Moderating Effects of BDNF Genetic Variants and Smoking on Cognition in PTSD Veterans

Abstract

Posttraumatic stress disorder (PTSD) is frequently associated with cognitive disturbances and high prevalence of smoking. This study evaluated cognition in war veterans with PTSD and control subjects, controlled for the effect of smoking and brain derived neurotrophic factor (BDNF) rs6265 and rs56164415 genotypes/alleles. Study included 643 male war veterans with combat related PTSD and 120 healthy controls. Genotyping was done by real time PCR. Cognitive disturbances were evaluated using the Positive and Negative Syndrome Scale (PANSS) cognition subscale and the Rey-Osterrieth Complex Figure (ROCF) test scores. Diagnosis (p < 0.001), BDNF rs56164415 (p = 0.011) and smoking (p = 0.028) were significant predictors of the cognitive decline in subjects with PTSD. BDNF rs56164415 T alleles were more frequently found in subjects with PTSD, smokers and non-smokers, with impaired cognition, i.e., with the higher PANSS cognition subscale scores and with the lower ROCF immediate recall test scores. Presence of one or two BDNF rs56164415 T alleles was related to cognitive decline in PTSD. The T allele carriers with PTSD had advanced cognitive deterioration in smokers and nonsmokers with PTSD, and worse short-term visual memory function. Our findings emphasize the role of the BDNF rs56164415 T allele and smoking in cognitive dysfunction in war veterans with PTSD.

Interaction of Brain-derived Neurotrophic Factor, Exercise, and Fear Extinction: Implications for Post-traumatic Stress Disorder

“…The Val66Met polymorphism has been associated with PTSD diagnosis and symptom severity, although there are some inconsistencies between findings. Studies have found that the Met allele is overrepresented in PTSD populations compared to the Val/Val genotype [ 96 - 101 ]. The Met allele has also been associated with higher PTSD symptom severity than the Val/Val genotype [ 80 , 96 , 102 , 103 ].…”

A proposed mechanism for the MDMA-mediated extinction of traumatic memories in PTSD patients treated with MDMA-assisted therapy

“…Brain-derived neurotrophic factor (BDNF) and its associated receptor, tropomyosin receptor kinase B (TrkB), have come under increasing scrutiny for their role in several psychiatric disorders including PTSD ( 100 , 104 , 107 , 113 , 127 – 131 ). The synthesis of BDNF precursor pro-BDNF occurs in microglia, astrocytes, and glutaminergic neurons which is secreted along with the mature form of the neurotrophin, both of which are active ( 127 ).…”

“…Brain-derived neurotrophic factor (BDNF) and its associated receptor, tropomyosin receptor kinase B (TrkB), have come under increasing scrutiny for their role in several psychiatric disorders including PTSD ( 100 , 104 , 107 , 113 , 127 – 131 ). The synthesis of BDNF precursor pro-BDNF occurs in microglia, astrocytes, and glutaminergic neurons which is secreted along with the mature form of the neurotrophin, both of which are active ( 127 ). BDNF signaling is associated with multiple aspects of neuroplasticity including the upregulation and phosphorylation of NMDARs and increases in the complexity, size, and number of dendritic spines at the synapse and is necessary for long-term potentiation and memory consolidation ( 132 , 133 ).…”

“…BDNF signaling is associated with multiple aspects of neuroplasticity including the upregulation and phosphorylation of NMDARs and increases in the complexity, size, and number of dendritic spines at the synapse and is necessary for long-term potentiation and memory consolidation ( 132 , 133 ). In PTSD, BDNF in the hippocampus is essential for fear memory extinction, and it has been suggested that a deficit of BDNF may underly hippocampal synaptic loss and the subsequent inhibition of the extinction process ( 113 , 127 , 129 ). The impact of BDNF activity in the amygdala (and the dACC) is less clear in PTSD and is locus dependent.…”