Skip to main content
SpringerLink
Log in

Neurotoxicity in Depression

  • Living reference work entry
  • First Online:
Handbook of Neurotoxicity

Abstract

Despite years of research, the pathophysiology of depression and the mechanism of action in antidepressant drugs largely remain unknown. The subsequent hypotheses examining depression witnessed attention being paid to the decrease of the serotonin and noradrenaline synaptic concentrations, adaptive changes in the neurotransmitters receptor, activation of the immune system, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, and enhanced glutamatergic activity. Current research suggests that disturbed neuronal plasticity and the degeneration of neurons and glia cells may be involved in the pathogenesis of depression. In fact, in depressed patients, structural changes are observed in several brain regions, mainly in the hippocampus. Also, in various animal models of depression, morphological alteration in neurons and glial cells is present besides depression-like behavioral changes. A lot of evidence indicates that an increased amount or activity of glucocorticoids, glutamate, and proinflammatory cytokines is the reason for these changes. In both animal models of depression and postmortem studies, a reduced neurogenesis in the dentate gyrus of the hippocampus; a decrease in the total number of neurons and astrocytes; a reduction of the dendritic length, branching density, or the number of synapses; and a decrease in the brain-derived neurotrophic factor were observed. Moreover, activation of microglia, a source of proinflammatory cytokines and reactive oxygen species, has a disadvantageous effect on neurons and astrocytes. However, it should be noted that not all of the studies demonstrate neurodegenerative changes in depression, or the glucocorticoids’ detrimental action, so further studies are needed in order to clearly determine the contribution of neurotoxic agents in the pathogenesis of depression and also the importance of the neuroprotective properties of some antidepressant drugs in their therapeutic effect.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Abbreviations

5HT:

Serotonin

ACTH:

Adrenocorticotropic hormone

BDNF:

Brain-derived neurotrophic factor

CMS:

Chronic mild stress

CREB:

Cyclic AMP response element-binding protein

CRF:

Corticotropin-releasing factor

CRP:

C-reactive protein

CUMS:

Chronic unpredictable mild stress

CUS:

Chronic unpredictable stress

GFAP:

Glial fibrillary acidic protein

HPA:

Hypothalamic-pituitary-adrenal

LPS:

Lipopolysaccharide

MDD:

Major depressive disorder

mPFC:

Medial prefrontal cortex

NA:

Noradrenaline

NLRP3:

Nod-like receptor protein 3

NMDA:

N-methyl-D-aspartate

NOS:

Nitric oxide synthase

PFC:

Prefrontal cortex

ROS:

Reactive oxygen species

SNRI:

Selective noradrenaline reuptake inhibitors

SSRI:

Selective serotonin reuptake inhibitors

TCA:

Tricyclic antidepressant

References

  • Alcocer-Gómez, E., Casas-Barquero, N., Williams, M. R., Romero-Guillena, S. L., Cañadas-Lozano, D., Bullón, P., Sánchez-Alcazar, J. A., Navarro-Pando, J. M., & Cordero, M. D. (2017). Antidepressants induce autophagy dependent-NLRP3-inflammasome inhibition in major depressive disorder. Pharmacological Research, 121, 114–121.

    Article  PubMed  CAS  Google Scholar 

  • Alcocer-Gómez, E., de Miguel, M., Casas-Barquero, N., Núñez-Vasco, J., Sánchez-Alcazar, J. A., Fernández-Rodríguez, A., & Cordero, M. D. (2014). NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder. Brain, Behavior, and Immunity, 36, 111–117.

    Article  PubMed  CAS  Google Scholar 

  • Autry, A. E., Adachi, M., Nosyreva, E., Na, E. S., Los, M. F., Cheng, P. F., Kavalali, E. T., & Monteggia, L. M. (2011). NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature, 475, 91–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bachis, A., Cruz, M. I., Nosheny, R. L., & Mocchetti, I. (2008). Chronic unpredictable stress promotes neuronal apoptosis in the cerebral cortex. Neuroscience Letters, 442, 104–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baez, M., & Volosin, M. (1994). Corticosterone influence forced swim-induced immobility. Pharmacology, Biochemistry and Behavior, 49, 729–736.

    Article  CAS  PubMed  Google Scholar 

  • Banasr, M., & Duman, R. S. (2008). Glial loss in the prefrontal cortex is sufficient to induce depressive- like behaviors. Biological Psychiatry, 64, 863–870.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bartholomä, P., Erlandsson, N., Kaufmann, K., Rössler, O. G., Baumann, B., Wirth, T., Giehl, K. M., & Thiel, G. (2002). Neuronal cell death induced by antidepressants: Lack of correlation with Egr-1, NF-kB and extracellular signal-regulated protein kinase activation. Biochemical Pharmacology, 63, 1507–1516.

    Article  PubMed  Google Scholar 

  • Bath, K. G., Jing, D. Q., Dincheva, I., Neeb, C. C., Pattwell, S. S., Chao, M. V., Lee, F. S., & Ninan, I. (2012). BDNF Val66Met impairs fluoxetine-induced enhancement of adult hippocampus plasticity. Neuropsychopharmacology, 37, 1297–1304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baumann, B., Bornschlegl, C., Krell, D., & Bogerts, B. (1997). Changes in CSF spaces differ in endogenous and neurotic depression a planimetric CT scan study. Journal of Affective Disor-ders, 45, 179–188.

    Article  CAS  Google Scholar 

  • Baxter, L. R., Jr., Phelps, M. E., Mazziotta, J. C., Schwartz, J. M., Selin, C. E., & Sumida, R. M. (1985). Cerebral metabolic rates for glucose in mood disorders. Studies with positron emission tomography and fluorodeoxyglucose F 18. Archives of General Psychiatry, 42, 441–447.

    Article  PubMed  Google Scholar 

  • Baxter, L. R., Jr., Schwartz, J. M., Phelps, M. E., Mazziotta, J. C., Guze, B. H., Selin, C. E., Gerner, R. H., & Sumida, R. M. (1989). Reduction of prefrontal cortex glucose metabolism common to three types of depression. Archives of General Psychiatry, 46, 243–250.

    Article  CAS  PubMed  Google Scholar 

  • Beneyto, M., Kristiansen, L. V., Oni-Orisan, A., McCullumsmith, R. E., & Meador-Woodruff, J. H. (2007). Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology, 32, 1888–1902.

    Article  CAS  PubMed  Google Scholar 

  • Berton, O., & Nestler, E. J. (2006). New approaches to antidepressant drug discovery: Beyond monoamines. Nature Reviews Neuroscience, 7, 137–151.

    Article  CAS  PubMed  Google Scholar 

  • Besedovsky, H. O., & del Ray, A. (1996). Immune-neuro-endocrine interactions: Facts and hypothesis. Endocrine Reviews, 17, 64–102.

    Article  CAS  PubMed  Google Scholar 

  • Block, T. S., Kushner, H., Kalin, N., Nelson, C., Belanoff, J., & Schatzberg, A. (2018). Combined analysis of mifepristone for psychotic depression: Plasma levels associated with clinical response. Biological Psychiatry, 84, 46–54.

