Psykotisk depression Ph.d. Projekt Klinisk Forskermøde Risskov d. 30/3 2011 Søren Dinesen Østergaard Læge, Ph.d. Studerende Enheden for Psykiatrisk Forskning Aalborg Psykiatriske Hospital Aarhus Universitetshospital sdo@rn.dk Plan 15.10 Provokation 15.20 Baggrund 15.30 Oversigt over studier 15.35 Resultater 15.45 Diskussion 1
DSM-IV symptom-kriterier 5 of the following symptoms, one of which should be depressed mood or anhedonia must be present for at least two weeks: 1. Depressed mood 2. Loss of pleasure in usual activities (anhedonia) 3. Feelings of worthlessness or inappropriate guilt 4. Inability to concentrate 5. Fatigue or loss of energy 6. Insomnia or hypersomnia 7. Psychomotor agitation or retardation 8. Significant weight loss or gain 9. Recurrent thoughts of death or suicide ANTAL KOMBINATIONSMULIGHEDER MED 5 SYMPTOMER? 1890 2
Depression er så uspecifikt at det kan sidestilles med åndenød Åndenød Akut (Pneumothorax, asthma, emboli) Kronisk (KOL, cancer, hjertesvigt) Genetisk (cystisk fibrose) Normalt (utrænet på Mt. Everest) Ætiologi : bakteriel Infektion Behandling : Antibiotika Depression Akut (vaskulær, tsunami + død familie) Kronisk (dystymi, depressiv persona) Genetisk (familiær, endogen) Normalt (følsomhed + krævende situation) Ætiologi : Serotonin-mangel Behandling : SSRI 3
Hvorfor psykotisk depression? 2 patienter.... og 1 bog + Negligeret gg emne 4
Depression Undergruppering Depressiv enkeltepisode / Periodisk depression: Let grad Moderat grad Svær grad } Melankoliform / non-melankoliform - Uden psykotiske symptomer - Med psykotiske symptomer - Stemningskongruente - Stemningsinkongruente Psykotisk vs. ikke-psykotisk depression Biologi Arvelighed Symptomatologi Prognose Behandlingsrespons 5
Overordnet hypotese Psykotisk og non-psykotisk depression er ikke 2 sider af samme sag Depressiv enkeltepisode / Periodisk depression: Let grad } Melankoliform / non-melankoliform Moderat grad Svær grad - Uden psykotiske symptomer Psykotisk depressiv - Med enkeltepisode/ psykotiske symptomer Periodisk psykotisk depression: - Stemningskongruent - Stemningsinkongruent The Clinical Significance of Psychotic Depression According to HoNOS HoNOS = Health of the Nation Outcome Scale 12 items rates fra 0-4 efter semi-struktureret interview Alle patienter indlagt i Hillerød fra 2000-2010 HoNOS rating ved indlæggelse og udskrivelse 357 patienter med diagnosen svær depression 232 non-pd (F32.2+F33.2) & 125 PD (F32.3+F33.3) 6
TABLE 1. HoNOS scores of patients with psychotic depression (PD) and non psychotic depression (non-pd) at admission and discharge ADMISSION DISCHARGE Non-PD PD Non-PD PD HoNOS Item (n=232) (n=125) (n=232) (n=125) 1. Aggression 0.20 (0.56) 0.36 (0.79) * 0.10 (0.36) 0.09 (0.36) 2. Self-harm 0.60 (1.12) 0.55 (1.13) 0.09 (0.42) 0.06 (0.45) 3. Drug or alcohol use 0.29 (0.78) 0.30 (0.83) 0.13 (0.55) 0.09 (0.44) 4. Cognitive problems 0.49 (0.85) 0.66 (0.97) # 0.40 (0.78) 0.49 (0.84) 5. Physical illness and disability 0.78 (1.14) 0.69 (1.14) 0.57 (1.00) 0.63 (1.12) 6. Hallucinations and delusions 0.33 (0.79) 1.37 (1.34) *** 0.09 (0.36) 0.45 (0.91) *** 7. Depression 2.59 (0.90) 2.50 (1.13) 0.86 (0.95) 