Relationship between Brain-Derived Neurotrophic Factor and Schneiderian First Rank Symptoms in Antipsychotic-Naïve Schizophrenia

Sunil Vasu Kalmady,Ganesan Venkatasubramanian,Dania Jose,Venkataram Shivakumar,Bangalore N Gangadhar,Vasanthapuram Ravi

doi:10.3389/fpsyt.2013.00064

Abstract

Neurodevelopmental aberrations influenced by neurotrophic factors are among the important paradigms to understand schizophrenia pathogenesis. Among various neurotrophic factors, Brain-Derived Neurotrophic Factor (BDNF) is strongly implicated by previous research studies. Evaluating co-morbidity free, antipsychotic-naïve schizophrenia patients for BDNF levels and examining the correlates of this factor with symptoms might facilitate elucidation of its pathogenetic role without confounds of potential influencing factors. In this study, 59 co-morbidity free, antipsychotic-naïve schizophrenia patients were compared with 60 healthy controls for serum BDNF levels. In addition, the relationship between Schneiderian First Rank Symptoms (FRS) and BDNF level in patients was examined. As a group, schizophrenia patients (28.8 ± 11.7 ng/mL) had significantly lower serum BDNF than healthy controls (34.9 ± 8.2 ng/mL) after controlling for the potential confounding effects of age and sex (F = 7.8; p = 0.006). Further analyses revealed FRS status to have significant effect on plasma BDNF after controlling for the potential confounding effects of age and sex (F = 4.5; p = 0.01). Follow-up post hoc analyses revealed FRS(+) patients to have significant deficit in plasma BDNF level in comparison with healthy controls (p = 0.002); however, FRS(−) patients did not differ from healthy controls (p = 0.38). Our study observations add further support to the role for BDNF in schizophrenia pathogenesis and suggest a potential novel link between deficient BDNF and FRS.

Highlights

Neurodevelopmental model postulates schizophrenia as a behavioral outcome of an aberration in brain development processes that begins long before the onset of clinical symptoms and is caused by a combination of genetic and environmental factors [1]
Follow-up post hoc analyses revealed First Rank Symptoms (FRS)(+) patients to have significant deficit in plasma Brain-Derived Neurotrophic Factor (BDNF) level in comparison with healthy controls (p = 0.002); FRS(−) patients did not differ from healthy controls (p = 0.38)
We evaluated serum BDNF in antipsychotic-naïve schizophrenia patients (N = 59) in comparison with healthy controls (N = 60)

Summary

Introduction

Neurodevelopmental model postulates schizophrenia as a behavioral outcome of an aberration in brain development processes that begins long before the onset of clinical symptoms and is caused by a combination of genetic and environmental factors [1]. Gene-environment interaction especially involving genetic factors and obstetric complications have been put forth as one of the important mechanisms that increase the risk toward schizophrenia [2]. The genetic factors that interact with obstetric complications have been postulated to encompass hypoxiaischemia regulated genes and Brain-Derived Neurotrophic Factor (BDNF) gene is one among them [2]. Given the increasing emphasis on the role of neurotrophic factors in the neurodevelopmental pathogenesis of schizophrenia [3], BDNF has attracted significant attention in schizophrenia research studies. BDNF, the most widely distributed neurotrophin in the central nervous system, is highly expressed in brain regions that are critically implicated in the pathogenesis of schizophrenia – the prefrontal cortex and hippocampus [6]. BDNF has been demonstrated to interact with various neurotransmitter systems that are implicated in schizophrenia, such as dopamine, glutamate, serotonin, and GABA [7]

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Conclusion