Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Intermediate phenotypes and genetic mechanisms of psychiatric disorders

Nature Reviews Neuroscience volume 7, pages 818–827 (2006)Cite this article

Abstract

Genes are major contributors to many psychiatric diseases, but their mechanisms of action have long seemed elusive. The intermediate phenotype concept represents a strategy for characterizing the neural systems affected by risk gene variants to elucidate quantitative, mechanistic aspects of brain function implicated in psychiatric disease. Using imaging genetics as an example, we illustrate recent advances, challenges and implications of linking genes to structural and functional variation in brain systems related to cognition and emotion.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The complex path from genes to behavioural and disease phenotype: mediation through brain circuitry.
Figure 2: Intermediate phenotypes as tools for gene discovery versus neural mechanism characterization.
Figure 3: COMT Val(108/158)Met polymorphism and its effect on prefrontal function.
Figure 4: Effects of COMT Val(108/158)Met on prefrontal cortex activity linked to extracellular dopamine.
Figure 5: Effects of COMT Val(108/158)Met on midbrain–prefrontal interactions and 22q11.2 syndrome.

Similar content being viewed by others

References

  1. Sullivan, P. F., Kendler, K. S. & Neale, M. C. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch. Gen. Psychiatry 60, 1187–1192 (2003).

    PubMed  Google Scholar 

  2. Sullivan, P. F., Neale, M. C. & Kendler, K. S. Genetic epidemiology of major depression: review and meta-analysis. Am. J. Psychiatry 157, 1552–1562 (2000).

    CAS  PubMed  Google Scholar 

  3. Weinberger, D. R. et al. Prefrontal neurons and the genetics of schizophrenia. Biol. Psychiatry 50, 825–844 (2001).

    CAS  PubMed  Google Scholar 

  4. Meyer-Lindenberg, A. et al. Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype. Nature Neurosci. 8, 594–596 (2005).

    CAS  PubMed  Google Scholar 

  5. Meyer-Lindenberg, A. et al. Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. Nature Neurosci. 5, 267–271 (2002).

    CAS  PubMed  Google Scholar 

  6. Pezawas, L. et al. 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression. Nature Neurosci. 8, 828–834 (2005).

    CAS  PubMed  Google Scholar 

  7. Waldman, I. D. Statistical approaches to complex phenotypes: evaluating neuropsychological endophenotypes for attention-deficit/hyperactivity disorder. Biol. Psychiatry 57, 1347–1356 (2005).

    PubMed  Google Scholar 

  8. Goldman, D., Oroszi, G. & Ducci, F. The genetics of addictions: uncovering the genes. Nature Rev. Genet. 6, 521–532 (2005).

    CAS  PubMed  Google Scholar 

  9. Belmonte, M. K. et al. Autism as a disorder of neural information processing: directions for research and targets for therapy. Mol. Psychiatry 9, 646–663 (2004).

    CAS  PubMed  Google Scholar 

  10. Riley, B. P. & McGuffin, P. Linkage and associated studies of schizophrenia. Am. J. Med. Genet. 97, 23–44 (2000).

    CAS  PubMed  Google Scholar 

  11. Menzel, S. Genetic and molecular analyses of complex metabolic disorders: genetic linkage. Ann. NY Acad. Sci. 967, 249–257 (2002).

    CAS  PubMed  Google Scholar 

  12. Harrison, P. J. & Weinberger, D. R. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol. Psychiatry 10, 40–68 (2005).

    CAS  PubMed  Google Scholar 

  13. Risch, N. Genetic linkage and complex diseases, with special reference to psychiatric disorders. Genet. Epidemiol. 7, 3–16; discussion 17–45 (1990).

    Google Scholar 

  14. Gottesman, I. I. & Shields, J. A polygenic theory of schizophrenia. Proc. Natl Acad. Sci. USA 58, 199–205 (1967).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Page, G. P., George, V., Go, R. C., Page, P. Z. & Allison, D. B. 'Are we there yet?': Deciding when one has demonstrated specific genetic causation in complex diseases and quantitative traits. Am. J. Hum. Genet. 73, 711–719 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Deschepper, C. F., Boutin-Ganache, I., Zahabi, A. & Jiang, Z. In search of cardiovascular candidate genes: interactions between phenotypes and genotypes. Hypertension 39, 332–336 (2002).

