ABSTRACT
Recent evidence suggests that purinergic system dysfunction may play a role in the pathophysiology and therapeutics of bipolar disorder (BPD). Uric acid is a key nitrogenous end product of purine metabolism. In addition to being a potential marker of treatment response, high levels of uric acid may represent a state marker during mania. In this study, we assessed the presence of purinergic dysfunction in 20 treatment-naïve first episode patients with BPD who were experiencing a manic episode. Patients were matched with 24 healthy controls. We found that acutely manic patients had significantly higher levels of plasma uric acid (4.85+/-1.60 mg/dL) compared to healthy controls (2.96+/-0.63 mg/dL, p<0.001; F=28.1). No association between uric acid levels with severity of manic symptoms was observed. These results support the role of purinergic system dysfunction in BPD early in the course of illness, and suggest that this phenomenon is not the result of chronicity or medication exposure. Overall, our findings suggest a novel mechanism in the pathophysiology of BPD.
Subject(s)
Bipolar Disorder/blood , Uric Acid/blood , Analysis of Variance , Bipolar Disorder/diagnosis , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Male , Severity of Illness IndexABSTRACT
Predator stress is a type of psychogenic stress induced by an innate recognition of threat. S100B, a calcium-binding protein secreted by astrocytes, has been associated with neurotrophic or neurotoxic action in several neuropsychiatric disorders. It has been recently demonstrated that serum S100B levels in rats are increased after stress by immobilization [S. Scaccianoce, P. Del Bianco, G. Pannitteri, F. Passarelli, Relationship between stress and circulating levels of S100B protein, Brain Res. 1004 (2004) 208-11]. This study aimed to measure cerebrospinal fluid (CSF) S100B in rats after an acute stress situation, which is induced by exposure to a predator. S100B was measured in CSF and in hippocampal and cortical slices by ELISA. Forty-three male Wistar rats, aged 70 days, were randomly assigned to handled (control) or stressed groups (exposed to a cat for 5 min). CSF and brain tissue were removed 1 or 24 h after the procedures. Rats exposed to the cat demonstrated a biphasic change in CSF S100B levels. An increase was observed at 1 h after cat exposure, and a decrease was observed 24 h later, although this was not accompanied by changes in S100B content in hippocampus or cerebral cortex. The effectiveness of the stressor used was confirmed by increased freezing response (during cat exposure) and increased anxiety in the plus maze test (1 h after cat exposure). These results indicate that CSF S100B is changed by stress, reinforcing the possibility that this protein is involved in the adaptive response to stress and/or in secondary neuropsychiatric disorders.