A new look on an old issue: comprehensive review of neurotransmitter studies in cerebrospinal fluid of patients with schizophrenia and antipsychotic effect on monoamine’s metabolism
Matthieu Gasnier 1*, Pierre Ellul 2, Marion Plaze 3, Pierre Abdel Ahad 3
1Department of Psychiatry, Mood Center Paris Saclay, Assistance Publique-Hôpitaux de Paris, France, 2Child and adolescent psychiatry department, Hôpital Robert Debré, Paris, Assistance publique Hopitaux de Paris, France, 3Department of Psychiatry, Service hospitalo universitaire, centre Hospitalier Sainte Anne, Paris, France
Received: September 21, 2020; Revised: November 30, 2020; Accepted: December 28, 2020; Published online: December 28, 2020.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Context: Neurotransmitters metabolism has a key role in the physiopathology of schizophrenia as demonstrated by studies measuring monoamines metabolites in patient’s cerebrospinal fluid (CSF) since the beginning of the antipsychotic use. This comprehensive review aims to understand the anomalies of CSF monoamines in schizophrenia and their correlation with clinical and paraclinical features. We also review the influence of antipsychotic treatment on CSF monoamines and discuss the connection with metabolic and inflammatory processes.
Results: Studies comparing CSF HVA levels between patients and controls are miscellaneous, due to the heterogeneity of samples studies. However, low HVA is associated with more positive symptoms and a poorer outcome and negatively correlated with brain ventricle size. Based on humans and animals’ studies, antipsychotic treatments increase HVA during the first week of administration and decrease progressively over the time with a fall-off after withdrawal. 5HIAA levels do not seem to be different in the patient’s CSF compared to controls. Considering metabolic co-factors of NT synthesis, there is evidence supporting an increase of kynurenic acid (KYNA) in the CSF of patients with schizophrenia. Few studies explore folate metabolism in CSF. Literature also emphasizes the relationship between folate metabolism, inflammation and monoamine’s metabolism.
Conclusion: Those results suggest that the CSF monoamines could be correlated with schizophrenia symptoms and treatment outcome. However, further studies, exploring the role of CSF monoamines as biomarkers of disease severity and response to treatment are needed. They should assess the antipsychotic prescription, inflammatory markers and folate metabolism as potential confounding factors.
Keywords: neurotransmitters, schizophrenia, cerebrospinal fluid, inflammation, antipsychotic drugs