BDNF rs6265 differentially influences neurometabolites in the anterior cingulate of healthy and bipolar disorder subjects

Author(s)

Scotti-Muzzi, Estevao ; Chile, Thais ; Vallada, Homero ; Otaduy, Maria Concepcion Garcia ; Soeiro-de-Souza, Marcio Gerhardt

• Document type: Journal article
• Source: BRAIN IMAGING AND BEHAVIOR; v. N/A, p. 12-pg., 2023-01-11.

Abstract

Brain-derived neurotrophic factor (BDNF) is the most abundant brain neurotrophin and plays a critical role in neuronal growth, survival and plasticity, implicated in the pathophysiology of Bipolar Disorders (BD). The single-nucleotide polymorphism in the BDNF gene (BDNF rs6265) has been associated with decreased hippocampal BDNF secretion and volume in met carriers in different populations, although the val allele has been reported to be more frequent in BD patients. The anterior cingulate cortex (ACC) is a key center integrating cognitive and affective neuronal connections, where consistent alterations in brain metabolites such as Glx (Glutamate + Glutamine) and N-acetylaspartate (NAA) have been consistently reported in BD. However, little is known about the influence of BDNF rs6265 on neurochemical profile in the ACC of Healthy Controls (HC) and BD subjects. The aim of this study was to assess the influence of BDNF rs6265 on ACC neurometabolites (Glx, NAA and total creatine- Cr) in 124 euthymic BD type I patients and 76 HC, who were genotyped for BDNF rs6265 and underwent a 3-Tesla proton magnetic resonance imaging and spectroscopy scan ((1) H-MRS) using a PRESS ACC single-voxel (8cm(3)) sequence. BDNF rs6265 polymorphism showed a significant two-way interaction (diagnosis x genotype) in relation to NAA/Cr and total Cr. While met carriers presented increased NAA/Cr in HC, BD-I subjects with the val allele revealed higher total Cr, denoting an enhanced ACC metabolism likely associated with increased glutamatergic metabolites observed in BD-I val carriers. However, these results were replicated only in men. Therefore, our results support evidences that the BDNF rs6265 polymorphism exerts a complex pleiotropic effect on ACC metabolites influenced by the diagnosis and sex. (AU)

• FAPESP's process: 10/12286-8 - Genetic association study between single nucleotide polymorphism and cognitive performance in young bipolar I patients: Licavalgene
• Grantee: Márcio Gerhardt Soeiro-de-Souza
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 12/23796-2 - "Genetic association study between cognitive performance, polymorphisms of GAD1/Reelin and 3T magnetic ressonance spectroscopy of GABA/glutamate in bipolar I disorder and healthy controls"
• Grantee: Márcio Gerhardt Soeiro-de-Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral