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Can neuroscience be integrated into the DSM-V?


To date, the diagnosis of mental disorders has been based on clinical observation, specifically: the identification of symptoms that tend to cluster together, the timing of the symptoms' appearance, and their tendency to resolve, recur or become chronic. The Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Disease, the manuals that specify these diagnoses and the criteria for making them, are currently undergoing revision. It is thus timely to ask whether neuroscience has progressed to the point that the next editions of these manuals can usefully incorporate information about brain structure and function.

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  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (American Psychiatric Association, Washington D.C., 2000)

  2. The ICD-10 Classification of Mental and Behavioural Disorders (World Health Organization, Geneva, 1992).

  3. Mayberg, H. S. et al. Deep brain stimulation for treatment-resistant depression. Neuron 45, 651–660 (2005).

    CAS  Article  Google Scholar 

  4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Third edition (American Psychiatric Association, Washington D. C., 1980).

  5. Robins, E. & Guze, S. B. Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia. Am. J. Psychiatry 126, 983–987 (1970).

    CAS  Article  Google Scholar 

  6. Pope, H. G. Jr & Lipinski, J. F. Jr. Diagnosis in schizophrenia and manic-depressive illness: a reassessment of the specificity of 'schizophrenic' symptoms in the light of current research. Arch. Gen. Psychiatry 35, 811–828 (1978).

    Article  Google Scholar 

  7. Kendel, R. E. Clinical validity. Psychol. Med. 19, 45–55 (1989).

    Article  Google Scholar 

  8. Kendler, K. S. & Gardner, C. O. Jr. Boundaries of major depression: an evaluation of DSM-IV criteria. Am. J. Psychiatry 155, 172–177 (1998).

    CAS  PubMed  Google Scholar 

  9. Meehl, P. E. Schizotaxia revisited. Arch. Gen. Psychiatry 46, 935–944 (1989).

    CAS  Article  Google Scholar 

  10. Fanous, A., Gardner, C., Walsh, D. & Kendler, K. S. Relationship between positive and negative symptoms of schizophrenia and schizotypal symptoms in nonpsychotic relatives. Arch. Gen. Psychiatry 58, 669–673 (2001).

    CAS  Article  Google Scholar 

  11. Tsuang, M. T., Stone, W. S., Tarbox, S. I. & Faraone, S. V. in Advancing DSM: Dilemmas in Psychiatric Diagnosis (eds Phillips, K. A., First, M. B. & Pincus, H. A.) 105–128 (American Psychiatric Association, Washington D. C., 2003).

    Google Scholar 

  12. Hoekstra, R. A., Bartels, M., Verweij, C. J. & Boomsma, D. I. Heritability of autistic traits in the general population. Arch. Pediatr. Adolesc. Med. 161, 372–377 (2007).

    Article  Google Scholar 

  13. Widiger, T. A. & Costa, P. T. Jr. Personality and personality disorders. J. Abnorm. Psychol. 103, 78–91 (1994).

    CAS  Article  Google Scholar 

  14. Fairburn, C. G. & Bohn, K. Eating disorder NOS (EDNOS): an example of the troublesome “not otherwise specified” (NOS) category in DSM-IV. Behav. Res. Ther. 43, 691–701 (2005).

    Article  Google Scholar 

  15. de Bruin, E. I., Ferdinand, R. F., Meester, S., de Nijs, P. F. & Verheij, F. High rates of psychiatric co-morbidity in PDD-NOS. J. Autism Dev. Disord. 37, 877–886 (2007).

    Article  Google Scholar 

  16. Goldstein, S. & Schwebach, A. J. The comorbidity of pervasive developmental disorder and attention deficit hyperactivity disorder: results of a retrospective chart review. J. Autism Dev. Disord. 34, 329–339 (2004).

    Article  Google Scholar 

  17. Reiersen, A. M., Constantino, J. N., Volk, H. E. & Todd, R. D. Autistic traits in a population-based ADHD twin sample. J. Child Psychol. Psychiatry 48, 464–472 (2007).

    Article  Google Scholar 

  18. Kessler, R. C., Chiu, W. T., Demler, O., Merikangas, K. R. & Walters, E. E. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch. Gen. Psychiatry 62, 617–627 (2005).

    Article  Google Scholar 

  19. Weiss, R. D. et al. Substance use and perceived symptom improvement among patients with bipolar disorder and substance dependence. J. Affect. Disord. 79, 279–283 (2004).

    Article  Google Scholar 

  20. Kendler, K. S., Neale, M. C., Kessler, R. C., Heath, A. C. & Eaves, L. J. Major depression and generalized anxiety disorder. Same genes, (partly) different environments? Arch. Gen. Psychiatry. 49, 716–722 (1992).

    CAS  Article  Google Scholar 

  21. Skodol, A. E. et al. The borderline diagnosis I: psychopathology, comorbidity, and personality structure. Biol. Psychiatry 51, 936–950 (2002).

    Article  Google Scholar 

  22. Craddock, N., O'Donovan, M. C. & Owen, M. J. The genetics of schizophrenia and bipolar disorder: dissecting psychosis. J. Med. Genet. 42, 193–204 (2005).

    CAS  Article  Google Scholar 

  23. Happe, F., Ronald, A. & Plomin, R. Time to give up on a single explanation for autism. Nature Neurosci. 9, 1218–1220 (2006).

    CAS  Article  Google Scholar 

  24. Florez, J. C., Hirschhorn, J. & Altshuler, D. The inherited basis of diabetes mellitus: implications for the genetic analysis of complex traits. Annu. Rev. Genomics Hum. Genet. 4, 257–291 (2003).

    CAS  Article  Google Scholar 

  25. Paez, J. G. et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304, 1497–1500 (2004).

    CAS  Article  Google Scholar 

  26. Binder, E. B. et al. Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nature Genet. 36, 1319–1325 (2004).

    CAS  Article  Google Scholar 

  27. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth edition (American Psychiatric Association, Washington D.C., 1994).

  28. Kendler, K. S., Gatz, M., Gardner, C. O. & Pedersen, N. L. A Swedish national twin study of lifetime major depression. Am. J. Psychiatry 163, 109–114 (2006).

    Article  Google Scholar 

  29. Freitag, C. M. The genetics of autistic disorders and its clinical relevance: a review of the literature. Mol. Psychiatry 12, 2–22 (2007).

    CAS  Article  Google Scholar 

  30. Kety, S. S., Rosenthal, D., Wender, P. H. & Schulsinger, F. Mental illness in the biological and adoptive families of adopted schizophrenics. Am. J. Psychiatry 128, 302–306 (1971).

    CAS  Article  Google Scholar 

  31. Kendler, K. S., Gruenberg, A. M. & Strauss, J. S. An independent analysis of the Copenhagen sample of the Danish Adoption Study of schizophrenia. III. The relationship between paranoid psychosis (delusional disorder) and the schizophrenia spectrum disorders. Arch. Gen. Psychiatry 38, 985–987 (1981).

    CAS  Article  Google Scholar 

  32. Sigvardsson, S., Bohman, M. & Cloninger, C. R. Replication of the Stockholm Adoption Study of alcoholism. Confirmatory cross-fostering analysis. Arch. Gen. Psychiatry 53, 681–687 (1996).

    CAS  Article  Google Scholar 

  33. Merikangas, K. R. & Risch, N. Will the genomics revolution revolutionize psychiatry? Am. J. Psychiatry 160, 625–635 (2003).

    Article  Google Scholar 

  34. Botstein, D. & Risch, N. Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease. Nature Genet. 33 (Suppl.), 228–237 (2003).

    CAS  Article  Google Scholar 

  35. Daiger, S. P., Bowne, S. J. & Sullivan, L. S. Perspective on genes and mutations causing retinitis pigmentosa. Arch. Ophthalmol. 125, 151–158 (2007).

    CAS  Article  Google Scholar 

  36. McClellan, J. M., Susser, E. & King, M. C. Maternal famine, de novo mutations, and schizophrenia. JAMA 296, 582–584 (2006).

    CAS  Article  Google Scholar 

  37. Kendler, K. S., Davis, C. G. & Kessler, R. C. The familial aggregation of common psychiatric and substance use disorders in the National Comorbidity Survey: a family history study. Br. J. Psychiatry 170, 541–548 (1997).

    CAS  Article  Google Scholar 

  38. Stefansson, H. et al. Neuregulin 1 and susceptibility to schizophrenia. Am. J. Hum. Genet. 71, 877–892 (2002).

    Article  Google Scholar 

  39. Levinson, D. F. The genetics of depression: a review. Biol. Psychiatry 60, 84–92 (2006).

    CAS  Article  Google Scholar 

  40. 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  Article  Google Scholar 

  41. 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  Article  Google Scholar 

  42. 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  Article  Google Scholar 

  43. 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  Article  Google Scholar 

  44. Cardon, L. R. Genetics. Delivering new disease genes. Science 314, 1403–1405 (2006).

    CAS  Article  Google Scholar 

  45. Sladek, R. et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445, 881–885 (2007).

    CAS  Article  Google Scholar 

  46. Cannon, T. D. et al. Cortex mapping reveals regionally specific patterns of genetic and disease-specific gray-matter deficits in twins discordant for schizophrenia. Proc. Natl Acad. Sci. USA 99, 3228–3233 (2002).

    CAS  Article  Google Scholar 

  47. Thompson, P. M. et al. Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia. Proc. Natl Acad. Sci. USA 98, 11650–11655 (2001).

    CAS  Article  Google Scholar 

  48. Drevets, W. C. Functional neuroimaging studies of depression: the anatomy of melancholia. Annu. Rev. Med. 49, 341–361 (1998).

    CAS  Article  Google Scholar 

  49. Mayberg, H. S. et al. Cingulate function in depression: a potential predictor of treatment response. Neuroreport 8, 1057–1061 (1997).

    CAS  Article  Google Scholar 

  50. 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  Google Scholar 

  51. Faraone, S. V. et al. Diagnostic accuracy and linkage analysis: how useful are schizophrenia spectrum phenotypes? Am. J. Psychiatry 152, 1286–1290 (1995).

