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Inflammation and depression: Is there a causal connection with dementia?

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Abstract

Epidemiological studies show that there is a correlation between chronic depression and the likelihood of dementia in later life. There is evidence that inflammatory changes in the brain are pathological features of both depression and dementia. This suggests that an increase in inflammation-induced apoptosis, together with a reduction in the synthesis of neurotrophic factors caused by a rise in brain glucocorticoids, may play a role in the pathology of these disorders. A reduction in the neuroprotective components of the kynurenine pathway, such as kynurenic acid, and an increase in the neurodegenerative components, 3-hydroxykynurenine and quinolinic acid, contribute to the pathological changes. Such changes are postulated to cause neuronal damage and thereby predispose chronically depressed patients to dementia.

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References

  • Abas, MA, BJ Sahakian and R Levy (1990) Neuropsychological deficits and CT scan changes in elderly depressives.Psychol. Med. 20, 507–520.

    PubMed  CAS  Google Scholar 

  • Adler Gand A Jajcevic (2001) Clinical and magnetic resonance imaging correlates of hypothalamic-pituitary-adrenal axis function in elderly depressed patients.Neurosci. Lett. 298, 142–144.

    PubMed  CAS  Google Scholar 

  • Altman J (1965) Autoradiographic and histological studies of postnatal neurogenesis in rats, with special reference to postnatal neurogenesis in some brain regions.J. Comp. Neurol. 122, 431–474.

    Google Scholar 

  • Altman J (1969) Autoradiographic and histological studies of postnatal neurogenesis 4. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb.J. Comp. Neurol. 137, 433–457.

    PubMed  CAS  Google Scholar 

  • Altman J and GD Das (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats.J. Comp. Neurol. 124, 319–335.

    PubMed  CAS  Google Scholar 

  • Arango V, MD Underwood, AV Gubbi and JJ Mann (1995) Localised alterations in pre- and post-synaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims.Brain Res. 688, 121–133.

    PubMed  CAS  Google Scholar 

  • Ashtari M, BS Greenwald, E Kramer-Ginsberg, J Hu, H Wu, M Patel, P Aupperle and S Pollack (1999) Hippocampal/amygdale volumes in geriatric depression.Psychol. Med. 29, 629–638.

    PubMed  CAS  Google Scholar 

  • Axelson DS, PM Doraiswamy and WM McDonald (1993) Hypercortisolemia and hippocampal changes in depression.Psychiatr. Res. 47, 163–173.

    CAS  Google Scholar 

  • Beats BC, BJ Sahakian and R Levy (1996) Cognitive performance in tests sensitive to frontal lobe dysfunction in elderly depressed.Psychol. Med. 26, 591–603.

    PubMed  CAS  Google Scholar 

  • Bell-MacGinty S, MA Butters, CC Meltzer, PJ Greer, CF Reynolds3rd and JT Becker (2002) Brain morphometric abnormalities in geriatric depression:long-term neuro-biological effects of illness duration.Am. J. Psychiatr. 159, 1424–1427.

    Google Scholar 

  • Biver F, D Wikler, F Lotstra, P Damhaut, S Goldman and J Mendlewicz (1997) Serotonin 5HT2 receptor imaging in major depression: focal changes in orbito-insular cortex.Br. J. Psychiatr. 171, 444–448.

    CAS  Google Scholar 

  • Blazer DG (2003) Depression in late life:review and conclusions.J. Geriatr. A Biol. Sci. Med. Sci. 58, 249–265.

    Google Scholar 

  • Bowley MP, WC Drevets, D Ongur and JL Price (2000) Glial changes in the amygdale and entorhinal cortex in mood disorders.Soc. Neurosci. Abstr. 26, 876.10.

    Google Scholar 

  • Bremner JD, M Narayan, ER Anderson, LH Staib, HL Miller and DS Charney (2000) Hippocampal volume reduction in major depression.Am. J. Psychiatr. 157, 115–118.

    PubMed  CAS  Google Scholar 

  • Burt DB, MJ Zember and G Niederehe (1995) Depression and memory impairment: a meta-analysis of the association, its pattern and specificity.Psychol. Bull. 117, 285–305.

    PubMed  CAS  Google Scholar 

  • Buxbaum JD, EH Koo and P Greengard (1993) Protein phosphorylation inhibits production of Alzheimer amyloid beta A4 peptide.Proc. Natl. Acad. Sci. USA 90, 9195–9198.

    PubMed  CAS  Google Scholar 

  • Calabrese JR, AG Skwerer, B Barna, AD Gulledge, R Valenzuela, A Butkus, S Subichin and NE Krupp (1986) Depression, immunocompetence and prostaglandins of the E series.Psychiatr. Res. 17, 41–47.

    CAS  Google Scholar 

  • Campbell IK, LJ Roberts and IP Wicks (2003) Molecular targets in immune mediated diseases: the case of TNF and rheumatoid arthritis.Immunol. Cell Biol. 81, 354–366.

    PubMed  CAS  Google Scholar 

  • Carlin JM, EC Borden, PM Sondel and GI Byrne (1987) Biologic response modifier induced indoleamine 2,3-dioxygenase activity in human peripheral blood mononuclear cell cultures.J. Immunol. 139, 2414–2418.

    PubMed  CAS  Google Scholar 

  • Chen P, M Ganguli, BH Mulsant and ST De Kosky (1999) The temporal relationship between depressive symptoms and dementia: a community based prospective study.Arch. Gen. Psychiatr. 56, 261–266.

    PubMed  CAS  Google Scholar 

  • Chiarugi A, M Calvani, E Meli, E Traggiai and F Moroni (2001) Synthesis and release of neurotoxic kynurenine metabolites by human derived macrophages.J. Neuroimmunol. 120, 190–198.

    PubMed  CAS  Google Scholar 

  • Coffey CE, WE Wilkinson, IA Parashos, SA Soady, RJ Sullivan, LJ Patterson, GS Figiel, MC Webb, CE Spritzer and WT Djang (1992) Quantitative cerebral anatomy of the aging human brain: a cross-sectional study using magnetic resonance imaging.Neurology 42, 527–536.

    PubMed  CAS  Google Scholar 

  • Cohen-Cory S (2002)The developing synapse: construction and modification of synaptic structures and circuits.Science 298, 770–776.

    PubMed  CAS  Google Scholar 

  • Cotter DR, CE Pariante and IP Everall (2001) Gial cell abnormalities in major psychiatric disorders: the evidence and implications.Brain Res. Bull. 55, 585–595.

    PubMed  CAS  Google Scholar 

  • Cuzzocrea S, DP Riley, AP Caputi and D Salvemini (2001) Antioxidant therapy: a new approach to shock, inflammation and ischaemia/reperfusion injury.Pharmacol. Rev. 53, 135–159.

    PubMed  CAS  Google Scholar 

  • Drevets WC, JL Price, JR Simpson Jr, RD Todd, T Reich, M Vannier and ME Raichle (1997) Subgenual prefrontal cortex abnormalities in mood disorders.Nature 386, 824–827.

    PubMed  CAS  Google Scholar 

  • Duman RS (1998) Novel therapeutic approaches beyond the serotonin receptor.Biol. Psychiatr. 44, 324–335.

    CAS  Google Scholar 

  • Fujioka T, A Fujioka and RS Duman (2004) Activation of cAMP signalling facilitates the morphological maturation of newborn neurons in adult hippocampus.J. Neurosci. 24, 319–328.

    PubMed  CAS  Google Scholar 

  • Geerlings MI, RA Schoevers, AT Beckman, C Jonker, DJ Deeg, B Schmand, HJ Ader, LM Bouter and W Van Tilburg (2000) Depression and risk of cognitive decline and Alzheimer’s disease. Results of two prospective community based studies in the Netherlands.Br. J. Psychiatr. 176, 568–575.

    CAS  Google Scholar 

  • Green RC, LA Cupples, A Kurz, S Auerbach, R Go, D Sadovnick, R Duara, WA Kukull, H Chui, T Edeki, PA Griffith, RP Friedland, D Bachman and L Farrer (2003) Depression as a risk factor for Alzheimer’s disease: the MIRAGE study.Arch. Nerurol. 60, 753–759.

    Google Scholar 

  • Gilbertson HW, ME Sherton, A Ciszewski, K Kasai, NB Lasko, SP Orr and RK Pitman (2002) Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma.Nature Neurosci. 5, 1242–1247.

    PubMed  CAS  Google Scholar 

  • Grant RS and V Kapoor (1998) Murine glial cells regenerate NAD, after peroxide-induced depletion, using nicotinic acid, nicotinamide or quinolinic acid as substrates.J. Neurochem. 70, 1759–1763.

