1. The Lundby Study 50 years Per Nettelbladt, head 1996- The Lundby Study Clinical Sciences Lund University Lund Sweden

2. Some historical events 1947-1997 The pill in the 1960-ies The Vietnam war in 1965-1975 The fall of the Berlin wall in 1989 Immigration, computers, television, cellphones etc.

3. Deinstitutionalization and Nosology 1947 -1997 Deinstitutionalization 1984- Sectorization Nosology 1952 DSM-I 1994 DSM-IV 1992 ICD-10

4. Psychopharmacology 1947 -1997 1949 Lithium 1952Neuroleptics 1957 (1962, Sweden)Tricyclic Antidepressants Monoamine Oxidase Inhibitors 1960 Benzodiazepines 1986Acetylcholineesteras inhibitors 1988 (1993, Sweden) Serotonin-specific reuptake inhibitors 1990Atypical neuroleptics

5. Brain Imaging 1947 -1997 1980- Computed Tomography(CT) Magnetic Resonance Imaging(MRI) Single Photon Emission Computed TomographySPECT Positron Emission TomographyPET Cerebral Blood FlowCBF

6. Alcohol policy The Bratt system (1917 – 1955) implied that abusers could lose their right to buy alcohol Ration book for wine and spirits was done away with in 1955 The local and county boards of alcohol started their activity in the 1930s. The boards were closed down 1973.

7. Mentally retarded (Karl Grunewald) 1967 Social Welfare Act for the Mentally Retarded 1980 Dual diagnosis: Mental retardation Mental Disorder

9. Does it make sense to do repeated surveys? – the Lundby Study, 1947-1997 Representativeness of the Lundby sample Inter-rater reliability of mental disorder over time (50 yrs) Attrition in the 1997-investigation Other methodological considerations

10. The Lundby Area In 1947 the Lundby area was a farming district. In the years 1947-1997 it changed into a suburban community. Between 1947-1997 60% of the Lundby population 1947 had moved out of the area.

11. Representativity of the Lundby cohort Having existed in 50 years the Lundby sample can be considered to be an initially rural population who has been exposed to the changes of society in Sweden between 1947- 1997. The population consists of parents and their children, siblings and other relatives

12. The 1997 field workers and the staff Field workers: Per Nettelbladt Per Toråker Cecilia Mattisson Mats Bogren Erik Hofvendahl Staff: Anders Odensten Lena Otterbeck

13. The 1947 Lundby field workers Hans Larsson Carl-Erik Uddenberg Erik Essen-Möller Gaylor White

14. The 1957 field worker and one of the 1972 field workers Olle Hagnell

15. One of the 1972 field workers and one of the 1997 field workers Leif Öjesjö

16. Diagnostic agreement over time between researchers 1957-1972 and researchers 1997 before re-evaluation Degree of impairment: Very severe +severe +medium (N=200) Cohen´s kappa Mental disorder0.6 Neurosis0.6 Psychosis Not calculated, too few Organic brain syndrome0.5

17. Re-evaluation in 1997 (C.M.,M.B) Some diagnoses were unevenly distributed Probands with the diagnoses tiredness/tiredness+, mixed neurosis, schizophrenia, organic syndrome before 1972 were re-evaluated All probands with two or more episodes before 1972 were re-evaluated in order to calibrate the episode lengths 1947-1972 with the ones 1972-1997 All probands who had got a diagnosis on the cut off date 1 July 1972 were re-evaluated.

18. Re-evaluation in 1957 ”Being interested in the theory of natural and pathologic variation put forward by Sjöbring (1879-1956) we were eager to search for lesional factors……. Individual traits and morbidity in a Swedish rural population (E.E-M et al., 1956) In 1957 the diagnoses made in 1947 were reevaluated and since then the Lundby diagnoses have been made according to the same principles.

19. Lundby diagnostics (continued) A great methodological advantage of the Lundby Study is the free diagnostic descriptions. They make it possible in retrospect to adapt the Lundby data to modern operationalised diagnostic systems (DSM-IV, ICD-10). In the present follow-up study it is, for reasons of comparability, necessary to use the Lundby diagnostics together with current diagnostic systems such as DSM-IV and ICD-10.

20. The Lundby diagnosis depression and corresponding DSM-IV diagnoses (N=42)

21. Diagnoses 1997 DSM-IV ICD-10 LUNDBY DIAGNOSES: Organic Brain Syndromes, Psychosis and Neurosis. These diagnoses were divided into subgroups. Only one diagnosis comes into question as the system is hierarchical with Organic Brain disorder taking precedence of Psychotic disorder, which in turn overrides Neurotic disorders

22. Neurosis (insight) Anxiety proper and Anxiety+ Depression proper and Depression+ Tiredness proper and Tiredness+ Mixed Neurosis

23. Psychosis (no insight) Schizophrenia Other psychosis

24. Organic Brain Syndrome Organic syndrome:Reduced comprehension, memory difficulties, concrete behavior, lack of emotional gradation etc. Dementia: Multi-infarct dementia: Sudden onset, focal Senile dementia (includingAlzheimer´s disease): Slow insidious onset and progress

25. Assessment of personality 1997 This was done according to DSM-IV, ICD-10, the Lundby tradition and the personality dimensions of Henrik Sjöbring Validity (cautious, tense,meticulous – self- confident, calm, expansive) Solidity (quick, flexible, subjective – steady, comprehensive, objective) Stability (warm, concrete, heavy – cool, abstract, clever) Capacity (intelligence)

26. What is a case? A Lundby diagnosis does not necessarily imply caseness, for which additional criteria can be used, a certain degree of impairment, a certain duration etc.

27. Impairment in Lundby The impairment rating according to Lundby corresponds to the Global Assessment of Functioning(GAF) Scale: ImpairmentGAF 0 100 - 81 1 = minimal80 -71 2 = mild70 - 61 3 = medium60 - 51 4 = severe50 – 31 5 = very severe30-1

28. Caseness According to Eaton (Eaton et al., 1997) the Lundby diagnosis Depression of medium and severe degree of impairment roughly corresponds to major Depression in DSM- IV. Caseness. Medium (GAF 60-51), severe (GAF 50-31) and very severe (GAF 30-1) impairment

29. Effects of a high degree of impairment The consistency over time increases Less recall bias because more serious disorders are easier to remember The chance to detect the disorder in the patient register increases

32. Why were not diagnostic schedules used? Too time-consuming to use diagnostic schedules like SCAN or CIDI Diagnostic schedules are based upon one interview Diagnostic schedules can not be used to evaluate the deceased The information collected before 1972 was not considered to be appropriate for re-evaluation with a diagnostic schedule

33. How was a best estimate consensus diagnosis reached in 1997? Regular seminars together with the researchers in 1957 (O.H.) and 1972 (O.H., L.Ö.) All information about a proband was brought to together Discussion within the research team until consensus was reached

34. Which were the methods to reach a best estimate consensus diagnosis in 1997? Field-worker was a psychiatrist Contact, information and consent Semi-structered interview Self-rating questionnaires Registers in the Lundby study 1947-1972 Registers in the Lundby study 1997 Other sources of information

35. Contact, information and consent Every proband was first contacted with an introductory letter. Some days later the field worker phoned the proband and made an appointment for the interview. At the beginning of the interview the proband was presented a letter of information and a letter of consent permitting us to collect information about the proband from hospital records.

36. Semi-structured interview The proband´s health and care July 1, 1972 - July 1, 1997 (also somatic health) The prevalence of illnesses on July 1st, 1997 Family stress and work stress Health in relatives and partner The proband´s personality and adjustment ability

37. When the interview was finished, the proband was given a set of self-rating questionnaires: Hopkins Symptom Check List (HSCL - 25): Anxiety and depression Nottingham Health Profile (NHP): Quality of life Interview Schedule for Social Interaction (ISSI): Social network Sense of coherence scale (SOC): Comprehensibility, manageability and meaningfulness Self-rating questionnaires

38. Registers in the Lundby Study 1947-1972 Parish and Central Population Registration Location, date and official death certificates. Kinship between probands of the 1947 cohort down to 1/32 (eighteenth century). The Swedish Central Bureau of Statistics (SCB): The proband´s present name and adress, former address, marital status, date of changes, identification number of spouse and parents, present assessment of income, legal incapacity, official death certificates.

39. Registers in the Lundby Study 1947-1972(continued) Social Insurance Office: Since 1955 all subjects in Sweden were from the birth compulsorily connected to the Social Insurance Office. Admissions to hospitals, out- patient consultations, sick-leaves, sick pensions. County temperance boards: The local and county boards of alcohol started their activity in the 1930s. The boards were closed down 1973. National police board (the criminal register): No information after 1988.

40. Registers in the Lundby Study 1997 The Swedish census registration: Habitation adressses, civil status, spouse identity and date of death The Cause of Death Register The Patient Register: In-patient care in all Sweden. Diagnoses, sex, age, domicile, hospital, speciality etc. Provides us with data after 1972. Out-patient health care consumption in the Lundby area 1975-1994 (primary health care) and 1981-1994 (hospital care)

41. Other sources of informtion Hospital case notes, psychiatric and non- psychiatric, autopsy reports Key-informants: Mostly relatives and nursing staff

42. Sufficient information Information collected at an interview or Information from two other sources ( family members, other key informants, information collected by case-notes or official registers in non-refusing probands)

43. Number of sources of information There were more sources of information in the period 1947-1972 as compared with the period 1972-1997

44. Information 1947-1997 Year Alive Dead Total Interview Other sources Insufficient Other sources Insufficient information information 1947 2520 13 17 2550 1957 2826* 473* 11* 233 20 3563 1972 2777 46 4 481 2 3310 1997 1559 82 156 1018 12 2827 Survivors from 1947 + newcomers 1957

