Measuring disorganized speech in schizophrenia: automated analysis explains variance in cognitive deficits beyond clinician-rated scales.

BACKGROUND: Conveying information cohesively is an essential element of communication that is disrupted in schizophrenia. These disruptions are typically expressed through disorganized symptoms, which have been linked to neurocognitive, social cognitive, and metacognitive deficits. Automated analysis can objectively assess disorganization within sentences, between sentences, and across paragraphs by comparing explicit communication to a large text corpus. METHOD: Little work in schizophrenia has tested: (1) links between disorganized symptoms measured via automated analysis and neurocognition, social cognition, or metacognition; and (2) if automated analysis explains incremental variance in cognitive processes beyond clinician-rated scales. Disorganization was measured in schizophrenia (n = 81) with Coh-Metrix 3.0, an automated program that calculates basic and complex language indices. Trained staff also assessed neurocognition, social cognition, metacognition, and clinician-rated disorganization. RESULTS: Findings showed that all three cognitive processes were significantly associated with at least one automated index of disorganization. When automated analysis was compared with a clinician-rated scale, it accounted for significant variance in neurocognition and metacognition beyond the clinician-rated measure. When combined, these two methods explained 28-31% of the variance in neurocognition, social cognition, and metacognition. CONCLUSIONS: This study illustrated how automated analysis can highlight the specific role of disorganization in neurocognition, social cognition, and metacognition. Generally, those with poor cognition also displayed more disorganization in their speech-making it difficult for listeners to process essential information needed to tie the speaker's ideas together. Our findings showcase how implementing a mixed-methods approach in schizophrenia can explain substantial variance in cognitive processes.

New insights into the pharmacokinetics and pharmacodynamics of natalizumab treatment for patients with multiple sclerosis, obtained from clinical and in vitro studies.

BACKGROUND: The monoclonal antibody natalizumab (NAT) inhibits the migration of lymphocytes throughout the blood-brain barrier by blocking very late antigen (VLA)-4 interactions, thereby reducing inflammatory central nervous system (CNS) activity in patients with multiple sclerosis (MS). We evaluated the effects of different NAT treatment regimens. METHODS: We developed and optimised a NAT assay to measure free NAT, cell-bound NAT and VLA-4 expression levels in blood and cerebrospinal fluid (CSF) of patients using standard and prolonged treatment intervals and after the cessation of therapy. RESULTS: In paired CSF and blood samples of NAT-treated MS patients, NAT concentrations in CSF were approximately 100-fold lower than those in serum. Cell-bound NAT and mean VLA-4 expression levels in CSF were comparable with those in blood. After the cessation of therapy, the kinetics of free NAT, cell-bound NAT and VLA-4 expression levels differed. Prolonged intervals greater than 4 weeks between infusions caused a gradual reduction of free and cell-bound NAT concentrations. Sera from patients with and without NAT-neutralising antibodies could be identified in a blinded assessment. The NAT-neutralising antibodies removed NAT from the cell surface in vivo and in vitro. Intercellular NAT exchange was detected in vitro. CONCLUSIONS: Incorporating assays to measure free and cell-bound NAT into clinical practice can help to determine the optimal individual NAT dosing regimen for patients with MS.