Neuroanatomical correlates of suicide in psychosis: the possible role of von Economo neurons

Abstract

Suicide is the most important incident in psychiatric disorders. Psychological pain and empathy to pain involves a neural network that involves the anterior cingulate cortex (ACC) and the anterior insula (AI). At the neuronal level, little is known about how complex emotions such as shame, guilt, self-derogation and social isolation, all of which feature suicidal behavior, are represented in the brain. Based on the observation that the ACC and the AI contain a large spindle-shaped cell type, referred to as von Economo neuron (VEN), which has dramatically increased in density during human evolution, and on growing evidence that VENs play a role in the pathophysiology of various neuropsychiatric disorders, including autism, psychosis and dementia, we examined the density of VENs in the ACC of suicide victims. The density of VENs was determined using cresyl violet-stained sections of the ACC of 39 individuals with psychosis (20 cases with schizophrenia, 19 with bipolar disorder). Nine subjects had died from suicide. Twenty specimen were available from the right, 19 from the left ACC. The density of VENs was significantly greater in the ACC of suicide victims with psychotic disorders compared with psychotic individuals who died from other causes. This effect was restricted to the right ACC. VEN density in the ACC seems to be increased in suicide victims with psychosis. This finding may support the assumption that VEN have a special role in emotion processing and self-evaluation, including negative self-appraisal.

Figure 1. The localization and distribution of VENs in the ACC of suicide victims and non-suicide subjects.

(A) Cresyl violet stained section displays the cortical layers I, II, III, Va, Vb and VI of the anterior cingulate cortex (ACC). (B) Numerous von Economo neurons (VENs, arrowheads) are localized in layer Vb, adjacent to layer Va, where large pyramidal cells are frequent. (C) The VENs (for localization see arrow in A) with elongated somata and bipolar dendrites (red arrowheads) can easily be distinguished from neighbored triangular-shaped pyramidal cell somata (black arrowheads). (D) VEN density in the ACC of suicide victims and non-suicide subjects with psychosis (values for the right ACC are shown in red, values for the left ACC are marked in blue; black: total values; “0” indicates no suicide, “1” indicates suicide cases). The representative distributions of VENs in subjects with schizophrenia (E, F) and bipolar disorder (G, H) reflect the high VEN density in suicide victims (E, G) when compared with non-suicide subject (F, H). Suicide victims exhibit more VENs (red arrowheads) clustering (I, K); in non-suicide subjects VENs are localized more solitary (J, K). cc, corpus callosum. Scale bars in A = 2 mm; in B = 50 µm; in C = 10 µm; in H for E–H = 1 mm, in L for I–L = 50 µm.