A Longitudinal Study of Alterations of Hippocampal Volumes and Serum BDNF Levels in Association to Atypical Antipsychotics in a Sample of First-Episode Patients with Schizophrenia

Abstract

BackgroundSchizophrenia is associated with structural and functional abnormalities of the hippocampus, which have been suggested to play an important role in the formation and emergence of schizophrenia syndrome. Patients with schizophrenia exhibit significant bilateral hippocampal volume reduction and progressive hippocampal volume decrease in first-episode patients with schizophrenia has been shown in many neuroimaging studies. Dysfunction of the neurotrophic system has been implicated in the pathophysiology of schizophrenia. The initiation of antipsychotic medication alters the levels of serum Brain Derived Neurotrophic Factor (BDNF) levels. However it is unclear whether treatment with antipsychotics is associated with alterations of hippocampal volume and BDNF levels.MethodsIn the present longitudinal study we investigated the association between serum BDNF levels and hippocampal volumes in a sample of fourteen first-episode drug-naïve patients with schizophrenia (FEP). MRI scans, BDNF and clinical measurements were performed twice: at baseline before the initiation of antipsychotic treatment and 8 months later, while the patients were receiving monotherapy with second generation antipsychotics (SGAs).ResultsWe found that left hippocampal volume was decreased (corrected left HV [t = 2.977, df = 13, p = .011] at follow-up; We also found that the higher the BDNF levels change the higher were the differences of corrected left hippocampus after 8 months of treatment with atypical antipsychotics (Pearson r = 0.597, p = 0.024).ConclusionsThe association of BDNF with hippocampal volume alterations in schizophrenia merits further investigation and replication in larger longitudinal studies.

Decreased cortical thickness in drug naïve first episode schizophrenia: In relation to serum levels of BDNF

“…Our study found similar correlation pattern. In a recent longitudinal study in 14 first episode schizophrenia patients, Rizos et al found a positive association between changes of BDNF levels and changes of left hippocampal volume after 8 months of antipsychotic treatment (Rizos et al, 2014) suggesting that neuroprotective effect through modulation of BDNF levels could in turn protect against brain tissue loss (Siekmeier and vanMaanen, 2013;Wakade et al, 2002). Based on these findings, an absence or reduction of the positive relationship between brain morphology of insula and serum levels of BDNF that present in the healthy cohort may suggest a breakdown in the protective role or neurotrophic effect of BDNF in these brain regions in psychosis, which is consistent with the neurotrophic theory of schizophrenia (Weinberger, 1987).…”

Fatty acid binding proteins and the nervous system: Their impact on mental conditions

“…In human, MRI images revealed that patients with neurological and/or psychiatric diseases, including Alzheimer's disease, schizophrenia and depression, have a smaller volume of hippocampi than those of control subjects (Francis et al, 2013;Guo et al, 2014;Heckers and Konradi, 2010;Prestia et al, 2014;Reif et al, 2006;Rizos et al, 2014). One possibility for those findings is that neurogenesis may be decreased in those patients.…”

Progression from selective to general involvement of hippocampal subfields in schizophrenia

“…A recent large-scale multi-site consortium study found that among the subcortical regions examined in schizophrenia, the largest magnitude of volume deficits was in the hippocampus. 7 However, it is less clear whether the volume deficits of the hippocampus worsen during the course of illness, with some studies finding no atrophy over time 8–11 and other studies suggesting progressive volume loss that begins at early stages 12–14 .…”