Hippocampal dysfunction in schizophrenia: association with brain-derived neurotrophic factor genotype

Abstract

Functional genetic variation in BDNF (brain-derived neurotrophic factor) is posited to impact neural activity in the hippocampus in a manner relevant to schizophrenic pathophysiology. To test this hypothesis, 47 medication-free patients with schizophrenia or schizoaffective disorder and 74 healthy control individuals underwent genotyping for the BDNF Val66Met single-nucleotide polymorphism and [15O]H2O positron emission tomography during rest, sensorimotor (0 bk) and working memory (2 bk) conditions. When compared with their genotype-matched control cohort, only patients carrying the BDNF Met variant showed diminished mean whole-hippocampus perfusion, regardless of scanning condition (bar graphs; Bonferroni-corrected post-hoc tests: P ¼ 0.0004 (rest), P ¼ 0.004 (0 bk), P ¼ 0.02 (2 bk)). Mean voxel-wise resting perfusion maps rendered to hippocampal surfaces are likewise shown for each group with warmer colors (color bar), indicating greater normalized regional cerebral blood flow values. This research was supported by the

Neurodevelopment, GABA System Dysfunction, and Schizophrenia

“…Genetic variants of the BDNF gene associated with schizophrenia (Neves-Pereira et al, 2005) produce progressive cortical and hippocampal structural changes, as well as behavioral impairment (Egan et al, 2003a;Pezawas et al, 2004). A genetic variant of BDNF associated with increased risk for psychiatric disorders including schizophrenia (Egan et al, 2003b;Gratacos et al, 2007) is linked to reduced cortical and hippocampal volumes and impaired learning and memory, presumably by interfering with the development and maintenance of neurons and synapses (Egan et al, 2003b;Eisenberg et al, 2013;Hariri et al, 2003;Pezawas et al, 2004;Szeszko et al, 2005;Tost et al, 2013). However, these findings are not always replicated and more studies are needed to clarify the mechanisms of the Val66Met allele and psychiatric illness (Kanazawa et al, 2007).…”

Understanding Schizophrenia as a Disorder of Consciousness: Biological Correlates and Translational Implications from Quantum Theory Perspectives

“… 90 ) Deficient BDNF is an established pathogenetic factor in schizophrenia 91 – 93 ); importantly, BDNF links the hippocampus deficits in schizophrenia 94 , 95 ) with microtubule abnormalities. 96 , 97 ) Indeed, the microtubule mice model of schizophrenia (STOP-null mice) demonstrates striking aberrations involving hippocampus. 83 , 98 ) Finally, BDNF also links microtubules with cell signalling pathways (Akt/GSK) as well as cell cycle involvement in schizophrenia pathogenesis 89 , 99 ); in addition, microtubule is intricately connected with these biological pathways as well 99 ) as well as with the immune pathogenetic perspectives 100 ) in schizophrenia.…”