Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients
Introduction
Impaired brain development is often implicated in the etiology of schizophrenia (Kerwin and Murray, 1992, Marenco and Weinberger, 2000). Recent evidence indicates that abnormal signaling of cytokines and growth factors influences neuronal differentiation and synaptic plasticity to perturb brain development and function (Nawa et al., 2000). Gene manipulation studies in mice indicate that neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), are important for normal development of the central nervous system (Croll et al., 1999, Xu et al., 2000). Accordingly, impairments in their signaling may be implicated in various psychiatric diseases such as schizophrenia, mood disorder and autism (Altar, 1999, Nawa et al., 2000, Chen et al., 2001, Vaidya and Duman, 2001, Nelson et al., 2001). For example, BDNF levels are elevated and, conversely, BDNF receptor (TrkB) expression is down-regulated in the corticolimbic system of patients with schizophrenia (Takahashi et al., 2000). Animal experiments revealed the opposite effects of haloperidol on BDNF and TrkB levels in the brain, indicating that these changes likely cannot be ascribed to treatment with antipsychotic drugs (Angelucci et al., 2000). Moreover, the latest studies have revealed a strong link between BDNF signals and dopaminergic function in the brain (Batchelor et al., 2000, Guillin et al., 2001). Together, these findings suggest that neurotrophic abnormality might be associated with schizophrenic pathology or etiology.
High levels of BDNF and TrkB are expressed in the brain and in various peripheral tissues including muscle and blood cells in humans (Shibayama and Koizumi, 1996, Radka et al., 1996). Assuming that regulation of BDNF expression, release or signaling is profoundly affected by schizophrenia, it is possible that a similar abnormality in BDNF also occurs in other peripheral tissues. In the present investigation, we measured BDNF protein levels in human blood and serum and examined the production and release of this neurotrophic factor in the periphery in schizophrenic patients.
Section snippets
Subjects and procedure
Human blood was collected from two independent pairs of groups: 35 normal healthy volunteers who had no history of psychiatric or neurologic disorders and 34 chronic patients with schizophrenia (Group I), as well as 27 volunteers and 34 schizophrenic patients (Group II), after they had provided written informed consent (see details in Table 1). All of the experiments were performed with the authorization of Niigata University Ethics Committee. A part of the whole blood was collected into tubes
Results
Serum BDNF levels were measured using sandwich EIA. Most of the BDNF values did not fit to a standard distribution curve and were therefore subjected to non-parametric analyses. The authenticity of this assay was confirmed previously; its cross-reactivity against other neurotrophins is less than 0.2% (Nawa et al., 1995). Serum was collected from both chronic schizophrenic patients (n=34) and age-matched healthy volunteers (n=35; Table 1). Serum BDNF levels in healthy human volunteers were very
Discussion
Using a two-site EIA, we demonstrated that human serum BDNF levels in schizophrenic patients are significantly reduced to 55% of control levels. BDNF levels in the whole blood are not reduced. Almost all schizophrenic patients were treated with typical antipsychotics, but the BDNF reduction in serum is not likely to be due to their chronic treatment, because patients’ serum BDNF levels do not correlate with their daily doses of antipsychotics. Animal experiments also support this explanation.
Acknowledgments
We thank Ms Higuchi for technical assistance and volunteers who provided us with control blood. This work was supported by the Japanese Society for the Promotion of Science (RFTF-96L00203, 13GS0014) and Special Coordination Funds for Promoting Science and Technology, Target-Oriented Brain Science Program (MECSST, Japan).
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2021, Biological PsychiatryCitation Excerpt :However, as serum levels of proBDNF are not reduced in depressed patients while those of mature BDNF are (85), a ratio between mature BDNF and proBDNF has been suggested as a biomarker for bipolar disorder (86) and for discriminating between bipolar and major depressive disorder with reasonable sensitivity (87). Notably, a decrease in serum BDNF levels is not specific to depression: serum BDNF levels have been reported to be decreased also in schizophrenia (88–90) and in autism (91,92). While serum BDNF levels were low in patients with depression and schizophrenia, whole-blood BDNF levels were not different between patients and control subjects (72,88).