Impulsivity and Saliva Cortisol in Patients with Suicide Attempt and Controls.

OBJECTIVES: The objective of this study was to prove concepts in the characterization of suicidal patients and the possible usefulness of those markers to potentially identify patients with a higher risk for suicidality. METHODS: Patients with a recent suicide attempt were compared with patients suffering from depression, adjustment disorder, anxiety, or eating disorders without suicidality, healthy controls and remitted patients with a history of at least 1 suicide attempt (≥1 year). We analyzed impulsivity (Barratt Impulsivity Scale, BIS) and saliva cortisol concentrations. RESULTS: Independently of suicidality and disease state patients display higher BIS scores than healthy controls. Saliva cortisol levels tend to be higher in patients in the acute disease state than in remitted patients and healthy controls. CONCLUSIONS: Saliva cortisol may be a useful marker that reveals alterations in nonsuicidal patients suffering from depression, adjustment disorder, anxiety, or eating disorders who might be at risk.

Adjunctive lithium treatment in the prevention of suicidal behavior in patients with depression and comorbid personality disorders.

OBJECTIVE: Patients with both major depression and personality disorders have a high risk of suicidal behavior. Lithium is meant to have anti-suicidal properties in patients with affective disorders. The anti-suicidal effect of lithium in patients with affective disorders and comorbid personality disorders has not been investigated yet. METHODS: A post-hoc analysis of a subsample of patients with depression and comorbid personality disorder (PD) and a recent suicide attempt (n = 19) from the prospective, placebo-controlled lithium intervention study (N = 167), was conducted. RESULTS: Three patients in the lithium group (n = 8) and two patients in the placebo group (n = 11) presented a suicide attempt throughout the course of the study. No differences related to suicidal behavior could be detected between the placebo group and the group with lithium intervention. CONCLUSIONS: On the basis of the small sample size, among patients with comorbid PD, lithium does not seem to have an effect on suicidal behavior in contrast to patients with affective disorders without comorbid PD.

Cerebrospinal fluid biomarkers for major depression confirm relevance of associated pathophysiology.

Individual characteristics of pathophysiology and course of depressive episodes are at present not considered in diagnostics. There are no biological markers available that can assist in categorizing subtypes of depression and detecting molecular variances related to disease-causing mechanisms between depressed patients. Identification of such differences is important to create patient subgroups, which will benefit from medications that specifically target the pathophysiology underlying their clinical condition. To detect characteristic biological markers for major depression, we analyzed the cerebrospinal fluid (CSF) proteome of depressed vs control persons, using two-dimensional polyacrylamide gel electrophoresis and time-of-flight (TOF) mass spectrometry peptide profiling. Proteins of interest were identified by matrix-assisted laser desorption ionization TOF mass spectrometry (MALDI-TOF-MS). Validation of protein markers was performed by immunoblotting. We found 11 proteins and 144 peptide features that differed significantly between CSF from depressed patients and controls. In addition, we detected differences in the phosphorylation pattern of several CSF proteins. A subset of the differentially expressed proteins implicated in brain metabolism or central nervous system disease was validated by immunoblotting. The identified proteins are involved in neuroprotection and neuronal development, sleep regulation, and amyloid plaque deposition in the aging brain. This is one of the first hypothesis-free studies that identify characteristic protein expression differences in CSF of depressed patients. Proteomic approaches represent a powerful tool for the identification of disease markers for subgroups of patients with major depression.

Maternal suicidality and suicide risk in offspring.

A considerable number of studies linking family history and high risk for suicide have reported that suicidality runs in families. Community studies that avoid a selection effect confirm these findings. These results seem independent of comorbidities such as depression, anxiety, substance use, and personality disorders. Furthermore, the results are stable over treatment settings, different age groups, and gender. Community studies interviewing families directly (family interview method) are primarily focused on maternal suicidality and suicidality in offspring. Two studies observed some indications for suicide attempts in young offspring of mothers (and fathers) who had attempted suicide compared with offspring of mothers who had no suicidality.

Smoking predicts suicidality: findings from a prospective community study.

