BDNF and Cognitive impairment: These results suggest a mechanism through which genetic variation in CACNA1C may affect cognitive flexibility and RL, because previous studies have shown that mice lacking activity-regulated expression of Bdnf show impaired RL and altered spike-timing-dependent plasticity in the PFC.35,36 These results also suggest that therapeutic approaches aimed at enhancing prefrontal BDNF levels may be efficacious in alleviating some of the cognitive impairments seen in neuropsychiatric disorders.