    PubMed  CAS  Google Scholar 

  • Greenwald BS, E Kramer-Ginsberg, B Bogerts, M Ashtari, P Aupperie, H Wu, L Allen, D Zeman and M Patel (1997) Quantitative magnetic resonance imaging findings in geriatric depression. Possible link between late-onset depression and Alzheimer’s disease.Psychol. Med. 27, 421–431.

    PubMed  CAS  Google Scholar 

  • Griffin DE, SL Wesselingh and JC McArthur (1994) Elevated CNS prostaglandins in human immunodeficiency virus associated dementia.Ann. Neurol. 35, 592–597.

    PubMed  CAS  Google Scholar 

  • Guillemin, GJ, SJ Kerr, GA Smythe, DG Smith, V Kapoor, PJ Armati, J Croitoru and BJ Brew (2001) The kynurenine pathway metabolism in human astrocytes: pathway for neuroprotection. J.Neurochem. 78, 842–853.

    CAS  Google Scholar 

  • Guillemin GJ, G Smythe, O Takikawa and BJ Brew (2005) Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes and neurons.Glia 49, 15–23.

    PubMed  Google Scholar 

  • Harvey BH (1996) Affective disorders and nitric oxide: a role in pathways to relapse and refractoriness?Hum. Psychopharmacol. 11, 309–319.

    CAS  Google Scholar 

  • Hayaishi O (1980)Biochemical and Medical Aspects of Tryptophan Metabolism (Elsevier:Amsterdam/North Holland Biomedical Press).

    Google Scholar 

  • Heyes MP K Saito, EO Major, S Milstien, SP Markey and JH Vickers (1993) A mechanism of quinolinic acid formation by brain in inflammatory neurological disease.Brain 16, 1425–1450.

    Google Scholar 

  • Heyes MP, CL Achim, CA Wiley, EO Major, K Saito and SP Markey (1996) Human microglia convert l-tryptophan into the neurotoxin quinolinic acid.Biochem. J. 320 (part 2) 595–597.

    PubMed  CAS  Google Scholar 

  • Hua JY and SJ Smith (2004) Neural activity and the dynamics of central nervous system development.Nature Neurosci. 7, 446–451.

    Google Scholar 

  • Ikeda-Matsuo Y, Y Ikegaya, N Matsuki, S Uematsu, S Akira and Y Sasaki (2005) Microglia specific expresión of microsomalprosta-glandin E2 synthase-1 contributes to lipopolysaccharide- induced PGE2 production.J. Neurochem. 94, 1546–1558.

    PubMed  CAS  Google Scholar 

  • Irwin M, TL Smith and JC Gillin (1997) Low natural killer cell cytotoxicity in major depression.Life Sci. 41, 2127–2133.

    Google Scholar 

  • Kanne SM, DA Balota, M Storandt, DW McKeel Jr and JC Morris (1998) Relating anatomy to function in Alzheimer’s disease: neuropsychological profiles predict regional neuropathology 5 years later.Neurology 50, 979–985.

    PubMed  CAS  Google Scholar 

  • Kaplan MS and DH Bell (1983) Neuronal proliferation in the 9 month old rodent-radioautographic study of granule cells in the hippocampus.Exp. Brain Res. 52, 1–5.

    PubMed  CAS  Google Scholar 

  • Katon W and MD Sullivan (1990) Depression and chronic medical illness.J. Clin. Psychiatr. 51, 3–11.

    Google Scholar 

  • Katz LC and CJ Shatz (1996) Synaptic activity and the construction of cortical circuits.Science 274, 1133–1138.

    PubMed  CAS  Google Scholar 

  • Kim DH, ME Payne, RM Levy, JR MacFall and DC Steffens (2002) APOE genotype and hippocampal volume change in geriatric depression.Biol. Psychiatr. 51, 426–429.

    CAS  Google Scholar 

  • Kim JP and DW Choi (1987) Quinolinate neurotoxicity in cortical cell cultures.Neuroscience 23, 423–432.

    PubMed  CAS  Google Scholar 

  • Klein J (2005) Functions and pathophysiological roles of phospholipase D in the brain.J. Neurochem. 94, 1473–1487.

    PubMed  CAS  Google Scholar 

  • Krishnan KR, WM McDonald, PR Escalona, PM Doraiswamy, G Na, MM Husain, GS Figiel, OB Boyko, EH Ellinwood and CB Nemeroff (1992) Magnetic resonance imaging of the caudate nuclei in depression.: preliminary observations.Arch. Gen. Psychiatr. 49, 553–557.

    PubMed  CAS  Google Scholar 

  • Kronfol Z and JD House (1987) Depression, HPA activity and lymphocyte function.Acta Psychiatr. Scand. 80, 142–147.

    Google Scholar 

  • Kukekov VG, ED Laywell, O Suslov, K Davies, B Scheffler, LB Thomas, TF O’Brien, M Kusakabe and DA Steindler (1999) Multipotent stem/progenitor cells with similar properties arise from two neurogenic regions of adult human brain.Exp. Neurol. 156, 333–344.

    PubMed  CAS  Google Scholar 

  • Landfield PW and JC Eldridge (1994) Evolving aspects of the glucocorticoid hypothesis of brain aging: hormonal modulation of neuronal calcium homeostasis.Neurobiol. Aging 15, 579–588.

    PubMed  CAS  Google Scholar 

  • Leonard BE (2001) Brain cytokines and the psychopathology of depression, In:Antidepressants (Leonard BE, Ed.) (Birkhauser Verlag:Basel), pp 109–120.

    Google Scholar 

  • Leonard BE and A-M Myint (2006) Changes in the immune system in depression and dementia: causal or co-incidental effects?Dialogues Clin. Neurosci. 8(2), 163–174.

    PubMed  Google Scholar 

  • Liu B and JS Hong (2003) Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic interventions.J. Pharmacol. Exp. Ther. 304, 1–7.

    PubMed  Google Scholar 

  • Lyketsos CG and J Olin (2002) Depression in Alzheimer’s disease: overview and treatment.Biol. Psychiatr. 52, 243–252.

    Google Scholar 

  • MacQueen GM, S Campbell, B McEwen, K MacDonald, S Amano, RT Joffe, C Nahmias and LT Young (2003) Course of illness, hippocampal volume and hippocampal function in major depression.Proc. Natl. Acad. Sci. USA 100, 1387–1392.

    PubMed  CAS  Google Scholar 

  • Maes M, E Bosmans, R De Jongh, G Kenis, E Vandoolaeghe and H Neels (1997) Increased serum IL-6 and IL-1R antagonist concentrations in major depression and treatment resistant depression.Cytokine 9, 853–858.

    PubMed  CAS  Google Scholar 

  • Malberg JE, AJ Eisch, EJ Nessler and RS Duman (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus.J. Neurosci. 20, 9104–9110.

    PubMed  CAS  Google Scholar 

  • Manji HK, WC Drevets and DS Charney (2001) The cellular neurobiology of depression.Nature Med. 7, 541–547.

    PubMed  CAS  Google Scholar 

  • Marshall PS (1993) Allergy and depression: a neurochemical threshold model of the relation between the illnesses.Psychol. Bull. 113, 23–43.

    PubMed  CAS  Google Scholar 

  • Mayne TJ, E Vittinghoff, MA Chesney, DC Barrett and TJ Coates (1996) Depressive affect and survival among gay and bisexual men infected with HIV.Arch. Int. Med. 156, 223–228.

    Google Scholar 

  • McEwen BS (1997) Possible mechanisms for atrophied human hippocampus.Mol. Psychiatr. 2, 255–262.

    CAS  Google Scholar 

  • McGeer PL, S Itagaki, BE Boyes and EG McGeer (1998) Reactive microglia are positive for HLA-DR in the sustantia nigra of Parkinson’s and Alzheimer’s disease brains.Neurology 38, 1285–1291.

    Google Scholar 

  • Meyers CA and AD Valentine (1995) Neurologic and psychiatric adverse effects of immunological therapy.CNS Drugs 3, 56–68.

    Google Scholar 

  • Mellor AL and DH Munn (1999) Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation.Immunol. Today 20, 469–473.

    PubMed  CAS  Google Scholar 

  • Meyers CA and AD Valentine (1995) Neurologic and psychiatric adverse effects of immunological therapy.CNS Drugs 3, 56–68.

    Google Scholar 

  • Minden SL and RB Schiffer (1990) Affective disorder in multiple sclerosis.Gen. Hosp. Psychiatr. 9, 426–434.

    Google Scholar 

  • Modrego PJ and J Ferrandez (2004) Depression in patients with mild cognitive impairment increases the risk of developing dementia of the Alzheimer type: a prospective study.Arch. Neurol. 61, 1290–1293.

