Dendritic spine alterations in schizophrenia

Abstract

Schizophrenia is a chronic illness affecting approximately 0.5-1% of the world's population. The etiology of schizophrenia is complex, including multiple genes, and contributing environmental effects that adversely impact neurodevelopment. Nevertheless, a final common result, present in many subjects with schizophrenia, is impairment of pyramidal neuron dendritic morphology in multiple regions of the cerebral cortex. In this review, we summarize the evidence of reduced dendritic spine density and other dendritic abnormalities in schizophrenia, evaluate current data that informs the neurodevelopment timing of these impairments, and discuss what is known about possible upstream sources of dendritic spine loss in this illness.

Keywords: Adolescence; Dendritic spine; Kalirin; MAP2; Postmortem; Schizophrenia.

Figure 1. Model for investigation of mechanisms of dendritic spine pathology in schizophrenia

Some proteins have alterations that are present in a large proportion of individuals with schizophrenia (e.g. Kalirin (KALRN) and MAP2, shown in green). These conserved protein alterations may arise because they are downstream of (or are themselves affected by) multiple genetic variants that contribute to the risk of schizophrenia. Both common genetic variants of small effect (red) and rare genetic variants of larger effect (blue) can contribute to risk. The affected proteins exist within larger functional networks of interacting proteins, some examples of which are also shown. Dendritic spines are enlarged and stabilized, or shrunken and eliminated, as a net effect of competing signals from these functional networks that regulate cytoskeleton dynamics. Thus, fully understanding the mechanisms by which conserved protein alterations result in spine loss will benefit from concurrent investigation of the broader network, as either additive or protective alterations in the many intervening proteins may also be present.