BACKGROUND: The temporal relationship between smoking and suicidality is not yet clear. This article examines associations between smoking and suicidality and their temporal ordering of onset. METHODS: Baseline and four-year follow-up data were used from the Early Developmental Stages of Psychopathology (EDSP) study, a prospective longitudinal study of adolescents and young adults in Munich, Germany. We assessed smoking (occasional and regular), nicotine dependence, suicidal ideation and suicide attempts using the standardized Munich-Composite International Diagnostic Interview (M-CIDI). RESULTS: Suicide ideation and suicide attempts were strongly associated with occasional and regular smoking and nicotine dependence at baseline (Odds ratios [OR] range from 1.4 to 16.4). In the prospective analyses, prior occasional, regular smoking and nicotine dependence increased the risk for new onset of suicide ideation (OR range from 1.5 to 2.7) and prior regular smoking and nicotine dependence increased also the risk for onset of suicide attempt(s) (OR range between 3.1 and 4.5). Pre-existing suicidality could not be shown to be associated with subsequent smoking or nicotine dependence. Associations remained stable when participants who fulfilled DSM-IV-criteria for major depression were excluded. LIMITATIONS: The sample is confined to an age cohort of 14 to 24 years. No completed suicides could be observed. CONCLUSIONS: The presence of associations between prior smoking and subsequent suicidality, in concert with the lack of associations between prior suicidality and subsequent smoking suggests the existence of an independent pathway from smoking to suicidality.

Molecular genetic findings in suicidal behavior: what is beyond the serotonergic system?

Various studies provide consistent evidence for a genetic component in suicidal behavior. First molecular genetic studies concentrated on genes of the serotonergic system based on the biochemical evidence that serotonergic neurotransmission is implicated in this behavior. Furthermore, genes of the dopaminergic and noradrenergic neurotransmitter systems have also been the subjects of investigations in this context. Some epidemical and clinical studies showed that low serum cholesterol levels are associated with suicidal behavior and genes involved in these pathways have been investigated. Microarray experiments provide the possibility of genome-wide gene expression analysis and help to investigate associated molecular mechanisms. The aim of this article is to review molecular genetic studies in suicidal behavior and to emphasize findings on new genes.

The accuracy of prevalence estimations for suicide attempts. how reliably do adolescents and young adults report their suicide attempts?

This study explores the accuracy of prevalence estimations for suicide attempts. Data came from the Early Developmental Stages of Psychopathology (EDSP) Study, a prospective community study (mean follow-up period was 42 months) of 3,021 respondents aged 14 to 24 years at the outset of the study. Suicide attempters are at least 1.6 times more likely to drop out than subjects with no suicide attempts and suicidal ideas. A total of 8% of all suicide attempters answered in the negative the depression-related gate questions of all surveys. One-third of all baseline suicide attempters did not report their suicide attempt again at the four years later assessment. In particular, 80% of all nonreporters were female, and almost 60% were aged 14-17 at baseline.

Crisis intervention after the Tsunami in Phuket and Khao Lak.

After the Tsunami disaster in Southeast Asia, India, Sri Lanka, and Africa, the German government set up a crisis task force that implemented crisis-intervention teams covering Thailand (Phuket and Khao Lak), Sri Lanka, and Sumatra. Two crisis teams were sent to Phuket; the first one on 28 December 2004, and the second one on 3 January 2005, each for an average of 1 week. This intervention was primarily for the benefit of German citizens and their expatriates and relatives caught up in a major catastrophe as well as the German helpers. This article describes the organizational structures of the German crisis intervention, protective factors for the helpers, psychiatric syndromes--often acute traumata, the problems of the identification process for relatives, and crisis intervention itself. Consequences for further crisis intervention after natural disasters are discussed.

Platelet 5-HT2A receptor binding and tryptophan availability in depression are not associated with recent history of suicide attempts but with personality traits characteristic for suicidal behavior.

BACKGROUND: 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. METHODS: 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 binding in platelets and tryptophan/amino acid ratio in plasma were measured. Acute psychopathology and personality traits as well as characteristics of suicide attempts were assessed. RESULTS: 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 an appropriate tool. Alterations in the serotonergic system are associated with trait aggression and other character dimensions.

High cholesterol, triglycerides, and body-mass index in suicide attempters.

Low cholesterol concentrations and cholesterol-lowering therapies have been suggested to be associated with increased suicidality. This article examined the association of cholesterol, triglycerides, and body-mass index (BMI) with suicidal ideation and suicide attempts. Findings are based on a nationally representative community sample of n = 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 = 1,205). The results of this study are compatible with two recent epidemiological cohort studies showing a positive association between cholesterol and completed suicide.

Proteomic analysis of the CSF in unmedicated patients with major depressive disorder reveals alterations in suicide attempters.

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.

Maternal suicidality and risk of suicidality in offspring: findings from a community study.

OBJECTIVE: This study evaluated the associations between suicidal ideation and suicide attempts in mothers and various aspects of suicidality in their offspring in a representative community sample. METHOD: Baseline and 4-year follow-up data were used from the Early Developmental Stages of Psychopathology study, a prospective, longitudinal community study of adolescents and young adults. Results are based on 933 adolescents who completed follow-up and for whom direct diagnostic information for the biological mother was available. Suicidal ideation and suicide attempts were assessed in adolescents and mothers with the Munich-Composite International Diagnostic Interview. RESULTS: Compared to offspring of mothers without suicidality, offspring of mothers reporting suicide attempts showed a remarkably higher risk for suicidal thoughts and suicide attempts and a tendency toward suicide attempts at an earlier age. Associations were comparable for male and female offspring. Transmission of maternal suicidality was roughly stable with control for maternal comorbid psychopathology. CONCLUSIONS: The offspring of mothers with suicide attempts are at a markedly increased risk for suicidality themselves and tend to manifest suicide attempts earlier than offspring of mothers without suicidality. Suicidality seems to run in families, independent of depression and other psychopathology.

A multicenter study about Neurobiology of Suicidal Behavior: design, development, and preliminary results.

The subproject 1.5 "Neurobiology of Suicidal Behavior" is a multicenter study assessing peripheral parameters of the serotonergic, noradrenergic, and dopaminergic transmitter systems. Additionally, stress hormones and the lipid system as well as inhibitory and excitatory amino acids will be investigated. The different parameters are collected in cerebral spinal fluid (CSF), blood, and saliva. Patients with a depressive spectrum disorder with and without a suicide attempt (during the last three weeks) and being medication free for two weeks are included in the study. So far, 103 patients and controls have been recruited. The design and development of this project as well as interconnections with the others subprojects are described. Preliminary results about the stress hormone system and suicidality are presented.

Suicide prevention by lithium SUPLI--challenges of a multi-center prospective study.

Several studies have shown that there is a significantly increased risk of suicide related mortality in patients with a positive history of suicide attempts. The SUPLI-Study is the first prospective, randomized, double blind, placebo controlled multi-center trial focusing on the proposed suicide preventive effects of lithium in patients with suicidal behavior but not suffering from bipolar disorder or recurrent major depressive disorder. Patients with a recent history of a suicide attempt are treated with lithium versus placebo during a 12 month period. The hypothesis is that lithium treatment will lead to a 50% reduction of suicidal behavior. The protocol of the study and preliminary results are presented.

Suicidality, bipolar disorders, and pharmacotherapy.

Although the existence of mood disorders was identified centuries ago, the present state of knowledge is unsatisfactory. This special issue of Archives of Suicide Research (ASR), the official journal of the International Academy for Suicide Research, presents the state of the science and collects new empirical data. Different aspects of suicidality in bipolar and bipolar spectrum disorders are outlined and the prophylactic aspects of pharmacotherapy are noted, especially the anti-suicide effect of lithium. A call for further study is, however, necessary.

Mania, hypomania, and suicidality: findings from a prospective community study.

We examined prospectively whether mania and hypomania are associated with an elevated risk for suicidality in a community sample of adolescents and young adults. Baseline and four-year follow-up data were used from the Early-Developmental-Stages-of-Psychopathology (EDSP) Study, a prospective longitudinal study of adolescents and young adults in Munich. Suicidal tendencies (ideation/attempts), mania, and hypomania were assessed using the standardized Munich-Composite-International-Diagnostic-Interview. At baseline, mania/hypomania was associated to a different degree with suicidality (Odds ratios [OR] range from 1.9 to 13.7). In the prospective analyses, the risk for subsequent incident suicidal ideation was increased in the presence of prior mania (38.0% vs. 14.1%; OR = 4.4; 95% CI = 1.4-13.5). No associations could be found between prior mania/hypo-mania and incident suicide attempts. The prospective analyses revealed a remarkable relationship between preexisting mania and increased risk for subsequent suicidal ideation.

Vasopressin in CSF and plasma in depressed suicide attempters: preliminary results.

Increased plasma arginine vasopressin (AVP) concentrations have been reported in depressed suicide attempters. Plasma AVP is primarily produced by the magnocellular system in response to increased plasma osmolality, and central AVP may be independently regulated. In the present study we investigated cerebrospinal fluid (CSF) and plasma AVP concentrations in depressed patients and controls. Nineteen drug-free depressed psychiatric inpatients (nine suicide attempters) and nine neurological control subjects underwent lumbar puncture and psychiatric evaluation. CSF and plasma concentrations of AVP, serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and cortisol were assayed. In 15 depressed patients (eight suicide attempters), the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) test was performed to examine the hypothalamic-pituitary-adrenocortical (HPA) system. There were no differences between depressed subjects and controls in all parameters measured. Suicide attempters did not differ from nonattempters. In depressed patients, plasma AVP correlated positively with cortisol. There was no relationship between CSF AVP and monoamine metabolites in CSF.