Ulla Knorr1, Anja Hviid Simonsen2, Henrik Zetterberg3, Kaj Blennow4, Steen Gregers Hasselbalch2, Lars Vedel Kessing5. 1. Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Department O, section 6233, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark; University of Copenhagen, Faculty of Health and Medical Sciences, Denmark. Electronic address: ulla.knorr@regionh.dk. 2. Danish Dementia Research Center, University of Copenhagen, Faculty of Health and Medical Sciences, section 6922, Rigshospitalet, Blegdamvej 9, DK-2100 Copenhagen, Denmark; University of Copenhagen, Faculty of Health and Medical Sciences, Denmark. 3. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, S-431 80 Mölndal, Sweden; Department of Molecular Neuroscience, UCL, Institute of Neurology, Queen Square, London WCIN 3BG, United Kingdom; UK Dementia Research Institute at UCL, London WC1N 3BG, United Kingdom. 4. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, S-431 80 Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, S-431 80 Mölndal, Sweden. 5. Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Department O, section 6233, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark; University of Copenhagen, Faculty of Health and Medical Sciences, Denmark.
Abstract
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.
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.
Authors: Anniella Isgren; Andreas Göteson; Jessica Holmén-Larsson; Aurimantas Pelanis; Carl Sellgren; Erik Joas; Timea Sparding; Henrik Zetterberg; Erik Smedler; Joel Jakobsson; Mikael Landén Journal: Mol Psychiatry Date: 2022-08-19 Impact factor: 13.437