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9 - Genetics and Family Influences on Olfaction: A Focus in Schizophrenia

from Section II - Social Functioning: Role of Evolution, Genetics and Gender

Published online by Cambridge University Press:  17 August 2009

By
Raquelle Mesholam-Gately  and
Larry J. Seidman
Edited by
Warrick J. Brewer ,
David Castle  and
Christos Pantelis
Foreword by
Peter Doherty
Warrick J. Brewer
Affiliation:
Mental Health Research Institute of Victoria, Melbourne
David Castle
Affiliation:
University of Melbourne
Christos Pantelis
Affiliation:
University of Melbourne
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Summary

Introduction

Family or genetic ‘high-risk’ studies have described olfactory deficits in asymptomatic or non-fully symptomatic first-degree relatives (siblings, offspring, parents) of individuals diagnosed with a variety of neuropsychiatric diseases, including Alzheimer's disease (Schiffman et al., 2002; Serby et al., 1996), Parkinson's disease (Berendse et al., 2001; Montgomery et al., 1999), Progressive Supranuclear Palsy (Baker & Montgomery, 2001), and schizophrenia (Kopala et al., 1998; 2001; Moberg et al., 1996; Turetsky et al., 2003). The reader is referred to Chapters 13, 14 and 16 for further discussion of olfaction in Parkinsonian disorders and schizophrenia respectively. Such findings tempt a host of questions, which suggest that the assessment of olfaction in studies of persons at risk for illness has the potential to open the ‘window to the mind’ even wider ….

The study of olfaction as a biological marker or risk indicator for illness is in its infancy compared to established strategies such as studies of attention (Cornblatt & Keilp, 1994). However, a number of issues are raised by the presence of olfactory abnormalities in first-degree biological relatives. Does olfactory functioning provide clues to the genetic underpinnings of complex neuropsychiatric diseases? Can it represent a biological marker for a compromised neural system? If so, what role does it play within the relationship between genes, environmental influences and the clinical manifestations of neuropsychiatric illnesses?

Keywords

endophenotypesfamily high-risk studiesgenetic high-risk studiesolfactory systemschizophrenia
Type
Chapter
Information
Olfaction and the Brain , pp. 167 - 182
Publisher: Cambridge University Press
Print publication year: 2006

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References

Arolt, V., Lencer, R., Nolte, A., et al. (1996) Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease. Am J Med Genet, 67, 564–79.Google Scholar
Austin, C. P., Ky, B., Ma, L., et al. (2004) Expression of Disrupted-In-Schizophrenia-1, a schizophrenia-associated gene, is prominent in the mouse hippocampus throughout brain development. Neuroscience, 124, 3–10.Google Scholar
Baker, K. B. & Montgomery, E. B. Jr. (2001) Performance on the PD test battery by relatives of patients with progressive supranuclear palsy. Neurology, 56, 25–30.Google Scholar
Barinaga, M. (2001) Olfaction. Smell's course is predetermined. Science, 294, 1269–71.Google Scholar
Berendse, H. W., Booij, J., Francot, C. M., et al. (2001) Subclinical dopaminergic dysfunction in asymptomatic Parkinson's disease patients' relatives with a decreased sense of smell. Ann Neurol, 50, 34–41.Google Scholar
Braff, D. L., Geyer, M. A. & Swerdlow, N. R. (2001) Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology, 156, 234–58.Google Scholar
Brewer, W. J., Wood, S. J., McGorry, P. D., et al. (2003) Impairment of olfactory identification ability in individuals at ultra-high risk for psychosis who later develop schizophrenia. Am J Psychiatry, 160, 1790–4.Google Scholar
Cadenhead, K. S., Swerdlow, N. R., Shafer, K. M., et al. (2000) Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits. Am J Psychiatry, 157, 1660–8.Google Scholar
Cain, W. S. (1977) Bilateral interaction in olfaction. Nature, 268, 50–52.Google Scholar
Calkins, M. E. & Iacono, W. G. (2000) Eye movement dysfunction in schizophrenia: a heritable characteristic for enhancing phenotype definition. Am J Med Genet, 97, 72–6.Google Scholar
Callicott, J. J., Egan, M. F., Mattay, V. S., et al. (2003) Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. Am J Psychiatry, 160, 709–19.Google Scholar
Cannon, T. D., Huttunen, M. O., Lonnqvist, J., et al. (2000) The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia. Am J Hum Genet, 67, 369–82.Google Scholar
Cannon, T. D., Zorrilla, L. E., Shtasel, D., et al. (1994) Neuropsychological functioning in siblings discordant for schizophrenia and healthy volunteers. Arch Gen Psychiatry, 51, 651–61.Google Scholar
Carlson, C. S., Eberle, M. A., Kruglyak, L., et al. (2004) Mapping complex disease loci in whole-genome association studies. Nature, 429, 446–52.Google Scholar
Cirillo, M. A. & Seidman, L. J. (2003) Verbal declarative memory dysfunction in schizophrenia: from clinical assessment to genetics and brain mechanisms. Neuropsychology Rev, 13, 43–77.Google Scholar
Clementz, B. A., Geyer, M. A. & Braff, D. L. (1998) Poor P50 suppression among schizophrenia patients and their first-degree biological relatives. Am J Psychiatry, 155, 1691–4.Google Scholar
Conklin, H. M., Curtis, C. E., Katsanis, J., et al. (2000) Verbal working memory impairment in schizophrenia patients and their first-degree relatives: evidence from the digit span task. Am J Psychiatry, 157, 275–7.Google Scholar
Cornblatt, B. A. & Keilp, J. G. (1994) Impaired attention, genetics, and the pathophysiology of schizophrenia. Schizophr Bull, 20, 31–46.Google Scholar
Cornblatt, B., Lencz, T. & Obuchowski, M. (2002) The schizophrenia prodrome: treatment and high-risk perspectives. Schizophr Res, 54, 177–86.Google Scholar
Deems, D. A. & Doty, R. L. (1987) Age-related changes in the phenyl ethyl alcohol odor detection threshold. Trans Penns Acad Ophthalmol Otolaryngol, 39, 646–50.Google Scholar
Dickey, C. C., McCarley, R. W., Voglmaier, M. M., et al. (1999) Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter. Biol Psychiatry, 45, 1393–402.Google Scholar
Docherty, N. M. (1995) Linguistic reference performance in parents of schizophrenic patients. Psychiatry, 58, 20–7.Google Scholar
Doty, R. L., Shaman, P. & Dann, M. (1984) Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav, 32, 489–502.Google Scholar
