0
0

Chapter 38. GeneticsFundamentals Relevant to Child and Adolescent Psychiatry

James J. McGough, M.D.; Stanley F. Nelson, M.D.
DOI: 10.1176/appi.books.9781585623921.465680

Sections

Excerpt

Psychiatry has always struggled with the relative importance of nature versus nurture (McGuffin and Southwick 2003). In recent decades, advances in neuroscience have transformed debate over whether mental illness is biological or behavioral to an understanding that all behavior is biological and that this biology arises from genes, environments, and their interactions. Basic concepts in psychiatric genetics inform our current understanding of the biological basis of behavioral disorders and ongoing efforts to identify improved approaches to treatment. A glossary of common genetics terms is provided in Table 38–1.

Your session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
 
Username
Password
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

FIGURE 38–1. Basic structure of nucleic acids.Nucleotides are three-part structures composed of a nitrogen-containing base, a five-carbon sugar, and a phosphate group. Chains of nucleic acid are formed by phosphate bonds between the 5' and 3' carbons of alternating nucleotide sugar molecules.

FIGURE 38–2. Chromosome structure.During cell division, chromosomal material becomes tightly compacted and individual chromosomes become visible as four-armed structures joined at a common centromere. Between cell divisions, chromosomal material is dispersed within the nucleus in a seemingly disorganized mass of DNA and protein.

FIGURE 38–3. Mitosis and meiosis.In mitosis, somatic cells proceed through stages of prophase, metaphase, anaphase, and telophase resulting in two identical daughter cells. In meiosis, germ cells initially follow the same stages of division resulting in two identical daughter cells, followed by a second meiotic division, during which stages of prophase, metaphase, anaphase, and telophase are repeated but result in four haploid germ cells.

FIGURE 38–4. Crossing over and recombination.During prophase of the first meiotic division, homologous arms of chromosome pairs become intertwined, in a process known as crossing over, and can undergo recombination, or exchange of DNA segments. Recombination serves to increase the genetic variability within chromosomes prior to segregation of homologous pairs into separate haploid daughter cells.

FIGURE 38–5. A "typical" gene and steps in polypeptide synthesis.DNA transcription is initiated at the 5' end of the gene and proceeds in a 3' direction, beginning at the promoter region. Transcribed precursor mRNA undergoes subsequent modifications into mature RNA prior to release in the cytoplasm where it serves to translate cell proteins.
Table Reference Number
TABLE 38–1. Glossary of common genetics terms

References

Arranz MJ, Munro J, Birkett J, et al: Pharmacogenetic prediction of clozapine response. Lancet 355:1615–1616, 2000
[PubMed]
 
Asherson P, Curran S: Approaches to gene mapping in complex disorder and their application in child psychiatry and psychology. Br J Psychiatry 179:122–128, 2001
[PubMed]
 
Bartels M, van Beijsterveldt CE, Derks EM, et al: a longitudinal multiple informant study of problem behavior. Twin Res Hum Genet 10:3–11, 2007
[PubMed]
 
Brooks KJ, Mill J, Guindalini C, et al: A common haplotype of the dopamine transporter gene associated with attention-deficit/hyperactivity disorder and interacting with maternal use of alcohol during pregnancy. Arch Gen Psychiatry 63:74–81, 2005
 
Caspi A, Moffitt TE: Gene-environment interactions in psychiatry: joining forces with neuroscience. Nat Rev Genet 7:583–590, 2006
[PubMed]
 
Caspi A, McClay J, Moffit TE, et al: Role of genotype in the cycle of violence in maltreated children. Science 297:851–854, 2002
[PubMed]
 
Caspi A, Sugden, Moffit TE, et al: Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389, 2003
[PubMed]
 
Cassidy SB, Dykens E, Williams CA: Prader-Willi and Angelman syndromes: sister imprinted disorders. Am J Med Genet 97:136–146, 2000
[PubMed]
 
Craddock N, O'Donovan MC, Owen MF: The genetics of schizophrenia and bipolar disorder: dissecting psychosis. J Med Genet 42:193–204, 2005
[PubMed]
 
Dean M: Approaches to identify genes for complex human diseases: lessons from Mendelian disorders. Hum Mutat 22:261–274, 2003
[PubMed]
 
DeChiara TM, Robertson EJ, Efstratiadis A: Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64:849–859, 1991
[PubMed]
 
Falconer DS: The inheritance of liability to certain diseases estimated from the incidence among relatives. Ann Hum Genet 29:51–76, 1965
 
Faraone SV, Perlis RH, Doyle AE, et al: Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 57:1313–1323, 2005
[PubMed]
 
Fergusson-Smith AC, Surani MA: Imprinting and the epigenetic asymmetry between parental genomes. Science 293:1086–1089, 2001
 
Finn CT, Smoller JW: Genetic counseling in psychiatry. Harv Rev Psychiatry 14:109–121, 2006
[PubMed]
 
Gottesman II, Gould TD: The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160:636–645, 2003
[PubMed]
 
Grisel JE: Quantitative trait locus analysis. Alcohol Res Health 24:169–174, 2000
[PubMed]
 
Hariri AR, Weinberger DR: Imaging genomics. Br Med Bull 65:259–270, 2003
[PubMed]
 
International HapMap Consortium: The International HapMap Project. Nature 426:789–796, 2003
 
Kahn RS, Khoury J, Nichols WC, et al: Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive-impulsive, inattentive, and oppositional behaviors. J Pediatr 143:104–110, 2003
[PubMed]
 
Kendler KS: Psychiatric genetics: a methodologic critique. Am J Psychiatry 162:3–11, 2005
[PubMed]
 
Kendler KS: Reflections on the relationship between psychiatric genetics and psychiatric nosology. Am J Psychiatry 163:1138–1146, 2006
[PubMed]
 
Lander E, Kruglyak L: Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 11:241–247, 1995
[PubMed]
 
Liddell MB, Williams J, Owen MJ: The dementias, in Psychiatric Genetics and Genomics. Edited by McGuffin P, Owen MJ, Gottesman II. New York, Oxford University Press, 2002, pp 341–397
 
Lin S, Chakravarti A, Cutler DJ: Exhaustive allelic transmission disequilibrium tests as a new approach to genome-wide association studies. Nat Genet 36:1181–1188, 2004
[PubMed]
 
McGough JJ: Attention-deficit/hyperactivity disorder pharmacogenomics. Bio Psychiatry 57:1367–1373, 2005
[PubMed]
 
McGough JJ, McCracken JT, Swanson J, et al: Pharmacogenetics of methylphenidate response in preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry 45:1314–1322, 2006
[PubMed]
 
McGuffin P, Southwick L: Fifty years of the double helix and its impact on psychiatry. Aust N Z J Psychiatry 37:657–661, 2003
[PubMed]
 
Moffit TE, Caspi A, Rutter M: Strategy for investigating interactions between measured genes and measured environments. Arch Gen Psychiatry 62:473–481, 2005
 
Muthen B, Asparouhov T, Rebollo I: Advances in behavioral genetics modeling using Mplus: applications of factor mixture modeling to twin data. Twin Res Hum Genet 9:313–324, 2006
[PubMed]
 
Neuman RJ, Lobos E, Reich W, et al: Prenatal smoking exposure and dopaminergic genes interact to cause a severe ADHD subtype. Biol Psychiatry 61:1320–1328, 2007
[PubMed]
 
Owen MJ, McGuffin P, Gottesman I: The future of postgenomic psychiatry, in Psychiatric Genetics and Genomics. Edited by McGuffin P, Owen MJ, Gottesman II. New York, Oxford University Press, 2002, pp 463–480
 
Pauls D: Genetics of childhood disorders, IV: linkage analysis. J Am Acad Child Adolesc Psychiatry 38:932–934, 1999
[PubMed]
 
Prathikanti S, Weinberger DR: Psychiatric genetics—the new era: genetic research and some clinical implications. Br Med Bull 73:102–122, 2005
 
Reik W, Lewis A: Co-evolution of X-chromosome inactivation and imprinting in mammals. Nat Rev Genet 6:403–410, 2005
[PubMed]
 
Reik W, Walter J: Genomic imprinting: parental influence on the genome. Nat Rev Genet 2:21–32, 2001
[PubMed]
 
Riordan JR, Rommens JM, Kerem B, et al: Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245:1066–1073, 1989
[PubMed]
 
Risch N: Searching for genetic determinants in the new millennium. Nature 405:847–856, 2000
[PubMed]
 
Risch N, Merikangas K: The future of genetic studies of complex human diseases. Science 273:1516–1589, 1996
[PubMed]
 
Roses AD: From genes to mechanisms to therapies: lessons to be learned from neurological disorders. Nature Med 2:267–269, 1996
[PubMed]
 
Schanen NC, Dahle EJ, Capozzoli F, et al: A new Rett syndrome family consistent with X-linked inheritance expands the X chromosome map. Am J Hum Genet 61:634–641, 1997
[PubMed]
 
Serretti A, Zanardi R, Rossini D, et al: Influence of tryptophan hydroxylase and serotonin transporter genes on fluvoxamine antidepressant activity. Mol Psychiatry 6:586–592, 2001
[PubMed]
 
Speilman RS, Ewens WJ: The TDT and other family-based tests for linkage disequilibrium and association. Am J Hum Genet 59:983–989, 1996
 
Stein LD: Human genome: end of the beginning. Nature 431:915–916, 2004
[PubMed]
 
Thapar A, Langley K, Fowler T, et al: Catechol-O-methyltransferase gene variant and birth weight predict early-onset antisocial behavior in children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry 62:1275–1278, 2005
[PubMed]
 
Wellcome Trust Case Control Consortium: Genome-wide association study of 14,000 cases of even common diseases and 3,000 shared controls. Nature 447:661–678, 2007
 
Xie HG, Kim RB, Wood AJ, et al: Molecular basis of ethnic differences in drug disposition and response. Annu Rev Pharmacol Toxicol 41:815–850, 2001
[PubMed]
 
+

CME Activity

Add a subscription to complete this activity and earn CME credit.
Sample questions:
1.
How frequently do DNA mutations occur in every replication cycle?
2.
Nonharmful changes in DNA can be passed on to subsequent generations. Mutations may or may not have effects on functioning. Which of the following describes a mutation that occurs in more than 1% of the population?
3.
Which of the following statements regarding chromosomes is false?
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Related Content
Articles
Books
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 6.  >
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 36.  >
The American Psychiatric Publishing Textbook of Geriatric Psychiatry, 4th Edition > Chapter 6.  >
The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th Edition > Chapter 2.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 3.  >
Topic Collections
Psychiatric News
Read more at Psychiatric News >>
PubMed Articles
 
  • Print
  • PDF
  • E-mail
  • Chapter Alerts
  • Get Citation