0.86 (1.10) 8. Other mental and behavioral problems 2.06 (1.09) 2.25 (1.09) # 0.92 (0.99) 0.87 (1.10) 9. Problems with relationships 1.22 (1.25) 1.02 (1.25) 0.59 (0.84) 0.51 (0.96) # 10. Problems with activities of daily living 1.08 (1.16) 1.16 (1.18) 0.58 (0.94) 0.61 (1.05) 11. Problems with living conditions 0.39 (0.91) 0.47 (0.96) 0.24 (0.69) 0.25 (0.71) 12. Problems with occupation and activities 0.52 (1.01) 0.52 (1.02) 0.33 (0.69) 0.32 (0.84) TOTAL 10.55 (5.32) 11.87 (5.78) * 4.91 (4.83) 5.23 (6.03) Severity-Psychosis hypothesis psychosis depression Spearman-koefficient = 0.12 7
Genetic Polymorphisms of the Glucocorticoid System in Psychotic Depression Physical morbidity preceding psychotic and non-psychotic depression Risk factors for psychotic and nonpsychotic depression Planlagte studier Testing the severity-psychosis Hypothesis of psychotic depression DEBUT UNIPOLAR PSYKOTISK DEPRESSION Predictors for suicide in psychotic depression Psychiatric morbidity preceding psychotic and non-psychotic depression Clinical validation of the Rating Scale for Psychotic Depression (RAS-PD) Predictors for bipolar disorder after unipolar psychotic depression Registerforskning - MFR vaccine versus autisme 8
Registerforskning Psychiatric Morbidity Preceding Psychotic and Non-psychotic Depression Psykiatriregisteret??? DEBUT SVÆR NON-PSYKOTISK DEPRESSION? Psykiatriregisteret?? DEBUT SVÆR PSYKOTISK DEPRESSION 9
TABLE 3. Diagnoses of mental disorders assigned prior to the onset of ICD-10 non-psychotic and psychotic severe depression Cum. Prevalence Cum. Prevalence OR AOR Non-psychotic Psychotic crude sex/age (n=16221) (n=7680) Disorders due to psychoactive substance 7.3 (6.9-7.7) 5.0 (4.5-5.5) 0.7 (0.6-0.8) *** 0.7 (0.6-0.8) *** Other affective disorders 1.5 (1.3-1.7) 1.1 (0.9-1.4) 0.7 (0.6-0.9) * 0.7 (0.6-0.9) ** Neurotic/stress/somatoform 17.2 (16.6-17.8) 15.3 (14.5-16.1) 0.9 (0.8-0.9) *** 0.9 (0.8-1.0) * Depression 26.9 (26.2-27.6) 26.6 (25.6-27.6) 1.0 (0.9-1.0) 0.9 (0.8-0.9) *** Intentional self-harm 1.9 (1.7-2.1) 1.5 (1.3-1.8) 0.8 (0.6-1.0) * 0.8 (0.7-1.0) Personality disorders 10.4 (9.9-10.9) 8.8 (8.2-9.5) 0.8 (0.8-0.9) 0.9 (0.8-1.0) Unspecified 4.6 (4.2-4.9) 4.8 (4.3-5.3) 1.1 (0.9-1.2) 1.2 (1.1-1.4) ** Childhood/adolescence disorders 0.6 (0.5-0.7) 0.5 (0.4-0.7) 0.9 (0.7-1.4) 1.2 (0.8-1.7) Organic disorder 2.9 (2.6-3.1) 5.0 (4.5-5.4) 1.8 (1.5-2.0) *** 1.4 (1.2-1.6) *** Developmental disorders 0.2 (0.2-0.3) 0.3 (0.2-0.4) 1.2 (0.7-2.0) 1.5 (0.9-2.5) Other non-psychotic disorders 1.3 (1.2-1.5) 1.9 (1.6-2.2) 1.4 (1.2-1.8) *** 1.8 (1.4-2.2) *** Other psychotic disorders 2.9 (2.6-3.1) 8.8 (8.2-9.4) 3.3 (2.9-3.7) *** 3.3 (2.9-3.8) *** Physical Morbidity Preceding Psychotic and Non-psychotic Depression Fysisk sygdom Depression Hjerte-kar-sygdom Stroke Diabetes Gigt-lidelser Cancer HIV Hepatitis Gigt 10
