Von Economo neuron density in the anterior cingulate cortex is reduced in early onset schizophrenia

Abstract

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.

Reduced anterior insula, enlarged amygdala in alcoholism and associated depleted von Economo neurons

“…Previously, VENs have been implicated in several neuropsychiatric disorders whose symptomatology include deficient emotional regulation and social cognition, e.g. behavioural variant frontotemporal dementia (Kim et al, 2012), autism (Santos et al, 2011), early-onset schizophrenia (Brune et al, 2010) and agenesis of the corpus callosum (Kaufman et al, 2008).…”

Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction

“…These neur ons are seen only in higher primates 62 and are thought to be involved in social processing in the wake of their rapid relaying ability. 63,64 Patients with early-onset schizophrenia with longer durations of illness exhibited a reduced VEN density in the anterior cingulate, 65 though no studies have explored this pathology in the insula. Preliminary evidence also suggests that VENs preferentially express the protein encoded by DISC1 (disrupted in schizophrenia 1).…”

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

“…Altered neuronal densities were reported in the prefrontal cortex (Akbarian et al, 1996;Anderson et al, 1996;Connor et al, 2009;Daviss and Lewis, 1995;Ikeda et al, 2004;Joshi et al, 2012;Morris et al, 2008;Rajkowska et al, 1998;Selemon et al, 1995Selemon et al, , 1998Selemon et al, , 2003Yang et al, 2011), auditory cortex (Dorph-Petersen et al, 2009), cingulate cortex (Benes, 1991(Benes, , 1993Brune et al, 2010;Connor et al, 2009), entorhinal cortex (Arnold et al, 1991;Falkai et al, 2000;Jakob and Beckmann, 1986;Kovalenko et al, 2003;Wang et al, 2011), fusiform cortex (Di Rosa et al, 2009), occipital cortex (Selemon et al, 1995), parietal cortex (Chance et al, 2005), visual cortex (Dorph-Petersen et al, 2007), thalamus (Young et al, 2000), hypothalamus (Bernstein et al, 1998), striatum (Kreczmanski et al, 2007), amygdala (Kreczmanski et al, 2007), and hippocampus (Konradi et al, 2011) in post-mortem brain tissue from schizophrenic patients. Interestingly, many of these reports show specific defects in GABAergic interneuron density or distribution (Benes et al, 1991;Chance et al, 2005;Daviss and Lewis, 1995;Di Rosa et al, 2009;Ikeda et al, 2004;Joshi et al, 2012;Konradi et al, 2011;Morris et al, 2008;Wang et al, 2011;Yang et al, 2011).…”