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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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slide1

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

slide3

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
slide4

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)

slide5

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

slide6

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
slide8

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)
slide9

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.

slide11

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

slide13

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).

slide14

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

slide15

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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