Peripheral BDNF: a candidate biomarker of healthy neural activity during learning is disrupted in schizophrenia

BACKGROUND Brain-derived neurotrophic factor (BDNF) is an important regulator of synaptogenesis and synaptic plasticity underlying learning. However, a relationship between circulating BDNF levels and brain activity during learning has not been demonstrated in humans. Reduced brain BDNF levels are found in schizophrenia and functional neuroimaging studies of probabilistic association learning in schizophrenia have demonstrated reduced activity in a neural network that includes the prefrontal and parietal cortices and the caudate nucleus. We predicted that brain activity would correlate positively with peripheral BDNF levels during probabilistic association learning in healthy adults and that this relationship would be altered in schizophrenia. METHOD Twenty-five healthy adults and 17 people with schizophrenia or schizo-affective disorder performed a probabilistic association learning test during functional magnetic resonance imaging (fMRI). Plasma BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS We found a positive correlation between circulating plasma BDNF levels and brain activity in the parietal cortex in healthy adults. There was no relationship between plasma BDNF levels and task-related activity in the prefrontal, parietal or caudate regions in schizophrenia. A direct comparison of these relationships between groups revealed a significant diagnostic difference. CONCLUSIONS This is the first study to show a relationship between peripheral BDNF levels and cortical activity during learning, suggesting that plasma BDNF levels may reflect learning-related brain activity in healthy humans. The lack of relationship between plasma BDNF and task-related brain activity in patients suggests that circulating blood BDNF may not be indicative of learning-dependent brain activity in schizophrenia.