45. The Lundby population July 1 1947- June 30 1997

46. Field investigation 1997-2000 July 1 1997 living probands: 1797 July 1 1997 deceased probands: 1766 (deceased 1972-1997: 1030) In all, 3563 probands The 1947-cohort: 2500 The 1957-cohort: 2612

47. Attrition rate 1947-1997 1947, 1957, 1972: Sufficient information 1-2% 1997: Interviews 13% Sufficient information 6%

48. Why were there refusals in 1997? In the 1947, 1957 and 1972 there were no refusals as the field workers made ”knock- on-the door visits”. In 1997 there was an introductory letter and then a fixed appointment when the field worker was invited to visit the proband

50. Overlapping strata (i.e.20-29 yrs) occur. No problem if enough obs yrs before and after 1972= (Balance) and first-inidence is equally distributed. ---------------------------- 1972 ---------------------------- 20, 21, 22,23, 24, 25, 26, 27, 28, 29 20, 21, 22,23, 24, 25, 26, 27, 28, 29 yrs ---------------------------- 1972 ----------------------------

51. The problem of healthy survivors: Neuroses. Obs yrs are cut off when a person dies or is taken ill with the disorder studied. One person can only be counted once with the disorder studied If onset for neuroses predominantly were at fifteen, there would have been a higher incidence (X-X-X) in 1947-1972 in the overlapping stratum as compared with 1972-97. But onset was evenly distributed. 72 ---------------------------------------------- 1947-721972-97 15 29 yrs x-x-x----------x x-x--------------x and so on ----------------------- 15-29 yrs15-29 yrs

53. The problem of healthy survivors: Organic Brain Syndrome (OBS): Obs yrs are cut off when a person dies or is taken ill with the disorder studied. One person can only be counted once with the disorder studied. If onset for OBS predominantly were at ninety, there would have been a higher incidence (X-X-X) in the overlapping stratum in 1972-1997 as compared with 1947-72. But a lower incidenc was found for 1972-1997 as compared with 1947-72. 72 ---------------------------------------------- 1947-721972-97 70 90 yrs x-----------x-x-x ----------------------- 70-90 yrs70-90 yrs

55. If dementia is studied and there are many persons in the young age intervals and few in the old ones before 1972,but many in the old ones and few in the young ones, there is a problem 72 ---------------------------------------------- 1947-721972-97 70 90 yrs x-----------x-x-x ----------------------- 70-90 yrs70-90 yrs

56. To sum up Overlapping strata may introduce a problem if incidence increases or decreases with age and there is an imbalance in the number of observation years from young and old in the overlapping strata However, most age specific strata are not overlapping.

57. Age standardised first-incidence per 1000 yrs at risk (with 95%CI) of contracting Neurotic, Psychotic and Organic Brain disorders. Misleading because no age specific rates. 1947-72 (n=3563)1972-97(n=2827) Neurotic Psychotic Organic Men 5.6 0.8 6.4 3.2 1.6 2.8 (4.7-6.5) (0.5-1.2) (5.3-7.5) (2.4-4.0) (1.0-2.2) (2.2-3.4) Women 8.4 0.8 4.5 4.0 0.7 2.4 (7.3-9.6) (0.4-1.1) (3.6-5.4) (3.1-5.0) (0.4-1.0) (1.9-3.0)

58. Neurotic disorders. First incidence (µ) together with 95% C.I C=First incidence cases. L=years at risk. *= age standardised first incidence rate. (Few person years in the age 15-29 1972-1997, but clear tendency) 1947-72 1972-97 Men Age C L µ 95% C.I. C L µ 95% C.I. 15-29 47 7920 5.9 4.2-7.6 7 1658 4.2 1.1-7.4 30-39 30 5310 5.6 3.6-7.7 9 3271 2.8 1.0-4.6 40-49 26 5331 4.9 3.0-6.8 14 4471 3.1 1.5-4.8 50-59 33 4712 7.0 4.6-9.4 12 4542 2.6 1.2-4.1 60-69 24 3246 7.4 4.4-10.4 9 4110 2.2 0.8-3.6 70-99 7 2574 2.7 0.7-4.7 16 3759 4.3 2.2-6.3 Total 167 29092 5.7 4.9-6.6 67 21810 3.1 2.3-3.8 5.6*4.7-6.5 3.2* 2.4-4.0

59. The Lundby cohort 1947-1997 1947Prevalence study 1957Prevalence study Incidence study: 10-year 1972Incidence study: 15-year and 25-year 1997Incidence study: 40-year and 50-year

60. The Lundby Study wishes to thank: The Lundby population

61. The Lundby Study wishes to thank: The Swedish Council for Planning and Coordination of Research The Swedish Council for Social Research The Swedish Medical Research Council The Medical Faculty, Lund University The Swedish Research Council

62. The Lundby Study Wishes to Thank (Continued): Region Skåne The Sjöbring Foundation, Division of Psychiatry, Lund University Hospital The Söderström-Königska Foundation

63. The Lundby Study also Wishes to Thank you for your attention!