The impact of depot and long acting injectable antipsychotics on serum levels of brain-derived neurotrophic factor in schizophrenic and schizoaffective patients: results of a 24-month longitudinal prospective study

Introduction: Schizophrenia (SCZ) and schizoaffective disorder (SAD) are severe and complex psychiatric disorders whose liability threshold is likely modulated by the interplay of biological, mainly genetic, and environmental factors. Consistent evidence has pointed to the role of serum brain-derived neurotrophic factor (BDNF) as a plausible illness biomarker in SCZ-spectrum disorders. There is no consensus, however, on the temporal trajectory of this decline. The decrease of peripheral BDNF could be constant, with premorbid levels roughly similar to those detected in unaffected individuals, linearly declining during the course of the illness. Alternatively, BDNF peripheral levels might fluctuate in association with acute psychopathological phases of the disorder. In this context, we sought to investigate the longitudinal variation of serum BDNF levels over 24 months in a cohort of Sardinian patients [Longitudinal Assessment of BDNF in Sardinian Psychotic patients (LABSP)]. Here, we present a secondary analysis of LABSP data, focusing on the impact of antipsychotic therapy, particularly depot and long-acting injectable (LAI), on the longitudinal trajectory of serum BDNF levels. Further, we tested whether genetic variation within the gene encoding for BDNF could moderate the relationship between BDNF serum levels and drug treatment. Methods: LABSP patients were assessed every six months for a series of psychopathological, cognitive and drug-related measures, as well as for BDNF serum levels over 24-month. Blood samples for each patient were taken at the same time of the day (between 8:00 and 10:00 AM). BDNF serum levels were determined using BDNF ELISA Kit. Four tag single nucleotide polymorphisms (SNPs) within BDNF gene (rs1519480, rs11030104, rs6265 (Val66Met), and rs7934165) were selected using standard parameters and analyzed with Polymerase Chain Reaction (PCR). Mixed-effects linear regression models (MLRM) was used to analyze longitudinal data. Results: Twenty-four patients out of 105 LABSP (22.9%) patients received therapy with depot/LAI. Analysis with MLRM showed a significant effect of depot/LAI treatment associated with increasing serum BDNF levels (Z = 1.9, p = 0.053). However, oral antipsychotics did not significantly impacted on the longitudinal trajectory of serum BDNF levels (Z = 0.15, p = 0.9). There was no moderating effect of variants within BDNF gene on the identified association. Conclusions: our study identified a significant longitudinal increase of serum BDNF in SCZ and SAD patients treated with depot/LAI antipsychotic therapy. The identification of a significant impact of this preparation of antipsychotic treatment on serum BDNF despite the limited sample size. The impact of depot and long acting injectable antipsychotics on serum levels of brain-derived neurotrophic factor in schizophrenic and schizoaffective patients: results of a 24-month longitudinal prospective study points to a moderate to large magnitude of effect that should be investigated in future prospective studies.