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Hippocampus

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

Schizophrenia is associated with structural and functional abnormalities in a variety of neural circuits. This chapter reviews studies of the hippocampus in schizophrenia.

The original finding was significantly smaller overall hippocampal volume in schizophrenia. Many studies have confirmed this original finding and have demonstrated it at the initial stage of the illness. While less prominent when compared to neurodegenerative illnesses, the volume difference is comparable to major depression and posttraumatic stress disorder.

More recent studies have explored region- and cell-specific alterations of hippocampal anatomy as well as functionally selective impairments of hippocampal function. Several studies have identified a decreased expression of the genes and proteins that characterize hippocampal interneurons. In addition, studies of regional cerebral blood flow have identified overall greater hippocampal activity and specific abnormalities of hippocampal recruitment during the performance of memory tasks.

Taken together, the evidence for a specific deficit of hippocampal interneurons is accumulating. Together with the neuroimaging findings, this pattern points to a disinhibition of hippocampal pyramidal cells in schizophrenia. Future studies will explore the molecular mechanisms of hippocampal dysfunction in schizophrenia and it's impact on the cognitive and social function in schizophrenia.

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Abbreviations

AMPA:

alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid

ERC:

entorhinal cortex

FEP:

first-episode psychosis

fMRI:

functional magnetic resonance imaging

GABA:

gamma-aminobutyric acid

GAD:

glutamic acid decarboxylase

PET:

positron emission tomography

PHC:

parahippocampal cortex

PRC:

perirhinal cortex

rCMRglc:

regional cerebral glucose metabolic rates

vGAT:

vesicular gamma-aminobutyric acid transporter

vGT:

vesicular glutamate transporter

References

  • Achim AM, Bertrand MC, Sutton H, Montoya A, Czechowska Y, et al. 2007. Selective abnormal modulation of hippocampal activity during memory formation in first-episode psychosis. Arch Gen Psychiatry 64: 999–1014.

    Article  PubMed  Google Scholar 

  • Achim AM, Lepage M. 2005. Episodic memory-related activation in schizophrenia: Meta-analysis. Br J Psychiatry 187: 500–509.

    Article  PubMed  Google Scholar 

  • Adler LE, Waldo MC. 1991. Counterpoint: A sensory gating–hippocampal  model of schizophrenia. Schizophr Bull 17(1):19–24.

    Article  PubMed  CAS  Google Scholar 

  • Altar CA, Jurata LW, Charles V, Lemire A, Liu P, et al. 2005. Deficient hippocampal neuron expression of proteasome, ubiquitin, and mitochondrial genes in multiple schizophrenia cohorts. Biol Psychiatry 58: 85–96.

    Article  PubMed  CAS  Google Scholar 

  • Arango C, Kirkpatrick B, Koenig J. 2001. At issue: Stress, hippocampal neuronal turnover, and neuropsychiatric disorders. Schizophr Bull 27: 477–480.

    Article  PubMed  CAS  Google Scholar 

  • Arnold SE. 2000. Hippocampal pathology. The Neuropathology of Schizophrenia. Progress and Interpretation. Harrison PJ, Roberts GW, editors. Oxford: Oxford University Press.

    Google Scholar 

  • Barbas H, Blatt GJ. 1995. Topographically specific hippocampal projections target functionally distinct prefrontal areas in the rhesus monkey. Hippocampus 5: 511–533.

    Article  PubMed  CAS  Google Scholar 

  • Bast T, Feldon J. 2003. Hippocampal modulation of sensorimotor processes. Prog Neurobiol 70: 319–345.

    Article  PubMed  CAS  Google Scholar 

  • Benes FM. 1999. Evidence for altered trisynaptic circuitry in schizophrenic hippocampus. Biol Psychiatry 46: 589–599.

    Article  PubMed  CAS  Google Scholar 

  • Benes FM, Berretta S. 2001. Gabaergic interneurons: Implications for understanding schizophrenia and bipolar disorder. Neuropsychopharmacology 25: 1–27.

    Article  PubMed  CAS  Google Scholar 

  • Benes FM, Khan Y, Vincent SL, Wickramasinghe R. 1996. Differences in the subregional and cellular distribution of GABAA receptor binding in the hippocampal formation of schizophrenic brain. Synapse 22: 338–349.

    Article  PubMed  CAS  Google Scholar 

  • Benes FM, Lim B, Matzilevich D, Walsh JP, Subburaju S, et al. 2007. Regulation of the GABA cell phenotype in hippocampus of schizophrenics and bipolars. Proc Natl Acad Sci USA 104: 10164–10169.

