- Email: [email protected]
Neuropsychiatry's offspring
Research Update
References 1 Park, D.C. et al. Models of visuospatial and verbal memory across the adult life span. Psychol. Aging (in press) 2 Craik, F.I.M. and Byrd, M. (1982) Aging and cognitive deficits: the role of attentional resources. In Aging and Cognitive Processes (Craik, F.I.M. and Trehub, S., eds), pp. 191–211, Plenum Press 3 Salthouse, T.A. (1996) The processing-speed theory of adult age differences in cognition. Psychol. Rev. 45, 403–428 4 Park, D.C. and Hall-Gutchess, A. (2000) Cognitive aging and everyday life. In Cognitive Aging: A Primer (Park, D.C. and Schwarz, N., eds), pp. 217–232, Psychology Press 5 Raz, N. (2000) Aging of the brain and its impact on cognitive performance: integration of structural and functional findings. In The Handbook of Aging and Cognition (Craik, F.I.M. and Salthouse, T.A., eds), pp.1–90, Lawrence Erlbaum 6 Cabeza, R. et al. (1997) Age-related differences in neural activity during memory encoding and retrieval: a positron emission tomography study. J. Neurosci. 17, 391–400
TRENDS in Cognitive Sciences Vol.6 No.6 June 2002
7 Reuter-Lorenz, P.A. et al. (2000) Age differences in the frontal lateralization of verbal and spatial working memory revealed by PET. J. Cogn. Neurosci. 12, 174–187 8 Cabeza, R. Hemispheric asymmetry reduction in older adults: the HAROLD model. Psychol. Aging (in press) 9 Grady, C.L. and Craik, F.I.M. (2000) Changes in memory processing with age. Curr. Opin. Neurobiol. 10, 224–231 10 Park, D.C. et al. (2001) Cerebral aging: integration of brain and behavioral models of cognitive function. Dialog. Clin. Neurosci. 3, 151–165 11 Craik, F.I.M. and McDowd, J.M. (1987) Age differences in recall and recognition. J. Exp. Psychol. Learn. Mem. Cogn. 13, 474–479 12 Eysenck, M.W. (1974) Age differences in incidental learning. Dev. Psychol. 10, 936–941 13 Logan, J.M. et al. (2002) Under-recruitment and non-selective recruitment: dissociable neural mechanisms associated with aging. Neuron 33, 827–840 14 Kelley, W.M. et al. (1998) Hemispheric specialization in human dorsal frontal cortex and
229
15
16
17
18
medial temporal lobe for verbal and nonverbal encoding. Neuron, 20, 927–936 McDermott, K.B. et al. (1999) Set- and codespecific activation in the frontal cortex: an fMRI study of encoding and retrieval of faces and words. J. Cogn. Neurosci. 11, 631–640 Reuter-Lorenz, P.A. et al. (2001) Neurocognitive ageing of storage and executive processes. Eur. J. Cogn. Psychol. 13, 257–278 Rypma, B. and D’Esposito, M. (2000) Isolating the neural mechanisms of age-related changes in human working memory. Nat. Neurosci. 3, 509–515 Kliegl, R. et al. (1989) Testing-the-limits and the study of adult age differences in cognitive plasticity of a mnemonic skill. Dev. Psychol. 25, 247–256
Denise C. Park Dept of Psychology, 3042 East Hall, University of Michigan, Ann Arbor, MI 48109-1109, USA. e-mail: [email protected]
Meeting Report
Neuropsychiatry’s offspring Philip Shaw The British Neuropsychiatry Association Annual Meeting was held at the Institute of Child Health, London, UK, on 21–22 February 2002.
