Is Neuregulin 1 Involved in Determining Cerebral Volumes in Schizophrenia? Preliminary Results Showing a Decrease in Superior Temporal Gyrus Volume

Abstract

Background/Aims: Reduced left superior temporal gyrus (STG) volume is one of the most replicated imaging findings in schizophrenia. However, it remains unclear whether genes play any role in our understanding of such structural alteration. It has been proposed that Neuregulin 1 (NRG1) might be a promising gene involved in schizophrenia, because of its role in neurodevelopment and neuroplasticity. In this study, the association between NRG1 and STG anatomy in patients with schizophrenia was explored for the first time. Methods: We investigated a 1-year treated prevalence cohort of patients with schizophrenia in contact with the South Verona Community-Based Mental Health Service. A blood sample was collected for DNA extraction and brain structure was assessed with an MRI scan. A total of 27 subjects with schizophrenia underwent both assessments and were included in the study. Results: We investigated the association between the polymorphism SNP8NRG222662 (rs4623364) of NRG1 and volume of the STG. We found that patients homozygous for the C allele had reduced left STG gray and white matter volumes in comparison to those homozygous for the G allele (p < 0.01 and p < 0.001, respectively). Conclusions: This exploratory study suggests that NRG1 may be involved in determining STG size in schizophrenia, and may play a role in the neurogenetic basis of the language disturbances seen in this disorder. However, due to our small sample size, the results should be regarded as preliminary and replicated in a larger sample.

A sequence variant in human KALRN impairs protein function and coincides with reduced cortical thickness

“…Knockdown of DISC1 in cultured cortical neurons also results in diminished dendritic spine number 19 , and frontal cortex pyramidal neurons in mice carrying DISC1 missense variants or truncations display reduced spine number and dendrite length than those in wildtypes 47, 48 . Similarly, patients carrying a schizophrenia-associated minor NRG1 allele have reduced superior temporal gyrus volumes as compared to patients carrying the major allele 49 , and mice lacking CNS expression of Erbb2 and Erbb4 exhibit reduced dendritic spine density in frontal cortex pyramidal neurons 50 . Furthermore, kalirin-7 has been shown to be essential for 5-HT2A receptor-induced dendritic spine growth 44 .…”

Bridging the Gap between Genes and Language Deficits in Schizophrenia: An Oscillopathic Approach

“…Risk polymorphisms of NRG1 are associated with increased IQs as well as memory and learning performance, along with language in subjects with bipolar disorder (Rolstad et al, 2015). Moreover, risk alleles for the gene correlate with reduced left superior temporal gyrus volumes (a robust imaging finding in schizophrenia, Tosato et al, 2012), a region related to language abilities (Aeby et al, 2013). Another gene of interest is PDGFR , which encodes the β subunit of the platelet-derived growth factor (PDGF) receptor, known to be involved in the development of the central nervous system.…”

Progressive Structural Brain Changes and NRG1 Gene Variants in First-Episode Nonaffective Psychosis

“…Based on the same SNP, McIntosh et al [53] reported an association with reduced WM density in the internal capsule among healthy individuals. For SNP8NRG222622, patients with schizophrenia homozygous for the at-risk allele showed reduced left superior temporal gyrus WM and GM volumes [54]. However, contrasting results have been found across the literature.…”