Oquendo and colleagues published an interesting study in 2003, in which they investigated the brains of 16 high-lethality and 9 low-lethality suicide attempters having a depressive episode. The patients were scanned in resting condition with ¹⁸F-FDG PET imaging in order to estimate regional brain activity in conditions where external activation is minimized or standardized. Subjects were scanned after a single-blind placebo and after fenfluramine hydrochloride administration on a second day. Fenfluramine is a serotonin agonist that provokes an increase in the presynaptic release of serotonin. Secondary and proportional to this postsynaptic receptor stimulation, the anterior pituitary gland releases prolactin in the circulation. If the serotonergic system is impaired, a blunted increase in prolactin is found (Malone et al. 1996; Correa et al. 2000). Besides an increase in prolactin, fenfluramine also increases frontal cortex metabolism (Soloff et al. 2003). The authors found that depressed high-lethality suicide attempters showed relative hypometabolism compared to low-lethality attempters in the ventral, medial, and lateral prefrontal cortex. This difference was more pronounced after fenfluramine administration. Lethality of the attempt appeared to be inversely correlated with metabolism in the ventromedial prefrontal cortex after challenge with fenfluramine. A lower mean regional cerebral metabolic rate of glucose uptake (rCMRglu) correlated with higher lethality of suicidal behavior. The authors also demonstrated that higher verbal fluency correlated positively with rCMRglu in the same regions of the prefrontal cortex and that lethality of the suicide attempt inversely correlated with prolactin after challenge. They found a lower CMRglu in high- versus low-lethality suicide attempters. This hypometabolism in frontal cortex structures was related to the degree of suicide intent and impulsivity and not to depression (Oquendo et al. 2003).

Leyton and coworkers (2006) measured regional serotonin synthesis in the brain with PET and α-(¹¹C)-methyl-L-tryptophan trapping in ten patients who had made a high-lethality suicide attempt and in 16 healthy controls. Suicide attempters showed reduced serotonin synthesis in the orbital and ventromedial prefrontal cortices. α-(¹¹C)-methyl-L-tryptophan trapping in these regions correlated negatively with suicide intent. Elevated α-(¹¹C)-methyl-L-tryptophan trapping was seen in the left thalamus, right paracentral lobule, and the left middle occipital cortex. The investigators concluded that low serotonin synthesis in the prefrontal cortex might lower the threshold for suicidal behavior.

A few studies used SPECT imaging to study functional changes in brain functions. Audenaert and coworkers (2001) studied nine patients who had recently (1–7 days) attempted suicide and compared these to 12 age-matched healthy controls using ¹²³I-5-I-R91150 SPECT. They found a significantly reduced binding index in the frontal cortex in the patient group. The binding index was significantly lower in the deliberate self-injury patients compared to the deliberate self-poisoning subjects. The results indicate a decrease in the number and/or in the binding affinity of 5-HT_2A receptors. Further analysis revealed a significant negative correlation between 5-HT_2A-receptor binding and levels of hopelessness, a very important clinical predictor of suicidal behavior (van Heeringen et al. 2003).

In a split-dose ^99mTc-ECD SPECT activation paradigm, Audenaert and colleagues (2001) included 20 depressed patients who had recently attempted suicide and compared them to 20 healthy volunteers. The neuropsychological activation consisted of a verbal fluency test. When compared to healthy volunteers, patients showed a blunted increase in perfusion in the prefrontal cortex during specific verbal fluency tasks. When comparing the activated brain regions between healthy volunteers and patients in the category fluency paradigm, a statistically significant blunting of the perfusion was observed in the patient group in the left gyrus frontalis inferior, right gyrus parietalis inferior, and bilateral gyrus cinguli anterior. There were no regions with significantly increased perfusion in the patient group compared to the controls. When comparing the activated brain regions between healthy and depressed subjects in the letter fluency paradigm, the authors found a statistically significant blunting of the perfusion in the depressed group in the left and right gyrus temporalis medius, right gyrus cinguli anterior, and hypothalamic region. There were no regions with significantly increased perfusion in the patient group compared to control subjects. The authors suggest that the blunted increase in prefrontal blood perfusion might be a biological reason for reduced drive and loss of initiative in attempted suicide patients.