Imaging genomics.

The recent completion of a working draft of the human genome sequence promises to provide unprecedented opportunities to explore the genetic basis of individual differences in complex behaviours and vulnerability to neuropsychiatric illness. Functional neuroimaging, because of its unique ability to assay information processing at the level of brain within individuals, provides a powerful approach to such functional genomics. Recent fMRI studies have established important physiological links between functional genetic polymorphisms and robust differences in information processing within distinct brain regions and circuits that have been linked to the manifestation of various disease states such as Alzheimer's disease, schizophrenia and anxiety disorders. Importantly, all of these biological relationships have been revealed in relatively small samples of healthy volunteers and in the absence of observable differences at the level of behaviour, underscoring the power of a direct assay of brain physiology like fMRI in exploring the functional impact of genetic variation.

[1]  Andreas Heinz,et al.  A relationship between serotonin transporter genotype and in vivo protein expression and alcohol neurotoxicity , 2000, Biological Psychiatry.

[2]  R. Weinshilboum,et al.  Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase. , 1999, Annual review of pharmacology and toxicology.

[3]  T L Babb,et al.  Hippocampal neuron loss and memory scores before and after temporal lobe surgery for epilepsy. , 1993, Archives of neurology.

[4]  R. Coppola,et al.  Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. , 1999, Cerebral cortex.

[5]  E H Cook,et al.  Cocaine, ethanol, and genotype effects on human midbrain serotonin transporter binding sites and mRNA levels. , 1998, The American journal of psychiatry.

[6]  Timothy B. Stockwell,et al.  The Sequence of the Human Genome , 2001, Science.

[7]  Klaus-Peter Lesch,et al.  Genetically driven variation in serotonin uptake: is there a link to affective spectrum, neurodevelopmental, and neurodegenerative disorders? , 1998, Biological Psychiatry.

[8]  J. Nurnberger,et al.  Genetics of bipolar affective disorder , 2000, Current psychiatry reports.

[9]  I. Deary,et al.  Neuroticism and polymorphisms in the serotonin transporter gene , 1999, Psychological Medicine.

[10]  M. Egan,et al.  Serotonin Transporter Genetic Variation and the Response of the Human Amygdala , 2002, Science.

[11]  M A Pericak-Vance,et al.  Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. , 1993, Neurology.

[12]  R. Ebstein,et al.  5-HT2C (HTR2C) serotonin receptor gene polymorphism associated with the human personality trait of reward dependence: interaction with dopamine D4 receptor (D4DR) and dopamine D3 receptor (D3DR) polymorphisms. , 1997, American journal of medical genetics.

[13]  J. V. Moran,et al.  Initial sequencing and analysis of the human genome. , 2001, Nature.

[14]  S. Sesack,et al.  Dopamine axons in primate prefrontal cortex: specificity of distribution, synaptic targets, and development. , 1998, Advances in pharmacology.

[15]  D. Galton,et al.  Apolipoprotein E genotyping in Alzheimer's disease. , 1996, Lancet.

[16]  P. Hrdina,et al.  Gender differences in association between serotonin transporter gene polymorphism and personality traits. , 2000, Psychiatric genetics.

[17]  K. Ohara,et al.  Functional polymorphism in the serotonin transporter promoter at the SLC6A4 locus and mood disorders , 1998, Biological Psychiatry.

[18]  L. Feuk,et al.  SNP association studies in Alzheimer's disease highlight problems for complex disease analysis. , 2001, Trends in genetics : TIG.

[19]  P. Propping,et al.  The electroencephalogram (EEG) as a research tool in human behavior genetics: Psychological examinations in healthy males with various inherited EEG variants , 1979, Human Genetics.

[20]  K. Ressler,et al.  Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders , 2000, Depression and anxiety.

[21]  A. Malhotra,et al.  Benefits and pitfalls encountered in psychiatric genetic association studies , 1999, Biological Psychiatry.

[22]  P. Goldman-Rakic Regional and cellular fractionation of working memory. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J C Mazziotta,et al.  Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. , 1995, JAMA.

[24]  D. Ball,et al.  The serotonin transporter gene and peer‐rated neuroticism , 1997, Neuroreport.

[25]  N. Freimer,et al.  Association analysis of candidate genes for neuropsychiatric disease: the perpetual campaign. , 2002, Trends in genetics : TIG.

[26]  Edward E. Smith,et al.  Temporal dynamics of brain activation during a working memory task , 1997, Nature.

[27]  Hiroshi Kunugi,et al.  Association between serotonin transporter gene polymorphism and anxiety-related traits , 1999, Biological Psychiatry.

[28]  J. Sääf,et al.  Psychoses in twins A 10 year clinical and biochemical follow-up study , 1989, Schizophrenia Research.

[29]  K. Lesch,et al.  Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region , 1996, Science.

[30]  M. Fredrikson,et al.  Human fear conditioning is related to dopaminergic and serotonergic biological markers. , 2001, Behavioral neuroscience.

[31]  I. Gottesman,et al.  At issue: genes, experience, and chance in schizophrenia--positioning for the 21st century. , 1997, Schizophrenia bulletin.

[32]  J. Flory,et al.  Neuroticism is not associated with the serotonin transporter (5-HTTLPR) polymorphism , 1999, Molecular Psychiatry.

[33]  Francesco Fera,et al.  The Amygdala Response to Emotional Stimuli: A Comparison of Faces and Scenes , 2002, NeuroImage.

[34]  J. Haines,et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. , 1993, Science.

[35]  George Bush,et al.  The emotional counting stroop paradigm: a functional magnetic resonance imaging probe of the anterior cingulate affective division , 1998, Biological Psychiatry.

[36]  P. McGuffin,et al.  Genomics and behavior. Toward behavioral genomics. , 2001, Science.

[37]  B. Axelrod Are Normative Data From the 64-Card Version of the WCST Comparable to the Full WCST? , 2002, The Clinical neuropsychologist.

[38]  R. Straub,et al.  Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[39]  J Melke,et al.  Serotonin transporter gene polymorphisms are associated with anxiety-related personality traits in women. , 2001, American journal of medical genetics.

[40]  Michael Davis,et al.  The amygdala: vigilance and emotion , 2001, Molecular Psychiatry.

[41]  Francesco Fera,et al.  Dextroamphetamine Modulates the Response of the Human Amygdala , 2002, Neuropsychopharmacology.

[42]  Mark S. Cohen,et al.  Patterns of brain activation in people at risk for Alzheimer's disease. , 2000, The New England journal of medicine.