Abnormalities of peripheral amino acid concentrations have been reported in schizophrenia since 1954 (Sackler, 1954), however results have been inconsistent and the neurobiological implications of these abnormalities remain unclear.

We measured serum levels of serine, glycine and glutamate in 14 chronic non-refractory patients with schizophrenia treated with traditional antipsychotics and in 12 first-degree relatives and compared the data to the serum levels from 12 refractory patients treated with clozapine and their first- degree relatives.

We found decreased serum levels of serine (p=0.048) and glutamate (p<0.001) in chronic non-refractory schizophrenia compared to refractory schizophrenia, but no differences in glycine levels.

Furthermore, the data demonstrated that first-degree relatives of non-refractory patients have increased serum levels of glycine (p=0.046)and decreased levels of glutamate (p<0.001), but no differences in serine serum levels compared to first degree-relatives of refractory patients

These data show that changes in serum amino acids may predominantly involved in central glutamatergic transmission in refractory schizophrenia. Also, it could be hypothesized that this differential pattern of serum aminoacids concentrations in first-degree relatives may be a biological marker and predictor involved in the response to antipsychotic treatments in schizophrenia patients.