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1. The relationship between blood–brain barrier dysfunction and neurocognitive impairments in first-episode psychosis: findings from a retrospective chart analysis

Author

Isabel Maurus, Sarah Wagner, Mattia Campana, Lukas Roell, Johanna Strauss, Piyumi Fernando, Susanne Muenz, Peter Eichhorn, Andrea Schmitt, Susanne Karch, Oliver Pogarell, Rolf R. Engel, Peter Falkai, Alkomiet Hasan, and Elias Wagner

Subjects
Schizophrenia, cerebrospinal fluid, cognition, working memory, working speed, Psychiatry, RC435-571
Abstract

Background Even before the onset of psychotic symptoms, individuals with schizophrenia display cognitive impairments. Simultaneously, increasing amounts of individuals exhibit dysfunction of the blood–brain barrier (BBB). However, the impact of BBB dysfunction on neurocognitive impairment in people with first-episode psychosis has not yet been investigated. Aims To advance understanding of said relationship, we considered one of the largest first-episode psychosis cohorts with cerebrospinal fluid parameters available, and investigated whether BBB dysfunction is related to working memory, working speed and attention. Method We conducted a retrospective chart review of 121 in-patients diagnosed with a first episode of a schizophrenia spectrum disorder. Patients underwent neurocognitive testing and a lumbar puncture within routine clinical care. To define BBB dysfunction, albumin cerebrospinal fluid/serum quotients, immunoglobulin G ratios and oligoclonal band types were evaluated, and gender-specific differences investigated. Neurocognitive functioning was assessed by the Wechsler Adult Intelligence Scale, Test of Attentional Performance and Repeatable Battery for the Assessment of Neuropsychological Status. We performed simple and multiple linear regression analyses to interpret associations of interest. Results Of those tested, 16% showed an alteration in albumin quotients and 12% had an oligoclonal band type indicating BBB dysfunction. Notably, male patients were more likely to have an increased albumin quotient and a higher immunoglobulin G ratio than female patients. We found no significant association between BBB dysfunction and neurocognitive assessments. Conclusions The hypothesised relationship between BBB and neurocognitive impairments was not detectable in our retrospective cohort. Further cerebrospinal fluid-based studies with a longitudinal assessment of cognitive functioning and disease trajectory are urgently needed.

Published
2023
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2. Association between aerobic fitness and the functional connectome in patients with schizophrenia

Author

Lukas Roell, Isabel Maurus, Daniel Keeser, Temmuz Karali, Boris Papazov, Alkomiet Hasan, Andrea Schmitt, Irina Papazova, Moritz Lembeck, Dusan Hirjak, Eliska Sykorova, Cristina E. Thieme, Susanne Muenz, Valentina Seitz, David Greska, Mattia Campana, Elias Wagner, Lisa Loehrs, Sophia Stoecklein, Birgit Ertl-Wagner, Johannes Poemsl, Astrid Roeh, Berend Malchow, Katriona Keller-Varady, Andreas Meyer-Lindenberg, and Peter Falkai

Subjects
Psychiatry and Mental health, Cross-Sectional Studies, Connectome, Schizophrenia, Brain, Humans, Bayes Theorem, Pharmacology (medical), ddc:610, General Medicine, Exercise, Magnetic Resonance Imaging, Biological Psychiatry
Abstract

Background Schizophrenia is accompanied by widespread alterations in static functional connectivity associated with symptom severity and cognitive deficits. Improvements in aerobic fitness have been demonstrated to ameliorate symptomatology and cognition in people with schizophrenia, but the intermediary role of macroscale connectivity patterns remains unknown. Objective Therefore, we aim to explore the relation between aerobic fitness and the functional connectome in individuals with schizophrenia. Further, we investigate clinical and cognitive relevance of the identified fitness-connectivity links. Methods Patients diagnosed with schizophrenia were included in this cross-sectional resting-state fMRI analysis. Multilevel Bayesian partial correlations between aerobic fitness and functional connections across the whole brain as well as between static functional connectivity patterns and clinical and cognitive outcome were performed. Preliminary causal inferences were enabled based on mediation analyses. Results Static functional connectivity between the subcortical nuclei and the cerebellum as well as between temporal seeds mediated the attenuating relation between aerobic fitness and total symptom severity. Functional connections between cerebellar seeds affected the positive link between aerobic fitness and global cognition, while the functional interplay between central and limbic seeds drove the beneficial association between aerobic fitness and emotion recognition. Conclusion The current study provides first insights into the interactions between aerobic fitness, the functional connectome and clinical and cognitive outcome in people with schizophrenia, but causal interpretations are preliminary. Further interventional aerobic exercise studies are needed to replicate the current findings and to enable conclusive causal inferences. Trial registration The study which the manuscript is based on is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Published
2022

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