Erlenmeyer-Kimling, L., Cornblatt, B., Friedman, D., et al. (1982) Neurological, electrophysiological, and attentional deviations in children at risk for schizophrenia. In Schizophrenia as a Brain Disease (eds Henn, F. A. & Nasrallah, H. A.), pp. 61–98. New York: Oxford University Press.
Faraone, S. V., Green, A. I., Seidman, L. J., et al. (2001) ‘Schizotaxia’: clinical implications and new directions for research. Schizophr Bull, 27, 1–18.Google Scholar
Faraone, S. V., Seidman, L. J., Kremen, W. S., et al. (1995) Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: a diagnostic efficiency analysis. J Abn Psychol, 104, 286–304.Google Scholar
Faraone, S. V., Seidman, L. J., Kremen, W. S., et al. (1996) Neuropsychological functioning among the elderly nonpsychotic relatives of schizophrenic patients. Schizophr Res, 21, 27–31.Google Scholar
Faraone, S. V., Seidman, L. J., Kremen, W. S., et al. (1999) Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: a 4-year follow-up study. J Abn Psychol, 108, 176–81.Google Scholar
Faraone, S. V., Seidman, L. J., Kremen, W. S., et al. (2000) Neuropsychologic functioning among the nonpsychotic relatives of schizophrenic patients: the effect of genetic loading. Biol Psychiatry, 48, 120–6.Google Scholar
Faraone, S. V., Seidman, L. J., Kremen, W. S., et al. (2003) Structural brain abnormalities among relatives of patients with schizophrenia: implications for linkage studies. Schizophr Res, 60, 125–40.Google Scholar
Frangou, S., Sharma, T., Alarcon, G., et al. (1997) The Maudsley Family Study, II: endogenous event-related potentials in familial schizophrenia. Schizophr Res, 23, 45–53.Google Scholar
Friedman, D. & Squires-Wheeler, E. (1994) Event-related potentials (ERPs) as indicators of risk for schizophrenia. Schizophr Bull, 20, 63–74.Google Scholar
Good, K. P., Martzke, J. S., Honer, W. G., et al. (1998) Left nostril olfactory identification impairment in a subgroup of male patients with schizophrenia. Schizophr Res, 33, 35–43.Google Scholar
Gottesman, II & Gould, T. D. (2003) The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry, 160, 636–45.Google Scholar
Gottesman, II & McGue, M. (1990) Mixed and mixed-up models for the transmission of schizophrenia. In Thinking Clearly about Psychology: Essays in Honor of Paul E. Meehl (ed Cichetti, D.). Minnesota: University of Minnesota Press.
Gottesman, II & Shields, J. (1972) Schizophrenia and Genetics: A Twin Study Vantage Point. New York: Academic Press.
Gottesman, II & Shields, J. (1973) Genetic theorizing and schizophrenia. Br J Psychiatry, 122, 15–30.Google Scholar
Holzman, P. S., Proctor, L. R., Levy, D. L., et al. (1974) Eye-tracking dysfunctions in schizophrenic patients and their relatives. Arch Gen Psychiatry, 31, 143–51.Google Scholar
Jones, D. T. & Reed, R. R. (1989) Golf: an olfactory neuron specific-G protein involved in odorant signal transduction. Science, 244, 790–5.Google Scholar
Kendler, K. S., McGuire, M., Gruenberg, A. M., et al. (1993) The Roscommon family study. III. Schizophrenia-related personality disorders in relatives. Arch Gen Psychiatry, 50, 781–8.Google Scholar
Kopala, L. C., Clark, C. C. & Bassett, A. (1991) Olfactory deficits in schizophrenia and chromosome 5. Biol Psychiatry, 29, 732–3.Google Scholar
Kopala, L. C., Good, K. P., Torrey, E. F., et al. (1998) Olfactory function in monozygotic twins discordant for schizophrenia. Am J Psychiatry, 155, 134–6.Google Scholar
Kopala, L. C., Good, K. P., Morrison, K., et al. (2001) Impaired olfactory identification in relatives of patients with familial schizophrenia. Am J Psychiatry, 158, 1286–90.Google Scholar
Kremen, W. S., Seidman, L. J., Pepple, J. R., et al. (1994) Neuropsychological risk indicators for schizophrenia: a review of family studies. Schizophr Bull, 20, 103–19.Google Scholar
Kremen, W. S., Goldstein, J. M., Seidman, L. J., et al. (1997) Sex differences in neuropsychological function in non-psychotic relatives of schizophrenic probands. Psychiatry Res, 66, 131–44.Google Scholar