    Article  CAS  PubMed  Google Scholar 

  • Boje, K. M., & Arora, P. K. (1992). Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death. Brain Research, 587, 250–256.

    Article  CAS  PubMed  Google Scholar 

  • Bremner, J. D., Vythilingam, M., Vermetten, E., Nazeer, A., Adil, J., Khan, S., Staib, L. H., & Charney, D. S. (2002). Reduced volume of orbitofrontal cortex in major depression. Biological Psychiatry, 51, 273–279.

    Article  PubMed  Google Scholar 

  • Brown, G. W., & Harris, T. (1978). Social origin of depression: A study of psychiatric disorder in women. Tavistock.

    Google Scholar 

  • Brown, E. S., Varghese, F. P., & McEwen, B. S. (2004). Association of depression with medical illness: Does cortisol play a role? Biological Psychiatry, 55, 1–9.

    Article  CAS  PubMed  Google Scholar 

  • Caetano, S. C., Hatch, J. P., Brambilla, P., Sassi, R. B., Nicoletti, M., Mallinger, A. G., Frank, E., Kupfer, D. J., Keshavan, M. S., & Soares, J. C. (2004). Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression. Psychiatry Research, 132, 141–147.

    Article  PubMed  Google Scholar 

  • Cai, W., Khaoustov, V. I., Xie, Q., Pan, T., Le, W., & Yoffe, B. (2005). Interferon-alpha-induced modulation of glucocorticoid and serotonin receptors as a mechanism of depression. Journal of Hepatology, 42, 880–887.

    Article  CAS  PubMed  Google Scholar 

  • Cameron, H. A., Tanapat, P., & Gould, E. (1998). Adrenal steroids and N-methyl-D-aspartate receptor activation regulate neurogenesis in the dentate gyrus of adult rats through a common pathway. Neuroscience, 82, 349–354.

    Article  CAS  PubMed  Google Scholar 

  • Carroll, B. J. (1982). The dexamethasone suppression test for melancholia. British Journal of Psychiatry, 140, 292–304.

    Article  CAS  Google Scholar 

  • Castanon, N., Médina, C., Mormède, C., & Dantzer, R. (2004). Chronic administration of tianeptine balances lipopolysaccharide-induced expression of cytokines in the spleen and hypothalamus of rats. Psychoneuroendocrinology, 29, 778–790.

    Article  CAS  PubMed  Google Scholar 

  • Cerqueira, J. J., Catania, C., Sotiropoulos, I., Schubert, M., Kalish, R., Almeida, O. F. X., Auer, D. P., & Sousa, N. (2005). Corticosteroid status influences the volume of the rat cingulate cortex – A magnetic resonance imaging study. Journal of Psychiatric Research, 39, 451–460.

    Article  CAS  PubMed  Google Scholar 

  • Charney, D. S., Menkes, D. B., & Heninger, G. R. (1981). Receptor sensitivity and the mechanism of action of antidepressant treatment. Implications for the etiology and therapy of depression. Archives of General Psychiatry, 38, 1160–1180.

    Article  CAS  PubMed  Google Scholar 

  • Chen, C. H., Ridler, K., Suckling, J., Williams, S., Fu, C. H., Merlo-Pich, E., & Bullmore, E. (2007). Brain imaging correlates of depressive symptom severity and predictors of symptom improvement after antidepressant treatment. Biological Psychiatry, 62, 407–414.

    Article  CAS  PubMed  Google Scholar 

  • Coffey, C. E., Wilkinson, W. E., Weiner, R. D., Parashos, I. A., Djang, W. T., Webb, M. C., Figiel, G. S., & Spritzer, C. E. (1993). Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study. Archives of General Psychiatry, 50, 7–16.

    Article  CAS  PubMed  Google Scholar 

  • Conti, P., Caraffa, A., Ronconi, G., Conti, C. M., Kritas, S. K., Mastrangelo, F., Tettamanti, L., & Theoharides, T. C. (2018). Impact of mast cells in depression disorder: Inhibitory effect of IL-37 (new frontiers). Immunologic Research, 66, 323–331.

    Article  CAS  PubMed  Google Scholar 

  • Cotter, D., Mackay, D., Landau, S., Kerwin, R., & Everall, I. (2001). Reduced glial cell density and neuronal volume in major depression in the anterior cingulate cortex. Archives of General Psychiatry, 58, 545–553.

    Article  CAS  PubMed  Google Scholar 

  • Czéh, B., Michaelis, T., Watanabe, T., Frahm, J., de Biurrun, G., van Kampen, M., Bartolomucci, A., & Fuchs, E. (2001). Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proceedings of the National Academy of Sciences, 98, 12796–12801.

    Article  Google Scholar 

  • Czéh, B., Simon, M., Schmelting, B., Hiemke, C., & Fuchs, E. (2006). Astroglial plasticity in the hippocampus is affected by chronic psychosocial stress and concomitant fluoxetine treatment. Neuropsychopharmacology, 31, 1616–1626.

    Article  PubMed  CAS  Google Scholar 

  • Czéh, B., Welt, T., Fischer, A. K., Erhardt, A., Schmitt, W., M€uller, M. B., Toschi, N., Fuchs, E., & Keck, M. E. (2002). Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: Effects on stress hormone levels and adult hippocampal neurogenesis. Biological Psychiatry, 52, 1057–1065.

    Article  PubMed  Google Scholar 

  • Dasari, M., Friedman, L., Jesberger, J., Stuve, T. A., Findling, F. L., Swales, T. P., & Schulz, S. C. (1999). A magnetic resonance imaging study of thalamic area in adolescent patients with either schizophrenia or bipolar disorder as compared to healthy controls. Psychiatry Research, 91, 155–162.

    Article  CAS  PubMed  Google Scholar 

  • de Kloet, E. R., Joëls, M., & Holsboer, F. (2005). Stress and the brain: From adaptation to disease. Nature Reviews Neuroscience, 6, 463–475.

    Article  PubMed  CAS  Google Scholar 

  • Deschwanden, A., Karolewicz, B., Feyissa, A. M., Treyer, V., Ametamey, S. M., Johayem, A., Burger, C., Auberson, Y. P., Sovago, J., Stockmeier, C. A., Buck, A., & Hasler, G. (2011). Reduced metabotropic glutamate receptor 5 density in major depression determined by [(11)C] ABP688 PET and postmortem study. American Journal of Psychiatry, 168, 727–734.

    Article  PubMed  Google Scholar 

  • Detka, J., Kurek, A., Basta-Kaim, A., Kubera, M., Lasoń, W., & Budziszewska, B. (2013). Neuroendocrine link between stress, depression and diabetes. Pharmacological Reports, 65, 1591–1600.

    Article  CAS  PubMed  Google Scholar 

  • Dhabhar, F. S., Burke, H. M., Epel, E. S., Mellon, S. H., Rosser, R., Reus, V. I., & Wolkowitz, O. M. (2009). Low serum IL-10 concentrations and loss of regulatory association between IL-6 and IL-10 inadults with major depression. Journal of Psychiatric Research, 43, 962–969.

    Article  PubMed  Google Scholar 

  • Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctot, K. L. (2010). A meta-analysis of cytokines in major depression. Biological Psychiatry, 67, 446–457.