Hybrid medical sub-specialties like neuropsychiatry can face an uncertain future. On the one hand they can wither from a lack of clinical relevance and an independent scientific grounding. On the other, as the recent meeting in London suggests, they can draw on the strengths of the parent disciplines and produce an impressive array of their own offspring. Like many, I’ve more or less forgotten about new variant CJD – the form of CJD that affects younger people. It’s a case of out of the media spotlight, out of mind. Such indifference is unwarranted according to the opening speaker at the conference, John Collinge (Institute of Neurology, London, UK). He gave a measured but startling account of some of the possible implications of his group’s finding of several major single genes underlying susceptibility to this disease. Thus the 100 or so people who have already died from the disease might represent only the tip of the iceberg; these are the genetically most susceptible, who develop symptoms of CJD quickly. Other, genetically different, groups http://tics.trends.com
of people already infected with the prion might have a more insidious evolution of the disease. The clinical relevance of CJD for those who work at the interface between psychiatry and neurology was then emphasized by Eve Johnstone, who noted the predominance in a large proportion of subjects of early psychiatric symptoms such as depression and personality changes. The recent debate over the triple MMR vaccine (very much in the media spotlight) has certainly had the positive effect of increasing public awareness of autism and Asperger’s syndrome. Simon Baron-Cohen (University of Cambridge, UK) gave a rather different account of the possible aetiology of these disorders when he argued that autism is an extreme of the male brain (see Opinion article in this issue, p. 248). In essence, he argued that on the whole men like machines (e.g. cars, computers) and women like social stimuli (i.e. people). This is not a culturally moulded phenomenon, though, as the tendency for males to be interested in inanimate objects is present at 24 hours after birth and appears to be fuelled by the ultimate masculine fuel – testosterone (measured in utero). People who have autism show an exaggerated pattern of relative strength in reasoning about inanimate stimuli and weakness in
dealing with social stimuli. Although highly controversial, the research presented by Baron-Cohen was fascinating and it was refreshing to hear an argument that the brain itself is responsible for at least some gender differences. With a whole conference dedicated to it in April this year in Texas, and even a mention in the Sunday papers, the brain structure of the season is surely the amygdala. Its role in the perception of emotions was explored by Ralph Adolphs (University of Iowa, USA), who illustrated how their subject with bilateral degeneration of the amygdala was impaired in the perception of fearful stimuli. In addition the amygdala was implicated in emotional memory, empathy and even in some forms of psychosis. Throughout the two-day meeting, an exploration of developments in the basic science underlying neuropsychiatric conditions was complemented with a consideration of clinical implications. For example, the session on auditory perception managed to integrate work focussed on single-cell recordings and functional imaging data (from Robert Zatorre, Montreal Neurological Institute, Canada) with a consideration of how this might account for auditory/musical hallucinations (Tim Griffiths, Newcastle University, UK).
1364-6613/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S1364-6613(02)01905-8
230
Research Update
Given the flourishing of new neuroimaging technologies it must be tempting to fill a conference with fabulous images of thought in action. However, the fact that brains belong to people was not forgotten. The challenges and rewards of working with people who have neuropsychiatric illnesses were discussed in several clinically oriented
TRENDS in Cognitive Sciences Vol.6 No.6 June 2002
talks. Sensitive subjects were not avoided, such as the subjective experience of illness in relation to neardeath experiences in children, and the impact of caring for a loved one who has CJD. This last topic was discussed by members of the human BSE foundation, who very kindly shared their experiences with delegates. The varied offspring
of neuropsychiatry were indeed very much in evidence during this encouraging meeting. Philip Shaw Clinical Lecturer in Neuropsychiatry Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, UK SE5 8AF. e-mail: [email protected]
Sex, genes and hormones Stacey A. Fannon, Regina M. Vidaver and Sherry A. Marts The multidisciplinary symposium convened by the Society for Women’s Health Research ‘Sex Begins in the Womb’ was held at the Crowne Plaza Cabana, Palo Alto, CA, USA, on 1 March 2002.
How do prenatal genetic and hormonal influences affect intelligence and behavior? This was one question explored at ‘Sex Begins in the Womb’, a multidisciplinary symposium convened by the Society for Women’s Health Research (Washington, DC, USA). This was the third in a series of Societysponsored meetings on the biology of sex differences and how those differences affect human health. Sex matters in mental retardation
Researchers have long recognized that males make up a majority of the mentally retarded (IQ ≤ 70) population. Genomic technologies are revealing why that imbalance exists. As Charles J. Epstein (University of California, San Francisco, CA, USA) explained, a person’s sex can influence the occurrence, nature and transmission of congenital diseases. Key conference outcomes • Certain genes contain triplet repeats that cause disease when expanded. Triplet repeats are more likely to expand through subsequent generations, increasing risk of disease. • Different syndromes can result from deletion in the same chromosomal region, depending on parent of origin. • Girls exposed to high levels of androgens in utero exhibit boy-typical behavior directly related to the degree of prenatal androgen excess. • A person’s sex can influence the occurrence, nature and transmission of congenital diseases.
