ReviewCSF diagnostics in psychiatry – present status – future projects
Section snippets
Introduction (related to personal communication with Hansotto Reiber)
In the nineties (20th century) Prof. Felgenhauer, then head of the Neurology Department in Göttingen University, gave a lecture in the neighboring Psychiatry department about the potential relevance of CSF analysis in psychiatry. He mourned infrequent indication of CSF lumbar puncture for psychiatric patients. This cooperation in diagnosis and education of assistant doctors was an old agreement from the seventies between the departments of psychiatry (Prof. E. Maier) and neurology (Prof. H.
Autoimmune encephalitis (AE) and mild encephalitis (ME)
There is increasing evidence now that refined differential diagnosis including modern CSF diagnostics is advantageous at least for a subgroup of patients before beginning psychopharmacological treatment. Most relevant herein is the recent discovery of various antineural autoantibodies. Patients in initial stages of autoimmune encephalitis (AE) typically present with exclusive psychiatric syndromes (Dalmau, Lancaster, Martinez-Hernandez, Rosenfeld, & Balice-Gordon, 2011). AE is a treatable
Basics of CSF analysis in psychiatric disorders
Basic CSF analysis includes cytology, protein analysis (albumin, IgG, IgA, IgM) and numbers of complementary parameters of diagnostic relevance like oligoclonal IgG and lactate (Wildemann et al., 2010). The parallel analysis of the CSF with serum samples and calculation of CSF/serum quotients is the base for the evaluation and interpretation of the immunoglobulin patterns in Reibergrams (Reiber & Peter, 2001). These diagrams eventually present disease-related, sometimes typical patterns and are
Actual CSF studies in severe mental illness
In schizophrenia spectrum psychoses, and also in severe depression, number of studies indicated CSF protein increases in subgroup of cases. Over the last decennia we performed several CSF studies and confirmed high prevalence of minor CSF abnormalities in both, in therapy resistant affective and in schizophrenia spectrum groups, which presented: about 20% CSF albumin increase, indicating moderate blood CSF barrier dysfunction; 15% slightly increased CSF cell numbers; 14% intrathecal humoral
Immune and cytokine findings in severe mental illness
The role of infectious agents is difficult to define in the ME scenario but agents likely play a contributive role (Bechter, 2013). Evidence has accumulated for several agents (Houenou et al., 2014, Leypoldt et al., 2013), also inflammatory metabolites may play a role (Bay-Richter et al., 2015). Many markers of immune activation/inflammation have been found (Davis, Moylan, Harvey, Maes, & Berk, 2014; Fillmann, Sinclair, Fung, Webster, & Weickert, 2014; Leboyer, Tamouza, Charron, Faucard, &
Conclusion
The current rapid development in neurology to detect more sensitively limbic encephalitis (LE) or autoimmune encephalitis (AE), is of great relevance for clinical psychiatry, as a number of cases present with exclusive psychiatric syndromes. Overall rare, these psychiatric patients may considerably profit from early immune suppressive or immune modulatory treatment (see redflags in Table 3), which was recommended to perform in neurology departments (Lennox, Coles, & Vincent, 2012). Other cases
Outlook
CSF research probably will gain increasing relevance for psychiatric research in the clinic in the near future and such perspective matches with the long standing experience in neurology, CSF analysis representing a most sensitive and specific method to detect neuroinflammation in the individual patient. Such perspective matches also with new insights into the role of the CSF spaces in physiology and pathophysiology, as the intrathecal spaces represent a compartment of its own with a specific
References (58)
- et al.
A role for inflammatory metabolites as modulators of the glutamate N-methyl-d-aspartate receptor in depression and suicidality
BBI
(2015) - et al.
Investigations of cerebrospinal fluid in Borna disease virus seropositive psychiatric patients
Eur. Psychiatry
(1995) Cerebrospinal fluid analysis in affective and schizophrenic spectrum disorders: identification of subgroups with immune responses and blood–CSF barrier dysfunction
Journal of Psychiatric Research
(2010)Updating the mild encephalitis hypothesis of schizophrenia
Progress NPBP
(2013)- et al.
The epidemiologic evidence linking autoimmune diseases and psychosis
Biological Psychiatry
(2014) - et al.
Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis
Lancet Neurology
(2011) - et al.
Antibody titres at diagnosis and during follow-up of anti-NMDA receptor encephalitis: a retrospective study
Lancet Neurology
(2014) - et al.
Cytomegalovirus seropositivity and serointensity are associated with hippocampal volume and verbal memory in schizophrenia and bipolar disorder
Progress in Neuropsychopharmacology & Biological Psychiatry
(2014) - et al.
Cerebrospinal fuid neopterin is brain-derived and not associated with blood–CSF barrier dysfunction in non-inflammatory affective and schizophrenic spectrum disorders
Journal of Psychiatric Research
(2013) - et al.
Minocycline rescues decrease in neurogenesis, increase in microglia cytokines and deficits in sensorimotor gating in an animal model of schizophrenia
BBI
(2014)
Flow cytometric analysis of T cell subsets in paired samples of cerebrospinal fluid and peripheral blood from patients with neurological and psychiatric disorders
Brain, Behavior, and Immunity
Cerebrospinal fluid and serum cytokine profiling to detect immune control of infectious and inflammatory neurological and psychiatric diseases
Cytokine
Flow rate of cerebrospinal fluid (CSF)—a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases
Journal of the Neurological Sciences
Antibody patterns vary arbitrarily between cerebrospinal fluid and aqueous humor of the individual multiple sclerosis patient: specificity-independent pathological B cell function
Journal of Neuroimmunology
Cerebrospinal fluid analysis—disease-related data patterns and evaluation programs
Journal of the Neurological Sciences
Definition and description of schizophrenia in the DSM-5
Schizophrenia Research
Uncovering the hidden risk architecture of the schizophrenias: confirmation in three independent genome-wide association studies
American Journal of Psychiatry
Neurological soft signs in the clinical course of schizophrenia: results of a meta-analysis
Front Psychiatry
Aging-induce type I interferon response at the choroid plexus negatively affects brain function
Science
Editorial_Quinckes’ pioneering 19th centuries CSF studies may inform 21th centuries research
NPBR
Mild encephalitis underlying psychiatrc disorder—a reconsideration and hypothesis exemplified on borna disease
NPBR
A case of therapy resistant depression with fatigue—seemingly streptococcal associated autoimmune disorder
Nervenarzt
Autoimmune diseases and severe infections as risk factors for schizophrenia—a 30-year population-based register study
American Journal of Psychiatry
Autoimmune diseases and infections as risk factors for schizophrenia
Annals of the New York Academy of Sciences
Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study
JAMA Psychiatry
The growing spectrum of antibody-associated inflammatory brain diseases in children
Neurology Neuroimmunology & Neuroinflammation
The role of transmitter diffusion and flow versus extracellular vesicles in volume transmission in the brain neural–glial networks
Philosophical Transactions of the Royal Society B
Consensus guidelines for the investigation and management of encephalitis in adults and children in Austrialia and New Zealand
Internal Medicine Journal
Anti-N-methyl-d-aspartate receptor encephalitis mimics viral encephalitis
Pediatric Infectious Disease Journal
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