TY - JOUR

T1 - Biomarkers in cerebrospinal fluid of patients with bipolar disorder versus healthy individuals

T2 - A systematic review

AU - Knorr, Ulla

AU - Simonsen, Anja Hviid

AU - Zetterberg, Henrik

AU - Blennow, Kaj

AU - Hasselbalch, Steen Gregers

AU - Kessing, Lars Vedel

PY - 2018

Y1 - 2018

N2 - Background: The pathophysiological processes of bipolar disorder (BD) may be detectable by the use of cerebrospinal fluid (CSF) biomarkers. Aim: We aimed for the first time to review studies of CSF biomarkers in patients with BD compared to healthy control individuals (HC). We investigated the effect of diagnosis, age, gender, clinical state, medication, technical characteristics of tests, fasting state and, cognitive function if applicable. Method: We did a systematic review according to the PRISMA Statement based on comprehensive database searches for studies on cerebrospinal biomarkers in patients with bipolar disorder versus HC. Risk of bias was systematically assessed. Results: The search strategy identified 410 studies of which thirty-four fulfilled the inclusion criteria. A total of 117 unique biomarkers were investigated, out of which 11 were evaluated in more than one study. Forty biomarkers showed statistically significant differences between BD and HC in single studies. Only the findings of elevated homovanillic acid and 5-hydroxy-indoleacetic acid were replicated across studies. Most studies had a cross sectional design and were influenced by risk of bias mainly due to small sample size, lack of data on mood state at the time of the CSF puncture and not considering potential confounders including age, gender, diagnoses, BMI, life style factors such as smoking, and psychotropic medication. Conclusion: Specific monoamine CSF biomarkers may be related to the pathophysiology of BD. Future studies must aim at increasing the level of evidence by validating the positive findings in prospective studies with stringent methodology.

AB - Background: The pathophysiological processes of bipolar disorder (BD) may be detectable by the use of cerebrospinal fluid (CSF) biomarkers. Aim: We aimed for the first time to review studies of CSF biomarkers in patients with BD compared to healthy control individuals (HC). We investigated the effect of diagnosis, age, gender, clinical state, medication, technical characteristics of tests, fasting state and, cognitive function if applicable. Method: We did a systematic review according to the PRISMA Statement based on comprehensive database searches for studies on cerebrospinal biomarkers in patients with bipolar disorder versus HC. Risk of bias was systematically assessed. Results: The search strategy identified 410 studies of which thirty-four fulfilled the inclusion criteria. A total of 117 unique biomarkers were investigated, out of which 11 were evaluated in more than one study. Forty biomarkers showed statistically significant differences between BD and HC in single studies. Only the findings of elevated homovanillic acid and 5-hydroxy-indoleacetic acid were replicated across studies. Most studies had a cross sectional design and were influenced by risk of bias mainly due to small sample size, lack of data on mood state at the time of the CSF puncture and not considering potential confounders including age, gender, diagnoses, BMI, life style factors such as smoking, and psychotropic medication. Conclusion: Specific monoamine CSF biomarkers may be related to the pathophysiology of BD. Future studies must aim at increasing the level of evidence by validating the positive findings in prospective studies with stringent methodology.

KW - Biomarker

KW - Bipolar disorder

KW - Cerebrospinal fluid

KW - Systematic review

U2 - 10.1016/j.euroneuro.2018.04.002

DO - 10.1016/j.euroneuro.2018.04.002

M3 - Review

C2 - 29802040

AN - SCOPUS:85047309938

VL - 28

SP - 783

EP - 794

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

IS - 7

ER -