    Article  PubMed  CAS  Google Scholar 

  • Benes FM, Wickramasinghe R, Vincent SL, Khan Y, Todtenkopf M. 1997. Uncoupling of GABA(A) and benzodiazepine receptor binding activity in the hippocampal formation of schizophrenic brain. Brain Res 755: 121–129.

    Article  PubMed  CAS  Google Scholar 

  • Bickford-Wimer PC, Nagamoto H, Johnson R, Adler LE, Egan M, Rose GM, Freedman R. 1990. Auditory sensory gating in hippocampal neurons: A model system in the rat. Biological Psychiatry 27: 183–192.

    Article  PubMed  CAS  Google Scholar 

  • Bleuler E. 1911. Dementia Praecox oder Gruppen der Schizophrenien. Leipzig: Franz Deutike.

    Google Scholar 

  • Bogerts B, Meertz E, Schonfeldt-Bausch R. 1985. Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage. Arch Gen Psychiatry 42: 784–791.

    Article  PubMed  CAS  Google Scholar 

  • Boos HB, Aleman A, Cahn W, Pol HH, Kahn RS. 2007. Brain volumes in relatives of patients with schizophrenia: A meta-analysis. Arch Gen Psychiatry 64: 297–304.

    Article  PubMed  Google Scholar 

  • Boyer P, Phillips JL, Rousseau FL, Ilivitsky S. 2007. Hippocampal abnormalities and memory deficits: New evidence of a strong pathophysiological link in schizophrenia. Brain Res Rev 54: 92–112.

    Article  PubMed  CAS  Google Scholar 

  • Buchsbaum MS, Haier RJ, Potkin SG, Nuechterlein K, Bracha HS, et al. 1992. Frontostriatal disorder of cerebral metabolism in never-medicated schizophrenics. Arch Gen Psychiatry 49: 935–942.

    Article  PubMed  CAS  Google Scholar 

  • Callicott JH, Straub RE, Pezawas L, Egan MF, Mattay VS, et al. 2005. Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc Natl Acad Sci USA 102: 8627–8632.

    Article  PubMed  CAS  Google Scholar 

  • Campbell S, Macqueen G. 2004. The role of the hippocampus in the pathophysiology of major depression. J Psychiatry Neurosci 29: 417–426.

    PubMed  Google Scholar 

  • Chang Q, Fischbach GD. 2006. An acute effect of neuregulin 1 beta to suppress alpha 7-containing nicotinic acetylcholine receptors in hippocampal interneurons. J Neurosci 26: 11295–11303.

    Article  PubMed  CAS  Google Scholar 

  • Csernansky JG, Joshi S, Wang L, Haller JW, Gado M, et al. 1998. Hippocampal morphometry in schizophrenia by high dimensional brain mapping. Proc Natl Acad Sci USA 95: 11406–11411.

    Article  PubMed  CAS  Google Scholar 

  • Davatzikos C, Shen D, Gur RC, Wu X, Liu D, et al. 2005. Whole-brain morphometric study of schizophrenia revealing a spatially complex set of focal abnormalities. Arch Gen Psychiatry 62: 1218–1227.

    Article  PubMed  Google Scholar 

  • Deakin JFW, Slater P, Simpson MDC, Gilchrist AC, Skan WJ, et al. 1989. Frontal cortical and left temporal glutamatergic dysfunction in schizophrenia. J Neurochem 52: 1781–1786.

    Article  PubMed  CAS  Google Scholar 

  • Dhikav V, Anand KS. 2007. Is hippocampal atrophy a future drug target? Med Hypotheses 68: 1300–1306.

    Article  PubMed  CAS  Google Scholar 

  • Dierks T, Linden DE, Jandl M, Formisano E, Goebel R, et al. 1999. Activation of Heschl’s gyrus during auditory hallucinations. Neuron 22: 615–621.

    Article  PubMed  CAS  Google Scholar 

  • Dwork AJ. 1997. Postmortem studies of the hippocampal formation in schizophrenia. Schizophr Bull 23: 403–421.

    Article  Google Scholar 

  • Eastwod SL, McDonald B, Burnet PWJ, Beckwith JP, Kerwin RW, et al. 1995. Decreased expression of mRNAs encoding non-NMDA glutamate receptors GluR1 and GluR2 in medial temporal lobe neurons in schizophrenia. Mol Brain Res 29: 211–223.

    Article  Google Scholar 

  • Eastwood SL, Burnet PW, Harrison PJ. 1997. GluR2 glutamate receptor subunit flip and flop isoforms are decreased in the hippocampal formation in schizophrenia: A reverse transcriptase-polymerase chain reaction (RT-PCR) study. Brain Res Mol Brain Res 44: 92–98.

    Article  PubMed  CAS  Google Scholar 

  • Eastwood SL, Harrison PJ. 2000. Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: A study of complexin mRNAs. Mol Psychiatry 5: 425–432.

    Article  PubMed  CAS  Google Scholar 

  • Eichenbaum H. 2004. Hippocampus: Cognitive processes and neural representations that underlie declarative memory. Neuron 44: 109–120.

    Article  PubMed  CAS  Google Scholar 

  • Eyler LT, Olsen RK, Nayak GV, Mirzakhanian H, Brown GG, et al. 2007. Brain response correlates of decisional capacity in schizophrenia: A preliminary FMRI study. J Neuropsychiatry Clin Neurosci 19: 137–144.

    Article  PubMed  Google Scholar 

  • Eyles DW, McGrath JJ, Reynolds GP. 2002. Neuronal calcium-binding proteins and schizophrenia. Schizophr Res 57: 27–34.

    Article  PubMed  CAS  Google Scholar 

  • Fletcher P. 1998. The missing link: A failure of fronto-hippocampal integration in schizophrenia. Nat Neurosci 1: 266–267.

    Article  PubMed  CAS  Google Scholar 

  • Freund TF, Buzsaki G. 1996. Interneurons of the hippocampus. Hippocampus 6: 347–470.

    Article  PubMed  CAS  Google Scholar 

  • Friston KJ, Liddle PF, Frith CD, Hirsch SR, Frackowiak RS. 1992. The left medial temporal region and schizophrenia. A PET study. Brain 115: 367–382.

    Article  PubMed  Google Scholar 

  • Gao XM, Sakai K, Roberts RC, Conley RR, Dean B, et al. 2000. Ionotropic glutamate receptors and expression of N-methyl-d-aspartate receptor subunits in subregions of human hippocampus: Effects of schizophrenia. Am J Psychiatry 157: 1141–1149.

    Article  PubMed  CAS  Google Scholar 

  • Geuze E, Vermetten E, Bremner JD. 2005. MR-based in vivo hippocampal volumetrics. 2. Findings in neuropsychiatric disorders. Mol Psychiatry 10: 160–184.

    Article  PubMed  CAS  Google Scholar 

  • Giedd JN, Jeffries NO, Blumenthal J, Castellanos FX, Vaituzis AC, et al. 1999. Childhood-onset schizophrenia: Progressive brain changes during adolescence. Biol Psychiatry 46: 892–898.

    Article  PubMed  CAS  Google Scholar 

  • Goldman MB, Mitchell CP. 2004. What is the functional significance of hippocampal pathology in schizophrenia? Schizophr Bull 30: 367–392.

    Article  PubMed  Google Scholar 

  • Goldman MB, Torres IJ, Keedy S, Marlow-O’Connor M, Beenken B, et al. 2007. Reduced anterior hippocampal formation volume in hyponatremic schizophrenic patients. Hippocampus 17: 554–562.

    Article  PubMed  CAS  Google Scholar 

  • Goldman-Rakic PS, Selemon LD, Schwartz ML. 1984. Dual pathways connecting the dorsolateral prefrontal cortex with the hippocampal formation and parahippocampal cortex in the rhesus cortex. Neuroscience 12: 719–743.

    Article  PubMed  CAS  Google Scholar 

  • Green M. 1996. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 153: 321–330.

    PubMed  CAS  Google Scholar 

  • Gur RE, Mozley PD, Resnick SM, Mozley LH, Shtasel DL, et al. 1995. Resting cerebral glucose metabolism in first-episode and previously treated patients with schizophrenia relates to clinical features. Arch Gen Psychiatry 52: 657–667.

    Article  PubMed  CAS  Google Scholar 

  • Harrison PJ. 1999. The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 122: 593–624.

    Article  PubMed  Google Scholar 

  • Harrison PJ. 2004. The hippocampus in schizophrenia: A review of the neuropathological evidence and its pathophysiological implications. Psychopharmacology (Berl) 174: 151–162.

    Article  CAS  Google Scholar 

  • Harrison PJ, Eastwood SL. 1998. Preferential involvement of excitatory neurons in medial temporal lobe in schizophrenia. Lancet 352: 1669–1673.

    Article  PubMed  CAS  Google Scholar 

  • Harrison PJ, Eastwood SL. 2001. Neuropathological studies of synaptic connectivity in the hippocampal formation in schizophrenia. Hippocampus 11: 508–519.

    Article  PubMed  CAS  Google Scholar 

  • Harrison PJ, McLaughlin D, Kerwin RW. 1991. Decreased hippocampal expression of a glutamate receptor gene in schizophrenia. Lancet 337: 450–452.

    Article  PubMed  CAS  Google Scholar 

  • Harrison PJ, Weinberger DR. 2005. Schizophrenia genes, gene expression, and neuropathology: On the matter of their convergence. Mol Psychiatry 10: 40–68; image 5.

    Article  PubMed  CAS  Google Scholar 

  • Heckers S. 1997. Neuropathology of schizophrenia: Cortex, thalamus, basal ganglia, and neurotransmitter-specific projection systems. Schizophr Bull 23: 403–421.

    Article  PubMed  CAS  Google Scholar 

  • Heckers S. 2001. Neuroimaging studies of the hippocampus in schizophrenia. Hippocampus 11: 520–528.

    Article  PubMed  CAS  Google Scholar 

  • Heckers S, Goff D, Schacter DL, Savage CR, Fischman AJ, et al. 1999. Functional imaging of memory retrieval in deficit vs nondeficit schizophrenia. Arch Gen Psychiatry 56: 1117–1123.

    Article  PubMed  CAS  Google Scholar 

  • Heckers S, Heinsen H, Geiger B, Beckmann H. 1991. Hippocampal neuron number in schizophrenia. A stereological study. Arch Gen Psychiatry 48: 1002–1008.

    Article  PubMed  CAS  Google Scholar 

  • Heckers S, Konradi C. 2002. Hippocampal neurons in schizophrenia. J Neural Transm 109: 891–905.

    Article  PubMed  CAS  Google Scholar 

  • Heckers S, Rauch SL, Goff D, Savage CR, Schacter DL, et al. 1998. Impaired recruitment of the hippocampus during conscious recollection in schizophrenia. Nat Neurosci 1: 318–323.

    Article  PubMed  CAS  Google Scholar 

  • Heckers S, Stone D, Walsh J, Shick J, Koul P, et al. 2002. Differential hippocampal expression of glutamic acid decarboxylase 65 and 67 messenger RNA in bipolar disorder and schizophrenia. Arch Gen Psychiatry 59: 521–529.

    Article  PubMed  CAS  Google Scholar 

  • Hemsley DR. 1993. A simple (or simplistic?) cognitive model for schizophrenia. Behav Res Ther 31: 633–645.

    Article  PubMed  CAS  Google Scholar 

  • Holt DJ, Kunkel L, Weiss AP, Goff DC, Wright CI, et al. 2006. Increased medial temporal lobe activation during the passive viewing of emotional and neutral facial expressions in schizophrenia. Schizophr Res 82: 153–162.

    Article  PubMed  Google Scholar 

  • Holt DJ, Weiss AP, Rauch SL, Wright CI, Zalesak M, et al. 2005. Sustained activation of the hippocampus in response to fearful faces in schizophrenia. Biol Psychiatry 57: 1011–1019.

    Article  PubMed  Google Scholar 

  • Honea R, Crow TJ, Passingham D, Mackay CE. 2005. Regional deficits in brain volume in schizophrenia: A meta-analysis of voxel-based morphometry studies. Am J Psychiatry 162: 2233–2245.

    Article  PubMed  Google Scholar 

  • Jessen F, Scheef L, Germeshausen L, Tawo Y, Kockler M, et al. 2003. Reduced hippocampal activation during encoding and recognition of words in schizophrenia patients. Am J Psychiatry 160: 1305–1312.

    Article  PubMed  Google Scholar 

  • Kawasaki Y, Maeda Y, Sakai N, Higashima M, Yamaguchi N, et al. 1996. Regional cerebral blood flow in patients with schizophrenia: Relevance to symptom structures. Psychiatry Res 67: 49–58.

    Article  PubMed  CAS  Google Scholar 

  • Kawasaki Y, Suzuki M, Maeda Y, Urata K, Yamaguchi N, et al. 1992. Regional cerebral blood flow in patients with schizophrenia. A preliminary report. Eur Arch Psychiatry Clin Neurosci 241: 195–200.

    Article  PubMed  CAS  Google Scholar 

  • Kerwin R, Patel S, Meldrum B. 1990. Quantitative autoradiographic analysis of glutamate binding sites in the hippocampal formation in normal and schizophrenic brain post mortem. Neuroscience 39: 25–32.

    Article  PubMed  CAS  Google Scholar 

  • Konradi C, Eaton M, MacDonald ML, Walsh J, Benes FM, et al. 2004. Molecular evidence for mitochondrial dysfunction in bipolar disorder. Arch Gen Psychiatry 61: 300–308.

    Article  PubMed  CAS  Google Scholar 

  • Kornhuber J, Mack-Burkhardt F, Riederer P, Hebenstreit GF, Reynolds GP, et al. 1989. [3H]MK-801 binding sites in postmortem brain regions of schizophrenic patients. J Neural Transm Gen Sect 77: 231–236.

    Article  CAS  Google Scholar 

  • Kraepelin E. 1913. Psychiatrie. Ein Lehrbuch für Studierende und Ärzte. Achte, vollständig umgearbeitete Auflage. III. Band. Klinische Psychiatrie. II. Teil. Leipzig: Barth Verlag.

    Google Scholar 

  • Krieckhaus EE, Donahoe JW, Morgan MA. 1992. Paranoid schizophrenia may be caused by dopamine hyperactivity of CA1 hippocampus. Biological Psychiatry 31(6):560–570.

    Article  PubMed  CAS  Google Scholar 

  • Lahti AC, Holcomb HH, Weiler MA, Medoff DR, Tamminga CA. 2003. Functional effects of antipsychotic drugs: Comparing clozapine with haloperidol. Biol Psychiatry 53: 601–608.

    Article  PubMed  CAS  Google Scholar 

  • Law AJ, Shannon Weickert C, Hyde TM, Kleinman JE, Harrison PJ. 2004. Neuregulin-1 (NRG-1) mRNA and protein in the adult human brain. Neuroscience 127: 125–136.

    Article  PubMed  CAS  Google Scholar 

  • Lawrie S. 2007. Distinguishing vulnerability, prediction, and progression in the preschizophrenic brain. Arch Gen Psychiatry 64: 250–251; author reply 252–253.

    Article  PubMed  Google Scholar 

  • Lawrie SM, Whalley H, Kestelman JN, Abukmeil SS, Byrne M, et al. 1999. Magnetic resonance imaging of brain in people at high risk of developing schizophrenia. Lancet 353: 30–33.

    Article  PubMed  CAS  Google Scholar 

  • Lepage M, Habib R, Tulving E. 1998. Hippocampal PET activations of memory encoding and retrieval: The HIPER model. Hippocampus 8: 313–322.

    Article  PubMed  CAS  Google Scholar 

  • Li B, Woo RS, Mei L, Malinow R. 2007. The neuregulin-1 receptor erbB4 controls glutamatergic synapse maturation and plasticity. Neuron 54: 583–597.

    Article  PubMed  CAS  Google Scholar 

  • Liddle PF, Friston KJ, Frith CD, Jones T, Hirsch SR, et al. 1992. Patterns of cerebral blood flow in schizophrenia. Br J Psychiatry 160: 179–186.

    Article  PubMed  CAS  Google Scholar 

  • Lipska BK, Peters T, Hyde TM, Halim N, Horowitz C, et al. 2006. Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs. Hum Mol Genet 15: 1245–1258.

    Article  PubMed  CAS  Google Scholar 

  • Malaspina D, Harkavy-Friedman J, Corcoran C, Mujica-Parodi L, Printz D, et al. 2004. Resting neural activity distinguishes subgroups of schizophrenia patients. Biol Psychiatry 56: 931–937.

    Article  PubMed  Google Scholar 

  • McCarley RW, Wible CG, Frumin M, Hirayasu Y, Levitt JJ, et al. 1999. MRI anatomy of schizophrenia. Biol Psychiatry 45: 1099–1119.

    Article  PubMed  CAS  Google Scholar 

  • Meador-Woodruff JH, Healy DJ. 2000. Glutamate receptor expression in schizophrenic brain. Brain Res Brain Res Rev 31: 288–294.

    Article  PubMed  CAS  Google Scholar 

  • Mechawar N, Lacoste B, Yu WF, Srivastava LK, Quirion R, 2007. Developmental profile of neuregulin receptor ErbB4 in postnatal rat cerebral cortex and hippocampus. Neuroscience 148: 126–139.

    Article  PubMed  CAS  Google Scholar 

  • Medoff DR, Holcomb HH, Lahti AC, Tamminga CA. 2001. Probing the human hippocampus using rCBF: Contrasts in schizophrenia. Hippocampus 11: 543–550.

    Article  PubMed  CAS  Google Scholar 

  • Nelson MD, Saykin AJ, Flashman LA, Riordan HJ. 1998. Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: A meta-analytic study. Arch Gen Psychiatry 55: 433–440.

    Article  PubMed  CAS  Google Scholar 

  • Newton SS, Duman RS. 2007. Neurogenic actions of atypical antipsychotic drugs and therapeutic implications. CNS Drugs 21: 715–725.

    Article  PubMed  CAS  Google Scholar 

  • Nordahl TE, Kusubov N, Carter C, Salamat S, Cummings AM, et al. 1996. Temporal lobe metabolic differences in medication-free outpatients with schizophrenia via the PET-600. Neuropsychopharmacology 15: 541–554.

    Article  PubMed  CAS  Google Scholar 

  • Olbrich HG, Braak H. 1985. Ratio of pyramidal cells versus non-pyramidal cells in sector CA1 of the human Ammon’s horn. Anatomy Embryol 173: 105–110.

    Article  CAS  Google Scholar 

  • Ongur D, Cullen TJ, Wolf DH, Rohan M, Barreira P, et al. 2006. The neural basis of relational memory deficits in schizophrenia. Arch Gen Psychiatry 63: 1268–1277.

    Article  Google Scholar 

  • Owen MJ, Craddock N, O’Donovan MC. 2005. Schizophrenia: Genes at last? Trends Genet 9: 518–525.

    Article  CAS  Google Scholar 

  • Ozawa S, Kamiya H, Tsuzuki K. 1998. Glutamate receptors in the mammalian central nervous system. Prog Neurobiol 54: 581–618.

    Article  PubMed  CAS  Google Scholar 

  • Pantelis C, Velakoulis D, Suckling J, McGorry P, Phillips L, et al. 2000. Left medial temporal volume reduction occurs during the transition from high-risk to first-episode psychosis. Schizophr Res 41: 35.

    Article  Google Scholar 

  • Phillips LJ, McGorry PD, Garner B, Thompson KN, Pantelis C, et al. 2006. Stress, the hippocampus and the hypothalamic-pituitary-adrenal axis: Implications for the development of psychotic disorders. Aust N Z J Psychiatry 40: 725–741.

    Article  PubMed  Google Scholar 

  • Port RL, Seybold KS. 1995. Hippocampal synaptic plasticity as a biological substrate underlying episodic psychosis. Biological Psychiatry 37(5):318–324.

    Article  PubMed  CAS  Google Scholar 

  • Porter RH, Eastwood SL, Harrison PJ. 1997. Distribution of kainate receptor subunit mRNAs in human hippocampus, neocortex and cerebellum, and bilateral reduction of hippocampal GluR6 and KA2 transcripts in schizophrenia. Brain Res 751: 217–231.

    Article  PubMed  CAS  Google Scholar 

  • Ragland JD, Gur RC, Raz J, Schroeder L, Kohler CG, et al. 2001. Effect of schizophrenia on frontotemporal activity during word encoding and recognition: A PET cerebral blood flow study. Am J Psychiatry 158: 1114–1125.

    Article  PubMed  CAS  Google Scholar 

  • Roberts DR. 1963. Schizophrenia and the brain. J Neuropsychiatry 5: 71–79.

    Google Scholar 

  • Roberts RC. 2007. Schizophrenia in translation: Disrupted in schizophrenia (DISC1): Integrating clinical and basic findings. Schizophr Bull 33: 11–15.

    Article  PubMed  Google Scholar 

  • Rossi A, Stratta P, Mancini F, Gallucci M, Mattei P, et al. 1994. Magnetic resonance imaging findings of amygdala-anterior hippocampus shrinkage in male patients with schizophrenia. Psychiatry Res 52: 43–53.

    Article  PubMed  CAS  Google Scholar 

  • Sawada K, Barr AM, Nakamura M, Arima K, Young CE, et al. 2005. Hippocampal complexin proteins and cognitive dysfunction in schizophrenia. Arch Gen Psychiatry 62: 263–272.

    Article  PubMed  CAS  Google Scholar 

  • Scherk H, Falkai P. 2004. [Changes in brain structure caused by neuroleptic medication]. Nervenarzt 75: 1112–1117.

    Article  PubMed  CAS  Google Scholar 

  • Scherk H, Falkai P. 2006. Effects of antipsychotics on brain structure. Curr Opin Psychiatry 19: 145–150.

    Article  PubMed  Google Scholar 

  • Seidman LJ, Faraone SV, Goldstein JM, Goodman JM, Kremen WS, et al. 1999. Thalamic and amygdala-hippocampal volume reductions in first-degree relatives of patients with schizophrenia: An MRI-based morphometric analysis. Biol Psychiatry 46: 941–954.

    Article  PubMed  CAS  Google Scholar 

  • Seidman LJ, Faraone SV, Goldstein JM, Kremen WS, Horton NJ, et al. 2002. Left hippocampal volume as a vulnerability indicator for schizophrenia. Arch Gen Psychiatry 59: 839–849.

    Article  PubMed  Google Scholar 

  • Seress L, Gulyas AI, Ferrer I, Tunon T, Soriano E, et al. 1993. Distribution, morphological features, and synaptic connections of parvalbumin- and calbindin D28k-immunoreactive neurons in the human hippocampal formation. J Comp Neurol 337: 208–230.

    Article  PubMed  CAS  Google Scholar 

  • Siekmeier PJ, Hasselmo ME, Howard MW, Coyle J. 2007. Modeling of context-dependent retrieval in hippocampal region CA1: Implications for cognitive function in schizophrenia. Schizophr Res 89: 177–190.

    Article  PubMed  Google Scholar 

  • Silbersweig DA, Stern E, Frith C, Cahill C, Holmes A, et al. 1995. A functional neuroanatomy of hallucinations in schizophrenia. Nature 378: 176–179.

    Article  PubMed  CAS  Google Scholar 

  • Sim K, DeWitt I, Ditman T, Zalesak M, Greenhouse I, et al. 2006. Hippocampal and parahippocampal volumes in schizophrenia: A structural MRI study. Schizophr Bull 32: 332–340.

    Article  PubMed  Google Scholar 

  • Smith ME. 2005. Bilateral hippocampal volume reduction in adults with post-traumatic stress disorder: A meta-analysis of structural MRI studies. Hippocampus 15: 798–807.

    Article  PubMed  Google Scholar 

  • Somogyi P, Klausberger T. 2005. Defined types of cortical interneurone structure space and spike timing in the hippocampus. J Physiol 562: 9–26.

    Article  PubMed  CAS  Google Scholar 

  • Steen RG, Hamer RM, Lieberman JA. 2005. Measurement of brain metabolites by 1H magnetic resonance spectroscopy in patients with schizophrenia: A systematic review and meta-analysis. Neuropsychopharmacology 30: 1949–1962.

    Article  PubMed  CAS  Google Scholar 

  • Steen RG, Mull C, McClure R, Hamer RM, Lieberman JA. 2006. Brain volume in first-episode schizophrenia: Systematic review and meta-analysis of magnetic resonance imaging studies. Br J Psychiatry 188: 510–518.

    Article  PubMed  Google Scholar 

  • Strange BA, Fletcher PC, Henson RN, Friston KJ, Dolan RJ. 1999. Segregating the functions of human hippocampus. Proc Natl Acad Sci USA 96: 4034–4039.

    Article  PubMed  CAS  Google Scholar 

  • Straub RE, Lipska BK, Egan MF, Goldberg TE, Callicott JH, et al. 2007. Allelic variation in GAD1 (GAD(67)) is associated with schizophrenia and influences cortical function and gene expression. Mol Psychiatry 12: 854–869.

    Article  PubMed  CAS  Google Scholar 

  • Suddath RL, Christison GW, Torrey EF, Casanova MF, Weinberger DR. 1990. Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. New Engl J Med 322: 789–794.

    Article  PubMed  CAS  Google Scholar 

  • Talamini LM, Meeter M, Elvevag B, Murre JM, Goldberg TE. 2005. Reduced parahippocampal connectivity produces schizophrenia-like memory deficits in simulated neural circuits with reduced parahippocampal connectivity. Arch Gen Psychiatry 62: 485–493.

    Article  PubMed  Google Scholar 

  • Talbot K, Eidem WL, Tinsley CL, Benson MA, Thompson EW, et al. 2004. Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia. J Clin Invest 113: 1353–1363.

    PubMed  CAS  Google Scholar 

  • Tamminga CA, Thaker GK, Buchanan R, Kirkpatrick B, Alphs LD, et al. 1992. Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome. Arch Gen Psychiatry 49: 522–530.

    Article  PubMed  CAS  Google Scholar 

  • Tebartz van Elst L, Ebert D, Hesslinger B. 2007. Amygdala volume status might reflect dominant mode of emotional information processing. Arch Gen Psychiatry 64: 251–252; author reply 252–253.

    Article  PubMed  Google Scholar 

  • Torrey EF, Barci BM, Webster MJ, Bartko JJ, Meador-Woodruff JH, et al. 2005. Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains. Biol Psychiatry 57: 252–260.

    Article  PubMed  CAS  Google Scholar 

  • Tregellas JR, Davalos DB, Rojas DC, Waldo MC, Gibson L, et al. 2007. Increased hemodynamic response in the hippocampus, thalamus and prefrontal cortex during abnormal sensory gating in schizophrenia. Schizophr Res 92: 262–272.

    Article  PubMed  Google Scholar 

  • Tsuang M. 2000. Schizophrenia: Genes and environment. Biol Psychiatry 47: 210–220.

    Article  PubMed  CAS  Google Scholar 

  • Velakoulis D, Pantelis C, McGorry PD, Dudgeon P, Brewer W, et al. 1999. Hippocampal volume in first-episode psychoses and chronic schizophrenia: A high-resolution magnetic resonance imaging study. Arch Gen Psychiatry 56: 133–141.

    Article  PubMed  CAS  Google Scholar 

  • Velakoulis D, Stuart GW, Wood SJ, Smith DJ, Brewer WJ, et al. 2001. Selective bilateral hippocampal volume loss in chronic schizophrenia. Biol Psychiatry 50: 531–539.

    Article  PubMed  CAS  Google Scholar 

  • Velakoulis D, Wood SJ, Wong MT, McGorry PD, Yung A, et al. 2006. Hippocampal and amygdala volumes according to psychosis stage and diagnosis: A magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals. Arch Gen Psychiatry 63: 139–149.

    Article  PubMed  Google Scholar 

  • Venables PH. 1992. Hippocampal function and schizophrenia. Experimental psychological evidence. Ann N Y Acad Sci 658: 111–127.

    Article  PubMed  CAS  Google Scholar 

  • Vita A, De Peri L, Silenzi C, Dieci M. 2006. Brain morphology in first-episode schizophrenia: A meta-analysis of quantitative magnetic resonance imaging studies. Schizophr Res 82: 75–88.

    Article  PubMed  CAS  Google Scholar 

  • Walker MA, Highley JR, Esiri MM, McDonald B, Roberts HC, et al. 2002. Estimated neuronal populations and volumes of the hippocampus and its subfields in schizophrenia. Am J Psychiatry 159: 821–828.

    Article  PubMed  Google Scholar 

  • Wang L, Joshi SC, Miller MI, Csernansky JG. 2001. Statistical analysis of hippocampal asymmetry in schizophrenia. Neuroimage 14: 531–545.

    Article  PubMed  CAS  Google Scholar 

  • Weiss AP, DeWitt I, Goff D, Ditman T, Heckers S. 2005. Anterior and posterior hippocampal volumes in schizophrenia. Schizophr Res 73: 103–112.

    Article  PubMed  Google Scholar 

  • Weiss AP, Heckers S. 1999. Neuroimaging of hallucinations: A review of the literature. Psychiatry Res Neuroimaging 92: 61–74.

    Article  CAS  Google Scholar 

  • Weiss AP, Heckers S. 2001. Neuroimaging of declarative memory in schizophrenia. Scand J Psychol 42: 239–250.

    Article  PubMed  CAS  Google Scholar 

  • Weiss AP, Schacter DL, Goff DC, Rauch SL, Alpert NM, et al. 2003. Impaired hippocampal recruitment during normal modulation of memory performance in schizophrenia. Biol Psychiatry 53: 48–55.

    Article  PubMed  Google Scholar 

  • Weiss AP, Zalesak M, DeWitt I, Goff D, Kunkel L, et al. 2004. Impaired hippocampal function during the detection of novel words in schizophrenia. Biol Psychiatry 55: 668–675.

    Article  PubMed  Google Scholar 

  • West MJ, Gundersen HJ. 1990. Unbiased stereological estimation of the number of neurons in the human hippocampus. J Comp Neurol 296: 1–22.

    Article  PubMed  CAS  Google Scholar 

  • Woo RS, Li XM, Tao Y, Carpenter-Hyland E, Huang YZ, et al. 2007. Neuregulin-1 enhances depolarization-induced GABA release. Neuron 54: 599–610.

    Article  PubMed  CAS  Google Scholar 

  • Wood SJ, Velakoulis D, Smith DJ, Bond D, Stuart GW, et al. 2000. A longitudinal study of hippocampal volume in first episode psychosis and chronic schizophrenia. Schizophr Res 52: 37–46.

    Article  Google Scholar 

  • Wright IC, Rabe-Hesketh S, Woodruff PW, David AS, Murray RM, et al. 2000. Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiatry 157: 16–25.

    PubMed  CAS  Google Scholar 

  • Zhang ZJ, Reynolds GP. 2000. A selective deficit in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia. Schizophr Res 49: 65.

    Google Scholar 

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Authors
  1. S. Heckers
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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, 10962, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Program in Cognitive Neuroscience and Schizophrenia, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, New York, 10962, USA

    Daniel Javitt (Director) (Director)

  3. Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, New York, 10962, USA

    Joshua Kantrowitz

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© 2009 Springer Science+Business Media, LLC

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Heckers, S. (2009). Hippocampus. In: Lajtha, A., Javitt, D., Kantrowitz, J. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30410-6_9

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