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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

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



A multicenter study about neurobiology of suicidal behaviour

  • 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


  • A multicenter study about neurobiology of suicidal behaviour

    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)


    A multicenter study about neurobiology of suicidal behaviour

    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


    A multicenter study about neurobiology of suicidal behaviour

    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



    A multicenter study about neurobiology of suicidal behaviour

    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)


    A multicenter study about neurobiology of suicidal behaviour

    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.


    A multicenter study about neurobiology of suicidal behaviour

    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



    A multicenter study about neurobiology of suicidal behaviour

    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).


    A multicenter study about neurobiology of suicidal behaviour

    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


    A multicenter study about neurobiology of suicidal behaviour

    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