Kremen, W. S., Faraone, S. V., Seidman, L. J., et al. (1998) Neuropsychological risk indicators for schizophrenia: a preliminary study of female relatives of schizophrenic and bipolar probands. Psychiatry Res, 79, 227–40.Google Scholar
Lee, K. H. & Williams, L. M. (2000) Eye movement dysfunction as a biological marker of risk for schizophrenia. Austr N Z J Psychiatry, 34, S91–100.Google Scholar
Lyons, M. J., Toomey, R., Seidman, L. J., et al. (1995) Verbal learning and memory in relatives of schizophrenics: preliminary findings. Biol Psychiatry, 37, 750–3.Google Scholar
Ma, L., Liu, Y., Ky, B., et al. (2002) Cloning and characterization of Disc1, the mouse ortholog of DISC1 (Disrupted-in-Schizophrenia 1). Genomics, 80, 662–72.Google Scholar
McCarley, R. W., Shenton, M. E., O'Donnell, B. F., et al. (1993) Auditory P300 abnormalities and left posterior superior temporal gyrus volume reduction in schizophrenia. Arch Gen Psychiatry, 50, 190–7.Google Scholar
McGue, M., Gottesman, II & Rao, D. C. (1983) The transmission of schizophrenia under a multifactorial threshold model. Am J Hum Genet, 35, 1161–78.Google Scholar
Moberg, P. J. & Turetsky, B. I. (2003) Scent of a disorder: olfactory functioning in schizophrenia. Curr Psychiatry Rep, 5, 311–9.Google Scholar
Moberg, P. J., Doty, R. L., Turetsky, B. I., et al. (1996) Olfactory functioning in siblings discordant for schizophrenia (Abs.). Biol Psychiatry, 39, 571–2.Google Scholar
Montag-Sallaz, M., Baarke, A. & Montag, D. (2003) Aberrant neuronal connectivity in CHL1-deficient mice is associated with altered information processing-related immediate early gene expression. J Neurobiol, 57, 67–80.Google Scholar
Montag-Sallaz, M., Schachner, M. & Montag, D. (2002) Misguided axonal projections, neural cell adhesion molecule 180 mRNA upregulation, and altered behavior in mice deficient for the close homolog of L1. Molec Cell Biol, 22, 7967–81.Google Scholar
Montgomery, E. B. Jr., Baker, K. B., Lyons, K., et al. (1999) Abnormal performance on the PD test battery by asymptomatic first-degree relatives. Neurology, 52, 757–62.Google Scholar
Myles-Worsley, M. (2002) P50 sensory gating in multiplex schizophrenia families from a Pacific island isolate. Am J Psychiatry, 159, 2007–12.Google Scholar
Park, S., Holzman, P. S. & Goldman-Rakic, P. S. (1995) Spatial working memory deficits in the relatives of schizophrenic patients. Arch Gen Psychiatry, 52, 821–8.Google Scholar
Sakurai, K., Migita, O., Toru, M., et al. (2002) An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. Molec Psychiatry, 7, 412–5.Google Scholar
Schiffman, S. S., Graham, B. G., Sattely-Miller, E. A., et al. (2002) Taste, smell and neuropsychological performance of individuals at familial risk for Alzheimer's disease. Neurobiol Aging, 23, 397–404.Google Scholar
Schwab, S. G., Hallmayer, J., Lerer, B., et al. (1998) Support for a chromosome 18p locus conferring susceptibility to functional psychoses in families with schizophrenia, by association and linkage analysis. Am J Hum Genet, 63, 1139–52.Google Scholar
Seidman, L. J., Talbot, N. L., Kalinowski, A. G., et al. (1991) Neuropsychological probes of fronto-limbic system dysfunction in schizophrenia. Olfactory identification and Wisconsin Card Sorting performance. Schizophr Res, 6, 55–65.Google Scholar
Seidman, L. J., Goldstein, J. M., Goodman, J. M., et al. (1997) Sex differences in olfactory identification and Wisconsin Card Sorting performance in schizophrenia: relationship to attention and verbal ability. Biol Psychiatry, 42, 104–15.Google Scholar
Seidman, L. J., Faraone, S. V., Goldstein, J. M., et al. (1999) Thalamic and amygdala-hippocampal volume reductions in first degree relatives of schizophrenic patients: an MRI-based morphometric analysis. Biol Psychiatry, 46, 941–54.Google Scholar
Seidman, L. J., Faraone, S. V., Goldstein, J. M., et al. (2002) Left hippocampal volume as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric study of non-psychotic first degree relatives. Arch Gen Psychiatry, 59, 839–49.Google Scholar
Seidman, L. J., Pantelis, C., Keshavan, M. S., et al. (2003) A review and a new report of medial temporal lobe dysfunction as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric family study of the parahippocampal gyrus. Schizophr Bull, 29, 803–28.Google Scholar
Seidman, L. J. & Wencel, H. E. (2003) Genetically mediated brain abnormalities in schizophrenia. Curr Psychiatry Rep, 5, 135–44.Google Scholar
Serby, M., Mohan, C., Aryan, M., et al. (1996) Olfactory identification deficits in relatives of Alzheimer's disease patients. Biol Psychiatry, 39, 375–7.Google Scholar
Shenton, M. E., Solovay, M. R., Holzman, P. S., et al. (1989) Thought disorder in the relatives of psychotic patients. Arch Gen Psychiatry, 46, 897–901.Google Scholar
Shenton, M. E., Kikinis, R., Jolesz, F. A., et al. (1992) Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. New Eng J Med, 327, 604–12.Google Scholar
Siegel, C., Waldo, M., Mizner, G., et al. (1984) Deficits in sensory gating in schizophrenic patients and their relatives. Evidence obtained with auditory evoked responses. Arch Gen Psychiatry, 41, 607–12.Google Scholar
Stone, W. S., Faraone, S. V. & Tsuang, M. T. (eds) (2004) Early Clinical Intervention and Prevention in Schizophrenia. Totowa, NJ: Humana Press.
Thermenos, H. W., Seidman, L. J., Breiter, H., et al. (2004) Functional magnetic resonance imaging during auditory verbal working memory in nonpsychotic relatives of persons with schizophrenia: a pilot study. Biol Psychiatry, 55, 490–500.Google Scholar
Toomey, R., Faraone, S. V., Seidman, L. J., et al. (1998) Association of neuropsychological vulnerability markers in relatives of schizophrenic patients. Schizophr Res, 31, 89–98.Google Scholar
Tsuang, M. T., Gilbertson, M. W. & Faraone, S. V. (1991) Genetic transmission of negative and positive symptoms in the biological relatives of schizophrenics. In Negative versus Positive Schizophrenia (eds Marneros, A., Andreasen, N. C. & Tsuang, M. T.), pp. 265–91. Berlin: Springer–Verlag.
Tsuang, M. T., Seidman, L. J. & Faraone, S. V. (1999a) New approaches to the genetics of schizophrenia: neuropsychological and neuroimaging studies of nonpsychotic first degree relatives of people with schizophrenia. In The Fourth Symposium on the Search for the Causes of Schizophrenia, Vol. IV (eds W. F. Gattaz & H. Hafner), pp. 191–207. Berlin: Springer.
Tsuang, M. T., Stone, W. S. & Faraone, S. V. (1999b) Schizophrenia: a review of genetic studies. Harv Rev Psychiatry, 7, 185–207.Google Scholar
Turetsky, B. I., Moberg, P. J., Yousem, D. M., et al. (2000) Reduced olfactory bulb volume in patients with schizophrenia. Am J Psychiatry, 157, 828–30.Google Scholar
Turetsky, B. I., Moberg, P. J., Arnold, S. E., et al. (2003) Low olfactory bulb volume in first-degree relatives of patients with schizophrenia. Am J Psychiatry, 160, 703–8.Google Scholar
Waldo, M. C., Adler, L. E. & Freedman, R. (1988) Defects in auditory sensory gating and their apparent compensation in relatives of schizophrenics. Schizophr Res, 1, 19–24.Google Scholar
Waldo, M. C., Carey, G., Myles-Worsley, M., et al. (1991) Codistribution of a sensory gating deficit and schizophrenia in multi-affected families. Psychiatry Res, 39, 257–68.Google Scholar
Waldo, M., Myles-Worsley, M., Madison, A., et al. (1995) Sensory gating deficits in parents of schizophrenics. Am J Med Genet, 60, 506–11.Google Scholar
Wang, M. M., Tsai, R. Y., Schrader, K. A., et al. (1993) Genes encoding components of the olfactory signal transduction cascade contain a DNA binding site that may direct neuronal expression. Molec Cell Biology, 13, 5805–13.Google Scholar
Young, D. A., Waldo, M., Rutledge, J. H. 3rd, et al. (1996) Heritability of inhibitory gating of the P50 auditory-evoked potential in monozygotic and dizygotic twins. Neuropsychobiology, 33, 113–17.Google Scholar

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