Schizophrenia (SCZ) and schizoaffective disorder (SAD) are severe and complex psychiatric disorders whose liability threshold is 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. Here, we present a secondary analysis of the Longitudinal Assessment of BDNF in Sardinian Psychotic patients (LABSP) study, focusing on the impact of antipsychotic therapy, particularly long‐acting injectable (LAI), on the longitudinal trajectory of serum BDNF levels and analyzing the effect of BDNF genetic variants. LABSP patients were assessed every 6 months for a series of measures, including the assessment of BDNF serum levels over 24 months. Blood samples for each patient were taken at the same time of the day (between 8:00 and 10:00 a.m.). BDNF serum levels were determined using the BDNF ELISA Kit. Four tag single nucleotide polymorphisms (SNPs) within the 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 (MLRMs) were used to analyze longitudinal data. Twenty‐four patients out of 105 LABSP (22.9%) patients received therapy with LAI. Analysis with MLRM showed a significant effect of LAI treatment associated with increasing serum BDNF levels ( Z = 2.2, p = 0.02). However, oral antipsychotics did not significantly impact the longitudinal trajectory of serum BDNF levels ( Z = 0.15, p = 0.9). There was no moderating effect of variants within the BDNF gene on the identified association. We identified a significant longitudinal increase in serum BDNF in SCZ and SAD patients treated with LAI antipsychotic therapy. The significant impact of this preparation of antipsychotic treatment on serum BDNF, despite the limited sample size, points to a moderate to large magnitude of effect that should be investigated in future prospective studies.

Do Long‐Acting Injectable Antipsychotics Influence Serum Levels of Brain‐Derived Neurotrophic Factor in People With Schizophrenia and Schizoaffective Disorder?