Elsevier

Biological Psychiatry

Volume 50, Issue 10, 15 November 2001, Pages 783-791
Biological Psychiatry

Aggressivity, suicide attempts, and depression: relationship to cerebrospinal fluid monoamine metabolite levels

https://doi.org/10.1016/S0006-3223(01)01170-2Get rights and content

Abstract

Background:We have proposed a stress-diathesis model for suicidal behavior, in which major depression is a stressor and the diathesis is shared with aggression. Neurotransmitter correlates of the stress or diathesis have not been adequately evaluated by previous studies, because they did not simultaneously examine the relationship of multiple neurotransmitters to all three psychopathologies in the same population. In the present study we investigated the relationship of monoamine metabolites to aggressivity, suicidal behavior, and depression in patients with mood disorders.

Methods: Ninety-three drug-free subjects with a major depressive episode underwent lumbar puncture and psychiatric evaluation. Cerebrospinal fluid CSF levels of 5hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA) and methoxy-hydroxy-phenylglycol (MHPG) were assayed. The relationships between monoamine metabolites and clinical variables were statistically evaluated.

Results: Higher lifetime aggressivity correlated significantly with lower CSF 5-HIAA. Lower CSF 5-HIAA and greater suicidal intent were found in high-lethality suicide attempters compared with low-lethality suicide attempters. Low-lethality attempters did not differ biologically from nonattempters. No correlation between CSF HVA and any of the psychopathological variables was found. Only aggression showed a trend statistically in correlating positively with CSF MHPG levels.

Conclusions: Lower CSF 5-HIAA concentration was independently associated with severity of lifetime aggressivity and a history of a higher lethality suicide attempt and may be part of the diathesis for these behaviors. The dopamine and norepinephrine systems do not appear to be as significantly involved in suicidal acts, aggression, or depression. The biological correlates of suicide intent warrant further study.

Introduction

Low cerebrospinal fluid (CSF) 5-hydroxyindolacetic acid (5-HIAA) is associated with a history of suicide attempts independently of psychiatric diagnosis (Mann et al 1996), correlates with the lethality of past suicide attempts (Mann and Malone 1997), and predicts a higher rate of future suicidal behavior Cooper et al 1992, Nordström et al 1994, Roy et al 1989. The relationships of other CSF amine metabolites to suicide attempts and other psychopathologies are less clear. Low CSF homovanillic acid (HVA) has been found by some investigators in alcoholic, violent offenders and in suicide attempters Åsberg et al 1984, Virkkunen et al 1996; however, others do not find a correlation between CSF HVA and suicidal behavior Mann and Malone 1997, Roy et al 1986. Agren (Ågren 1982) reported a complex relationship between methoxy-hydroxy-phenylglycol (MHPG) and suicidal behavior, but most studies are negative (Table 1). If serotonin, norepinephrine, and dopamine play a role in modulating the probability of suicidal behavior, then the question is, how? We hypothesized that these monoamine systems may do so by directly affecting the threshold or diathesis for self-directed and externally directed aggressive behavior, or by influencing the severity of depression, hopelessness, or suicidal ideation. Low CSF 5-HIAA, MHPG, and HVA have all been hypothesized to be part of major depression, but the published literature disagrees (Table 2). Low CSF 5-HIAA has been reported in relation to externally directed aggression (Table 3), but whether that also explains the relationship to suicide remains to be directly examined.

Cerebrospinal fluid MHPG is reported to be both higher and lower in depressed subjects, although rodent models of helplessness and despair are associated with depletion of norepinephrine and MHPG (Weiss et al 1994). The relationship of CSF MHPG to suicidal behavior and aggression is unclear Table 1, Table 3.

Lifetime suicidal behavior shows a close relationship to the severity of aggressive traits but not to objective severity of depression (Mann et al 1999). Therefore, determining the relationship of monoamine indices to suicidal behavior raises the question of their relationship to severity of depression and aggressive-impulsive traits and is important to obtain a fuller picture of the neurobiological correlates of suicide risk.

The aim of the present study was to determine whether CSF monoamine metabolites correlate with suicidal behavior because of a relationship to mood or through a diathesis that also underlies aggressive-impulsive traits.

Section snippets

Recruitment and ratings of psychopathology

Subjects (n = 93) were recruited from patients admitted to a university psychiatric teaching hospital for evaluation and treatment of a mood disorder. They all gave written informed consent for this study as required by the Institutional Review Board for Biomedical Research. All met criteria for a current major depressive episode. The duration of the drug-free status of the patients was established by a combination of drug screening, observation in the hospital, and a history obtained from the

Demographic characteristics, psychiatric diagnoses, and clinical variables

Demographic and clinical data are reported in Table 4. Mean scores on the HDRS and B-G scale for the whole group were in the moderate severity range (20.7 ± 6.3 and 20 ± 6.3, respectively). Fifty-nine subjects (63.4%) had a history of a suicide attempt. Forty subjects (67.8% of all attempters) had attempted suicide within 1 year of the lumbar puncture. The median of the time interval between the lumbar puncture and the most recent suicide attempt was 118 days or about 4 months (range: 3–9507).

Suicidal behavior

Lower levels of CSF 5-HIAA are associated with a history of more serious suicidal behavior in patients with mood disorders, and this finding confirms our previous report (Mann et al 1996) in a different set of patients with a major depressive episode. Moreover, as we found previously (Mann et al 1996), low lethality suicide attempters did not differ in CSF 5-HIAA levels from psychiatric control subjects (nonattempters with a mood disorder). This observation may explain why some studies find

Acknowledgements

This work was supported in part by Public Health Service grants MH 46745, 48514, and RR 00645

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