Kürşat ALTINBAŞ, SERHAT TUNÇ, Menekşe SILA YAZAR, Serap ÖZÇETİNKAYA, Sinan GÜLÖKSÜZ, Esat Timuçin ORAL

Kraepelin bugün yaşasaydı dikotomi varlığını sürdürüyor olur muydu?

Emil Kraepelin’in psikiyatrik sınıflandırma sistemlerinin temelini oluşturan dikotomisi, uzun yıllardır geçerliliğini sürdürmektedir. Öte yandan, genetik, biyolojik ve klinik araştırmalardan elde edilen güncel kanıtlara dayanarak önerilen boyutsal modellemelerin benzerlik göstermesi bu dikotomik görüşün gözden geçirilme gerekliliğini ortaya koymaktadır. Özellikle klinik pratikte, psikiyatrik tanı sistemlerinde kullanılan tanımlayıcı (descriptive) paradigma ile doğada görülen azımsanmayacak sayıdaki psikiyatrik olgunun yeterince iyi tanımlanamaması, klinisyenlerin ortak dil geliştirme gayretlerini engellemekte ve psikiyatrik tanıların stabilitesinin sorgulanmasına neden olmaktadır. Nitekim, psikotik ve duygudurum belirtilerinin bir arada görüldüğü hasta grubunda tanısal geçerliliğin oldukça düşük olduğu bildirilmektedir. Bununla birlikte, klinik belirtilerin kümelenme şekillerini faktör analizi ile değerlendiren çalışmalarda, bipolar bozukluk ve şizofreninin belirli oranlarda ortak belirti kümelerini gösterdiği bildirilmektedir. Ayrıca güncel genetik araştırmalarda her iki hastalığa özgü yatkınlık oluşturan aday genler olduğu gösterilmekle birlikte, bazı ortak aday genlerin paylaşıldığı ve bir çakışmanın (overlap) olduğu öne sürülmektedir. Genetikçilerin önerdiği boyutsal yaklaşım, klinik araştırmalardan elde edilen bilgilerle uyumlu gözükmektedir. Tüm bu klinik ve genetik kanıtlar ışığında, ünlü Alman bilim adamı Emil Kraepelin’in psikiyatride çığır açan dikotomik yaklaşımının bir asır sonra gözden geçirilmesi gerekmektedir. Kim bilir Kraepelin günümüzde yaşasaydı, belki de kendi modelini bir süre sonra değiştirecekti.

If Kraepelin was still alive would dichotomy still survive?

Emil Kraepelin’s dichotomy, which has been providing a basis for psychiatric classification, has been valid for many years. However, dimensional approaches based on the recent evidences from genetic, biological and clinical researches are in agreement, putting forth the need of this dichotomous view’s revision for consideration. In particular, failure of describing many of the psychiatric cases in nature with descriptive paradigm used for psychiatric classification in clinical practice hinders clinicians’ effort for developing a common language and leads to the questioning of psychiatric diagnoses’ stability. In fact, it has been stated that the descriptive validity was low in the patient group with both psychotic and affective symptoms. It has also been informed that bipolar disorder and schizophrenia were presented with common symptom clusters in the studies evaluating the patterns of clinical symptom clustering with factor analysis. Moreover, some of the candidate genes developing susceptibility for each disorder have been shown to be common in the recent genetic studies, suggesting there is an overlap between these disorders. It appears that dimensional approach suggested by geneticists is consistent with the data from clinical researches. In the light of these clinical and genetic evidences, famous German scientist Emil Kraepelin’s ground-breaking dichotomous approach in psychiatry should be revised after a century. Who knows if Kraepelin was still alive, maybe he would change his dichotomous view after a while.

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1. Möller HJ. Systematic of psychiatric disorders between categorical and dimensional approaches; Kraepelin’s beyond. Eur Arch Psychiatry Clin Neurosci 2008; 258 (Suppl.2):48-73.
2. Craddock N, Owen MJ. The beginning of the end for the Kraepelinian dichotomy. Br J Psychiatry 2005; 186:364-366.
3. Kendler KS, Zerbin-Rudin E. Abstract and review of “zur erbpathologie der schizophrenie” (Contribution to the genetics of schizophrenia) 1916. Am J Med Genet 1996; 67:343-346.
