The anterior cingulate cortex (ACC) represents a phylogenetically ancient region of the mammalian brain that has undergone recent adaptive changes in humans. It contains a large spindle-shaped cell type, referred to as von Economo neuron (VEN) that has been shown to be involved in the pathophysiology of various neuropsychiatric disorders. Schizophrenia is a group of disorders that is, in part, characterised by a disruption of neuronal migration in early ontogeny and presumably secondary degeneration after the first psychotic episode in some patients. Accordingly, we tested the hypothesis that the density of VENs is reduced in a neurodevelopmental subtype of schizophrenia, which we defined by an early onset of the disorder. The density of VENs was estimated in layer Vb of Brodmann's area 24 in 20 subjects diagnosed with schizophrenia. The results were compared with 19 specimens from patients with bipolar disorder as a clinical control and 22 non-psychiatric samples. The density of VENs did not differ between the three groups. However, the VEN density in the right ACC correlated with the age at onset, and inversely with the duration of the illness in schizophrenia, but not in bipolar disorder. Thus, patients with early onset schizophrenia (and longer duration of illness) had a reduced VEN density. Age, sex, postmortem interval, brain weight, and cortical thickness had no significant impact on the results. These findings suggest that VENs in the ACC are involved in neurodevelopmental and perhaps neurodegenerative processes specific to schizophrenia.

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.