    CAS  PubMed  Google Scholar 

  17. Gottesman, I. I. & Gould, T. D. The endophenotype concept in psychiatry: etymology and strategic intentions. Am. J. Psychiatry 160, 636–645 (2003).

    PubMed  Google Scholar 

  18. Almasy, L. & Blangero, J. Endophenotypes as quantitative risk factors for psychiatric disease: rationale and study design. Am. J. Med. Genet. 105, 42–44 (2001).

    CAS  PubMed  Google Scholar 

  19. Weinberger, D. R. Schizophrenia: new phenes and new genes. Biol. Psychiatry 46, 3–7 (1999).

    CAS  PubMed  Google Scholar 

  20. Alexander, G. E., DeLong, M. R. & Strick, P. L. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu. Rev. Neurosci. 9, 357–381 (1986).

    CAS  PubMed  Google Scholar 

  21. Goldman-Rakic, P. S., Selemon, L. D. & Schwartz, M. L. Dual pathways connecting the dorsolateral prefrontal cortex with the hippocampal formation and parahippocampal cortex in the rhesus monkey. Neuroscience 12, 719–743 (1984).

    CAS  PubMed  Google Scholar 

  22. Friston, K. J. The disconnection hypothesis. Schizophr. Res. 30, 115–125 (1998).

    CAS  PubMed  Google Scholar 

  23. Meyer-Lindenberg, A. S. et al. Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia. Arch. Gen. Psychiatry 62, 379–386 (2005).

    PubMed  Google Scholar 

  24. Dunnett, S. B., Meldrum, A. & Muir, J. L. Frontal-striatal disconnection disrupts cognitive performance of the frontal-type in the rat. Neuroscience 135, 1055–1065 (2005).

    CAS  PubMed  Google Scholar 

  25. Pantelis, C. et al. Frontal-striatal cognitive deficits in patients with chronic schizophrenia. Brain 120, 1823–1843 (1997).

    PubMed  Google Scholar 

  26. Swerdlow, N. R., Geyer, M. A. & Braff, D. L. Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology (Berl.) 156, 194–215 (2001).

    CAS  Google Scholar 

  27. Carlsson, A. A paradigm shift in brain research. Science 294, 1021–1024 (2001).

    CAS  PubMed  Google Scholar 

  28. Jaskiw, G. E., Karoum, F. K. & Weinberger, D. R. Persistent elevations in dopamine and its metabolites in the nucleus accumbens after mild subchronic stress in rats with ibotenic acid lesions of the medial prefrontal cortex. Brain Res. 534, 321–323 (1990).

    CAS  PubMed  Google Scholar 

  29. Williams, G. V. & Goldman-Rakic, P. S. Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature 376, 572–575 (1995).

    CAS  PubMed  Google Scholar 

  30. Schultz, W. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80, 1–27 (1998).

    CAS  PubMed  Google Scholar 

  31. Squire, L. R., Stark, C. E. & Clark, R. E. The medial temporal lobe. Annu. Rev. Neurosci. 27, 279–306 (2004).

    CAS  PubMed  Google Scholar 

  32. Harrison, P. J. & Eastwood, S. L. Neuropathological studies of synaptic connectivity in the hippocampal formation in schizophrenia. Hippocampus 11, 508–519 (2001).

    CAS  PubMed  Google Scholar 

  33. Heckers, S. Neuroimaging studies of the hippocampus in schizophrenia. Hippocampus 11, 520–528 (2001).

    CAS  PubMed  Google Scholar 

  34. Heckers, S. et al. Impaired recruitment of the hippocampus during conscious recollection in schizophrenia. Nature Neurosci. 1, 318–323 (1998).

    CAS  PubMed  Google Scholar 

  35. Simons, J. S. & Spiers, H. J. Prefrontal and medial temporal lobe interactions in long-term memory. Nature Rev. Neurosci. 4, 637–648 (2003).

    CAS  Google Scholar 

  36. Phillips, M. L., Drevets, W. C., Rauch, S. L. & Lane, R. Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biol. Psychiatry 54, 504–514 (2003).