    Article  CAS  PubMed  Google Scholar 

  • Drevets, W. C., Price, J. L., Simpson, J. R., Todd, R. D., Reich, T., Vannier, M., & Raichle, M. E. (1997). Subgenual prefrontal cortex abnormalities in mood disorders. Nature, 386, 824–827.

    Article  CAS  PubMed  Google Scholar 

  • Duman, R. S. (2002). Pathophysiology of depression: The concept of synaptic plasticity. European Psychiatry, 17, 306–310.

    Article  PubMed  Google Scholar 

  • Duman, R. S., Kodama, M., & Fujioka, T. (2004). Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat. Biological Psychiatry, 56, 570–580.

    Article  PubMed  Google Scholar 

  • Dunn, A. J., Wang, J., & Ando, T. (1999). Effects of cytokines on cerebral neurotransmission. Comparison with the effects of stress. Advances in Experimental Medicine and Biology, 46, 1117–1127.

    Google Scholar 

  • Erhardt, S., Blennow, K., Nordin, C., Skogh, E., Lindstrom, L. H., & Engberg, G. (2001). Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neuroscience Letters, 313, 96–98.

    Article  CAS  PubMed  Google Scholar 

  • Esplugues, J. V. (2002). NO as a signalling molecule in the nervous system. British Journal of Pharmacology, 135, 1079–1095.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feyissa, A. M., Chandran, A., Stockmeier, C. A., & Karolewicz, B. (2009). Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 33, 70–75.

    Article  CAS  PubMed  Google Scholar 

  • Finkel, M. S. (1996). Paroxetine is a novel nitric oxide synthase inhibitor. Psychopharmacology Bulletin, 32, 653–658.

    CAS  PubMed  Google Scholar 

  • Fox, M. E., & Lobo, M. K. (2019). The molecular and cellular mechanisms of depression: A focus on reward circuitry. Molecular Psychiatry, 24, 1798–1815.

    Article  PubMed  PubMed Central  Google Scholar 

  • Freis, E. (1954). Mental depression in hypertensives treated for long periods with large doses of reserpine. New England Journal of Medicine, 251, 1006–1008.

    Article  CAS  PubMed  Google Scholar 

  • Frodl, T. S., Koutsouleris, N., Bottlender, R., Born, C., Jäger, M., Scupin, I., Reiser, M., Möller, H. J., & Meisenzahl, E. M. (2008). Depression-related variation in brain morphology over 3 years: Effects of stress? Archives of General Psychiatry, 65, 1156–1165.

    Article  PubMed  Google Scholar 

  • Georgin-Lavialle, S., Moura, D. S., Salvador, A., Chauvet-Gelinier, J. C., Launay, J. M., Damaj, G., Côté, F., Soucié, E., Chandesris, M. O., Barète, S., Grandpeix-Guyodo, C., Bachmeyer, C., Alyanakian, M. A., Aouba, A., Lortholary, O., Dubreuil, P., Teyssier, J. R., Trojak, B., Haffen, E., Vandel, P., Bonin, B., French Mast Cell Study Group, Hermine, O., & Gaillard, R. (2016). Mast cells' involvement in inflammation pathways linked to depression: Evidence in mastocytosis. Molecular Psychiatry, 21, 1511–1516.

    Article  CAS  PubMed  Google Scholar 

  • Gorman, J. M., & Docherty, J. P. (2010). A hypothesized role for dendritic remodeling in the etiology of mood and anxiety disorders. Journal of Neuropsychiatry and Clinical Neurosciences, 22, 256–264.

    Article  PubMed  Google Scholar 

  • Gourley, S. L., Wu, F. J., Kiraly, D. D., Ploski, J. E., Kedves, A. T., Duman, R. S., & Taylor, J. R. (2007). Regionally specific regulation of ERK MAP kinase in a model of antidepressant – Sensitive chronic depression. Biological Psychiatry, 63, 353–359.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Grieve, S. M., Korgaonkar, M. S., Koslow, S. H., Gordon, E., & Williams, L. M. (2013). Widespread reductions in gray matter volume in depression. Neuroimage Clinical, 3, 332–339.

    Article  PubMed  PubMed Central  Google Scholar 

  • Guillemin, G. J., Kerr, S. J., Smythe, G. A., Smith, D. G., Kapoor, V., Armati, P. J., Croitoru, J., & Brew, B. J. (2001). Kynurenine pathway metabolism in human astrocytes: A paradox for neuronal protection. Journal of Neurochemistry, 78, 842–853.

    Article  CAS  PubMed  Google Scholar 

  • Gunning, F. M., Cheng, J., Murphy, C. F., Kanellopoulos, D., Acuna, J., Hoptman, M. J., Klimstra, S., Morimoto, S., Weinberg, J., & Alexopoulos, G. S. (2009). Anterior cingulate cortical volumes and treatment remission of geriatric depression. International Journal of Geriatric Psychiatry, 24, 829–836.

    Article  PubMed  Google Scholar 

  • Hannestad, J., Dellagioia, N., & Bloch, M. (2011). The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: A meta-analysis. Neuropsychopharmacology, 36, 2452–2459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hardingham, G. E., & Bading, H. (2010). Synaptic versus extrasynaptic NMDA receptor signaling; implications for neurodegenerative disorders. Nature Reviews Neuroscience, 11, 682–696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hashioka, S., Klegeris, A., Monji, A., Kato, T., Sawada, M., McGeer, P. L., & Kanba, S. (2007). Antidepressants inhibit interferon-gamma-induced microglial production of IL-6 and nitric oxide. Experimental Neurology, 206, 33–42.

    Article  CAS  PubMed  Google Scholar 

  • Hasler, G. (2010). Pathophysiology of depression: Do we have any solid evidence of interest to clinicians? World Psychiatry, 9, 155–161.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hastings, R. S., Parsey, R. V., Oquendo, M. A., Arango, V., & Mann, J. (2004). Volumetric analysis of the prefrontal cortex, amygdala, and hippocampus in major depression. Neuropsy-chopharmacology, 29, 952–959.

    Article  Google Scholar 

  • Hennings, J. M., Schaaf, L., & Fulda, S. (2012). Glucose metabolism and antidepressant medication. Current Pharmaceutical Design, 18, 5900–5919.

    Article  CAS  PubMed  Google Scholar 

  • Herman, J. P., Figueiredo, H., Mueller, N. K., Ulrich-Lai, Y., Ostrander, M. M., Choi, D. C., & Cullinan, W. E. (2003). Central mechanisms of stress integration: Hierarchical circuitry control-ling hypothalamo-pituitary-adrenocortical responsiveness. Frontiers in Neuroendocrinology, 24, 151–180.

    Article  CAS  PubMed  Google Scholar 

  • Hermine, O., Lortholary, O., Leventhal, P. S., Catteau, A., Soppelsa, F., Baude, C., Cohen-Akenine, A., Palmerini, F., Hanssens, K., Yang, Y., Sobol, H., Fraytag, S., Ghez, D., Suarez, F., Barete, S., Casassus, P., Sans, B., Arock, M., Kinet, J. P., Dubreuil, P., & Moussy, A. (2008). Case-control cohort study of patients' perceptions of disability in mastocytosis. PLoS One, 3, e2266.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Holsboer, F. (1999). The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety. Journal of Psychiatric Research, 33, 181–214.

    Article  CAS  PubMed  Google Scholar 

  • Howren, M. B., Lamkin, D. M., & Suls, J. (2009). Associations of depression with C-reactive protein, IL-1, and IL-6: A meta-analysis. Psychosomatic Medicine, 71, 171–186.

    Article  CAS  PubMed  Google Scholar 

  • Hwang, J., Zheng, L. T., Ock, J., Lee, M. G., Kim, S. H., Lee, H. W., Lee, W. H., Park, H. C., & Suk, K. (2008). Inhibition of glial inflammatory activation and neurotoxicity by tricyclic antidepressants. Neuropharmacology, 55, 826–834.

    Article  CAS  PubMed  Google Scholar 

  • Iwata, M., Ota, K. T., & Duman, R. S. (2013). The inflammasome: Pathways linking psychological stress, depression, and systemic illnesses. Brain, Behavior, and Immunity, 31, 105–114.

    Article  CAS  PubMed  Google Scholar 

  • Jaako-Movits, K., Zharkovsky, T., Pedersen, M., & Zharkovsky, A. (2006). Decreased hippocampal neurogenesis following olfactory bulbectomy is reversed by repeated citalopram admin- istration. Cellular and Molecular Neurobiology, 26, 1559–1570.

    Article  CAS  PubMed  Google Scholar 

  • Jayatissa, M. N., Bisgaard, C., Tingström, A., Papp, M., & Wiborg, O. (2006). Hippocampal cytogenesis correlates to escitalopram-mediated recovery in a chronic mild stress rat model of depression. Neuropsychopharmacology, 31, 2395–2404.

    Article  CAS  PubMed  Google Scholar 

  • Joca, S. R., & Guimarăes, F. S. (2006). Inhibition of neuronal nitric oxide synthase in the rat hippocampus induces antidepressant-like effects. Psychopharmacology, 185, 298–305.

    Article  CAS  PubMed  Google Scholar 

  • Johansen-Berg, H., Gutman, D. A., Behrens, T. E., Matthews, P. M., Rushworth, M. F., Katz, E., Lozano, A. M., & Mayberg, H. S. (2008). Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression. Cerebral Cortex, 18, 1374–1383.

    Article  CAS  PubMed  Google Scholar 

  • Karolewicz, B., Feyissa, A. M., Chandran, A., Legutko, B., Ordway, G. A., Rajkowska, G., & Stockmeier, C. A. (2009). Glutamate receptors expression in postmortem brain from depressed subjects. Biological Psychiatry, 65, 177S.

    Google Scholar 

  • Kawasaki, H., Chang, H. W., Tseng, H. C., Hsu, S. C., Yang, S. J., Hung, C. H., Zhou, Y., & Huang, S. K. (2014). A tryptophan metabolite, kynurenine, promotes mast cell activation through aryl hydrocarbon receptor. Allergy, 69, 445–452.

    Article  CAS  PubMed  Google Scholar 

  • Kellner, C. H., Rubinow, D. R., & Post, R. M. (1986). Cerebral ventricular size and cognitive impairment in depression. Journal of Affective Disorders, 10, 215–219.

    Article  CAS  PubMed  Google Scholar 

  • Kennedy, S. H., Konarski, J. Z., Segal, Z. V., Lau, M. A., Bieling, P. J., McIntyre, R. S., & Mayberg, H. S. (2007). Differences in brain glucose metabolism between responders to CBT and venlafaxine in a 16-week randomized controlled trial. American Journal of Psychiatry, 164, 778–788.

    Article  PubMed  Google Scholar 

  • Kent, S., Rodriguez, F., Kelley, K. W., & Dantzer, R. (1994). Reduction in food and water intake induced by microinjection of interleukin-1b in the ventromedial hypothalamus of the rat. Physiology and Behavior, 56, 1031–1036.

    Article  CAS  PubMed  Google Scholar 

  • Kim, J. S., Schmid-Burgk, W., Claus, D., & Kornhuber, H. H. (1982). Increased serum glutamate in depressed patients. Archives of Psychiatry and Neurological Sciences, 232, 299–304.

    CAS  PubMed  Google Scholar 

  • Kitagami, T., Yamada, K., Miura, H., Hashimoto, R., Nabeshima, T., & Ohta, T. (2003). Mech-anism of systemically injected interferon-alpha impeding monoamine biosynthesis in rats: Role of nitric oxide as a signal crossing the blood–brain barrier. Brain Research, 978, 104–114.

    Article  CAS  PubMed  Google Scholar 

  • Köhler, O., Benros, M. E., Nordentoft, M., Farkouh, M. E., Iyengar, R. L., Mors, O., & Krogh, J. (2014). Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry, 71, 1381–1391.

    Article  PubMed  Google Scholar 

  • Kole, M. H. P., Swan, L., & Fuchs, E. (2002). The antidepressant tianeptine persistently modulates glutamate receptor currents of the hippocampal CA3 commissural associational synapse in chronically stressed rats. European Journal of Neuroscience, 16, 807–816.

    Article  PubMed  Google Scholar 

  • Korgaonkar, M. S., Fornito, A., Williams, L. M., & Grieve, S. M. (2014). Abnormal structural networks characterize major depressive disorder: A connectome analysis. Biological Psychiatry, 76, 567–574.

    Article  PubMed  Google Scholar 

  • Kosten, T. A., Galloway, M. P., Duman, R. S., Russell, D. S., & D’Sa, C. (2008). Repeated unpredictable stress and antidepressants differentially regulate expression of the Bcl-2 family of apoptotic genes in rat cortical, hippocampal, and limbic brain structures. Neuropsychophar-macology, 33, 1545–1558.

    Article  CAS  Google Scholar 

  • Krohn, K., Rozovsky, I., Wals, P., Teter, B., Anderson, C. P., & Finch, C. E. (1999). Glial fibrillary acidic protein transcription responses to transforming growth factor-b1 and interleukin-1b are mediated by a nuclear factor-1-like site in the near-upstream promoter. Journal of Neurochemistry, 72, 1353–1361.

    Article  CAS  PubMed  Google Scholar 

  • Kronfol, Z. (2002). Immune dysregulation in major depression: A critical review of existing evidence. International Journal of Neuropsychopharmacology, 5, 333–343.

    Article  CAS  PubMed  Google Scholar 

  • Lacerda, A. L. T., Keshavan, M. S., Hardan, A. Y., Yorbik, O., Brambilla, P., Sassi, R. B., Nicoletti, M. A., Mallinger, A. G., Frank, E., Kupfer, D. J., & Soares, J. C. (2004). Anatomic evaluation of the orbitofrontal cortex in major depressive disorder. Biological Psychiatry, 55, 353–358.

    Article  PubMed  Google Scholar 

  • Laping, N. J., Teter, B., Nichols, N. R., Rozovbsky, I., & Finch, C. E. (1994). Glial fibrillary acidic protein: Regulation by hormones, cytokines and growth factors. Brain Pathology, 1, 259–275.

