Is Serum Brain-Derived Neurotrophic Factor a Biomarker for Cognitive Enhancement in Schizophrenia?

Abstract

Background Brain-derived neurotrophic factor (BDNF) plays a critical role in neurodevelopment and plasticity; decreased BDNF functioning may contribute to the pathogenesis of schizophrenia. However, BDNF levels are not static; in animal experiments, brain BDNF increases during spatial learning, and in clinical depression, successful antidepressant treatment raises serum BDNF. We asked: would neuroplasticity-based cognitive training in schizophrenia result in increased serum BDNF? Methods Fifty-six schizophrenia outpatients and 16 matched healthy comparison subjects were assessed on baseline cognitive performance and serum BDNF. Schizophrenia subjects were randomly assigned to either 50 hours (10 weeks) of computerized auditory training or a computer game control condition, followed by reassessment of cognition and serum BDNF. Results At baseline, schizophrenia participants had significantly lower-than-normal serum BDNF. Schizophrenia subjects who engaged in computerized cognitive training designed to improve auditory processing showed significant cognitive gains and a significant increase in serum BDNF compared with subjects who played computer games. This increase was evident after 2 weeks of training, and after 10 weeks in the active condition, subjects “normalized” their mean serum BDNF levels, whereas the control group showed no change. In the active condition, change in BDNF was significantly associated with improved quality of life. Conclusions Serum BDNF levels are significantly increased in clinically stable, chronically ill schizophrenia subjects after neuroplasticity-based cognitive training, but not after computer games. Serum BDNF levels may serve as a peripheral biomarker for the effects of intensive cognitive training and may provide a useful tool for the evaluation of cognitive enhancement methods in schizophrenia.

State of Art of Serum Brain-Derived Neurotrophic Factor in Schizophrenia

“…In our study, schizophrenic patients with reduced truncated-BDNF had worse efficency in all neurocognitive tests in relationship to the other patients with normal levels of truncated-BDNF, although the correlation between Trail Making Test Part A score and truncated-BDNF abundance do not reach the statistically significance. Our results further enlarge a recent research telling that evaluation of total serum BDNF may be useful to predict for a good outcome in neurocognitive enhancement sessions in schizophrenic patients (Vinogradov et al, 2009). Importantly, we also underline that four healthy subjects with low truncated-BDNF had poor scores in Trail Making Test B and Symbol Digit Coding attention test.…”

DNA methylation of BDNF as a biomarker of early-life adversity

“…Recent studies suggested that concentrations of BDNF protein in the blood (serum or plasma) may represent peripheral manifestation of depression (48) and schizophrenia (49) and could be used as a biomarker for therapeutic efficacy (50). Similarly, BDNF DNA methylation changes have been found in the peripheral blood of patients suffering from depression (13), bipolar disorder (12), schizophrenia (14), and eating disorders (51), and a change in BDNF DNA methylation status correlated with a positive response to psychotherapy in borderline personality disorder (52).…”

Prefrontal Cortical Changes Following Cognitive Training in Patients with Chronic Schizophrenia: Effects of Practice, Generalization, and Specificity

“…For example, cognitive training has been shown to be associated with increases in serum BDNF, which is known to have a role in neuronal development (Vinogradov et al, 2009). This suggests that behavioral changes following training may be the result of functional plasticity, as distinct from increased automated processing following repetitive practice.…”