Background: The pathophysiological processes of bipolar disorder (BD) may be detectable by the use of cerebrospinal fluid (CSF) biomarkers. Biomarkers for BD may in time assist with diagnosis, prediction of disease course, or identification of response outcome to treatments. Explorative biomarkers have been proposed in many studies but no CSF biomarkers are integrated into routine clinical practice.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 X studies of which thirty-four fulfilled the inclusion criteria.A total of 117 unique biomarkers were investigated. Forty biomarkers showed statistically significant differences between BD and HC. Eleven biomarkers were evaluated in more than one study. 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. limits; English language and human, using the following search terms both as keywords and as text words: Cerebrospinal fluid AND bipolar disorder. In addition reference lists of relevant studies were searched by hand.
Study selection and data collection processStudy titles and abstracts identified by the initial search were screened by UK. Subsequent retrieval of full text articles or other additional information, assessment for eligibility and data extraction was performed independently by two researchers; UK and AHS. Disagreements were resolved by discussion with LVK.The association between cognitive function in BD and various CSF markers has been sporadically investigated (4-7), but these data were not included in this review.
Data itemsA data sheet was constructed and the following data was extracted: Study identification, age, gender, duration of illness, BD subtype, symptom severity, duration of current affective state, medication use, smoking, alcohol use, BMI, exercise or physical activity, biomarker concentration in CSF, measurement method, blinding of analysts, time of day and fasting state at lumbar puncture.In comparisons between BD pati...