    Article  Google Scholar 

  • Lee, H. J., Kim, J. W., Yim, S. V., Kim, M. J., Kim, S. A., Kim, Y. J., Kim, C. J., & Chung, J. H. (2001). Fluoxetine enhances cell proliferation and prevents apoptosis in dentate gyrus of maternally separated rats. Molecular Psychiatry, 6, 725–728.

    Article  CAS  Google Scholar 

  • Lemaire, V., Koehl, M., Le Moal, M., & Abrous, D. N. (2000). Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proceedings of the National Academy of Sciences of the United States of America, 97, 11032–11037.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levine, J., Panchalingam, K., Rapoport, A., Gershon, S., McClure, R. J., & Pettegrew, J. W. (2000). Increased cerebrospinal fluid glutamine levels in depressed patients. Biological Psychiatry, 47, 586–593.

    Article  CAS  PubMed  Google Scholar 

  • Li, H., & Poulos, T. L. (2005). Structure-function studies on nitric oxide synthases. Journal of Inorganic Biochemistry, 99, 293–305.

    Article  CAS  PubMed  Google Scholar 

  • Liotti, M., Mayberg, H. S., McGinnis, S., Brannan, S. L., & Jerabek, P. (2002). Unmasking disease-specific cerebral blood flow abnormalities: Mood challenge in patients with remitted unipolar depression. American Journal of Psychiatry, 159, 1830–1840.

    Article  PubMed  Google Scholar 

  • Liu, B., & Hong, J. S. (2003). Role of microglia in inflammation-mediated neurodegenerative diseases:Mechanisms and strategies for therapeutic intervention. Journal of Pharmacology and Experimental Therapeutics, 304, 1–7.

    Article  CAS  PubMed  Google Scholar 

  • Lucassen, P. J., Vollmann-Honsdorf, G. K., Gleisberg, M., Czéh, B., De Kloet, E. R., & Fuchs, E. (2001). Chronic psychosocial stress differentially affects apoptosis in hippo- campal subregions and cortex of the adult tree shrew. European Journal of Neuroscience, 14, 161–166.

    Article  CAS  PubMed  Google Scholar 

  • MacMillan, S., Szeszko, P. R., Moore, G. J., Madden, R., Lorch, E., Ivey, J., Banerjee, S. P., & Rosenberg, D. R. (2003). Increased amygdala: Hippocampal volume ratios associated with severity of anxiety in pediatric major depression. Journal of Child and Adolescent Psychopharmacology, 13, 65–73.

    Article  PubMed  Google Scholar 

  • MacQueen, G. M., Campbell, S., McEwen, B. S., MacDonald, K., Amano, S., Joffe, R. T., Nahmias, C., & Young, L. T. (2003). Course of illness, hippocampal function, and. Hippocampal volume in major depression. Proceedings of the National Academy of Sciences of the United States of America, 3, 1387–1392.

    Article  CAS  Google Scholar 

  • Madsen, T. M., Greisen, M. H., Nielsen, S. M., Bolwig, T. G., & Mikkelsen, J. D. (2000). Electroconvulsive stimuli enhance both neuropeptide Y receptor Y1 and Y2 messenger RNA expression and levels of binding in the rat hippocampus. Neuroscience, 98, 33–39.

    Article  CAS  PubMed  Google Scholar 

  • Maes, M., D’Haese, P. C., Scharpé, S., D’Hondt, P., Cosyns, P., & De Broe, M. E. (1994). Hypozincemia in depression. Journal of Affective Disorders, 31, 135–140.

    Article  CAS  PubMed  Google Scholar 

  • Magarinos, A. M., & McEwen, B. S. (1995). Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: Involvement of glucocorticoid secretion and excitatory amino acid receptors. Neuroscience, 69, 89–98.

    Article  CAS  PubMed  Google Scholar 

  • Mayberg, H. S., Brannan, S. K., Tekell, J. L., Silva, J. A., Mahurin, R. K., McGinnis, S., & Jerabek, P. A. (2000). Regional metabolic effects of fluoxetine in major depression: Serial changes and relationship to clinical response. Biological Psychiatry, 48, 830–843.

    Article  CAS  PubMed  Google Scholar 

  • McEwen, B. S. (1999). Stress and hippocampal plasticity. Annual Review of Neuroscience, 22, 105–122.

    Article  CAS  PubMed  Google Scholar 

  • McEwen, B. S., & Chattarji, S. (2004). Molecular mechanisms of neuroplasticity and pharmaco-logical implications: The example of tianeptine. European Neuropsychopharmacology, 14, 497–502.

    Article  CAS  Google Scholar 

  • Miller, A. H., Maletic, V., & Raison, C. L. (2009). Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biological Psychiatry, 65, 732–741.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller, O. H., Moran, J. T., & Hall, B. J. (2016). Two cellular hypotheses explaining the initiation of ketamine’s antidepressant actions: Direct inhibition and disinhibition. Neuropharmacology, 100, 17–26.

    Article  CAS  PubMed  Google Scholar 

  • Mitani, H., Shirayama, Y., Yamada, T., Maeda, K., Ashby, C. R., Jr., & Kawahara, R. (2006). Correlation between plasma levels of glutamate, alanine and serine with severity of depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 30, 1155–1158.

    Article  CAS  PubMed  Google Scholar 

  • Młyniec, K., Gaweł, M., & Nowak, G. (2015). Study of antidepressant drugs in GPR39 (zinc receptor−/−) knockout mice, showing no effect of conventional antidepressants, but effectiveness of NMDA antagonists. Behavioural Brain Research, 287, 135–138.

    Article  PubMed  CAS  Google Scholar 

  • Moron, J. A., Zakharova, I., Ferrer, J. V., Merrill, G. A., Hope, B., Lafer, E. M., Lin, Z. C., Wang, J. B., Javitch, J. A., Galli, A., & Shippenberg, T. S. (2003). Mitogen-activated protein kinase regulates dopamine transporter surface expression and dopamine transport capacity. Journal of Neuroscience, 23, 8480–8488.

    Article  CAS  PubMed  Google Scholar 

  • Moura, D. S., Sultan, S., Georgin-Lavialle, S., Pillet, N., Montestruc, F., Gineste, P., Barete, S., Damaj, G., Moussy, A., Lortholary, O., & Hermine, O. (2011). Depression in patients with mastocytosis: Prevalence, features and effects of masitinib therapy. PLoS One, 6, e26375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murmu, M. S., Salomon, S., Biala, Y., Weinstock, M., Braun, K., & Bock, J. (2006). Changes of spine density and dendritic complexity in the prefrontal cortex in offspring of mothers exposed to stress during pregnancy. European Journal of Neuroscience, 24, 1477–1487.

    Article  PubMed  Google Scholar 

  • Musazzi, L., Treccani, G., & Popoli, M. (2015). Functional and structural remodeling of glutamate synapses in prefrontal and frontal cortex induced by behavioral stress. Frontiers in Psychiatry, 6, 60.

    Article  PubMed  PubMed Central  Google Scholar 

  • Myint, A. M., O’Mahony, S., Kubera, M., Kim, Y. K., Kenny, C., Kaim-Basta, A., Steinbusch, H. W., & Leonard, B. E. (2007). Role of paroxetine in interferon-alpha-induced immune and behavioural changes in male Wistar rats. Psychopharmacology, 21, 843–850.

    Article  CAS  Google Scholar 

  • Nair, A., & Bonneau, R. H. (2006). Stress-induced elevation of glucocorticoids increases microglia proliferation through NMDA receptor activation. Journal of Neuroimmunology, 171, 72–85.

    Article  CAS  PubMed  Google Scholar 

  • Nemeroff, C. B., & Owens, M. J. (2002). Treatment of mood disorders. Nature Neuroscience, 5, 1068–1070.

    Article  CAS  PubMed  Google Scholar 

  • Nibuya, M., Morinobu, S., & Duman, R. S. (1995). Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. Journal of Neuroscience, 15, 7539–7547.

    Article  CAS  PubMed  Google Scholar 

  • Nibuya, M., Nestler, E. J., & Duman, R. S. (1996). Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. Journal of Neuroscience, 16, 2365–2372.

    Article  CAS  PubMed  Google Scholar 

  • Nowak, G., Ordway, G. A., & Paul, I. A. (1995). Alterations in the N-methyl-D-aspartate receptor complex in the frontal cortex of suicide victims. Brain Research, 675, 157–164.

    Article  CAS  PubMed  Google Scholar 

  • Nowak, B., Zadrozna, M., Ossowska, G., Sowa-Kućma, M., Gruca, P., Papp, M., Dybała, M., Pilc, A., & Nowak, G. (2010). Alterations in hippocampal calcium binding neurons induced by stress models of depression. Preliminary assessment. Pharmacological Reports, 62, 1204–1210.

    Article  PubMed  Google Scholar 

  • Nudmamud-Thanoi, S., & Reynolds, G. P. (2004). The NR1 subunit of the glutamate/NMDA receptor in the superior temporal cortex in schizophrenia and affective disorders. Neuroscience Letters, 372, 173–177.

    Article  CAS  PubMed  Google Scholar 

  • O’Sullivan, J. B., Ryan, K. M., Curtin, N. M., Harkin, A., & Connor, T. J. (2009). Noradrenaline reuptake inhibitors limit neuroinflammation in rat cortex following a systemic inflammatory challenge: Implications for depression and neurodegeneration. The International Journal of Neuropsychopharmacology, 12, 687–699.

    Article  PubMed  CAS  Google Scholar 

  • Ohira, K., Hagihara, H., Miwa, M., Nakamura, K., & Miyakawa, T. (2019). Fluoxetine-induced dematuration of hippocampal neurons and adult cortical neurogenesis in the common marmoset. Molecular Brain, 12, 69.

    Article  PubMed  PubMed Central  Google Scholar 

  • Oliveira, R. M., Guimarăes, F. S., & Deakin, J. F. (2008). Expression of neuronal nitric oxide synthase in the hippocampal formation in affective disorders. Brazilian Journal of Medical and Biological Research, 41, 333–341.

    Article  CAS  PubMed  Google Scholar 

  • Ongur, D., Drevets, W. C., & Price, J. L. (1998). Glial reduction in the subgenual prefrontal cortex in mood disorders. Proceedings of the National Academy of Sciences of the United States of America, 95, 13290–13295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Osuch, E. A., Ketter, T. A., Kimbrell, T. A., George, M. S., Benson, B. E., Willis, M. W., Herscovitch, P., & Post, R. M. (2000). Regional cerebral metabolism associated with anxiety symptoms in affective disorder patients. Biological Psychiatry, 48, 1020–1023.

    Article  CAS  PubMed  Google Scholar 

  • Ozcan, H., Aydın, N., Aydın, M. D., Oral, E., Gündoğdu, C., Şipal, S., & Halıcı, Z. (2020). Olfactory bulbectomy and raphe nucleus relationship: A new vision for well-known depression model. Nordic Journal of Psychiatry, 74, 194–200.

    Article  PubMed  Google Scholar 

  • Pariante, C. M., Pearce, B. D., Pisell, T. L., Sanchez, C. I., Po, C., Su, C., & Miller, A. H. (1999). The proinflammatory cytokine, interleukin-1alpha, reduces glucocorticoid receptor transloca- tion and function. Endocrinology, 140, 4359–4366.

    Article  CAS  PubMed  Google Scholar 

  • Parker, K. J., Schatzberg, A. F., & Lyons, D. M. (2003). Neuroendocrine aspects of hypercor- tisolism in major depression. Hormones and Behavior, 43, 60–66.

    Article  CAS  PubMed  Google Scholar 

  • Pei, Z., Pang, H., Qian, L., Yang, S., Wang, T., Zhang, W., Wu, X., Dallas, S., Wilson, B., Reece, J. M., Miller, D. S., Hong, J. S., & Block, M. L. (2007). MAC1 mediates LPS-induced production of superoxide by microglia: The role of pattern recognition receptors in dopaminergic neurotoxicity. Glia, 55, 1362–1373.

    Article  PubMed  Google Scholar 

  • Petrilli, M. A., Kranz, T. M., Kleinhaus, K., Joe, P., Getz, M., Johnson, P., Chao, M. V., & Malaspina, D. (2017). The emerging role for zinc in depression and psychosis. Frontiers in Pharmacology., 8, 414.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pham, K., Nacher, J., Hof, P. R., & McEwen, B. S. (2003). Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. European Journal of Neuroscience, 17, 879–886.

    Article  PubMed  Google Scholar 

  • Phan, K. L., Wager, T., Taylor, S. F., & Liberzon, I. (2002). Functional neuroanatomy of emotion: A meta-analysis of emotion activation studies in PET and fMRI. NeuroImage, 16, 331–348.

    Article  PubMed  Google Scholar 

  • Pittenger, C., & Duman, R. S. (2008). Stress, depression, and neuroplasticity: A convergence of mechanisms. Neuropsychopharmacology, 33, 88–109.

    Article  CAS  PubMed  Google Scholar 

  • Prakash, A., Bharti, K., & Majeed, A. B. (2015). Zinc: Indications in brain disorders. Fundamental & Clinical Pharmacology, 29, 131–149.

    Article  CAS  Google Scholar 

  • Price, J. L., & Drevets, W. C. (2010). Neurocircuitry of mood disorders. Neuropsychophar-macology, 35, 192–216.

    Article  Google Scholar 

  • Qiao, H., An, S. C., Xu, C., & Ma, X. M. (2017). Role of proBDNF and BDNF in dendritic spine plasticity and depressive-like behaviors induced by an animal model of depression. Brain Research, 1663, 29–37.

    Article  CAS  PubMed  Google Scholar 

  • Qiao, H., Li, M. X., Xu, C., Chen, H. B., An, S. C., & Ma, X. M. (2016). Dendritic spines in depression: What we learned from animal models. Neural Plasticity, 2016, 8056370.

    Article  PubMed  PubMed Central  Google Scholar 

  • Raison, C. L., Dantzer, R., Kelley, K. W., Lawson, M. A., Woolwine, B. J., Vogt, G., Spivey, J. R., Saito, K., & Miller, A. H. (2010). CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: Relationship to CNS immune responses and depression. Molecular Psychiatry, 15, 393–403.

