Impaired cognitive flexibility during sleep deprivation among carriers of the Brain Derived Neurotrophic Factor (BDNF) Val66Met allele

Abstract

Accumulating evidence points to a genetic contribution to explain inter-individual vulnerability to sleep deprivation. A functional polymorphism in the BDNF gene, which causes a valine (Val) to methionine (Met) amino acid substitution at Codon 66, has been associated with cognitive impairment, particularly in populations with impaired frontal functioning. We hypothesised that sleep deprivation, which affects frontal function, may lead to cognitive dysfunction in Met allele carriers. To examine this, we investigated, in different BDNF genotypes, the effects of sleep deprivation on cognitive flexibility, as measured by response inhibition using the Stroop Color Naming Task. Thirty healthy, adults of European ancestry, including 12 heterozygous Met allele carriers and 18 Val/Val homozygotes, underwent 30-h of extended wakefulness under constant routine conditions. A computerised Stroop task was administered every 2 h. Error rate and reaction times increased with time awake for all individuals. Participants with the Val/Met genotype made more errors on incongruent trials after 20 h awake. While Val/Met participants also took significantly longer to respond when inhibiting a prepotent response irrespective of time awake, this was particularly evident during the biological night. Our study shows that carriers of the BDNF Met allele are more vulnerable to the impact of prolonged wakefulness and the biological night on a critical component of executive function, as measured by response inhibition on the Stroop task.

BDNF haploinsufficiency induces behavioral endophenotypes of schizophrenia in male mice that are rescued by enriched environment

“…Of note, such a general ASST performance deficit has been often observed in schizophrenic patients 81 – 83 . Our finding further supports human data showing that disruption of BDNF functioning leads to impaired cognitive flexibility 84 , 85 . Based on reports showing that interventions supporting BDNF function can facilitate and/or restore cognitive flexibility 86 , 87 , we housed our mice in EE that is known to increase BDNF brain levels 88 .…”

BDNF Val66Met polymorphism moderates the association between sleep spindles and overnight visual recognition

“…Met carriers fared equally with Val homozygotes in recognition accuracy in our study, although no other correlate with learning aside spindles was identified. Val66Met polymorphism affects the dynamics between sleep and learning in a complex manner, affecting also next-day cognition [119,120], which necessitates more research with varying settings. In addition, our sample consisted of closely-aged adolescents, with ongoing neural reorganization of brain [121], increasing thalamocortical functional connectivity [122] and altering spindle characteristics [78,123].…”

“…This undermines the deductibility of causal role of sleep spindles in learning. Further obscuring causation, having only one night with PSG recording prevented us from examining how learning affected sleep spindle characteristics, as well as from considering previous night's impact on learning[82,119,120]. Also, due to the lack of a waking control group we could not properly assess how, or whether, sleep affected the recognition accuracy scores.…”

Sleep deprivation effect on concentration of some reproductive hormones in healthy men and women volunteers

“…Sleep deprivation is related to several adverse physiological consequences such as disturbances of metabolic, immune, and endocrine function [9] with harmful stress that negatively affects the physiology of vital organs as the liver, kidneys, brain, and reproductive organs [10]. As a consequence of sleep deprivation is an increase in the level of stress factors that accelerates biological aging [11] and decreases serum testosterone concentration [12]. In healthy men, sleep deprivation has recorded a reduction in serum androgens including testosterone [10], which can hinder gonads function and greatly decline the fertility rate [13].…”

“…The impact of stress as a result of sleep deprivation promotes stimulation of hypothalamo-pituitary-adrenal axis (HPA axis), which elevates plasma corticosterone level and concomitant alteration in the level of testosterone [14] via alteration in LH pulses [11], and can exert adverse effects for different reproductive hormones [15]. So the study was carried out to explore the impact of sleep deprivation on the health and fertility states of individuals through evaluation of some blood and hormonal criteria.…”