TABLE 3. Diagnoses of physical disease assigned prior to the onset of ICD-10 non-psychotic and psychotic severe depression Cum. Prevalence Cum. Prevalence OR AOR Non-psychotic Psychotic crude (sex/age) (n=16,221) (n=7,680) Cushing syndrome 0.1 (0.0-0.1) 0.0 (0.0-0.0) 0.2 (0.0-1.9) 0.2 (0.0-1.9) Chronic renal disease 0.3 (0.2-0.4) 0.3 (0.2-0.4) 0.9 (0.5-1.4) 0.7 (0.4-1.2) Ischemic heart disease 7.7 (7.3-8.1) 8.0 (7.4-8.6) 1.0 (0.9-1.1) 0.7 (0.7-0.8) *** Hypertension 7.1 (6.7-7.5) 7.8 (7.2-8.4) 1.1 (1.0-1.2) 0.8 (0.8-0.9) ** Stroke 4.2 (3.9-4.5) 4.4 (3.9-4.9) 1.1 (0.9-1.2) 0.8 (0.7-0.9) ** Chronic lower pulmonary disease 3.7 (3.4-4.0) 3.8 (3.3-4.2) 1.0 (0.9-1.2) 0.8 (0.7-0.9) ** Inflammatory bowel diseases 1.3 (1.1-1.4) 1.1 (0.9-1.4) 0.9 (0.7-1.1) 0.9 (0.7-1.2) Cancer 6.6 (6.3-7.0) 7.9 (7.3-8.5) 1.2 (1.1-1.3) ** 0.9 (0.8-1.0) Intracranial injury 9.2 (8.8-9.7) 7.7 (7.1-8.3) 0.8 (0.7-0.9) *** 0.9 (0.8-1.0) * Rheumatoid arthritis/lupus 1.1 (1.0-1.3) 1.2 (0.9-1.4) 1.1 (0.8-1.4) 0.9 (0.7-1.2) Disorders of the thyroid gland 2.9 (2.6-3.1) 3.1 (2.7-3.5) 1.1 (0.9-1.3) 0.9 (0.7-1.0) Epilepsy 2.7 (2.4-2.9) 2.6 (2.2-2.9) 1.0 (0.8-1.1) 1.0 (0.9-1.2) CNS infection/inflammation 0.8 (0.7-0.9) 0.8 (0.6-1.0) 1.0 (0.8-1.4) 1.1 (0.8-1.4) Chronic hepatitis C/HIV-AIDS 0.1 (0.0-0.2) 0.1 (0.1-0.2) 1.0 (0.5-2.0) 1.1 (0.6-2.3) Diabetes 6.9 (6.6-7.3) 8.4 (7.8-9.0) 1.2 (1.1-1.4) *** 1.1 (1.0-1.2) Dementia 1.9 (1.7-2.1) 3.3 (2.9-3.7) 1.7 (1.5-2.0) *** 1.2 (1.0-1.4) * Parkinson s disease 0.5 (0.4-0.6) 1.0 (0.8-1.2) 1.9 (1.4-2.6) *** 1.3 (1.0-1.8) Composite score: non-pd > PD Predictors of Conversion to Bipolar Disorder after Unipolar Psychotic Depression Patienter med PD har øget risiko for at udvikle bipolar sygdom. Psykotisk depression er meget hyppig i det bipolare forløb. Øget forekomst af PD blandt 1. grads slægtninge af bipolare pt. Konvertering har prognostiske og behandlingsmæssige konsekvenser Hvad prædikterer konvertering? 11
Predictors of Conversion to Bipolar Disorder after Unipolar Psychotic Depression?? DEBUT UNIPOLAR PSYKOTISK DEPRESSION?? BIPOLAR SYGDOM Tak til Sune Straszek TABLE 2. Risk factors regarding conversion from unipolar psychotic depression to bipolar disorder BP-converters Non-converters HR AHR (n=484) (n=6186) Age at onset of PD (years) 51.0 (49.5-52.5) 55.1 (54.6-55.6) *** 1.00 (0.99-1.00) 0.99 (0.98-1.00) *** Female sex (%) 67.4 (63.5-71.2) 64.7 (63.6-65.9) 1.13 (0.95-1.34) Living alone (%) 53.7 (49.6-57.8) 58.4 (57.2-59.6) * 0.90 (0.76-1.06) Higher education than public school (%) 59.9 (55.3-64.5) 51.7 (50.3-53.2) ** 1.31 (1.8-1.59) 1.39 (1.15-1.83) ** Receiving i early retirement tpension (%) 21.8 (18.4-25.2) 2) 22.1 (21.0-23.1) 23 1) 088(072107) 0.88 (0.72-1.07) Mental disorder due to substance abuse (%) 21.1 (17.7-24.4) 13.3 (12.5-14.1) *** 1.59 (1.30-1.94) *** 1.45 (1.15-1.83) ** Organic mental disorder (%) 21.2 (17.9-24.6) 15.9 (15.0-16.8) ** 1.64 (1.34-2.00) *** 1.99 (1.55-2.56) *** Mood-incongruent psychotic symptoms (%) 2.3 (1.1-3.5) 2.1 (1.7-2.4) 1.12 (0.65-1.94) Depressive episodes (n) 6.2 (8.1) 4.5 (5.8) *** 1.02 (1.01-1.03) *** + 1.01 (1.00-1.02) * + Psychotic depressive episodes (n) 2.4 (1.9) 2.2 (2.3) 1.01 (0.98-1.04) Non-affective psychotic episodes (n) 0.8 (2.1) 0.6 (2.5) ** 1.02 (1.00-1.03) Number of psychiatric bed-days (n) 165.0 (191.7) 150.3 (214.7) 1.00 (1.00-1.00) MAO-I (%) 0.9 (0.1-1.6) 0.2 (0.1-0.3) ** 4.07 (1.69-9.82) ** SSRI (%) 33.2 (29.3-37.0) 15.4 (14.5-16.2) *** 2.24 (1.88-2.66) *** 2.36 (1.91-2.93) *** SNRI (%) 16.3 (13.3-19.4) 9.3 (8.6-10.0) *** 1.56 (1.25-1.95) *** 2.18 (1.69-2.81) *** TCA (%) 19.11 (15.9-22.4) 86 8.6 (8093)*** (8.0-9.3) 209(170258)*** 2.09 (1.70-2.58) 231(180298)*** 2.31 (1.80-2.98) NaSSA (%) 19.1 (15.9-22.4) 11.0 (10.3-11.8) *** 1.58 (1.28-1.95) *** 1.47 (1.14-1.88) ** Lithium (%) 12.1 (9.4-14.8) 3.5 (3.1-4.0) *** 2.93 (2.28-3.76) *** 1.96 (1.47-2.62) *** Antipsychotics (%) 38.9 (34.9-43.0) 23.1 (22.1-24.1) *** 1.71 (1.45-2.03) *** 12
