571420] 
[142] 
Sacher, J.; Neumann, J.; Fünfstück, T.; Soliman, A.; Villringer, A.; Schroeter, M.L. Mapping the depressed brain: a meta-analysis of structural and functional alterations in major depressive disorder. J. Affect. Disord.,  2011, 140(2), 142-148.
[PMID: 21890211] 
[143] 
Meyerhoff, D.J. Brain proton magnetic resonance spectroscopy of alcohol use disorders. Handb. Clin. Neurol.,  2014, 125, 313-337.
[http://dx.doi.org/10.1016/B978-0-444-62619-6.00019-7] [PMID: 25307583] 
[144] 
Becker, A.; Ehret, A.M.; Kirsch, P. From the neurobiological basis of comorbid alcohol dependence and depression to psychological treatment strategies: study protocol of a randomized controlled trial. BMC Psychiatry,  2017, 17(1), 153.
[http://dx.doi.org/10.1186/s12888-017-1324-0] [PMID: 28454522] 
[145] 
Becker, A.; Kirsch, M.; Gerchen, M.F.; Kiefer, F.; Kirsch, P. Striatal activation and frontostriatal connectivity during non-drug reward anticipation in alcohol dependence. Addict. Biol.,  2017, 22(3), 833-843.
[http://dx.doi.org/10.1111/adb.12352] [PMID: 28398011] 
[146] 
Sjoerds, Z.; van den Brink, W.; Beekman, A.T.; Penninx, B.W.; Veltman, D.J. Response inhibition in alcohol-dependent patients and patients with depression/anxiety: a functional magnetic resonance imaging study. Psychol. Med.,  2014, 44(8), 1713-1725.
[http://dx.doi.org/10.1017/S0033291713002274] [PMID: 24016382] 
[147] 
Frodl, T.; Amico, F. Is there an association between peripheral immune markers and structural/functional neuroimaging findings? Prog. Neuropsychopharmacol. Biol. Psychiatry,  2014, 48, 295-303.
[http://dx.doi.org/10.1016/j.pnpbp.2012.12.013] [PMID: 23313563] 
[148] 
Zahr, N.M.; Mayer, D.; Rohlfing, T.; Sullivan, E.V.; Pfefferbaum, A. Imaging neuroinflammation? A perspective from MR spectroscopy. Brain Pathol.,  2014, 24(6), 654-664.
[http://dx.doi.org/10.1111/bpa.12197] [PMID: 25345895] 
Cite As
Current Topics in Medicinal Chemistry

Immunological Disturbances and Neuroimaging Findings in Major Depressive Disorder (MDD) and Alcohol Use Disorder (AUD) Comorbid Patients

Abstract