http://tics.trends.com
Many disorders that cause mental retardation occur more frequently and/or more severely in males because the disorders are X-chromosome linked. A prime example is fragile-X syndrome, which occurs approximately twice as often in males than in females. The fragile-X phenotype includes long face, large ears, prominent jaw, and enlarged testicles in postpubertal males. Fragile-X syndrome is caused by expansion of a CGG triplet repeat in the gene encoding FMR-1, located on the X chromosome. Normal individuals have 6–50 copies of the CGG repeat, whereas people with fragile-X syndrome have 230–1000. A normal male might nevertheless have an intermediate number of repeats (50–230), and pass this ‘pre-mutation’ to his daughter. The repeat is likely to expand in future generations: if the expansion occurs in the daughter’s gametes, her sons would have a 50% chance of being affected. In addition to the sex of the child, that of the parent can determine the phenotype conferred by mutations of certain genetic loci through genomic imprinting, as Epstein noted. The prototypical example of this is a deletion in chromosome 15, which results in Prader–Willi syndrome (PWS) if the deletion affects the paternally derived chromosome, or Angelman syndrome (AS) if it affects the maternally derived chromosome. Although PWS and AS are caused by deletions in the same chromosomal regions, they show completely different phenotypes that indicate essential parent-of-origin effects. The effect of prenatal androgens on childhood behavior
Prenatal exposure to sex hormones can have powerful permanent effects, not only on genitalia but also on the developing brain. Sheri A. Berenbaum (Pennsylvania
State University, University Park, PA, USA) and colleagues (at Southern Illinois University School of Medicine, Carbondale, IL, USA; and Northwestern University School of Medicine and Evanston Hospital, Evanston, IL, USA) observed these effects in studies of girls with congenital adrenal hyperplasia (CAH) and their siblings [1]. Congenital adrenal hyperplasia is caused by an enzymatic defect in 21-hydroxylase, which exposes females to moderately elevated androgens during gestation. Without prenatal diagnosis and treatment, girls with CAH are born with masculinized genitalia. ‘Prenatal exposure to sex hormones can …on the developing have powerful effects… brain.’
Compared with their sisters, girls with CAH play more with boys’ toys (transportation and building toys), show less interest in infants and have higher spatial ability. This boy-typical play behavior is most pronounced in girls with the most severe type of CAH and is unrelated to how well the disease is initially controlled. One hypothesis is that girls with CAH exhibit boy-typical behaviors because of the parents’ response to a child with masculinized genitalia. However, Berenbaum described the work of Anna Nordenstrom and her colleagues (Karolinska Institute, Stockholm, Sweden) who found that boy-typical behavior directly relates to the degree of prenatal androgen excess at diagnosis, not parental behavior. Berenbaum’s continuing research with girls who have CAH includes a prospective study of girls with CAH detected through newborn screening.
1364-6613/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S1364-6613(02)01914-9
References 1 Park, D.C. et al. Models of visuospatial and verbal memory across the adult life span. Psychol. Aging (in press) 2 Craik, F.I.M. and Byrd, M. (1982) Aging and cognitive deficits: the role of attentional resources. In Aging and Cognitive Processes (Craik, F.I.M. and Trehub, S., eds), pp. 191–211, Plenum Press 3 Salthouse, T.A. (1996) The processing-speed theory of adult age differences in cognition. Psychol. Rev. 45, 403–428 4 Park, D.C. and Hall-Gutchess, A. (2000) Cognitive aging and everyday life. In Cognitive Aging: A Primer (Park, D.C. and Schwarz, N., eds), pp. 217–232, Psychology Press 5 Raz, N. (2000) Aging of the brain and its impact on cognitive performance: integration of structural and functional findings. In The Handbook of Aging and Cognition (Craik, F.I.M. and Salthouse, T.A., eds), pp.1–90, Lawrence Erlbaum 6 Cabeza, R. et al. (1997) Age-related differences in neural activity during memory encoding and retrieval: a positron emission tomography study. J. Neurosci. 17, 391–400
TRENDS in Cognitive Sciences Vol.6 No.6 June 2002
7 Reuter-Lorenz, P.A. et al. (2000) Age differences in the frontal lateralization of verbal and spatial working memory revealed by PET. J. Cogn. Neurosci. 12, 174–187 8 Cabeza, R. Hemispheric asymmetry reduction in older adults: the HAROLD model. Psychol. Aging (in press) 9 Grady, C.L. and Craik, F.I.M. (2000) Changes in memory processing with age. Curr. Opin. Neurobiol. 10, 224–231 10 Park, D.C. et al. (2001) Cerebral aging: integration of brain and behavioral models of cognitive function. Dialog. Clin. Neurosci. 3, 151–165 11 Craik, F.I.M. and McDowd, J.M. (1987) Age differences in recall and recognition. J. Exp. Psychol. Learn. Mem. Cogn. 13, 474–479 12 Eysenck, M.W. (1974) Age differences in incidental learning. Dev. Psychol. 10, 936–941 13 Logan, J.M. et al. (2002) Under-recruitment and non-selective recruitment: dissociable neural mechanisms associated with aging. Neuron 33, 827–840 14 Kelley, W.M. et al. (1998) Hemispheric specialization in human dorsal frontal cortex and
229
15
16
17
18
medial temporal lobe for verbal and nonverbal encoding. Neuron, 20, 927–936 McDermott, K.B. et al. (1999) Set- and codespecific activation in the frontal cortex: an fMRI study of encoding and retrieval of faces and words. J. Cogn. Neurosci. 11, 631–640 Reuter-Lorenz, P.A. et al. (2001) Neurocognitive ageing of storage and executive processes. Eur. J. Cogn. Psychol. 13, 257–278 Rypma, B. and D’Esposito, M. (2000) Isolating the neural mechanisms of age-related changes in human working memory. Nat. Neurosci. 3, 509–515 Kliegl, R. et al. (1989) Testing-the-limits and the study of adult age differences in cognitive plasticity of a mnemonic skill. Dev. Psychol. 25, 247–256
Denise C. Park Dept of Psychology, 3042 East Hall, University of Michigan, Ann Arbor, MI 48109-1109, USA. e-mail: [email protected]
Meeting Report
Neuropsychiatry’s offspring Philip Shaw The British Neuropsychiatry Association Annual Meeting was held at the Institute of Child Health, London, UK, on 21–22 February 2002.
