The dawn of cognitive genetics? Crucial developmental caveats

Attempts to bridge genetics and cognition are rapidly coming to the forefront of cognitive neuroscience. It is therefore crucial to evaluate the current state of knowledge about disorders of known genetic origin as a way of assessing whether, and if so how, links between genotype and cognitive phenotype can be drawn, however indirect these links might be. We review recent empirical findings from research on genetic disorders at three levels of description--cognitive, neural systems, and cellular--that caution against simple genotype-phenotype mappings at all levels. Most importantly, interdisciplinary efforts to integrate human genetics and cognition will need to operationalize the mechanisms driving both typical and atypical developmental processes over time.

[1]  Allan L. Reiss,et al.  fMRI Study of Cognitive Interference Processing in Females with Fragile X Syndrome , 2002, Journal of Cognitive Neuroscience.

[2]  Steven Pinker,et al.  Talk of genetics and vice versa , 2001, Nature.

[3]  S. Waisbren,et al.  Timing is everything: executive functions in children exposed to elevated levels of phenylalanine. , 2003, Neuropsychology.

[4]  H. Moser,et al.  Dendritic anomalies in disorders associated with mental retardation. , 1999, Cerebral cortex.

[5]  A preliminary report on dopamine system reactivity in PKU: acute effects of haloperidol on neuropsychological, physiological, and neuroendocrine functions , 2004, Psychopharmacology.

[6]  P. Huttenlocher Neural Plasticity: The Effects of Environment on the Development of the Cerebral Cortex , 2002 .

[7]  Laura Lakusta,et al.  Past tense formation in Williams syndrome , 2001 .

[8]  M. C. Caselli,et al.  Language acquisition in special populations: a comparison between Down and Williams syndromes , 2002, Neuropsychologia.

[9]  Hugo W. Moser,et al.  Dendritic Anomalies in Disorders Associated with Mental Retardation , 2000 .

[10]  Michael A. Arbib,et al.  The handbook of brain theory and neural networks , 1995, A Bradford book.

[11]  Sarah E. London,et al.  Parallel FoxP1 and FoxP2 Expression in Songbird and Human Brain Predicts Functional Interaction , 2004, The Journal of Neuroscience.

[12]  L. Schauble,et al.  Beyond Modularity: A Developmental Perspective on Cognitive Science. , 1994 .

[13]  A. Monaco,et al.  Deciphering the genetic basis of speech and language disorders. , 2003, Annual review of neuroscience.

[14]  R. Passingham,et al.  Oral Dyspraxia in Inherited Speech and Language Impairment and Acquired Dysphasia , 2000, Brain and Language.

[15]  A. Karmiloff-Smith,et al.  Different approaches to relating genotype to phenotype in developmental disorders. , 2002, Developmental psychobiology.

[16]  I. Weiler,et al.  Synaptic regulation of protein synthesis and the fragile X protein , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[17]  K. Cornish,et al.  Attention and language in fragile X. , 2004, Mental retardation and developmental disabilities research reviews.

[18]  S. Paterson,et al.  Language and number in Down syndrome: the complex developmental trajectory from infancy to adulthood. , 2001, Down's syndrome, research and practice : the journal of the Sarah Duffen Centre.

[19]  Annette Karmiloff-Smith,et al.  Developmental disorders , 1998 .

[20]  F. Munir,et al.  Differential Impact of the FMR-1 Full Mutation on Memory and Attention Functioning: A Neuropsychological Perspective , 2001, Journal of Cognitive Neuroscience.

[21]  J. Atkinson,et al.  Normal and anomalous development of visual motion processing: motion coherence and ‘dorsal-stream vulnerability’ , 2003, Neuropsychologia.

[22]  F. Vargha-Khadem,et al.  Behavioural analysis of an inherited speech and language disorder: comparison with acquired aphasia. , 2002, Brain : a journal of neurology.

[23]  J. Darnell,et al.  Microarray Identification of FMRP-Associated Brain mRNAs and Altered mRNA Translational Profiles in Fragile X Syndrome , 2001, Cell.

[24]  A. Monaco,et al.  FOXP2 expression during brain development coincides with adult sites of pathology in a severe speech and language disorder. , 2003, Brain : a journal of neurology.

[25]  Daniel Ansari,et al.  Atypical trajectories of number development: a neuroconstructivist perspective , 2002, Trends in Cognitive Sciences.

[26]  Daniel Ansari,et al.  What makes counting count? Verbal and visuo-spatial contributions to typical and atypical number development. , 2003, Journal of experimental child psychology.

[27]  Mark H. Johnson Functional brain development in humans , 2001, Nature Reviews Neuroscience.

[28]  D. Bishop,et al.  Cognitive Neuropsychology and Developmental Disorders: Uncomfortable Bedfellows , 1997, The Quarterly journal of experimental psychology. A, Human experimental psychology.

[29]  Mark F. Bear,et al.  Altered synaptic plasticity in a mouse model of fragile X mental retardation , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[30]  K. P. Unnikrishnan,et al.  A feedback model of visual attention , 1992, [Proceedings 1992] IJCNN International Joint Conference on Neural Networks.

[31]  A. Karmiloff-Smith,et al.  Cognitive modularity and genetic disorders. , 1999, Science.

[32]  T. Goldberg,et al.  Genes and the parsing of cognitive processes , 2004, Trends in Cognitive Sciences.

[33]  J. Wilding,et al.  Annotation: Deconstructing the attention deficit in fragile X syndrome: a developmental neuropsychological approach. , 2004, Journal of child psychology and psychiatry, and allied disciplines.

[34]  Jon Driver,et al.  To Look or Not to Look? Typical and Atypical Development of Oculomotor Control , 2005, Journal of Cognitive Neuroscience.

[35]  V Menon,et al.  Frontostriatal deficits in fragile X syndrome: relation to FMR1 gene expression. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[36]  C. Mervis,et al.  GTF2I hemizygosity implicated in mental retardation in Williams syndrome: Genotype–phenotype analysis of five families with deletions in the Williams syndrome region , 2003, American journal of medical genetics. Part A.

[37]  A. Karmiloff-Smith,et al.  Williams syndrome: from genotype through to the cognitive phenotype. , 2000, American journal of medical genetics.

[38]  Vinod Menon,et al.  Functional brain activation during arithmetic processing in females with fragile X syndrome is related to FMR1 protein expression , 2002, Human brain mapping.

[39]  P. McGuffin,et al.  Psychopathology in the postgenomic era. , 2003, Annual review of psychology.

[40]  J. Faubert,et al.  Integrative cortical dysfunction and pervasive motion perception deficit in fragile X syndrome , 2004, Neurology.

[41]  A. Karmiloff-Smith,et al.  Double Dissociations in Developmental Disorders? Theoretically Misconceived, Empirically Dubious , 2003, Cortex.

[42]  A. Karmiloff-Smith Development itself is the key to understanding developmental disorders , 1998, Trends in Cognitive Sciences.

[43]  Deborah D. Hatton,et al.  Variability in FMRP and early development in males with fragile X syndrome. , 2001, American journal of mental retardation : AJMR.

[44]  A. Monaco,et al.  A forkhead-domain gene is mutated in a severe speech and language disorder , 2001, Nature.

[45]  Kenneth Wexler,et al.  The development of inflection in a biologically based theory of language acquisition. , 1996 .

[46]  M. Mishkin,et al.  Language fMRI abnormalities associated with FOXP2 gene mutation , 2003, Nature Neuroscience.

[47]  J. Parisi,et al.  Developmental disorders. , 1997, Current opinion in neurology.

[48]  Dorothy V M Bishop,et al.  Motor immaturity and specific speech and language impairment: evidence for a common genetic basis. , 2002, American journal of medical genetics.

[49]  A T Hoogeveen,et al.  Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis. , 1997, Human molecular genetics.

[50]  Daniel Ansari,et al.  Atypical development of language and social communication in toddlers with Williams syndrome , 2002 .

[51]  J. Wilding,et al.  Further delineation of the executive deficit in males with fragile-X syndrome , 2002, Neuropsychologia.

[52]  Ursula Bellugi,et al.  Bridging cognition, the brain and molecular genetics: evidence from Williams syndrome , 1999, Trends in Neurosciences.

[53]  M. Gopnik,et al.  Familial aggregation of a developmental language disorder , 1991, Cognition.

[54]  Mark H Johnson,et al.  Spatial representation and attention in toddlers with Williams syndrome and Down syndrome , 2003, Neuropsychologia.

[55]  Stephen T Warren,et al.  A decade of molecular studies of fragile X syndrome. , 2002, Annual review of neuroscience.

[56]  Michael W. Spratling,et al.  Disordered visual processing and oscillatory brain activity in autism and Williams Syndrome , 2001, Neuroreport.

[57]  B. Oostra,et al.  Fragile X syndrome, the Fragile X related proteins, and animal models , 2002, Microscopy research and technique.

[58]  A. Karmiloff-Smith Précis of Beyond modularity: A developmental perspective on cognitive science , 1994, Behavioral and Brain Sciences.

[59]  M. Raijmakers Rethinking innateness: A connectionist perspective on development. , 1997 .

[60]  A. Diamond,et al.  Chapter 29. A Model System for Studying the Role of Dopamine in the Prefrontal Cortex during Early Development in Humans: Early and Continuously Treated Phenylketonuria , 2003 .

[61]  Julia Grant,et al.  Comprehension of Spatial Language Terms in Williams Syndrome: Evidence for an Interaction Between Domains of Strength and Weakness , 2004, Cortex.

[62]  J. Flint Animal models of anxiety and their molecular dissection. , 2003, Seminars in cell & developmental biology.

[63]  Jon Driver,et al.  Visual search in typically developing toddlers and toddlers with Fragile X or Williams syndrome. , 2004, Developmental science.

[64]  Katherine J. Alcock,et al.  Pitch and Timing Abilities in Inherited Speech and Language Impairment , 2000, Brain and Language.

[65]  Karl J. Friston,et al.  Neural basis of an inherited speech and language disorder. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[66]  Mark H. Johnson Brain development and cognition : a reader , 1993 .

[67]  Michael S. C. Thomas,et al.  Are developmental disorders like cases of adult brain damage? Implications from connectionist modelling , 2002, Behavioral and Brain Sciences.

[68]  Michael S. C. Thomas,et al.  Modeling language acquisition in atypical phenotypes. , 2003, Psychological review.

[69]  R. Passingham,et al.  Praxic and nonverbal cognitive deficits in a large family with a genetically transmitted speech and language disorder. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[70]  Michael S. C. Thomas,et al.  Exploring the Williams syndrome face-processing debate: the importance of building developmental trajectories. , 2004, Journal of child psychology and psychiatry, and allied disciplines.

[71]  C. Nelson,et al.  Handbook of Developmental Cognitive Neuroscience , 2001 .

[72]  Edward Zigler,et al.  Handbook of Mental Retardation and Development , 1998 .

[73]  Attentional Characteristics of Infants and Toddlers With Williams Syndrome During Triadic Interactions , 2003, Developmental neuropsychology.

[74]  M. C. Caselli,et al.  Early Linguistic Abilities of Italian Children With Williams Syndrome , 2003, Developmental neuropsychology.

[75]  K. Svoboda,et al.  Structure and function of dendritic spines. , 2002, Annual review of physiology.

[76]  V Menon,et al.  Anomalous brain activation during face and gaze processing in Williams syndrome , 2004, Neurology.

[77]  C. Temple Cognitive neuropsychology and its application to children. , 1997, Journal of child psychology and psychiatry, and allied disciplines.

[78]  Michael S. C. Thomas,et al.  What can developmental disorders tell us about the neurocomputational constraints that shape development? The case of Williams syndrome , 2003, Development and Psychopathology.

[79]  K. Mullen,et al.  Differential impact of the FMR1 gene on visual processing in fragile X syndrome. , 2003, Brain : a journal of neurology.

[80]  G. Elston Cortex, cognition and the cell: new insights into the pyramidal neuron and prefrontal function. , 2003, Cerebral cortex.

[82]  Andrea Beckel-Mitchener,et al.  Correlates across the structural, functional, and molecular phenotypes of fragile X syndrome. , 2004, Mental retardation and developmental disabilities research reviews.

[83]  Mark F Bear,et al.  The mGluR theory of fragile X mental retardation , 2004, Trends in Neurosciences.