تکانشگری مربوط به ناقل سروتونین مغزی ظرفیت متصل شونده در عمل اقدام به خودکشی

Altered monoaminergic activity has earlier been associated with violent suicidal behaviour. In this study whole brain binding potential of the serotonin transporter (5HTT) and dopamine transporter (DAT) was measured by single photon emission computerised tomography (SPECT) in 12 patients after a serious suicide attempt and in 12 age, sex and season matched healthy controls. Clinical and temperamental assessments were analysed for possible associations with 5HTT and DAT. We found no significant 5HTT or DAT differences between patients and controls. In patients, but not in controls, there was a significant correlation between whole brain 5HTT and DAT. Impulsiveness according to the Marke Nyman Temperament (MNT) was significantly correlated to 5HTT in suicide attempters, but not in controls. Neither of the transporters could be regarded as a marker for serious suicidal behaviour. A previously discussed connection between serotonin and dopamine was replicated in this study. In suicide attempters, low 5HTT was associated with impulsivity and to some extent with depressive disorder—key factors for suicidal behaviour.

Many studies of different body fluids of patients and controls have shown that impulsive violent and suicidal behaviour is associated with central serotonin and/or dopamine deficits. The findings have so far been mainly in depressed patients or in patients with alcoholism (for an overview, see e.g. Träskman-Bendz and Mann, 2000). The monoamine systems are to a large extent interconnected and modulate each other. An early study by Agren et al. (1986) showed a significant correlation between the serotonin and dopamine metabolites in lumbar cerebrospinal fluid, which was replicated by ourselves in suicide attempt patients (Engström et al., 1999). The CSF metabolite correlations prompted Roy et al. (1986) to use the ratios of the monoamine metabolites homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) in their calculations of cerebrospinal fluid findings, rather than each metabolite per se. The Agren et al. (1986) findings were mainly explained by a functional serotonergic influence on dopamine turnover. Similar theories on variations of interdependencies between serotonin and catecholamines during depression and recovery have been put forward by Geracioti et al. (1997). Recently developed brain imaging techniques have the advantage of offering studies of central monoamine metabolism in vivo. Audenart et al. (2001) studied serotonin-2a (5HT-2a)-receptors of male deliberate self-harm patients and healthy controls by use of single photon emission computed tomography (SPECT). They found an age-dependent 5HT-2a binding index. After correction for age the most prominent decrease of frontal 5HT-2a binding was found in patients who attempted suicide by violent means. SPECT can also be used to study monoamine transporters by use of the cocaine analogue 2-beta-carbomethoxy-3-beta-(4-iodophenyl)-tropane, labelled with 123-iodine, (123I-β-CIT) (Laruelle et al., 1994). In a Finnish study, brain monoamine transporters were studied in this way in impulsive violent individuals (Tiihonen et al., 1997). The analysis then showed that the serotonin transporter (5HTT) density in the midbrain of violent offenders was significantly lower than that in the healthy control subjects or the non-violent alcoholics. Reduced hypothalamic and thalamic 5HTT availability was found in bulimia patients by another research group (Tauscher et al., 2001). 123I-β-CIT SPECT has also been studied in drug-free depressed patients with (Willeit et al., 2000) or without Laasonen-Balk et al., 1999 and Malison et al., 1998 seasonal affective disorder (SAD). The results of these studies showed that both non-SAD patients and SAD-patients had significantly lower 123I-β-CIT binding (here reflecting availability of the 5HTT) in thalamus–hypothalamus or in brainstem than in healthy subjects, while the β-CIT uptake [in this case reflecting the dopamine transporter (DAT)] was significantly higher on both sides of the basal ganglia in non-SAD patients than healthy controls. A study of depressive drug-naı̈ve children and adolescents showed that they had significantly higher 5HTT availability in the hypothalamic/midbrain area than non-depressed subjects (Dahlstrom et al., 2000). A reduced brain 5HTT availability was seen in healthy controls during winter as compared to the summer season (Neumeister et al., 2001). The aim of the present study was to study brain serotonin and dopamine transporters of suicide attempters, not exposed to antidepressants or antipsychotics during 6 months before the attempt, in vivo. We expected to find a reduced 5HTT (reflecting a changed serotonin activity), especially in violent suicide attempters, and possibly a significant association between DAT and/or 5HTT and depressive disorder.