    CAS  Article  Google Scholar 

  52. Phillips, K. A., Price, L. H., Greenberg, B. D. & Rasmussen, S. A. in Advancing DSM: Dilemmas in Psychiatric Diagnosis (eds Phillips, K. A., First, M. B. & Pincus, H. A.) 57–84. (American Psychiatric Association, Washington D. C., 2003).

    Google Scholar 

  53. Cannon, T. D. et al. The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia. Am. J. Hum. Genet. 67, 369–382 (2000).

    CAS  Article  Google Scholar 

  54. Brahmbhatt, S. B., Haut, K., Csernansky, J. G. & Barch, D. M. Neural correlates of verbal and nonverbal working memory deficits in individuals with schizophrenia and their high-risk siblings. Schizophr. Res. 87, 191–204 (2006).

    Article  Google Scholar 

  55. Niendam, T. A. et al. A prospective study of childhood neurocognitive functioning in schizophrenic patients and their siblings. Am. J. Psychiatry 160, 2060–2062 (2003).

    Article  Google Scholar 

  56. Tan, H. Y. et al. Dysfunctional prefrontal regional specialization and compensation in schizophrenia. Am. J. Psychiatry 163, 1969–1977 (2006).

    Article  Google Scholar 

  57. Barch, D. M. et al. Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia. Arch. Gen. Psychiatry 58, 280–288 (2001).

    CAS  Article  Google Scholar 

  58. 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  Article  Google Scholar 

  59. Hyman, S. E. & Fenton, W. S. Medicine. What are the right targets for psychopharmacology? Science 299, 350–351 (2003).

    CAS  Article  Google Scholar 

  60. Etkin, A. et al. Individual differences in trait anxiety predict the response of the basolateral amygdala to unconsciously processed fearful faces. Neuron 44, 1043–1055 (2004).

    CAS  Article  Google Scholar 

  61. Shin, L. M. et al. A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. Arch. Gen. Psychiatry 62, 273–281 (2005).

    Article  Google Scholar 

  62. Phelps, E. A. & LeDoux, J. E. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 48, 175–178 (2005).

    CAS  Article  Google Scholar 

  63. Grob, G. N. Origins of DSM-I: a study in appearance and reality. Am. J. Psychiatry 148, 421–431 (1991).

    CAS  Article  Google Scholar 

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I gratefully acknowledge the probing discussions of my colleagues, whose ideas on this Opinion have tested and shaped my own thoughts over the past year. I would like to assert that this work represents my personal viewpoint, not an official position of the DSM-V Task Force, of which I am a member, or of the International Advisory Group to the World Health Organization for the Revision of ICD-10, Chapter V (Mental and Behavioral Disorders), of which I am the Chair.

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Steven E. Hyman has consulted for GlaxoSmithKline during the past year and is a member of the Novartis Scientific Advisory Board.

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An inability to experience pleasure.

Candidate gene

A gene implicated as one that confers an increased phenotypic risk, and which is thus deserving of further investigation (for example, in an association study). Candidate genes can be identified based on biological hypotheses, or as a result of their lying within a region of interest identified by a linkage study or a chromosomal break point (a so-called 'positional candidate').

Categorical diagnosis

A disease state that is qualitatively separable from the state of being 'well', for example, tuberculosis or leukaemia.

Diagnostic classification

A listing of diagnoses clustered by relatedness, for example, cancers, metabolic diseases, infectious diseases and unintentional injuries. The ICD was first developed to allow statistical reporting across countries, initially of mortality and later of morbidity.

Diagnostic criteria

The rules for making diagnoses. The DSM-IV and the ICD-10 (Chapter V) provide both classifications and diagnostic criteria.

Dimensional diagnosis

A diagnosis based on states that are defined as above-threshold on one or more quantitative scales or dimensions and that are continuous with the normal state. For example, hypertension is defined in terms of two dimensions: systolic and diastolic blood pressure.


A term generally used instead of the term 'disease' for medical conditions in which the causative factors or pathophysiology remain unknown.


The classification of diseases.


A diagnosis is reliable if the same conclusion is reached by two diagnosticians who examine the patient at approximately the same time (inter-rater reliability), or if a patient receives the same diagnosis if examined more than once within reasonably close time intervals (test-retest reliability).

Single nucleotide polymorphism

(SNP). The most common form of variation in human DNA sequences. It occurs when a single nucleotide (for example, thymine) replaces one of the other three nucleotides (for example, cytosine).

Spectrum disorders

A group of disorders that are thought to be related through the sharing of risk genes or pathophysiological mechanisms.


A cluster of symptoms that can result from different disease processes. For example, cough and fever can result from bacterial, viral or fungal infections, or from autoimmunity, with very different treatments and outcomes.

Valid diagnosis

A diagnosis that picks out a real entity based on aetiology or pathophysiology.


The extent to which a variable measures what it is intended to measure.

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Hyman, S. Can neuroscience be integrated into the DSM-V?. Nat Rev Neurosci 8, 725–732 (2007).

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