    Article  CAS  PubMed  Google Scholar 

  • Rajkowska, G. (2000). Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biological Psychiatry, 48, 766–777.

    Article  CAS  PubMed  Google Scholar 

  • Rajkowska, G., & Miguel-Hidalgo, J. J. (2007). Gliogenesis and glial pathology in depression. CNS and Neurological Disorders – Drug Targets, 6, 219–233.

    Article  CAS  PubMed  Google Scholar 

  • Rajkowska, G., Miguel-Hidalgo, J. J., Wei, J., Dilley, G., Pittman, S. D., Meltzer, H. Y., Overholser, J. C., Roth, B. L., & Stockmeier, C. A. (1999). Morphometric evidence for neuronal and glial prefrontal pathology in major depression. Biological Psychiatry, 45, 1085–1098.

    Article  CAS  PubMed  Google Scholar 

  • Reichenberg, A., Yirmiya, R., Schuld, A., Kraus, T., Haack, M., Morag, A., & Pollmächer, T. (2001). Cytokine-associated emotional and cognitive disturbances in humans. Archives of General Psychiatry, 58, 445–452.

    Article  CAS  PubMed  Google Scholar 

  • Roy, T., & Lloyd, C. E. (2012). Epidemiology of depression and diabetes: A systematic review. Journal of Affective Disorders, 142, S8–S21.

    Article  PubMed  Google Scholar 

  • Ruhé, H. G., Mason, N. S., & Schene, A. H. (2007). Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: A meta-analysis of monoamine depletion studies. Molecular Psychiatry, 12, 331–359.

    Article  PubMed  CAS  Google Scholar 

  • Saarelainen, T., Hendolin, P., Lucas, G., Koponen, E., Sairanen, M., MacDonald, E., Agerman, K., Haapasalo, A., Nawa, H., Aloyz, R., Ernfors, P., & Castrén, E. (2003). Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant- induced behavioral effects. Journal of Neuroscience, 23, 349–357.

    Article  CAS  PubMed  Google Scholar 

  • Sapolsky, R. M., Krey, L. C., & McEwen, B. S. (1986). The neuroendocrinology of stress and aging: The glucocorticoid cascade hypothesis. Endocrine Reviews, 7, 284–301.

    Article  CAS  PubMed  Google Scholar 

  • Schwarcz, R., & Pellicciari, R. (2002). Manipulation of brain kynurenines: Glial targets, neuronal effects, and clinical opportunities. Journal of Pharmacology and Experimental Therapeutics, 303, 1–10.

    Article  CAS  PubMed  Google Scholar 

  • Serra-Millàs, M., López-Vílchez, I., Navarro, V., Galán, A. M., Escolar, G., Penadés, R., Catalán, R., Fañanás, L., Arias, B., & Gastó, C. (2011). Changes in plasma and platelet BDNF levels induced by S-Citalopram in major depression. Psychopharmacology, 216, 1–8.

    Article  PubMed  CAS  Google Scholar 

  • Shah, P. J., Glabus, M. F., Goodwin, G. M., & Ebmeier, K. P. (2002). Chronic, treatment resistant depression and right fronto-striatal atrophy. British Journal of Psychiatry, 180, 434–440.

    Article  CAS  Google Scholar 

  • Sheline, Y. I., Gado, M. H., & Price, J. L. (1998). Amygdala core nuclei volumes are decreased in recurrent major depression. Neuroreport, 9, 2023–2028.

    Article  CAS  PubMed  Google Scholar 

  • Shimizu, E., Hashimoto, K., Okamura, N., Koike, K., Komatsu, N., Kumakiri, C., Nakazato, M., Watanabe, H., Shinoda, N., Okada, S., & Iyo, M. (2003). Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biological Psychiatry, 54, 70–75.

    Article  CAS  PubMed  Google Scholar 

  • Shirayama, Y., Chen, A. C.-H., Nakagawa, S., Russell, D. S., & Duman, R. S. (2002). Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. Journal of Neuroscience, 22, 3251–3261.

    Article  CAS  PubMed  Google Scholar 

  • Singh, M. K., Leslie, S. M., Packer, M. M., Zaiko, Y. V., Phillips, O. R., Weisman, E., Wall, D., Jo, B., & Rasgon, N. L. (2019). Brain and behavioral correlates of insulin resistance in youth with depression and obesity. Hormones and Behavior, 108, 73–83.

    Article  CAS  PubMed  Google Scholar 

  • Siwek, M., Dudek, D., Paul, I. A., Sowa-Kućma, M., Zieba, A., Popik, P., Pilc, A., & Nowak, G. (2009). Zinc supplementation augments efficacy of imipramine in treatment resistant patients: A double blind, placebo-controlled study. Journal of Affective Disorders, 118, 187–195.

    Article  CAS  PubMed  Google Scholar 

  • Skolnick, P., Layer, R. T., Popik, P., Nowak, G., Paul, I. A., & Trullas, R. (1996). Adaptation of N-methyl-D-aspartate receptors following antidepressant treatment: Implications for the phar-macotherapy of depression. Pharmacopsychiatry, 29, 23–26.

    Article  CAS  PubMed  Google Scholar 

  • Sonino, N., Fava, G. A., Belluardo, P., Girelli, M. E., & Boscaro, M. (1993). Course of depression in Cushing’s syndrome: Response to treatment and comparison with graves’ disease. Hormone Research, 39, 202–206.

    Article  CAS  PubMed  Google Scholar 

  • Sorra, K. E., & Harris, K. M. (2000). Overview on the structure, composition, function, development, and plasticity of hippocampal dendritic spines. Hippocampus, 10, 501–511.

    Article  CAS  PubMed  Google Scholar 

  • Sousa, N., Lukoyanov, N. V., Madeira, M. D., Almeida, O. F., & Paula-Barbosa, M. M. (2000). Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement. Neuroscience, 97, 253–266.

    Article  CAS  PubMed  Google Scholar 

  • Southam, E., & Garthwaite, J. (1993). The nitric oxide-cyclic GMP signalling pathway in rat brain. Neuropharmacology, 32, 1267–1277.

    Article  CAS  PubMed  Google Scholar 

  • Španová, A., Kovářů, H., Lisá, V., Lukásová, E., & Rittich, B. (1997). Estimation of apoptosis in C6 glioma cells treated with antidepressants. Physiological Research, 46, 161–164.

    PubMed  Google Scholar 

  • Steiner, J., Bogerts, B., Sarnyai, Z., Walter, M., Gos, T., Bernstein, H. G., & Myint, A. M. (2011). Bridging the gap between the immune and glutamate hypotheses of schizophrenia and major depression: Potential role of glial NMDA receptor modulators and impaired blood–brain barrier integrity. World Journal of Biological Psychiatry, 13(7), 482–492.

    Article  Google Scholar 

  • Stockmeier, C. A., Mahajan, G. J., Konick, L. C., Overholser, J. C., Jurjus, G. J., Meltzer, H. Y., Uylings, H. B. M., Friedman, L., & Rajkowska, G. (2004). Cellular changes in the postmortem hippocampus in major depression. Biological Psychiatry, 56, 640–650.