    PubMed  Google Scholar 

  37. Weinberger, D. R., Berman, K. F., Suddath, R. & Torrey, E. F. Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins. Am. J. Psychiatry 149, 890–897 (1992).

    CAS  PubMed  Google Scholar 

  38. Bertolino, A. et al. Altered development of prefrontal neurons in rhesus monkeys with neonatal mesial temporo-limbic lesions: a proton magnetic resonance spectroscopic imaging study. Cereb. Cortex 7, 740–748 (1997).

    CAS  PubMed  Google Scholar 

  39. Weinberger, D. R. Implications of normal brain development for the pathogenesis of schizophrenia. Arch. Gen. Psychiatry 44, 660–669 (1987).

    CAS  PubMed  Google Scholar 

  40. Lewis, D. A. et al. Dopamine transporter immunoreactivity in monkey cerebral cortex: regional, laminar, and ultrastructural localization. J. Comp. Neurol. 432, 119–136 (2001).

    CAS  PubMed  Google Scholar 

  41. Tunbridge, E. M., Bannerman, D. M., Sharp, T. & Harrison, P. J. Catechol-o-methyltransferase inhibition improves set-shifting performance and elevates stimulated dopamine release in the rat prefrontal cortex. J. Neurosci. 24, 5331–5335 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Tunbridge, E. M., Harrison, P. J. & Weinberger, D. R. Catechol-O-methyltransferase, cognition, and psychosis: Val158Met and beyond. Biol. Psychiatry 60, 141–151 (2006).

    CAS  PubMed  Google Scholar 

  43. Owen, M. J., Williams, N. M. & O'Donovan, M. C. The molecular genetics of schizophrenia: new findings promise new insights. Mol. Psychiatry 9, 14–27 (2004).

    CAS  PubMed  Google Scholar 

  44. Murphy, K. C. Schizophrenia and velo-cardio-facial syndrome. Lancet 359, 426–430 (2002).

    PubMed  Google Scholar 

  45. Chen, J. et al. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am. J. Hum. Genet. 75, 807–821 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Egan, M. F. et al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc. Natl Acad. Sci. USA 98, 6917–6922 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Goldberg, T. E. et al. Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Arch. Gen. Psychiatry 60, 889–896 (2003).

    CAS  PubMed  Google Scholar 

  48. Mattay, V. S. et al. Catechol O-methyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc. Natl Acad. Sci. USA 100, 6186–6191 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Akil, M. et al. Catechol-O-methyltransferase genotype and dopamine regulation in the human brain. J. Neurosci. 23, 2008–2013 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Callicott, J. H. et al. Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc. Natl Acad. Sci. USA 102, 8627–8632 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Gothelf, D. et al. COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome. Nature Neurosci. 8, 1500–1502 (2005).

    CAS  PubMed  Google Scholar 

  52. Craddock, N., Owen, M. J. & O'Donovan, M. C. The catechol-O-methyl transferase (COMT) gene as a candidate for psychiatric phenotypes: evidence and lessons. Mol. Psychiatry 11, 446–458 (2006).

    CAS  PubMed  Google Scholar 

  53. Fan, J. B. et al. Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis. Biol. Psychiatry 57, 139–144 (2005).

    CAS  PubMed  Google Scholar 

  54. Munafo, M. R., Bowes, L., Clark, T. G. & Flint, J. Lack of association of the COMT (Val158/108 Met) gene and schizophrenia: a meta-analysis of case-control studies. Mol. Psychiatry 10, 765–770 (2005).

    CAS  PubMed  Google Scholar 

  55. Schott, B. H. et al. The dopaminergic midbrain participates in human episodic memory formation: evidence from genetic imaging. J. Neurosci. 26, 1407–1417 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Cohen, M. X., Young, J., Baek, J. M., Kessler, C. & Ranganath, C. Individual differences in extraversion and dopamine genetics predict neural reward responses. Brain Res. Cogn Brain Res. 25, 851–861 (2005).

    CAS  PubMed  Google Scholar 

  57. Egan, M. F. et al. Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. Proc. Natl Acad. Sci. USA 101, 12604–12609 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. de Quervain, D. J. & Papassotiropoulos, A. Identification of a genetic cluster influencing memory performance and hippocampal activity in humans. Proc. Natl Acad. Sci. USA 103, 4270–4274 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Callicott, J. H. et al. Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. Am. J. Psychiatry 160, 709–719 (2003).

    PubMed  Google Scholar 

  60. Cannon, T. D. et al. Association of DISC1/TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory. Arch. Gen. Psychiatry 62, 1205–1213 (2005).

    CAS  PubMed  Google Scholar 

  61. Bertolino, A. et al. Prefrontal-hippocampal coupling during declarative memory is modulated by COMT Val158Met genotype. Biol. Psychiatry 4 Sept 2006 (doi: 10.1016/j.biopsych.2006.03.078).

  62. Shifman, S. et al. A highly significant association between a COMT haplotype and schizophrenia. Am. J. Hum. Genet. 71, 1296–1302 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Bray, N. J. et al. A haplotype implicated in schizophrenia susceptibility is associated with reduced COMT expression in human brain. Am. J. Hum. Genet. 73, 152–161 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Palmatier, M. A. et al. COMT haplotypes suggest P2 promoter region relevance for schizophrenia. Mol. Psychiatry 9, 859–870 (2004).

    CAS  PubMed  Google Scholar 

  65. Meyer-Lindenberg, A. et al. Impact of complex genetic variation in COMT on human brain function. Mol. Psychiatry 20 June 2006 (doi: 10.1038/sj.mp.4001860).

  66. Diaz-Asper, C. M. Weinberger, D. R. & Goldberg, T. E. Catechol-O-methyltransferase polymorphisms and some implications for cognitive therapeutics. NeuroRX 3, 97–105 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Devlin, B., Roeder, K. & Wasserman, L. Genomic control, a new approach to genetic-based association studies. Theor. Popul. Biol. 60, 155–166 (2001).

    CAS  PubMed  Google Scholar 

  68. Laurienti, P. J., Burdette, J. H. & Maldjian, J. A. Separating neural processes using mixed event-related and epoch-based fMRI paradigms. J. Neurosci. Methods 131, 41–50 (2003).

    PubMed  Google Scholar 

  69. Friedman, L. & Glover, G. H. Report on a multicenter fMRI quality assurance protocol. J. Magn. Reson. Imaging 23, 827–839 (2006).

    PubMed  Google Scholar 

  70. Hariri, A. R. et al. Serotonin transporter genetic variation and the response of the human amygdala. Science 297, 400–403 (2002).

    CAS  PubMed  Google Scholar 

  71. Friston, K. J. et al. Classical and Bayesian inference in neuroimaging: theory. Neuroimage 16, 465–483 (2002).

    CAS  PubMed  Google Scholar 

  72. Manji, H. K., Drevets, W. C. & Charney, D. S. The cellular neurobiology of depression. Nature Med. 7, 541–547 (2001).

    CAS  PubMed  Google Scholar 

  73. Mayberg, H. S. Limbic-cortical dysregulation: a proposed model of depression. J. Neuropsychiatry Clin. Neurosci. 9, 471–481 (1997).

    CAS  PubMed  Google Scholar 

  74. Drevets, W. C. et al. Subgenual prefrontal cortex abnormalities in mood disorders. Nature 386, 824–827 (1997).

    CAS  PubMed  Google Scholar 

  75. Mayberg, H. S. et al. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am. J. Psychiatry 156, 675–682 (1999).

    CAS  PubMed  Google Scholar 

  76. Paus, T. Primate anterior cingulate cortex: where motor control, drive and cognition interface. Nature Rev. Neurosci. 2, 417–424 (2001).

    CAS  Google Scholar 

  77. Stefanacci, L. & Amaral, D. G. Some observations on cortical inputs to the macaque monkey amygdala: an anterograde tracing study. J. Comp. Neurol. 451, 301–323 (2002).

    PubMed  Google Scholar 

  78. Sotres-Bayon, F., Bush, D. E. & LeDoux, J. E. Emotional perseveration: an update on prefrontal-amygdala interactions in fear extinction. Learn. Mem. 11, 525–535 (2004).

    PubMed  Google Scholar 

  79. Nemeroff, C. B. & Owens, M. J. Treatment of mood disorders. Nature Neurosci. 5, S1068–S1070 (2002).

    Google Scholar 

  80. Lesch, K. P. et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527–1531 (1996).

    CAS  PubMed  Google Scholar 

  81. Caspi, A. et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386–389 (2003).

    CAS  PubMed  Google Scholar 

  82. Hariri, A. R. et al. A susceptibility gene for affective disorders and the response of the human amygdala. Arch. Gen. Psychiatry 62, 146–152 (2005).

    CAS  PubMed  Google Scholar 

  83. Heinz, A. et al. Amygdala-prefrontal coupling depends on a genetic variation of the serotonin transporter. Nature Neurosci. 8, 20–21 (2005).

    CAS  PubMed  Google Scholar 

  84. Brown, S. M. et al. A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity. Mol. Psychiatry 10, 884–888, 805 (2005).

    CAS  PubMed  Google Scholar 

  85. Canli, T., Congdon, E., Gutknecht, L., Constable, R. T. & Lesch, K. P. Amygdala responsiveness is modulated by tryptophan hydroxylase-2 gene variation. J. Neural Transm. 112, 1479–1485 (2005).

    CAS  PubMed  Google Scholar 

  86. Sabol, S. Z., Hu, S. & Hamer, D. A functional polymorphism in the monoamine oxidase A gene promoter. Hum. Genet. 103, 273–279 (1998).

    CAS  PubMed  Google Scholar 

  87. Caspi, A. et al. Role of genotype in the cycle of violence in maltreated children. Science 297, 851–854 (2002).

    CAS  PubMed  Google Scholar 

  88. Meyer-Lindenberg, A. et al. Neural mechanisms of genetic risk for impulsivity and violence in humans. Proc. Natl Acad. Sci. USA 103, 6269–6274 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Fan, J., Fossella, J., Sommer, T., Wu, Y. & Posner, M. I. Mapping the genetic variation of executive attention onto brain activity. Proc. Natl Acad. Sci. USA 100, 7406–7411 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Svenningsson, P. et al. DARPP-32: an integrator of neurotransmission. Annu. Rev. Pharmacol. Toxicol. 44, 269–296 (2004).

    CAS  PubMed  Google Scholar 

  91. Weinberger, D. R. et al. Variation in PPP1R1B predicts risk for schizophrenia, cognitive function, and gene expression in brain. Am. J. Med. Genet. B Neuropsychiatr. Genet. 138B, 139–140 (2005).

    Google Scholar 

  92. Meyer-Lindenberg, A. et al. Neural mechanisms of genetic risk for impulsivity and violence in humans. Proc. Natl Acad. Sci. USA 103, 6269–6274 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Freedman, R. et al. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc. Natl Acad. Sci. USA 94, 587–592 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Goldman-Rakic, P. S., Muly, E. C. & Williams, G. V. D1 receptors in prefrontal cells and circuits. Brain Res. Brain Res. Rev. 31, 295–301 (2000).

    CAS  PubMed  Google Scholar 

  95. Seamans, J. K., Gorelova, N., Durstewitz, D. & Yang, C. R. Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons. J. Neurosci. 21, 3628–3638 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Institute of Mental Health's Intramural Research Program. We thank C. Rainey for help with figure preparation.

Author information

Authors and Affiliations

  1. Department of Health and Human Services, Andreas Meyer-Lindenberg is at the Unit for Systems Neuroscience in Psychiatry, Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute for Mental Health, National Institutes of Health, 9000 Rockville Pike, Bethesda, 20892, Maryland, USA

    Andreas Meyer-Lindenberg

  2. Department of Health and Human Services, Daniel R. Weinberger is at the Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute for Mental Health, National Institutes of Health, 9000 Rockville Pike, Bethesda, 20892, Maryland, USA

    Daniel R. Weinberger

Authors
  1. Andreas Meyer-Lindenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel R. Weinberger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Andreas Meyer-Lindenberg or Daniel R. Weinberger.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

DATABASES

OMIM

22q11.2 syndrome

autism

attention deficit hyperactivity disorder

major depression

schizophrenia

FURTHER INFORMATION

Unit for Systems Neuroscience in Psychiatry

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meyer-Lindenberg, A., Weinberger, D. Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat Rev Neurosci 7, 818–827 (2006). https://doi.org/10.1038/nrn1993

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn1993

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing