Biomarkers of neurodegeneration in neural autoantibody-associated psychiatric syndromes: A retrospective cohort study

Abstract

Background: Autoantibody-associated psychiatric syndromes are a novel disease entity that is not fully understood. Several lines of evidence suggest that neurodegenerative processes are involved here. We are investigating whether autoantibody-positive psychiatric syndromes differ from those that are autoantibody-negative in cerebrospinal fluid (CSF) neurodegeneration markers.

Methods: We retrospectively analyzed data from 167 psychiatric patients at the University Medical Center Göttingen from 2017 to 2020. We divided this patient cohort into two, namely antibody-positive and antibody-negative. We compared various clinical features, neurodegeneration markers, and their autoantibody status in CSF and serum. We then compared both cohorts' neurodegeneration markers to a representative Alzheimer cohort. We subdivided the patients into their diverse psychiatric syndromes according to the manual to assess and document psychopathology in psychiatry (the AMDP), and compared the neurodegeneration markers.

Results: Antibody-associated psychiatric syndromes do not appear to reveal significantly greater neurodegeneration than their antibody-negative psychiatric syndromes. 71% of antibody-positive patients fulfilled the criteria for a possible and 22% for a definitive autoimmune encephalitis. Our autoantibody-positive patient cohort's relative risk to develop an possible autoimmune encephalitis was 9%. We also noted that phosphorylated tau protein 181 (ptau 181) did not significantly differ between antibody-associated psychiatric syndromes and our Alzheimer cohort. The psycho-organic syndrome usually exhibits the most prominent neurodegeneration markers, both in antibody-positive and antibody-negative psychiatric patients.

Discussion: We did not find hints for neurodegenerative processes in our antibody-positive versus AD cohort considering total tau or amyloid markers. However, our findings indicate that the neurodegeneration marker ptau181 does not differ significantly between antibody-positive and Alzheimer cohorts, further suggesting axonal neurodegeneration in antibody-positive patients as AD patients have an elevated ptau181. The evidence we uncovered thus suggests that axonal neurodegeneration might affect patients suffering from autoantibody-associated psychiatric syndromes.

Keywords: Autoimmunity; Neural autoantibody; Neurodegeneration; Neurodegenerative biomarkers; Psychiatric syndrome.

Fig. 1

Differences in neurodegeneration biomarkers between psychiatric patients with and without neural autoantibodies and comparison cohort with AD. All neurodegeneration biomarkers differ significantly between AD (n = 27) and Ab-n (n = 95) and between AD and Ab-p (n = 28), except for Aβ40. Abbreviations: Ab-p = psychiatric patients with neural autoantibodies, Ab-n = psychiatric patients without neural autoantibodies, AD = comparative cohort with Alzheimer's disease, Tau protein = total tau protein, ptau 181 = phosphorylated tau protein 181, Aβ42 = amyloid-β-42, Aβ40 = amyloid-β-40, Ratio Aβ42/Aβ40 = Ratio amyloid-β-42/amyloid-β-40. All neural autoantibodies were put in one group as subgroups of specific autoantibodies would be too low to make any statement.

Fig. 2

Differences in neurodegeneration biomarkers between psychiatric patients with neural autoantibodies in peripheral blood, psychiatric patients with neural autoantibodies in peripheral blood and CSF, psychiatric patients without neural autoantibodies and comparison cohort with AD. All neurodegeneration biomarkers differ significantly between AD (n = 27) and Ab-n (n = 95) and between AD and Ab-p CSF (n = 10). Ptau 181 differs not significantly between AD (n = 27) and Ab-p PB (n = 28). Abbreviations: Ab-p PB = psychiatric patients with neural autoantibodies in peripheral blood (n = 28), Ab-p CSF = psychiatric patients with neural autoantibodies in peripheral blood and CSF (n = 10), Ab-n = psychiatric patients without neural autoantibodies (n = 95), AD = comparative cohort with AD (n = 27), Tau protein = total tau protein, ptau 181 = phosphorylated tau protein 181, Aβ42 = amyloid-β-42, Aβ40 = amyloid-β-40, Ratio Aβ42/Aβ40 = Ratio amyloid-β-42/amyloid-β-40.

Fig. 3

Differences in neurodegeneration biomarkers between syndromes and syndrome combinations – AMDP system. The psycho-organic syndrome or a syndrome coinciding with psychoorganic syndrome usually exhibited the most prominent neurodegeneration biomarkers in both autoantibody-positive and autoantibody-negative patients. Abbreviations: ns = not significant A–E: AMDP-Syndromes from psychiatric patients without neural autoantibodies, F–J: AMDP-Syndromes from psychiatric patients with neural autoantibodies, Tau protein = total tau protein, ptau 181 = phosphorylated tau protein 181, Aβ42 = amyloid-β-42, Aβ40 = amyloid-β-40, Ratio Aβ42/Aβ40 = Ratio amyloid-β-42/amyloid-β-40. Antibody-positive patients (Ab-p): depressive, parahallucinatory, psychoorganic syndrome (t-tau: n = 2, ptau181: n = 2, Aβ40: n = 2, Aβ42: n = 2, Aβ42/40: n = 2); depressive, psychoorganic syndrome (t-tau: n = 9, ptau181: n = 9, Aβ40: n = 10, Aβ42: n = 10, Aβ42/40: n = 10); depressive, psychoorganic, apathic snyndrome (t-tau: n = 3, ptau181: n = 3, Aβ40: n = 3, Aβ42: n = 3, Aβ42/40: n = 3); psychoorganic syndrome (t-tau: n = 4, ptau181: n = 4, Aβ40: n = 4, Aβ42: n = 4, Aβ42/40: n = 4). Antibody-negative patients (Ab-n): depressive syndrome (t-tau: n = 5, ptau181: n = 5, Aβ40: n = 5 Aβ42: n = 5, Aβ42/40: n = 5); depressive, parahallucinatory syndrome (t-tau: n = 3, ptau181: n = 3, Aβ40: n = 2, Aβ42: n = 3, Aβ42/40: n = 3); depressive, parahallucinatory, neurological syndrome (t-tau: n = 2, ptau181: n = 2, Aβ40: n = 2, Aβ42: n = 2, Aβ42/40: n = 2); depressive, psychoorganic, parahallucinatory syndrome (t-tau: n = 2, ptau181: n = 2, Aβ40: n = 3, Aβ42: n = 3, Aβ42/40: n = 3); depressive, psychoorganic syndrome (t-tau: n = 21, ptau181: n = 21, Aβ40: n = 19, Aβ42: n = 21, Aβ42/40: n = 21); depressive, psychoorganic, apathic syndrome (t-tau: n = 2, ptau181: n = 2, Aβ40: n = 2, Aβ42: n = 2, Aβ42/40: n = 2); depressive, psychoorganic, neurological syndrome (t-tau: n = 9, ptau181: n = 9, Aβ40: n = 9, Aβ42: n = 9, Aβ42/40: n = 9); depressive, psychoorganic, vegetative syndrome (t-tau: n = 2, ptau181: n = 2, Aβ40: n = 2, Aβ42: n = 2, Aβ42/40: n = 2); depressive, compulsive-obsessive syndrome (t-tau: n = 2, ptau181: n = 2, Aβ40: n = 2, Aβ42: n = 2, Aβ42/40: n = 2); parahallucinatory syndrome (t-tau: n = 2, ptau181: n = 2, Aβ40: n = 2, Aβ42: n = 2, Aβ42/40: n = 2); parahallucinatory, hostility syndrome (t-tau: n = 2, ptau181: n = 2, Aβ40: n = 2, Aβ42: n = 2, Aβ42/40: n = 2); parahallucinatory, psychoorganic syndrome (t-tau: n = 5, ptau181: n = 5, Aβ40: n = 5, Aβ42: n = 5, Aβ42/40: n = 5); psychoorganic syndrome (t-tau: n = 16, ptau181: n = 16, Aβ40: n = 16, Aβ42: n = 16, Aβ42/40: n = 16); psychoorganic, apathic syndrome (t-tau: n = 2, ptau181: n = 2, Aβ40: n = 2, Aβ42: n = 2, Aβ42/40: n = 2); psychoorganic, depressive, vegetative, neurological syndrome (t-tau: n = 2, ptau181: n = 2, Aβ40: n = 2, Aβ42: n = 2, Aβ42/40: n = 2).