Hybrid medical sub-specialties like neuropsychiatry can face an uncertain future. On the one hand they can wither from a lack of clinical relevance and an independent scientific grounding. On the other, as the recent meeting in London suggests, they can draw on the strengths of the parent disciplines and produce an impressive array of their own offspring. Like many, I’ve more or less forgotten about new variant CJD – the form of CJD that affects younger people. It’s a case of out of the media spotlight, out of mind. Such indifference is unwarranted according to the opening speaker at the conference, John Collinge (Institute of Neurology, London, UK). He gave a measured but startling account of some of the possible implications of his group’s finding of several major single genes underlying susceptibility to this disease. Thus the 100 or so people who have already died from the disease might represent only the tip of the iceberg; these are the genetically most susceptible, who develop symptoms of CJD quickly. Other, genetically different, groups http://tics.trends.com
of people already infected with the prion might have a more insidious evolution of the disease. The clinical relevance of CJD for those who work at the interface between psychiatry and neurology was then emphasized by Eve Johnstone, who noted the predominance in a large proportion of subjects of early psychiatric symptoms such as depression and personality changes. The recent debate over the triple MMR vaccine (very much in the media spotlight) has certainly had the positive effect of increasing public awareness of autism and Asperger’s syndrome. Simon Baron-Cohen (University of Cambridge, UK) gave a rather different account of the possible aetiology of these disorders when he argued that autism is an extreme of the male brain (see Opinion article in this issue, p. 248). In essence, he argued that on the whole men like machines (e.g. cars, computers) and women like social stimuli (i.e. people). This is not a culturally moulded phenomenon, though, as the tendency for males to be interested in inanimate objects is present at 24 hours after birth and appears to be fuelled by the ultimate masculine fuel – testosterone (measured in utero). People who have autism show an exaggerated pattern of relative strength in reasoning about inanimate stimuli and weakness in
dealing with social stimuli. Although highly controversial, the research presented by Baron-Cohen was fascinating and it was refreshing to hear an argument that the brain itself is responsible for at least some gender differences. With a whole conference dedicated to it in April this year in Texas, and even a mention in the Sunday papers, the brain structure of the season is surely the amygdala. Its role in the perception of emotions was explored by Ralph Adolphs (University of Iowa, USA), who illustrated how their subject with bilateral degeneration of the amygdala was impaired in the perception of fearful stimuli. In addition the amygdala was implicated in emotional memory, empathy and even in some forms of psychosis. Throughout the two-day meeting, an exploration of developments in the basic science underlying neuropsychiatric conditions was complemented with a consideration of clinical implications. For example, the session on auditory perception managed to integrate work focussed on single-cell recordings and functional imaging data (from Robert Zatorre, Montreal Neurological Institute, Canada) with a consideration of how this might account for auditory/musical hallucinations (Tim Griffiths, Newcastle University, UK).