Psykometri Psykometri = måling af psykiske fænomener HAM-D, HAM-A, A MADRS, PANSS, BPRS, YMRS Grundlag for kvantitativ forskning i psykopatologi (al psykofarmaka) Unidimensionalitet = samlet score svarer til global sværhedsgrad HAM-D17 er ikke unidimensionel bruges i 95% af kliniske studier 13
HAMD 6 Depressed mood Anhedonia Feelings of guilt Psychomotor retardation Psychic anxiety Somatic symptoms (tiredness) HAMD17 items: Manglende appetit, vægttab, dårlig søvn (3 items) Rating Scale for Psychotic Depression (RAS-PD) I kliniske forsøg med PD anvendes typisk HAMD 17 + items fra BPRS. Depressions-dimension + psykose-dimension RAS-PD: Baseret på Bech-Rafaelsen Melankoli skala (MES) Modificeret med tillæg af psykotisk overbygning + tillæg af rene psykose items Semistruktureret interview-guide 14
Rating Scale for Psychotic Depression (RAS-PD) 1. Decreased sleep 12. Suicidal ideation 13. Suspicion / persecution 2. Tiredness 14. Hallucinations 3. Work and interests 15. Delusions 4. Decreased mood 16. Lack of insight 5. Difficulty concentrating 17. Desorganised thinking 6. Anxiety 18. Decreased verbal activity 7. Emotional withdrawal 19. Decreased motor activity 8. Guilt 20. Agitation 9. Worthlessness 21. Motor-disturbances / catatonia 10. Disorientation 22. Mood-congruence or Mood-incongruence 11. Hypochondriasis Validering af RAS-PD 50 patienter med diagnosen unipolar psykotisk depression Interviewes ved opstart af indlæggelse/ambulant forløb 25 interviewes igen ved udskrivelse/afslutning Interview baseret på semi-struktureret guide optages på video Rates på RAS-PD af 2 uafhængige læger (inter-rater reliability) Global sværhedsgrad vurderes af erfaren psykiater på skala fra 1-10 RAS-PD Δ RAS-PD Global score Δ Global score 15
Genetic Polymorphisms of the Glucocorticoid System in Psychotic Depression HPA-akse dysregulation og depression Behandlingsrespons Psykotisk vs. non-psykotisk depression Mifepristone Genetikken bag HPA-dysregulation (25 SNPs) Forskel psykotisk vs. ikke-psykotisk depression Genetic Polymorphisms of the Glucocorticoid System in Psychotic Depression Antal patienter Non-psychotic Psychotic 250 patienter med psykotisk depression 400 patienter med ikke-psykotisk depression Antal HPA risiko-alleller 16
Environmental and Familial Risk factors for psychotic and non-psychotic depression Environmental and Familial Risk factors for psychotic and non-psychotic depression Paternal/Maternal age Season of birth Small for gestational age Urbanicity Loss of parent/sibling??? DEBUT SVÆR NON-PSYKOTISK DEPRESSION Family history of mental disorder - Schizophrenia - Bipolar - Depression - Other psychoses - Any diagnosis??? DEBUT SVÆR PSYKOTISK DEPRESSION 17