Neurobiology of suicidal behavior
In a multicenter study funded by the German Ministry for Education and Research, peripheral parameters (assessed in CSF, blood, saliva) of the aforementioned systems are investigated in depressed patients with and without a suicide attempt. 109 patients have been included in the six different centers so far.
The integrative and multivariable design of the present study enables us to investigate possible interactions between serotonergic, noradrenergic and dopaminergic activity, the HPA axis, and lipid metabolism. The various neurobiological parameters are to be correlated with the psychopathology and varying clinical aspects of suicidal behavior (violent vs. non-violent suicide attempts, suicidal vs. parasuicidal behavior, psychometric scores of impulsivity and aggression). The prospective design is suitable for evaluating the predictive value, the time course, and the stability over time of the assessed neurobiological parameters. Such alterations might be regarded as possible ”trait markers” related to the vulnerability or diathesis of suicidal behavior.
Abnormalities in the serotonergic (5-HT) system have been implicated in the pathogenesis of suicidal behavior. Studies on peripheral serotonergic parameters as a measure for central serotonergic function in suicidal patients appear to be promising, yet failed to show a clear association with suicidality. The objective of this study was to elucidate the role of serotonergic blood parameters in depressed suicidal patients and to examine their usefulness as a potential biological marker for suicidality. A number of personality traits were assessed in order to provide a basis for a psychobiological model of suicidal behavior. Depressed patients with a recent suicide attempt (SA; n=59) were compared to those without history of suicide attempts (NSA; n=28). 5-HT2a receptor activity in platelets and tryptophan/aminoacid ratio in plasma were measured. Acute psychopathology and personality traits as well as characteristics of suicide attempts were assessed. There was no significant difference between SA and NSA in terms of peripheral serotonergic parameters as well as personality traits. However, the whole sample showed associations between certain personality traits and serotonergic platelet parameters. Furthermore, we observed a relation between suicidal ideation, lethality of suicide attempts and peripheral serotonergic markers.
Limitations: The number of cases with data on peripheral markers is relatively low. The potential influence of antidepressant medication previous to study inclusion has to be taken into account. The study focussed on depressed patients only. Conclusions: Low serotonergic function is involved in the pathogenesis of suicidality, whereas the use of platelet 5-HT2A receptor activity and tryptophan availability as biological markers for suicidality in depressed patients could not be proven as an appropriate tool. Alterations in the serotonergic system are associated with trait aggression and other character dimensions.
Fig. 1. CRH-concentrations in relation to ACTH and Cortisol in patients with (solid line) and without (dashed line) a suicide attempt
Low cholesterol concentrations and cholesterol-lowering therapies have been suggested to be associated with increased suicidality. Findings are based on a nationally representative community sample of n ¼ 4,181 subjects (18–65 years) examined with a standardized diagnostic interview (CIDI) for (DSM-IV) mental disorders. Controlling for age and gender the study revealed a moderate positive association between cholesterol, triglycerides, BMI, and suicide attempts in subjects with depressive symptoms during the past 12 months (n ¼ 1,205). The results of this study are compatible with two recent epidemiological cohort studies showing a positive association between cholesterol and completed suicide.
This is the first report on proteomic analysis of the cerebrospinal fluid (CSF) in unmedicated suicide attempters and non-attempters with major depressive disorder. Two-dimensional (2D) gel electrophoresis revealed that suicide attempters differed from non-attempters in one protein with an approximate molecular weight of 33 kD and an isoelectric point of 5.2. Proteomic analysis of the CSF is a promising non hypothesis-driven screening method for the detection of new candidate genes in neurobiological suicide research.
Low platelet MAO-B activity has been associated with various forms of impulsive behavior and suicidality. In 87 patients with affective spectrum disorders (58% suffering from MDE) the potential association between platelet MAO-B activity and suicidality was examined. 59 of the patients had committed suicide attempt recently (SA), 28 patients were acutely depressed without having shown suicidal thoughts or suicidal behavior in the past (NA). SA and NA were comparable as to their diagnoses and general demographic and psychopathological parameters. A multitude of parameters focussing on psychopathology, personality and various aspects of suicidal behavior were assessed in detail. MAO-B activity did not differ between SA and NA. No systematic correlations existed between MAO-B activity and any dimensions of suicidal behavior or psychopathology. However, higher MAO-B activity in SA was associated with a fatal intention of the suicide attempt. Altogether, our findings do not support a consistent association of platelet MAO-B activity and suicidal behavior in general, but specific facets of suicidality might be associated.
Research groups involved:
Brigitta Bondy M.D, Ludwig-Maximilians-University Munich, Dept. of Psychiatry
Dan Rujescu M.D., Ludwig-Maximilians-University Munich, Dept. of Psychiatry
Bruno Müller-Oerlinghausen, M.D., Drug Commission of the German Medical Association, Berlin
Fritz Hohagen M.D., Erik Lauterbach M.D., University of Schleswig-Holstein, Dept. of Psychiatry and Psychotherapy
Isabella Heuser M.D., Jürgen Schley, Charité-Universitätsmedizin Berlin, Klinik und Hochschulambulanz für Psychiatrie und Psychotherapie
Christine Frahnert, Barbara Hawellek M.D., Marie Luise Rao M.D., University of Bonn, Dept. of Psychiatry and Psychotherapy
Werner Felber M.D., Ute Lewizka M.D., Technical University of Dresden, Dept. of Psychiatry and Psychotherapy
Publications:
Lewitzka U, Müller-Oerlinghausen B; Brunner J; Hawellek B Rujescu D; Ising M; Lauterbach E; Broocks A; Bondy B; Rao M, Frahnert C; Felber W; Heuser I; Hohagen F; Maier W; Bronisch T (2008) Is MAO-B activity in platelets associated with the occurrence of suicidality and behavioural personality traits in depressed patients? Acta Psychiatrica Scandinavica 117: 41-49
Brunner J., Bronisch T., Pfister H., Jacobi F., Höfler M., Wittchen H.-U. (2006) High cholesterol, triglycerides, and body-mass index in suicide attempters. Archives of Suicide Research 10: 1-9
Lauterbach E., Brunner J., Hawellek B., Ising M., Bondy B., Rao M.-L., Frahnert C., Lewitzka U., Rujescu D., Müller-Oerlinghausen B., Schley J., Heuser I., Maier W., Felber W., Bronisch T. (2006) Platelet 5-HT2A receptor activity and tryptophan availability in depression are not associated with recent history of suicide attempts but with personality traits characteristic for suicidal behavior. Journal of Affective Disorders 91: 57-62
Bronisch T., Brunner J., Bondy B., Rujescu D., Bishof G., Heuser I., Müller-Oerlinghausen B., Hawellek B., Maier W., Rao M. L., Felber W. , Lewitzka U., Oehler M., Broocks A. , Hohagen F., Lauterbach E. (2005) A multicenter study about neurobiology of suicidal behavior. Design, development and preliminary Results. Archives of Suicide Research 9:19-26
Brunner J., Bronisch T., Uhr M., Ising M., Binder E., Holsboer F., Turck C.W. (2005) Proteomic analysis of the CSF in unmedicated patients with major depressive disorder reveals alterations in suicide attempters. European Archives of Psychiatry & Clinical Neuroscience 255: 438-440
Brunner J. and Bronisch T. (2003) Cholesterol, essential fatty acids, and suicide. Author´s reply to a letter by Takeshi and Soya. Pharmacopsychiatry 36: 83-86
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