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A multicenter study about neurobiology of suicidal behaviour

A multicenter study about neurobiology of suicidal behaviour. T. Bronisch, J. Brunner, B. Bondy, D. Rujescu, G. Bischof, I. Heuser, B. Müller-Oerlinghausen, B. Hawellek, W. Maier, M.L. Rao, W.Felber, U. Lewitzka, M. Oehler, A. Brooks, F. Hohagen, E.Lauterbach 3rd International Symposium

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A multicenter study about neurobiology of suicidal behaviour

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  1. A multicenter study about neurobiology of suicidal behaviour T. Bronisch, J. Brunner, B. Bondy, D. Rujescu, G. Bischof, I. Heuser, B. Müller-Oerlinghausen, B. Hawellek, W. Maier, M.L. Rao, W.Felber, U. Lewitzka, M. Oehler, A. Brooks, F. Hohagen, E.Lauterbach 3rd International Symposium Research Net Depression Tutzing 06.10.2003

  2. Centres

  3. Patients: • Inclusion criteria:Drug-free for two weeks (exception: BZD) • Psychiatric disorders: • – Affective disorders • – Personality disorders • – Adjustment disorder with depressed mood – With or without suicidal ideation/suicide attpts • Exclusion criteria:Psychiatric diagnoses: • – Organic Brain Syndrome • – Addiction (two months prior to enrolment) • – Schizophrenic PsychosesMajor disorder of internal medicine • Pregnancy, Breast-feeding

  4. Assessment of psychopathology: Diagnoses: Axis I: Clinical Interview according to DSM-IV (MINI) Axis II: Clinical Interview (SCID II) Suicidality:Suicide Intent Scale (SIS) (Beck 1974) Medical Damage Scale (MDS) (Beck 1975) Risk Rescue Scale (RRS) (Weisman 1972) Scale for Suicidal Ideation (SSI) (Beck 1974) Hopelessness Scale (BHS) (Beck 1974) Typology of Parasuicide (Felber 1998) Depression:Observer's rating: HAM-D21 (Hamilton) Self rating: BDI (Beck Depression Scale) Anxiety:Trait: STAI (Spielberger) State: HAM-A (Hamilton) General psychopathology:BPRS Aggressivity/Impulsivity:FAF (modified Buss Durkee) STAXI (Spielberger) BIRS (Barrat Impulsivity Rating Scale) IRS (Lecrubier Impulsivity Rating Scale) Personality traits:TCI (Cloninger)

  5. Neurobiological parameters — assessed and evaluated by the different centres: MaterialParametersCentres CSF (and plasma) HPA system: MPI-P CRH, ACTH, Cortisol Munich AVP, Oxytocin Excitatory and inhibitory amino acids 5-HT system: 5-HIAA, 5-HT NA system: MHPG DA system: HVA Blood (and platelets) 5-HT2A receptors (platelets) LMU Munich MAO-B (platelets) Berlin tryptophan, other amino acids (plasma) Berlin 5-HT concentration (platelets) Bonn cholesterol, essential fatty acids (plasma) MPI-P Munich Saliva cortisol Dresden Molecular- and see subproject 5 LMU and pharmacogenetics Bonn

  6. Tasks which have been successfully resolved I • The whole project has been subdivided in four subprojects: • 1. Lithium Intervention Study • 2. Molecular Genetics • 3. Peripheral Parameter • 4. CSF

  7. Applications to the Ethics Committees

  8. Tasks which have been successfully resolved II • all six centers met regularly • biological target variables has been defined • psychopathological target variables has been defined • psychopathological assessment instruments has been established • a case record form has been developed • laboratory tests had been selected and established in the different centers • logistics of the distribution of the specimens has been developed • laboratory personnel has been engaged in the different laboratories • analyses of the assessed parameters had been performed • a data collection center has been established (Luebeck) • three independent data banks has been established, • which can be connected with each other: • 1. data bank for peripheral parameter • 2. data bank for the Lithium Intervention Study • 3. data bank for molecular genetics • a double data entry has been performed (30.09.2003)

  9. Recruitment of patients: (1) The majority of patients so far included were inpatients of the six centres participating in subproject 1.5 (neurobiology of suicidal behaviour). (2) Additional patients could be recruited as in- and outpatients of the lithium-intervention study (subproject 1.2). . We intend to match suicidal and non-suicidal patients for diagnoses, age, sex and seasonality. For matched pairs comparisons, a high sample size will be necessary Minimum sample size of 42 for both patient groups.

  10. Results Recruitment of patients and controls (recruitment period: January 1, 2001 —April 30, 2003) Molecular Peripheral CSF Genetics Parameters Recruited 213 103 (67 SA) 44

  11. Participation in the different Subprojects

  12. Scientific results and publications The existing literature has been reviewed with critical reference to methodological and conceptual deficits by the research groups of Prof . Bronisch ( Brunner et al. 1999, 2001a and 2002a) and Prof . Müller - Oerlinghausen ( Müller - Oerlinghausen and Roggenbach 2002, Franke et al. 2002). The center LMU ( Bondy et al. 2000 a) found a higher frequency of the short allele of the 5-HT promoter region ( 5-HTTLPR ) in suicide victims. The same group could not replicate a polymorphism of the 5-HT receptor in suicide 2A victims and patients with suicidal ideation ( Bondy et al. 2000 b). The research group of Müller - Oerlinghausen and the group of the Charité surprisingly showed that no statistical correlation exists between V of the 5- max HT transporter in platelets and the 44- bp polymorphism and the 17bp variable number of tandem repeat (Kaiser et al. 2002). Brunner et al. (2001 a) found lower CRH concentrations in the CSF of suicide attempters as compared to psychiatric controls. A preliminary study showed no differences in CSF AVP between depressed suicide attempters and psychiatric and neurological controls ( Brunner et al.2002b). Lower cholesterol concentrations in suicide attempters have been reported in clinical studies, however, cholesterol-lowering therapies do not increase the risk of suicide ( Brunner et al. 2001 b, 2002c).

  13. Publications of the First Results of the Muticentre Study Brunner J et al. (2001) Decreased corticotropin releasing hormone (CRH) concentrations in the cerebrospinal fluid of eucortisolemic suicide attempters. Journal of Psychiatric Research 35: 1-9 Brunner et al. (2002) Vasopressin in CSF and serum in depressed suicide attempters: correlations with monoamine metabolites and dexamethasone CRH test. European Neuropsychopharmacology 12: 489-494 Brunner et al. (2003) Proteomics analysis of the CSF in unmedicated patients with major depressive disorder reveals alterations in suicide attempters submitted

  14. Follow-up The recruitment of the patients could not be finished within the first three years of funding between January 2000 to December 2002 because the approval of the applications to the local ethics committees resulted in a delay of one year, so that the recruitment of the neurobiological parameters started later than planned: at the beginning of 2001 instead of 2000. Expected closing of the recruitment of patients according to the analysis of the matching process: December 2003. 2004: Data analysis, evaluation and publishing of the data. Networking Subproject 1.2: Lithium-intervention study Subproject 5: Molecular- and pharmacogenetics

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