1364-6613/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S1364-6613(02)01905-8
230
Research Update
Given the flourishing of new neuroimaging technologies it must be tempting to fill a conference with fabulous images of thought in action. However, the fact that brains belong to people was not forgotten. The challenges and rewards of working with people who have neuropsychiatric illnesses were discussed in several clinically oriented
TRENDS in Cognitive Sciences Vol.6 No.6 June 2002
talks. Sensitive subjects were not avoided, such as the subjective experience of illness in relation to neardeath experiences in children, and the impact of caring for a loved one who has CJD. This last topic was discussed by members of the human BSE foundation, who very kindly shared their experiences with delegates. The varied offspring
of neuropsychiatry were indeed very much in evidence during this encouraging meeting. Philip Shaw Clinical Lecturer in Neuropsychiatry Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, UK SE5 8AF. e-mail: [email protected]
Sex, genes and hormones Stacey A. Fannon, Regina M. Vidaver and Sherry A. Marts The multidisciplinary symposium convened by the Society for Women’s Health Research ‘Sex Begins in the Womb’ was held at the Crowne Plaza Cabana, Palo Alto, CA, USA, on 1 March 2002.
How do prenatal genetic and hormonal influences affect intelligence and behavior? This was one question explored at ‘Sex Begins in the Womb’, a multidisciplinary symposium convened by the Society for Women’s Health Research (Washington, DC, USA). This was the third in a series of Societysponsored meetings on the biology of sex differences and how those differences affect human health. Sex matters in mental retardation
Researchers have long recognized that males make up a majority of the mentally retarded (IQ ≤ 70) population. Genomic technologies are revealing why that imbalance exists. As Charles J. Epstein (University of California, San Francisco, CA, USA) explained, a person’s sex can influence the occurrence, nature and transmission of congenital diseases. Key conference outcomes • Certain genes contain triplet repeats that cause disease when expanded. Triplet repeats are more likely to expand through subsequent generations, increasing risk of disease. • Different syndromes can result from deletion in the same chromosomal region, depending on parent of origin. • Girls exposed to high levels of androgens in utero exhibit boy-typical behavior directly related to the degree of prenatal androgen excess. • A person’s sex can influence the occurrence, nature and transmission of congenital diseases.
http://tics.trends.com
Many disorders that cause mental retardation occur more frequently and/or more severely in males because the disorders are X-chromosome linked. A prime example is fragile-X syndrome, which occurs approximately twice as often in males than in females. The fragile-X phenotype includes long face, large ears, prominent jaw, and enlarged testicles in postpubertal males. Fragile-X syndrome is caused by expansion of a CGG triplet repeat in the gene encoding FMR-1, located on the X chromosome. Normal individuals have 6–50 copies of the CGG repeat, whereas people with fragile-X syndrome have 230–1000. A normal male might nevertheless have an intermediate number of repeats (50–230), and pass this ‘pre-mutation’ to his daughter. The repeat is likely to expand in future generations: if the expansion occurs in the daughter’s gametes, her sons would have a 50% chance of being affected. In addition to the sex of the child, that of the parent can determine the phenotype conferred by mutations of certain genetic loci through genomic imprinting, as Epstein noted. The prototypical example of this is a deletion in chromosome 15, which results in Prader–Willi syndrome (PWS) if the deletion affects the paternally derived chromosome, or Angelman syndrome (AS) if it affects the maternally derived chromosome. Although PWS and AS are caused by deletions in the same chromosomal regions, they show completely different phenotypes that indicate essential parent-of-origin effects. The effect of prenatal androgens on childhood behavior
Prenatal exposure to sex hormones can have powerful permanent effects, not only on genitalia but also on the developing brain. Sheri A. Berenbaum (Pennsylvania
State University, University Park, PA, USA) and colleagues (at Southern Illinois University School of Medicine, Carbondale, IL, USA; and Northwestern University School of Medicine and Evanston Hospital, Evanston, IL, USA) observed these effects in studies of girls with congenital adrenal hyperplasia (CAH) and their siblings [1]. Congenital adrenal hyperplasia is caused by an enzymatic defect in 21-hydroxylase, which exposes females to moderately elevated androgens during gestation. Without prenatal diagnosis and treatment, girls with CAH are born with masculinized genitalia. ‘Prenatal exposure to sex hormones can …on the developing have powerful effects… brain.’
Compared with their sisters, girls with CAH play more with boys’ toys (transportation and building toys), show less interest in infants and have higher spatial ability. This boy-typical play behavior is most pronounced in girls with the most severe type of CAH and is unrelated to how well the disease is initially controlled. One hypothesis is that girls with CAH exhibit boy-typical behaviors because of the parents’ response to a child with masculinized genitalia. However, Berenbaum described the work of Anna Nordenstrom and her colleagues (Karolinska Institute, Stockholm, Sweden) who found that boy-typical behavior directly relates to the degree of prenatal androgen excess at diagnosis, not parental behavior. Berenbaum’s continuing research with girls who have CAH includes a prospective study of girls with CAH detected through newborn screening.
1364-6613/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S1364-6613(02)01914-9