The biological bases of cognitive impairment in schizophrenia are poorly understood and may lie in insults in neurodevelopment, leading to alterations in critical structures. Synapses proteins are claimed to have etiopathogenic roles and more direct effects on core cognitive functions. Adducins family proteins seem of great interest, as they are fundamental constituents of synapses, involved in actin cytoskeleton assembly-disassembly, responsible of synaptic plasticity. ADD2 is more prominently expressed in brain tissues and influences memory and learning, commonly impaired in schizophrenia. In the present study we tested 342 patients with schizophrenia for three common adducins genetic variants, ADD1 rs4961, ADD2 rs4984 and ADD3 rs3731566, reported to have significant effects on circulatory system in humans. Neuropsychological measures were evaluated with the Brief Assessment of Cognition in Schizophrenia (BACS), a broad battery evaluating core cognitive domains. The analysis showed significant effects of ADD2 genotype on almost every cognitive domain. Moreover, significant interactions between ADD1 and ADD3 were also observed on some BACS subtests, namely Symbol Coding and Verbal Memory. Our findings suggest that adducins are involved in cognitive impairment in schizophrenia. This effect may result both from a direct mechanism affecting synaptic building and plasticity and indirectly as a consequence of vascular insults.