4. Sorias S. Çoğul kişilik bozukluğu tanısının geçerliliği. Turk Psikiyatri Derg 2000; 11:251-268.
5. López J, Baca E, Botillo C, Quintero J, Navarro R, Negueruela M, Pérez M, Basurte I, Fernández A, Jiménez M, González J. Diagnostic errors and temporal stability in bipolar disorder. Actas Esp Psiquiatr 2008; 36:205-209.
6. Hafner H, an der Heiden W, Maurer K. Evidence for separate diseases? Stages of one disease or different combinations of symptom dimensions? Eur Arch Psychiatry Clin Neurosci 2008; 258 (Suppl.2):85-89.
7. Boks MP, Leask S, Vermunt JK, Kahn RS. The structure of psychosis revisited: The role of mood symptoms. Schizophr Res 2007; 93:178-185.
8. Altınbaş K, Guloksüz S, Cantürk YG, Yıldırım HE, Kalelioğlu T, Saatçioğlu Ö, Oral T. Hypomanic symptoms in schizophrenia and other psychotic disorders. presented in 4th Biennial Conference of the International Society for Bipolar Disorders, 2010.
9. Naber D, Holzbach R, Perro C, Hippius H. Clinical management of clozapine patients in relation to efficacy and side-effects. Br J Psychiatry Suppl 1992; 17:54-59.
10. Calabrese JR, Kimmel SE, Woyshville MJ, Rapport DJ, Faust CJ, Thompson PA, Meltzer HY. Clozapine for treatment-refractory mania. Am J Psychiatry 1996; 153:759-764.
11. Green AI, Tohen M, Patel JK, Banov M, DuRand C, Berman I, Chang H, Zarate C Jr, Posener J, Lee H, Dawson R, Richards C, Cole JO, Schatzberg AF. Clozapine in the treatment of refractory psychotic mania. Am J Psychiatry 2000; 157:982-986.
12. Johnstone EC, Crow TJ, Frith CD, Owens DG. The Northwick Park “functional” psychosis study: diagnosis and treatment response. Lancet 1988; 2:119-125.
13. Glick ID, Bosch J, Casey DE. A double-blind randomized trial of mood stabilizer augmentation using lamotrigine and valproate for patients with schizophrenia who are stabilized and partially responsive. J Clin Psychopharmacol 2009; 29:267-271.
14. Demjaha A, Morgan K, Morgan C, Landau S, Dean K, Reichenberg A, Sham P, Fearon P, Hutchinson G, Jones PB, Murray RM, Dazzan P. Combining dimensional and categorical representation of psychosis: the way forward for DSM-V and ICD-11? Psychol Med 2009; 39:1943-1955.
15. Altınbaş K, Smith DJ, Craddock N. Rediscovering the bipolar spectrum. Nöropsikiyatri Arşivi 2011; 48:167-170.
16. Van Os J, Kapur S. Schizophrenia. Lancet 2009; 374:635-645.
17. Van Os J. ‘Salience syndrome’ replaces ‘schizophrenia’ in DSM-V and ICD-11: psychiatry’s evidence-based entry into the 21st century? Acta Psychiatr Scand 2009; 120:363-372.
18. Craddock N, O’Donovan MC, Owen MJ. Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology. Schizophr Bull 2006; 32:9-16.
19. Lander ES, Schork NJ. Genetic dissection of complex traits. Science 1994; 30:2037-2048.
20. Craddock N, Jones I. Genetics of bipolar disorder. J Med Genet 1999; 36:585-594.
21. Cardno AG, Gottesman II. Twin studies of schizophrenia: from bow-and-arrow concordances to star wars Mx and functional genomics. Am J Med Genet 2000; 97:12-17.
22. Kendler KS. Reflections on the relationship between psychiatric genetics and psychiatric nosology. Am J Psychiatry 2006; 163:1138-1146.
23. Baron M, Risch N, Hamburger R, Mandel B, Kushner S, Newman M , Drumer D, Belmaker RH. Genetic linkage between X-chromosome markers and bipolar affective illness. Nature 1987; 326:289-292.
24. Egeland JA, Gerhard DS, Pauls DL, Sussex JN, Kidd KK, Allen CR, Hostetter AM, Housman DE. Bipolar affective disorders linked to DNA markers on chromosome 11. Nature 1987; 325:783–787.
25. Sherrington R, Brynjolfsson B, Petursson H, Potter M, Dudleston K, Barraclough B, Wasmuth J, Dobbs M, Gurling H. Localization of a susceptibility locus for schizophrenia on chromosome 5. Nature 1988; 336:164-167.
26. Lewis CM, Levinson DF, Wise LH, Delisi LE, Straub RE, Hovatta I, Williams NM, Schwab SG, Pulver AE, Faraone SV, Brzustowicz LM, Kaufmann CA, Garver DL, Gurling HM, Lindholm E, Coon H, Moises HW, Byerley W, Shaw SH, Mesen A, Sherrington R, O’Neill FA, Walsh D, Kendler KS, Ekelund J, Paunio T, Lönnqvist J, Peltonen L, O’Donovan MC, Owen MJ, Wildenauer DB, Maier W, Nestadt G, Blouin JL, Antonarakis SE, Mowry BJ, Silverman JM, Crowe RR, Cloninger CR, Tsuang MT, Malaspina D, Harkavy-Friedman JM, Svrakic DM, Bassett AS, Holcomb J, Kalsi G, McQuillin A, Brynjolfson J, Sigmundsson T, Petursson H, Jazin E, Zoëga T, Helgason T. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: schizophrenia. Am J Hum Genet 2003; 73:34-48.
27. Segurado R, Detera-Wadleigh SD, Levinson DF, Lewis CM, Gill M, Nurnberger JI Jr, Craddock N, DePaulo JR, Baron M, Gershon ES, Ekholm J, Cichon S, Turecki G, Claes S, Kelsoe JR, Schofield PR, Badenhop RF, Morissette J, Coon H, Blackwood D, McInnes LA, Foroud T, Edenberg HJ, Reich T, Rice JP, Goate A, McInnis MG, McMahon FJ, Badner JA, Goldin LR, Bennett P, Willour VL, Zandi PP, Liu J, Gilliam C, Juo SH, Berrettini WH, Yoshikawa T, Peltonen L, Lönnqvist J, Nöthen MM, Schumacher J, Windemuth C, Rietschel M, Propping P, Maier W, Alda M, Grof P, Rouleau GA, Del-Favero J, Van Broeckhoven C, Mendlewicz J, Adolfsson R, Spence MA, Luebbert H, Adams LJ, Donald JA, Mitchell PB, Barden N, Shink E, Byerley W, Muir W, Visscher PM, Macgregor S, Gurling H, Kalsi G, McQuillin A, Escamilla MA, Reus VI, Leon P, Freimer NB, Ewald H, Kruse TA, Mors O, Radhakrishna U, Blouin JL, Antonarakis SE, Akarsu N. Genome scan meta- analysis of schizophrenia and bipolar disorder, part III: bipolar disorder. Am J Hum Genet 2003; 73:49-62.
28. Kendler KS, Greenspan RJ. The nature of genetic influences on behavior: lessons from “simpler” organisms. Am J Psychiatry 2006; 163:1683-1694.
29. Flint J. Analysis of quantitative trait loci that influence animal behavior. J Neurobiol 2003; 54:46-77.
30. Craddock N, O’Donovan MC, Owen MJ. Phenotypic and genetic complexity of psychosis. Br J Psychiatry 2007; 190:200-203.
31. Williams NM, Green EK, Macgregor S, Dwyer S, Norton N, Williams H, Raybould R, Grozeva D, Hamshere M, Zammit S, Jones L, Cardno A, Kirov G, Jones I, O’Donovan MC, Owen MJ, Craddock N. Variation at the DAOA/G30 locus influences susceptibility to major mood episodes but not psychosis in schizophrenia and bipolar disorder. Arch Gen Psychiatry 2006; 63:366-373.
32. St Clair D, Blackwood D, Muir W, Carothers A, Walker M, Spowart G, Gosden C, Evans HJ. Association within a family of a balanced autosomal translocation with major mental illness. Lancet 1990; 336:13-16.
33. Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS, Semple CA, Devon RS, St Clair DM, Muir WJ, Blackwood DH, Porteous DJ. Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum Mol Genet 2000; 9:1415-1423.
34. Hamshere ML, Bennett P, Williams N, Segurado R, Cardno A, Norton N, Lambert D, Williams H, Kirov G, Corvin A, Holmans P, Jones L, Jones I, Gill M, O’Donovan MC, Owen MJ, Craddock N. Genomewide linkage scan in schizoaffective disorder: significant evidence for linkage at 1q42 close to DISC1, and suggestive evidence at 22q11 and 19p13. Arch Gen Psychiatry 2005; 62:1081-1088.
35. Kendell R, Jablensky A. Distinguishing between the validity and utility of psychiatric diagnoses. Am J Psychiatry 2003; 160:4-12.
36. Cardno AG, Rijsdijk FV, Sham PC, Murray RM, McGuffin P. A twin study of genetic relationships between psychotic symptoms. Am J Psychiatry 2002; 159:539-545.
37. Berrettini W. Evidence for shared susceptibility in bipolar disorder and schizophrenia. Am J Med Genet C Semin Med Genet 2003; 123:59-64.
38. Lichtenstein P, Yip BH, Björk C, Pawitan Y, Cannon TD, Sullivan PF, Hultman CM. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 2009; 373:234-239.
39. Green EK, Grozeva D, Jones I, Jones L, Kirov G, Caesar S, Gordon-Smith K, Fraser C, Forty L, Russell E, Hamshere ML, Moskvina V, Nikolov I, Farmer A, McGuffin P; Wellcome Trust Case Control Consortium, Holmans PA, Owen MJ, O’Donovan MC, Craddock N. Bipolar disorder risk allele at CACNA1C also confers risk to recurrent major depression and to schizophrenia. Mol Psychiatry 2010; 15:1016-1022.
40. Ferreira MA, O’Donovan MC, Meng YA, Jones IR, Ruderfer DM, Jones L, Fan J, Kirov G, Perlis RH, Green EK, Smoller JW, Grozeva D, Stone J, Nikolov I, Chambert K, Hamshere ML, Nimgaonkar VL, Moskvina V, Thase ME, Caesar S, Sachs GS, Franklin J, Gordon-Smith K, Ardlie KG, Gabriel SB, Fraser C, Blumenstiel B, Defelice M, Breen G, Gill M, Morris DW, Elkin A, Muir WJ, McGhee KA, Williamson R, MacIntyre DJ, MacLean AW, St CD, Robinson M, Van Beck M, Pereira AC, Kandaswamy R, McQuillin A, Collier DA, Bass NJ, Young AH, Lawrence J, Ferrier IN, Anjorin A, Farmer A, Curtis D, Scolnick EM, McGuffin P, Daly MJ, Corvin AP, Holmans PA, Blackwood DH, Gurling HM, Owen MJ, Purcell SM, Sklar P, Craddock N, Wellcome Trust Case Control Consortium. Wellcome Trust Case Control Consortium. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 2008; 40:1056-1058.
41. Akiskal HS. Cyclothymic disorder: validating criteria for inclusion in the bipolar affective group. Am J Psychiatry 1977; 134:1227- 1233.
42. Klerman GL. The spectrum of mania. Compr Psychiatry 1981; 22:11-20.
43. Angst J. The bipolar spectrum. Br J Psychiatry 2007; 190:189- 191.
44. Vieta E, Phillips ML. Deconstructing bipolar disorder: a critical review of its diagnostic validity and a proposal for DSM-V and ICD-11. Schizophr Bull 2007; 33:886-892.
45. Flint J, Munafo MR. The endophenotype concept in psychiatric genetics. Psychol Med 2007; 37:163-180.
46. Meyer-Lindenberg M, Weinberger DR. Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat Rev Neurosci 2006; 7:818-827.
47. Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003; 160:636-645.
48. Cannon TD, Keller MC. Endophenotypes in the genetic analyses of mental disorders. Annu Rev Clin Psychol 2006; 2:267-290.
49. Tan HY, Callicott JH, Weinberg DR. Intermediate phenotypes in schizophrenia genetics redux: is it a no brainer? Mol Psychiatry 2008; 13:233-238.
50. Walters JTR, Owen MJ. Endophenotypes in psychiatric genetics. Mol Psychiatry 2007; 12:886-890.
51. Lenox RH, Gould TD, Manji HK. Endophenotypes in bipolar disorder. Am J Med Genet 2002; 114:391-406.
52. Schulze TG, McMahon FJ. Defining the phenotype in human genetic studies: Forward genetics and reverse phenotyping. Hum Hered 2004; 58:131-138.
53. McMahon FJ, Simpson SG, McInnis MG, Badner JA, MacKinnon DF, DePaulo JR. Linkage of bipolar disorder to chromosome 18q and the validity of bipolar II disorder. Arch Gen Psychiatry 2001; 58:1025-1031.
54. Iannuzzi MC, Baughman RP. Reverse phenotyping in sarcoidosis. Am J Respir Crit Care Med 2007; 175:4-5.