Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 31 October 2003:
Vol. 302. no. 5646, pp. 822 - 826
DOI: 10.1126/science.1092132
Prev | Table of Contents | Next

Review

The Genetics of Adult-Onset Neuropsychiatric Disease: Complexities and Conundra?

James L. Kennedy,1 Lindsay A. Farrer,2 Nancy C. Andreasen,3 Richard Mayeux,4 Peter St George-Hyslop1*

Genetic factors play a major role in the etiology of adult-onset neurodegenerative and neuropsychiatric disorders. Several highly penetrant genes have been cloned for rare, autosomal-dominant, early-onset forms of neurodegenerative diseases. These genes have provided important insights into the mechanisms of these diseases (often altering neuronal protein processing). However, the genes associated with inherited susceptibility to late-onset neurodegenerative diseases, schizophrenia, and bipolar disorder appear to have smaller effects and are likely to interact with each other (and with nongenetic factors) to modulate susceptibility and/or disease phenotype. Several strategies have recently been applied to address this complexity, leading to the identification of a number of candidate susceptibility loci/genes.

1 Departments of Psychiatry and Medicine, Centre for Addiction and Mental Health, Centre for Research in Neurodegenerative Diseases, University of Toronto; and Department of Medicine (Division of Neurology), The University Health Network, Toronto, Ontario M5S 3H9, Canada.
2 Departments of Medicine, Neurology, and Genetics & Genomics, Boston University School of Medicine; and Departments of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
3 Department of Psychiatry, University of Iowa; and Departments of Psychiatry and Neurology, University of New Mexico, The MIND Institute, Albuquerque, NM 87106, USA.
4 Gertrude H. Sergievsky Center, Taub Institute of Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

* To whom correspondence should be addressed. E-mail: p.hyslop{at}utoronto.ca

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Autonomic Dysfunction in Unaffected First-Degree Relatives of Patients Suffering From Schizophrenia.
K.-J. Bar, S. Berger, M. Metzner, M. K. Boettger, S. Schulz, C. T. Ramachandraiah, J. Terhaar, A. Voss, V. K. Yeragani, and H. Sauer (2009)
Schizophr Bull
   Abstract »    Full Text »    PDF »
Factor Structure of the Restricted Academic Situation Scale: Implications for ADHD.
S. Karama, L. Ben Amor, N. Grizenko, A. Ciampi, V. Mbekou, M. Ter-Stepanian, P. Lageix, C. Baron, G. Schwartz, and R. Joober (2009)
J Atten Disord 12, 442-448
   Abstract »    PDF »
Loss of {gamma}-Secretase Function Impairs Endocytosis of Lipoprotein Particles and Membrane Cholesterol Homeostasis.
I. Y. Tamboli, K. Prager, D. R. Thal, K. M. Thelen, I. Dewachter, C. U. Pietrzik, P. St. George-Hyslop, S. S. Sisodia, B. De Strooper, M. T. Heneka, et al. (2008)
J. Neurosci. 28, 12097-12106
   Abstract »    Full Text »    PDF »
Genetic Research in Schizophrenia: New Tools and Future Perspectives.
L. Bertram (2008)
Schizophr Bull 34, 806-812
   Abstract »    Full Text »    PDF »
Schizophrenia, Psychiatric Genetics, and Darwinian Psychiatry: An Evolutionary Framework.
G. D. Pearlson and B. S. Folley (2008)
Schizophr Bull 34, 722-733
   Abstract »    Full Text »    PDF »
High-Resolution Serum Proteomic Profiling of Alzheimer Disease Samples Reveals Disease-Specific, Carrier-Protein-Bound Mass Signatures.
M. F. Lopez, A. Mikulskis, S. Kuzdzal, D. A. Bennett, J. Kelly, E. Golenko, J. DiCesare, E. Denoyer, W. F. Patton, R. Ediger, et al. (2005)
Clin. Chem. 51, 1946-1954
   Abstract »    Full Text »    PDF »
Association of late-onset Alzheimer's disease with genetic variation in multiple members of the GAPD gene family.
Y. Li, P. Nowotny, P. Holmans, S. Smemo, J. S. K. Kauwe, A. L. Hinrichs, K. Tacey, L. Doil, R. van Luchene, V. Garcia, et al. (2004)
PNAS 101, 15688-15693
   Abstract »    Full Text »    PDF »
Clinical Trials in Late Life: New Science in Old Paradigms.
B. D. Lebowitz (2004)
Gerontologist 44, 452-458
   Abstract »    Full Text »    PDF »
A Genetic Mechanism Implicates Chromosome 11 in Schizophrenia and Bipolar Diseases.
A. J. S. Klar (2004)
Genetics 167, 1833-1840
   Abstract »    Full Text »    PDF »
Neural system-enriched gene expression: relationship to biological pathways and neurological diseases.
J. Zhang, A. Moseley, A. G. Jegga, A. Gupta, D. P. Witte, M. Sartor, M. Medvedovic, S. S. Williams, C. Ley-Ebert, L. M. Coolen, et al. (2004)
Physiol Genomics 18, 167-183
   Abstract »    Full Text »    PDF »
Somatic and germline mosaicism in sporadic early-onset Alzheimer's disease.
J. A. Beck, M. Poulter, T. A. Campbell, J. B. Uphill, G. Adamson, J. F. Geddes, T. Revesz, M. B. Davis, N. W. Wood, J. Collinge, et al. (2004)
Hum. Mol. Genet. 13, 1219-1224
   Abstract »    Full Text »    PDF »
Alzheimer's disease: one disorder, too many genes?.
L. Bertram and R. E. Tanzi (2004)
Hum. Mol. Genet. 13, R135-141
   Abstract »    Full Text »    PDF »
An Epigenetic Hypothesis for Human Brain Laterality, Handedness, and Psychosis Development.
A.J.S. KLAR (2004)
Cold Spring Harb Symp Quant Biol 69, 499-506
   Abstract »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)