    PubMed  Google Scholar 

  • Moncada S, A Higgs and R Furchgott (1997) International Union of Pharmacology: nomenclature in nitric oxide research.Pharmacol. Rev. 49, 137–142.

    PubMed  CAS  Google Scholar 

  • Musso T, GL Gusella, A Brooks, DL Longo and L Varesio (1994) Interleukin-4 inhibits indoleamine 2,3-dioxygenase expression in human monocytes.Blood 83, 1408–1411.

    PubMed  CAS  Google Scholar 

  • Myint A-M and Y-K Kim (2003) Cytokine-serotonin interactionsthrough indoleamine 2,3-dixygenase: a neurodegenerative hypothesis of depression.Med. Hypoth. 61, 519–525.

    CAS  Google Scholar 

  • Myint A-M, BE Leonard, HW Steinbusch and Y-K Kim (2005) Th1,Th2 and Th3 cytokine alterations in major depression.J. Affect. Disord. 88, 169–173.

    Google Scholar 

  • Myint A-M, Y-K Kim, R Verkerk, S Scharpe, H Steinbusch and B Leonard (2006a) Kynurenine pathway in major depression: evidence of impaired neuroprotection.J. Affect. Disord. 2006 Sep 1; [Epub ahead of print].

  • Myint A-M, SM O’Mahony, M Kubera et al. (2006b) Role of paroxetine in interferon-alpha induced immune and behavioural changes in male Wister rats.J. Psychopharmacol. (in press).

  • Nathan C (1992) Nitric oxide as a secretory product of mammalian cells.FASEB J. 6, 3051–3064.

    PubMed  CAS  Google Scholar 

  • Nibuya M, S Morinobuand RS Duman (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroshock seizures and antidepressant drug treatments.J. Neurosci. 15, 7549–7547.

    Google Scholar 

  • Nibuya M, M Takahashi, DS Russell and RS Duman (1999) Chronic stress increases catalytic TrkB mRNA in rat hippocampus.Neurosci. Lett. 267, 81–84.

    PubMed  CAS  Google Scholar 

  • Nitsch RM, M Deng, JH Growdon and RJ Wurtman (1996) Serotonin 5HT2a and 5HT2C receptors stimulate amyloid precursor protein ectodomain secretion.J. Biol. Chem. 271, 4188–4194.

    PubMed  CAS  Google Scholar 

  • O’Brien JT, R Erkinjuntti, B Reisberg, G Roman, T Sawada, L Pantoni, JV Bowler, C Ballard, C DeCarli, PB Gorelick, K Rockwood, A Burns, S Gauthier and ST DeKosky (2003) Vascular cognitive impairment.Lancet Neurol. 2, 89–98.

    PubMed  Google Scholar 

  • O’Brien JT, D Ames, I Schweitzer, P Colman, P Desmond and B Tress (1996) Clinical and magnetic resonance imaging correlates of HPA axis function in depressed and Alzheimer’s disease patients.Br. J. Psychiatr. 168, 679–687.

    CAS  Google Scholar 

  • O’Brien JT, A Lloyd, I McKeith, A Gholkar and N Ferrier (2004) A longitudinal study of hippocampal volume, cortisol levels and cognition in older depressed patients.Am. J. Psychiatr. 161, 2081–2090.

    PubMed  Google Scholar 

  • O’Mahony SM, A-M Myint, H Steinbusch and BE Leonard (2005) Efavirenz induces depressive like behaviour, increased stress response and changes in the immune response in rats.Neuroimmunol. 12, 293–298.

    CAS  Google Scholar 

  • Olin JT, IR Katz, BS Meyers, LS Schneider and BD Lebowitz (2002) Provisional diagnostic criteria for depression in Alzheimer’s disease: rationale and background.Am. J. Geriatr. Psychiatr. 10, 129–141.

    Google Scholar 

  • Ongur D, WC Drevets and JL Price (1998) Glia reduction in sub-genual pre-frontal cortex in mood disorders.Proc. Natl. Acad. Sci. USA 95, 13290–13295.

    PubMed  CAS  Google Scholar 

  • Papassotiropoulos A, M Bagli, F Jessen, ML Rao, SG Schwab and R Heun (1999) Early-onset and late-onset depression are independent of the genetic polymorphism of apolipoprotein E.Dement. Geriatr. Cogn. Disord. 10, 258–261.

    PubMed  CAS  Google Scholar 

  • Perkins MN and TW Stone (1982) An iontophorectic investigation of the actions of convulsant kynurenines and their interaction with endogenous quinolinic acid.Brain Res. 247, 184–187.

    PubMed  CAS  Google Scholar 

  • Posener JA, L Wang, JL Price,et al. (2003) High dimensional mapping of the hippocampus in depression.Am. J. Psychiatr. 160, 83–89.

    PubMed  Google Scholar 

  • Rajkowska G, JJ Miguel-Hidalgo, J Wei, G Dilley, SD Pittman, HY Meltzer, JC Overholser, BL Roth and CA Stockmeier (1999) Morphometric evidence for neuronal and glia pre-frontal cell pathology in major depression.Biol. Psychiatr. 45, 1085–1098.

    CAS  Google Scholar 

  • Rapp MA, K Dahlman, M Sano, HT Grossman, V Haroutunian and JM Gorman (2005) Neuropsychological differences between late onset and recurrent geriatric major depression.Am. J. Psychiatr. 162, 691–698.

    PubMed  Google Scholar 

  • Rapp MA, M Schnaider-Beeri, HT Grossman, M Sano, DP Perl, DP Purohit, JM Gorman and V Haroutunian (2006) Increased hippocampal plaques and tangles in patients with Alzheimer’s disease with a life-time history of major depression.Arch. Gen. Psychiatr. 63, 161–167.

    PubMed  Google Scholar 

  • Reynolds BA and S Weiss (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system.Science 255 (5052), 1707–1710.

    PubMed  CAS  Google Scholar 

  • Russo-Neustadt AA, RC Beard, YM Huang and CW Cotman (2000) Physical activity and antidepressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus.Neuroscience 101, 305–312.

    PubMed  CAS  Google Scholar 

  • Saarelainen T (2003) Activation of the trkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant -induced behavioural effects.J. Neurosci. 23, 349–357.

    PubMed  CAS  Google Scholar 

  • Sairanen M, G Lucas, P Emfors, M Castren and E Castren (2005) BDNF and antidepressant drugs have different but co-ordinated effects on neuronal turnover, proliferation and survival in the adult dentate gyrus.J. Neurosci. 25, 1089–1094.

    PubMed  CAS  Google Scholar 

  • Santarelli L (2003) Requirement of hippocampal neurogenesis for the behavioural effects of antidepressants.Science 301, 805–809.

    PubMed  Google Scholar 

  • Sapolsky RM (2000) Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders.Arch. Gen. Psychiatr. 57, 925–935.

    PubMed  CAS  Google Scholar 

  • Schrott LM and LS Crnic (1996) Anxiety behaviour, exploratory behaviour and activity in NZB x and NZB F1 hybrid mice: role of genotype and autoimmune disease progression.Brain Behav. Immunol. 10, 260–274.

    CAS  Google Scholar 

  • Sheline YI (2006) Brain structural changes associated with depression, In:Depression and Brain Dysfunction (Gilliam FG, AM Kanner and YL Sheline, Eds.) (Taylor & Francis:London), pp 85–104.

    Google Scholar 

  • Sheline YI, PW Wang, MH Gado, JG Csernansky and MW Vannier (1996) Hippocampal atrophy in recurrent major depression.Proc. Natl. Acad. Sci. USA 93, 3908–3913.

    PubMed  CAS  Google Scholar 

  • Sheline YI, M Sanghavi, MA Mintun and MH Gado (1999) Depression duration, but not age, predicts hippocampal volume loss in medically healthy women with recurrent major depression.J. Neurosci. 19, 5034–5043.

    PubMed  CAS  Google Scholar 

  • Sluzewska A, J Rybakowski, E Bosmans, M Sobieska, R Berghmans, M Maes and K Wiktorowicz (1996) Indicators of immune activation in major depression.Psychiatr. Res. 64, 162–167.

    Google Scholar 

  • Smith R (1991) The macrophage theory of depression.Med. Hypotheses 35, 298–306.

    PubMed  CAS  Google Scholar 

  • Smith MA, S Makino, R Kvetnansky and RM Post (1995) Effects of stress on neurotrophic factor expression in the rat brain.Ann. NY Acad. Sci. 771, 234–239.

    PubMed  CAS  Google Scholar 

  • Song H and M Poo (2001) The cell biology of neuronal navigation.Nat. CellBiol. 3, E81-E88.

    CAS  Google Scholar 

  • Song C, T Dinan and BE Leonard (1994) Changes in immunoglobulins, complement and acute phase proteins in depressed patients and normal controls.J. Affect. Disord. 30, 283–288.

    PubMed  CAS  Google Scholar 

  • Song C, A Lin, S Bonaccorso, C Heide, R Verkerk, G Kenis, E Bosmans, S Scharpe, A Whelan, P Cosyns, R de Jongh and M Maes (1998) The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression.J. Affect. Disord. 49, 211–219.

    PubMed  CAS  Google Scholar 

  • Song C, DF Horrobin and BE Leonard (2006) The comparison of changes in behavior, neurochemistry, endocrine, and immune functions after different routes, doses and durations of administrations of IL-1beta in rats.Pharmacopsychiatry 39(3), 88–99.

    PubMed  CAS  Google Scholar 

  • Stanfield BB and JE Trice (1988) Evidence that granule cells generated in the dentate gyrus of adult rats extend axonal projections.Exp. Brain Res. 72, 399–406.

    PubMed  CAS  Google Scholar 

  • Steffens DC and KR Krishnan (1998) Structural neuroimaging and mood disorders: recent findings, implications for classification, and future directions.Biol. Psychiatr. 43, 705–712.

    CAS  Google Scholar 

  • Steffens DC, BL Plassman, MJ Helms, KA Welsh-Bohmer, AM Saunders and JC Breitner (1997) A twin study of late-onset depression and apolipoprotein E4 as risk factors for Alzheimer’s disease.Biol. Psychiatr. 41, 851–856.

    CAS  Google Scholar 

  • Steffens DC, CE Byrum, DR McQuoid, DL Greenberg, ME Payne, TF Blitchington, JR MacFall and KR Krishnan (2000) Hippocampal volume in geriatric depression.Biol. Psychiatr. 48, 301–309.

    CAS  Google Scholar 

  • Steffens DC, ME Payne, DL Greenberg, CE Byrum, KA WelshBohmer, HR Wagner and JR MacFall (2002) Hippocampal volume and incident dementia in geriatric depression.Am. J. Geriatr. Psychiatr. 10, 62–71.

    Google Scholar 

  • Stern Y, MP McDermott, S Albertet al. (2001) Factors associated with incident human immunodeficiency virus dementia.Arch. Neurol. 58, 473–479.

    PubMed  CAS  Google Scholar 

  • Stone TW and LG Darlington (2002) Endogenous kynurenins as targets for drug discovery and development.Nat. Rev. Drug Discov. 1, 609–620.

    PubMed  CAS  Google Scholar 

  • Strittmatter WJ, AM Saunders, D Schmechel, M Pericak-Vance, J Enghild, GS Salvesen and AD Roses (1993) Apolipoprotein E: high avidity binding to beta amyloid and increased frequency of type 4 allele in late-onset Familial Alzheimer’s disease.Proc. Natl. Acad. Sci. USA 90, 1977–1981.

    PubMed  CAS  Google Scholar 

  • Vaidya VA, JA Siuciak, F Du and RS Duman (1999) Hippocampal mossy fiber sprouting induced by chronic electroconvulsive seizures.Neuroscience 89, 157–166.

    PubMed  CAS  Google Scholar 

  • Visser PJ, FR Verhey, RW Ponds, A Kester and J Jolles (2000) Distinction between preclinical Alzheimer’s disease and depression.J. Am. Geriatr. Soc. 48, 479–484.

    PubMed  CAS  Google Scholar 

  • Vythilingham M (2002) Childhood trauma associated with smaller hippocampal volume in women with major depression.Am. J. Psychiatr. 159, 2072–2080.

    Google Scholar 

  • Wichers MC, GH Koek, G Robaeys, R Verkerk, S Scharpe and M Maes (2005) IDO and interferon alpha induced depressive symptoms: a shift in hypothesis from tryptophan depletion.Mol. Psychiatr. 10, 538–544.

    CAS  Google Scholar 

  • Young SN, PE Smith, RO Pihl and FR Ervin (1985) Tryptophan depletion causes a rapid lowering of mood in normal males.Psychopharmacol. (Berl.) 87, 173–177.

    CAS  Google Scholar 

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E.Leonard, B., Myint, A. Inflammation and depression: Is there a causal connection with dementia?. neurotox res 10, 149–160 (2006). https://doi.org/10.1007/BF03033243

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  • DOI: https://doi.org/10.1007/BF03033243

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