    Article  PubMed  PubMed Central  Google Scholar 

  • Strawbridge, R., Arnone, D., Danese, A., Papadopoulos, A., Herane Vives, A., & Cleare, A. J. (2015). Inflammation andclinical response to treatment in depression: A meta-analysis. European Neuropsychopharmacology, 25, 1532–1543.

    Article  CAS  PubMed  Google Scholar 

  • Szewczyk, B., Kubera, M., & Nowak, G. (2011). The role of zinc in neurodegenerative inflammatory pathways in depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35, 693–701.

    Article  CAS  PubMed  Google Scholar 

  • Szewczyk, B., Poleszak, E., Pilc, A., & Nowak, G. (2010). Ionic glutamate modulators in depression (zinc, magnesium). In P. Skolnick (Ed.), Glutamate-based therapies for psychiatric disorders (M. J Parnham & J. Bruinvels (Series Eds.), Milestones in drug therapy; pp. 21–38), Springer.

    Google Scholar 

  • Trullas, R., & Skolnick, P. (1990). Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. European Journal of Pharmacology, 185, 1–10.

    Article  CAS  PubMed  Google Scholar 

  • Tsopelas, C., Stewart, R., Savva, G. M., Brayne, C., Ince, P., Thomas, A., & Matthews, F. E. (2011). Neuropathological correlates of late-life depression in older people. The British Journal of Psychiatry, 198, 109–114.

    Article  PubMed  Google Scholar 

  • Turchan-Cholewo, J., Dimayuga, F. O., Gupta, S., Keller, J. N., Knapp, P. E., Hauser, K. F., & Bruce-Keller, A. J. (2009). Morphine and HIV-Tat increase microglial-free radical production and oxidative stress: Possible role in cytokine regulation. Journal of Neurochemistry, 108, 202–215.

    Article  CAS  PubMed  Google Scholar 

  • Tynan, R. J., Weidenhofer, J., Hinwood, M., Cairns, M. J., Day, T. A., & Walker, F. R. (2012). A comparative examination of the anti-inflammatory effects of SSRI and SNRI antidepressants on LPS stimulated microglia. Brain, Behavior, and Immunity, 26, 469–479.

    Article  CAS  PubMed  Google Scholar 

  • Valentine, A. D., Meyers, C. A., Kling, M. A., Richelson, E., & Hauser, P. (1998). Mood and cognitive side-effects of interferon-a therapy. Seminars in Oncology, 25, 39–47.

    CAS  PubMed  Google Scholar 

  • Van Craenenbroeck, K., De Bosscher, K., Vanden Berghe, W., Vanhoenacker, P., & Haegeman, G. (2005). Role of glucocorticoids in dopamine-related neuropsychiatric disorders. Molecular and Cellular Endocrinology, 245, 10–22.

    Article  PubMed  CAS  Google Scholar 

  • Vollmayr, B., Simonis, C., Weber, S., Gass, P., & Henn, F. (2003). Reduced cell proliferation in the dentate gyrus is not correlated with the development of learned helplessness. Biological Psychiatry, 54, 1035–1040.

    Article  PubMed  Google Scholar 

  • Wang, T., Pei, Z., Zhang, W., Liu, B., Langenbach, R., Lee, C., Wilson, B., Reece, J. M., Miller, D. S., & Hong, J. S. (2005). MPP+ induced COX-2 activation and subsequent dopaminergic neurodegeneration. FASEB Journal, 19, 1134–1136.

    Article  CAS  PubMed  Google Scholar 

  • Watanabe, Y., Gould, E., & McEwen, B. S. (1992). Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Research, 588, 341–345.

    Article  CAS  PubMed  Google Scholar 

  • Wellman, C. L. (2001). Dendritic reorganization in pyramidal neurons in medial prefrontal cortex after chronic corticosterone administration. Journal of Neurobiology, 49, 245–253.

    Article  CAS  PubMed  Google Scholar 

  • Weniger, G., Lange, C., & Irle, E. (2006). Abnormal size of the amygdala predicts impaired emotional memory in major depressive disorder. Journal of Affective Disorders, 94, 219–229.

    Article  PubMed  Google Scholar 

  • Wu, C. W., Chen, Y. C., Yu, L., Chen, H. I., Jen, C. J., Huang, A. M., Tsai, H. J., Chang, Y. T., & Kuo, Y. M. (2007). Treadmill exercise counteracts the suppressive effects of peripheral lipopolysaccharide on hippocampal neurogenesis and learning and memory. Journal of Neu-rochemistry, 103, 2471–2481.

    Article  CAS  Google Scholar 

  • Zanos, P., & Gould, T. D. (2018). Mechanisms of ketamine action as an antidepressant. Molecular Psychiatry, 23, 801–811.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, Y., Gu, F., Chen, J., & Dong, W. (2010). Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat. Brain Research, 1366, 141–148.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, Y., Liu, L., Liu, Y.-Z., Shen, X.-L., Wu, T.-Y., Zhang, T., Wang, W., Wang, Y.-X., & Jiang, C.-L. (2015). NLRP3 inflammasome mediates chronic mild stress-induced depression in mice via neuroinflammation. International Journal of Neuropsychopharmacology, 18, 1–8.

    Article  CAS  Google Scholar 

  • Zhang, Y., Yu, C., Zhou, Y., Li, K., Li, C., & Jiang, T. (2009). Decreased gyrification in major depressive disorder. Neuroreport, 20, 378–380.

    Article  PubMed  Google Scholar 

  • Zobel, A. W., Nickel, T., Kunzel, H. E., Ackl, N., Sonntag, A., Ising, M., & Holsboer, F. (2000). Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: The first 20 patients treated. Journal of Psychiatric Research, 34, 171–181.

    Article  CAS  PubMed  Google Scholar 

  • Zunszain, P. A., Anacker, C., Cattaneo, A., Choudhury, S., Musaelyan, K., Myint, A. M., Thuret, S., Price, J., & Pariante, C. M. (2012). Interleukin-1b: A new regulator of the kynurenine pathway affecting human hippocampal neurogenesis. Neuropsychopharmacology, 37, 939–949.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland

    Irena Smaga

  2. Department of Toxicology, Jagiellonian University Medical College, Kraków, Poland

    Weronika Krzyżanowska, Bartosz Pomierny, Alicja Maciejska, Alicja Skórkowska & Bogusława Budziszewska

  3. Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland

    Bogusława Budziszewska, Andrzej Pilc & Gabriel Nowak

  4. Jagiellonian University Medical College, Kraków, Poland

    Andrzej Pilc

  5. Department of Pharmacobiology, Jagiellonian University Medical College, Kraków, Poland

    Gabriel Nowak

Authors
  1. Irena Smaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weronika Krzyżanowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bartosz Pomierny
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alicja Maciejska
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alicja Skórkowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bogusława Budziszewska
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Andrzej Pilc
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gabriel Nowak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabriel Nowak .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Smaga, I. et al. (2021). Neurotoxicity in Depression. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-030-71519-9_176-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-71519-9_176-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-71519-9

  • Online ISBN: 978-3-030-71519-9

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation