Current Psychiatry Reports

, Volume 5, Issue 4, pp 311–319 | Cite as

Scent of a disorder: Olfactory functioning in schizophrenia

  • Paul J. Moberg
  • Bruce I. Turetsky


The use of olfactory probes to assess frontal and temporal-limbic system functioning in patients with schizophrenia has garnered increasing interest among basic and clinical investigators. Deficits in odor identification, detection threshold sensitivity, discrimination, and memory have been reported and are thought to represent a centrally mediated deficit in the processing of this information. These impairments are seen in affected probands, first-degree family members, and those at risk for developing the illness, suggesting a genetic vulnerability or predisposition to chemosensory abnormalities. The observed deficits are not explained by gender, medication use, cognitive impairment, or smoking status, and support the hypothesis of primary dysfunction in the olfactory system. Along this same line, structural abnormalities in the peripheral and central olfactory brain regions, as well as disruptions of the basic physiology of this system, have been described. The study of olfactory processing in schizophrenia has already advanced the knowledge of the neural substrate for this disorder. Because the olfactory system continuously regenerates throughout life, it allows for a unique view of an ongoing neurodevelopmental process.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Seidman L, Oscar-Berman M, Kalinowski AG, et al.: Experimental and clinical neuropsychological measures of prefrontal dysfunction in schizophrenia. Neuropsychology 1995, 9:481–490.CrossRefGoogle Scholar
  2. 2.
    Fuster JM: The Prefrontal Cortex: Anatomy, Physiology, and Neuropsychology of the Frontal Lobe. New York: Raven Press; 1989.Google Scholar
  3. 3.
    Weinberger DR, Berman KF, Suddath R, Torrey EF: Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins. Am J Psychiatry 1992, 149:890–897.PubMedGoogle Scholar
  4. 4.
    Andreasen NC, Ehrhardt JC, Swayze VW, et al.: Magnetic resonance imaging of the brain in schizophrenia: the pathophysiologic significance of structural abnormalities. Arch Gen Psychiatry 1990, 47:35–44.PubMedGoogle Scholar
  5. 5.
    Calev A, Venables PH, Monk AF: Evidence for distinct verbal memory pathologies in severely and mildly disturbed schizophrenics. Schizophr Bull 1983, 9:247–264.PubMedGoogle Scholar
  6. 6.
    Gur RE, Gur RC, Skolnick BE, et al.: Brain function in psychiatric disorders, III: regional cerebral blood flow in unmedicated schizophrenics. Arch Gen Psychiatry 1985, 42:329–334.PubMedGoogle Scholar
  7. 7.
    Gur RE, Mozley PD, Resnick SM, et al.: Resting cerebral glucose metabolism in first-episode and previously treated patients with schizophrenia relates to clinical features. Arch Gen Psychiatry 1995, 52:657–667.PubMedGoogle Scholar
  8. 8.
    McCarley RW, Faux SF, Shenton ME, et al.: Event-related potentials in schizophrenia: their biological and clinical correlates and a new model of schizophrenic pathophysiology. Schizophr Res 1991, 4:209–231.PubMedCrossRefGoogle Scholar
  9. 9.
    Saykin AJ, Gur RC, Gur RE, et al.: Neuropsychological function in schizophrenia: selective impairment in memory and learning. Arch Gen Psychiatry 1991, 48:618–624.PubMedGoogle Scholar
  10. 10.
    Shenton ME, Kikinis R, Jolesz FA, et al.: Abnormalities of the left temporal lobe and thought disorder in schizophrenia: a quantitative magnetic resonance imaging study. N Engl J Med 1992, 327:604–612.PubMedCrossRefGoogle Scholar
  11. 11.
    Turetsky B, Cowell PE, Gur RC, et al.: Frontal and temporal lobe brain volumes in schizophrenia: relationship to symptoms and clinical subtype. Arch Gen Psychiatry 1995, 52:1061–1070.PubMedGoogle Scholar
  12. 12.
    Moberg PJ, Agrin R, Gur RE, et al.: Olfactory dysfunction in schizophrenia: a qualitative and quantitative review. Neuropsychopharmacology 1999, 21:325–340. Comprehensive quantitative (meta-analytic) review of the English language literature on olfactory dysfunction in schizophrenia. Documented no effect of gender, medication, or smoking on the deficit in olfactory processing in these patients.PubMedCrossRefGoogle Scholar
  13. 13.
    Kopala LC, Clark C, Hurwitz T: Olfactory deficits in neuroleptic naive patients with schizophrenia. Schizophr Res 1993, 8:245–250.PubMedCrossRefGoogle Scholar
  14. 14.
    Moberg PJ, Doty RL, Turetsky BI, et al.: Olfactory identification deficits in schizophrenia: correlation with duration of illness. Am J Psychiatry 1997, 154:1016–1018.PubMedGoogle Scholar
  15. 15.
    Martzke JS, Kopala LC, Good KP: Olfactory dysfunction in neuropsychiatric disorders: review and methodological considerations. Biol Psychiatry 1997, 42:721–732.PubMedCrossRefGoogle Scholar
  16. 16.
    Arnold SE, Trojanowski JQ: Recent advances in defining the neuropathology of schizophrenia. Acta Neuropathol 1996, 92:217–231.PubMedCrossRefGoogle Scholar
  17. 17.
    Eslinger PJ, Damasio AR, Van Hoesen GW: Olfactory dysfunction in man: anatomical and behavioral aspects. Brain Cogn 1982, 1:259–285.PubMedCrossRefGoogle Scholar
  18. 18.
    Eslinger PJ, Damasio AR, Van Hoesen GW: Olfactory dysfunction in man: anatomical and behavioral aspects. Brain Cogn 1982, 1:259–285.PubMedCrossRefGoogle Scholar
  19. 19.
    Doty RL, Perl DP, Steele JC, et al.: Olfactory dysfunction in three neurodegenerative diseases. Geriatrics 1991, 46:47–51.PubMedGoogle Scholar
  20. 20.
    Greer CA: Structural organization of the olfactory system. In Smell and Taste in Health and Disease. Edited by Getchell TV, Doty RL, Bartoshuk LM, Snow JB. New York: Raven Press; 1991:65–81.Google Scholar
  21. 21.
    Kratskin I: Functional anatomy, central connections, and neurochemistry of the mammalian olfactory bulb. In Handbook of Olfaction and Gustation. New York: Marcel Dekker; 1995:103–126.Google Scholar
  22. 22.
    Moran DT, Rowley JC, III, Jafek BW, Lovell MA: The fine structure of the olfactory mucosa in man. J Neurocytol 1982, 11:721–746.PubMedCrossRefGoogle Scholar
  23. 23.
    Price J: The central olfactory and accessory olfactory systems. In Neurobiology of Taste and Smell. Edited by Finger TESW. New York: Wiley; 1987.Google Scholar
  24. 24.
    Lewis PR, Shute CC: The cholinergic limbic system: projections to hippocampal formation, medial cortex, nuclei of the ascending cholinergic reticular system, and the subfornical organ and supra-optic crest. Brain 1967, 90:521–540.PubMedCrossRefGoogle Scholar
  25. 25.
    Potter H, Nauta WJ: A note on the problem of olfactory associations of the orbitofrontal cortex in the monkey. Neuroscience 1979, 4:361–367.PubMedCrossRefGoogle Scholar
  26. 26.
    Tanabe T, Yarita H, Iino M, et al.: An olfactory projection area in orbitofrontal cortex of the monkey. J Neurophysiol 1975, 38:1269–1283.PubMedGoogle Scholar
  27. 27.
    Good KP, Martzke JS, Honer WG, Kopala LC: Left nostril olfactory identification impairment in a subgroup of male patients with schizophrenia. Schizophr Res 1998, 33:35–43.PubMedCrossRefGoogle Scholar
  28. 28.
    Dunn TP, Weller MP: Olfaction in schizophrenia. Percept Mot Skills 1989, 69:833–834.PubMedGoogle Scholar
  29. 29.
    Kohler CG, Moberg PJ, Gur RE, et al.: Olfactory dysfunction in schizophrenia and temporal lobe epilepsy. Neuropsychiatry Neuropsychol Behav Neurol 2001, 14:83–88.PubMedGoogle Scholar
  30. 30.
    Good KP, Martzke JS, Milliken HI, et al.: Unirhinal olfactory identification deficits in young male patients with schizophrenia and related disorders: association with impaired memory function. Schizophr Res 2002, 56:211–223.PubMedCrossRefGoogle Scholar
  31. 31.
    Smutzer G, Lee VM, Trojanowski JQ, Arnold SE: Human olfactory mucosa in schizophrenia. Ann Otol Rhinol Laryngol 1998, 107:349–355.PubMedGoogle Scholar
  32. 32.
    Arnold SE, Han L-Y, Moberg PJ, et al.: Dysregulation of olfactory receptor neuron lineage in schizophrenia. Arch Gen Psychiatry 2001, 58:829–835. A landmark study documenting abnormalities of the olfactory system at a molecular level. A preponderance of immature olfactory neurons were observed in epithelium suggesting an abnormality of neuronal regeneration, differentiation, and migration in patients with schizophrenia.PubMedCrossRefGoogle Scholar
  33. 33.
    Potter H, Butters N: An assessment of olfactory deficits in patients with damage to prefrontal cortex. Neuropsychologia 1980, 18:621–628.PubMedCrossRefGoogle Scholar
  34. 34.
    Adams R, Victor M: Principles of Neurology. New York: McGraw Hill; 1985.Google Scholar
  35. 35.
    Jones-Gotman M, Zatorre RJ: Olfactory identification deficits in patients with focal cerebral excision. Neuropsychologia 1988, 26:387–400.PubMedCrossRefGoogle Scholar
  36. 36.
    Chapman LJ, Chapman JP: The measurement of differential deficit. J Psychiatr Res 1978, 14:303–311.PubMedCrossRefGoogle Scholar
  37. 37.
    Doty RL, McKeown DA, Lee WW, Shaman P: A study of the test-retest reliability of ten olfactory tests. Chem Senses 1995, 20:645–656.PubMedCrossRefGoogle Scholar
  38. 38.
    Doty RL, Smith R, McKeown DA, Raj J: Tests of human olfactory function: principal components analysis suggests that most measure a common source of variance. Percept Psychophys 1994, 56:701–707.PubMedGoogle Scholar
  39. 39.
    Eichenbaum H, Morton TH, Potter H, Corkin S: Selective olfactory deficits in case HM. Brain 1983, 106:459–472.PubMedCrossRefGoogle Scholar
  40. 40.
    Eskenazi B, Cain WS, Novelly RA, Mattson R: Odor perception in temporal lobe epilepsy patients with and without temporal lobectomy. Neuropsychologia 1986, 24:553–562.PubMedCrossRefGoogle Scholar
  41. 41.
    Rausch R, Serafetinides EA: Specific alterations of olfactory function in humans with temporal lobe lesions. Nature 1975, 255:557–558.PubMedCrossRefGoogle Scholar
  42. 42.
    West SE, Doty RL: Influence of epilepsy and temporal lobe resection on olfactory function. Epilepsia 1995, 36:531–542.PubMedCrossRefGoogle Scholar
  43. 43.
    Martinez B, Cain WS, de Wijk RA, et al.: Olfactory functioning before and after temporal lobe resection for intractable seizures. Neuropsychology 1993, 7:351–363.CrossRefGoogle Scholar
  44. 44.
    Doty RL, Brugger WE, Jurs PC, et al.: Intranasal trigeminal stimulation from odorous volatiles: psychometric responses from anosmic and normal humans. Physiol Behav 1978, 20:175–185.PubMedCrossRefGoogle Scholar
  45. 45.
    Campbell I, Gregson RAM: Olfactory short term memory in normal, schizophrenic and brain-damaged cases. Aust J Psychol 1972, 24:179–185.Google Scholar
  46. 46.
    Doty R: Olfactory system. In Smell and Taste in Health and Disease. Edited by Getchell TV, Bartoshuk LM, Snow JB. New York: Raven Press; 1991:175–203.Google Scholar
  47. 47.
    Harrison PJ, Pearson RC: Olfaction and psychiatry. Br J Psychiatry 1989, 155:822–828.PubMedCrossRefGoogle Scholar
  48. 48.
    Pantelis C, Brewer W: Neuropsychological and olfactory dysfunction in schizophrenia: relationship of frontal syndromes to syndromes of schizophrenia. Schizophr Res 1995, 17:35–45.PubMedCrossRefGoogle Scholar
  49. 49.
    Serby M, Larson PM, Kalkstein D: Olfaction and neuropsychiatry. In Science of Olfaction. Edited by Serby MJ. New York: Springer-Verlag; 1992:559–581.Google Scholar
  50. 50.
    Bradley EA: Olfactory acuity to a pheromonal substance and psychotic illness. Biol Psychiatry 1984, 19:899–905.PubMedGoogle Scholar
  51. 51.
    Kopala L, Clark C, Hurwitz TA: Sex differences in olfactory function in schizophrenia. Am J Psychiatry 1989, 146:1320–1322.PubMedGoogle Scholar
  52. 52.
    Geddes J, Huws R, Pratt P: Olfactory acuity in the positive and negative syndromes of schizophrenia. Biol Psychiatry 1991, 29:774–778.PubMedCrossRefGoogle Scholar
  53. 53.
    Isseroff R, Stoler M, Ophir D, et al.: Olfactory sensitivity to androstenone in schizophrenic patients. Biol Psychiatry 1987, 22:922–925.PubMedCrossRefGoogle Scholar
  54. 54.
    Serby M, Larson P, Kalkstein D: Olfactory sense in psychoses. Biol Psychiatry 1990, 28:830.PubMedCrossRefGoogle Scholar
  55. 55.
    Warner MD, Peabody CA, Csernansky JG: Olfactory functioning in schizophrenia and depression. Biol Psychiatry 1990, 27:457–458.PubMedCrossRefGoogle Scholar
  56. 56.
    Hurwitz T, Clark C: Response to Warner et al. 1990 [letter]. Biol Psychiatry 1990, 23:448.Google Scholar
  57. 57.
    Brewer WJ, Edwards J, Anderson V, et al.: Neuropsychological, olfactory, and hygiene deficits in men with negative symptom schizophrenia. Biol Psychiatry 1996, 40:1021–1031. One of the first studies to link deficits in odor identification to clinical symptomatology. Specifically, an inverse relationship between negative symptoms and performance on the UPSIT was observed.PubMedCrossRefGoogle Scholar
  58. 58.
    Houlihan DJ, Flaum M, Arnold SE, et al.: Further evidence for olfactory identification deficits in schizophrenia. Schizophr Res 1994, 12:179–182.PubMedCrossRefGoogle Scholar
  59. 59.
    Hurwitz T, Kopala L, Clark C, Jones B: Olfactory deficits in schizophrenia. Biol Psychiatry 1988, 23:123–128.PubMedCrossRefGoogle Scholar
  60. 60.
    Kopala LC, Good KP, Honer WG: Olfactory hallucinations and olfactory identification ability in patients with schizophrenia and other psychiatric disorders. Schizophr Res 1994, 12:205–211.PubMedCrossRefGoogle Scholar
  61. 61.
    Kopala LC, Good K, Honer WG: Olfactory identification ability in pre- and postmenopausal women with schizophrenia. Biol Psychiatry 1995, 38:57–63.PubMedCrossRefGoogle Scholar
  62. 62.
    Kopala L, Good K, Martzke J, Hurwitz T: Olfactory deficits in schizophrenia are not a function of task complexity. Schizophr Res 1995, 17:195–199.PubMedCrossRefGoogle Scholar
  63. 63.
    Malaspina D, Wray AD, Friedman JH, et al.: Odor discrimination deficits in schizophrenia: association with eye movement dysfunction. J Neuropsychiatry Clin Neurosci 1994, 6:273–278.PubMedGoogle Scholar
  64. 64.
    Moberg PJ, Doty RL, Mahr RN, et al.: Olfactory identification in elderly schizophrenia and Alzheimer’s disease. Neurobiol Aging 1997, 18:163–167.PubMedCrossRefGoogle Scholar
  65. 65.
    Seidman L, Talbot NL, Kalinowski AG, et al.: Neuropsychological probes of fronto-limbic dysfunction in schizophrenia: olfactory identification and Wisconsin Card Sorting performance. Schizophr Res 1992, 6:55–56.CrossRefGoogle Scholar
  66. 66.
    Seidman LJ, Goldstein JM, Goodman JM, et al.: Sex differences in olfactory identification and Wisconsin Card Sorting performance in schizophrenia: relationship to attention and verbal ability. Biol Psychiatry 1997, 42:104–115.PubMedCrossRefGoogle Scholar
  67. 67.
    Wu J, Buchsbaum MS, Moy K, et al.: Olfactory memory in unmedicated schizophrenics. Schizophr Res 1993, 9:41–47.PubMedCrossRefGoogle Scholar
  68. 68.
    Sreenivasan K, Abraham A, Verghese A: Right temporal lobe functions in psychiatric disorders. Ind J Clin Psychol 1987, 14:40–42.Google Scholar
  69. 69.
    Clark C, Kopala L, Hurwitz T, Li D: Regional metabolism in microsmic patients with schizophrenia. Can J Psychiatry 1991, 36:645–650.PubMedGoogle Scholar
  70. 70.
    Kopala LC, Clark CC, Bassett A: Olfactory deficits in schizophrenia and chromosome 5. Biol Psychiatry 1991, 29:732–733.PubMedCrossRefGoogle Scholar
  71. 71.
    Cohen J: Statistical Power Analysis for the Behavioral Sciences. New York: Academic Press; 1977.Google Scholar
  72. 72.
    Kopala LC, Lewine R, Good KP, et al.: Clinical features of schizophrenia in a woman with hyperandrogenism. J Psychiatry Neurosci 1997, 22:56–60.PubMedGoogle Scholar
  73. 73.
    Doty RL, Shaman P, Dann M: Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav 1984, 32:489–502.PubMedCrossRefGoogle Scholar
  74. 74.
    Kopala LC, Good KP, Morrison K, et al.: Impaired olfactory identification in relatives of patients with familial schizophrenia. Am J Psychiatry 2001, 158:1286–1290. This study found that nonsymptomatic first-degree relatives also showed odor identification impairments that fell intermediate to the affected proband and healthy matched control individuals. These data suggest a genetic contribution to the psychophysical deficits in schizophrenia and that such deficits may aggregate in these families.PubMedCrossRefGoogle Scholar
  75. 75.
    Becker E, Hummel T, Piel E, et al.: Olfactory event-related potentials in psychosis-prone subjects. Int J Psychophysiol 1993, 15:51–58.PubMedCrossRefGoogle Scholar
  76. 76.
    Kwapil TR, Chapman JP, Chapman LJ, Miller MB: Deviant olfactory experiences as indicators of risk for psychosis. Schizophr Bull 1996, 22:371–382.PubMedGoogle Scholar
  77. 77.
    Mohr C, Hubener F, Laska M: Deviant olfactory experiences, magical ideation, and olfactory sensitivity: a study with healthy German and Japanese subjects. Psychiatry Res 2002, 111:21–33.PubMedCrossRefGoogle Scholar
  78. 78.
    Park S, Schoppe S: Olfactory identification deficit in relation to schizotypy. Schizophr Res 1997, 26:191–197.PubMedCrossRefGoogle Scholar
  79. 79.
    Turetsky BI, Moberg PJ, Yousem DM, et al.: Reduced olfactory bulb volume in patients with schizophrenia. Am J Psychiatry 2000, 157:828–830. The first study to demonstrate a significant reduction in olfactory bulb volume in patients with schizophrenia, suggesting a structural and (perhaps) neurodevelopmental basis for the observed behavioral impairments.PubMedCrossRefGoogle Scholar
  80. 80.
    Turetsky BI, Moberg PJ, Arnold SA, et al.: Reduced olfactory bulb volume in 1st-degree relatives of patients with schizophrenia. Am J Psychiatry 2003, 160:703–708.PubMedCrossRefGoogle Scholar
  81. 81.
    Bertollo DN, Cowen MA, Levy AV: Hypometabolism in olfactory cortical projection areas of male patients with schizophrenia: an initial positron emission tomography study. Psychiatry Res 1996, 60:113–116.PubMedCrossRefGoogle Scholar
  82. 82.
    Malaspina D, Lignelli A, Pererra G, et al.: SPECT imaging of odor identification in schizophrenia. Psychiatry Res 1998, 82:53–63.PubMedCrossRefGoogle Scholar
  83. 83.
    Crespo-Facorro B, Paradiso S, Andreasen NC, et al.: Neural mechanisms of anhedonia in schizophrenia. JAMA 2001, 286:427–435. A functional imaging study (PET) indicating that the ability to attach the appropriate valence to pleasant and unpleasant odors is disrupted in schizophrenia. These findings suggest that abnormalities in olfactory-limbic brain regions may underlie emotional disturbances in schizophrenia.PubMedCrossRefGoogle Scholar
  84. 84.
    Turetsky B, Moberg PJ, Owzar K, et al.: Physiologic impairment of olfactory stimulus processing in schizophrenia. Biol Psychiatry 2003, 53:403–411. The first activation study of olfactory processing using a sophisticated air-dilution olfactometer, which precisely controlled for sniffing, stimulus onset, humidity, and mechanical artifacts.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc. 2003

Authors and Affiliations

  • Paul J. Moberg
    • 1
  • Bruce I. Turetsky
  1. 1.Department of PsychiatryBrain Behavior Laboratory, University of Pennsylvania School of MedicinePhiladelphiaUSA

Personalised recommendations