NEUROINFLAMMATORY BIOMARKERS: CLINICAL AND PHARMACOLOGICAL IMPLICATIONS IN BIPOLAR DISORDER
Creators: name: AMODEO, GIOVANNI
Publisher: name: Universit� degli Studi di Siena
Year: 2021

description: Several studies have attempted to identify the neuroinflammatory mechanisms of bipolar disorder, with the aim of understanding the degree to which these mechanisms could impact on the progression of the disease and on the efficacy of drug treatment. Most of the results pointed to a low-grade inflammatory state of central nervous system during the acute phases of bipolar disorder (depressive or manic episode). The present study aimed to evaluate the levels of protein C reactive (CRP) and leukocytes during the acute phase of bipolar disorder. Our hypothesis was that patients with bipolar disorder would show increased neuroinflammatory biomarkers during the acute phase of the disease. Therefore, we recruited 104 patients with bipolar disorder, consecutively admitted to our inpatient unit, and evaluated the blood levels of protein C reactive (CRP) and the white blood cell count at the following time points: 1) admission to the inpatient unit (T0), a setting where all patients are experiencing acute symptoms; 2) 7 � 4 days after admission (T1), 3) in the stabilized-post-acute phase (T2).
Consistent with our hypothesis, we found significantly higher levels of inflammatory biomarkers at T0, compared to T1. T2 was performed on a smaller sample both for CRP (n=40) and leukocytes (n=57). Specifically, at T0 we found that 21,5% of subjects had CRP values greater than 0,5 mg/dl, and 11,5 % of subjects had leukocyte alteration. At T1: we found that 14,4 % of subjects had CRP values greater than 0,5 mg/dl, and 13,46% of subjects had leukocyte alteration. At T2, 72,7% of patients who had abnormal CRP and 75% of patients who had abnormal leukocytes at T0, reverted to normal values.

Patients who were already in treatment with one or more mood stabilizers (valproic acid, carbamazepine, lithium) at T0 had mean values of CRP of 0,22 mg/dl (DS �0,32). Patients who were not already treated with mood stabilizers (valproic acid, carbamazepine, lithium) at T0 had mean values of CRP of 0,42 mg/dl (DS �0,52). The difference was statistically significant (p=0.026).
CRP and leukocytes average values tended to decrease from T0 to T2 and this was statistically significant (p 0,0036 for CRP and p 0,0039 for leukocytes) for those patients who showed abnormal values upon intake to the inpatient unit. Patients with increased leukocytes at T0 and started a mood stabilizers therapy upon admission, showed a statistically significant decrease in leukocytes count (p 0,0037).
We conclude that a sub-population of bipolar patients shows a low-grade of systemic inflammation during the acute phase of illness. Mood stabilizers may exert a protective role against CRP and leukocytes alterations, as suggested by the lower levels of CRP and lower degree of leukocyte alteration in patients who were already treated with this drugs at intake to the inpatient unit and as suggested by their improvement in those patients who were not already treated with mood stabilizers and started these medications at admission. It remains to be established if the improvement was due to the mood stabilizers or, more in general, to the amelioration of their psychiatric symptoms. 
The limits of our study include: relatively small sample size, short duration, inability to control for all the other variables that may have influenced our study results .