Biomedical subjects

Declan P McKernan

Publications and source records attributed to Declan P McKernan.

3 recordsLinked to original sources

PubMed2026

Investigating the relationship between Toll-like receptor activity, low-grade inflammation, cognitive deficits, and antipsychotic drug dose in schizophrenia patients: a moderation analysis.

BACKGROUND: Schizophrenia (SZ) is a debilitating psychiatric disorder where patients experience cognitive decline. Antipsychotic drugs alleviate positive symptoms but do not improve cognitive performance. We previously demonstrated that Toll-like receptors (TLRs), involved in cytokine production, can predict cognitive deficits in SZ patients. In this study, we aim to investigate the potential moderating effects of antipsychotic drugs on the associations between cytokines, TLRs, and cognition. METHODS: In total, 280 participants (201 controls and 79 cases of SZ) were recruited in Ireland. Venous blood from the participants was stimulated with TLR ligands. Levels of cytokines were measured from plasma and post-blood stimulation. The participants were administered a battery of cognitive tasks using the Cambridge Neuropsychological Test Automated Battery and Wechsler Adult Intelligence Scale-IIIR. Olanzapine equivalents were calculated using the defined daily dose method. RESULTS: The results indicate that antipsychotic drug dose does not predict TLR activity or cognition, indicating that antipsychotic drug dose does not have a direct effect on cognition or TLR activity. However, the relationship between TLR4 activity and visual learning and memory is moderated by the antipsychotic drug dose (B = -0.065; p < 0.001), where increasing doses have a decreasing impact on their relationship. CONCLUSIONS: Our data indicate that the dose of antipsychotic drugs alone cannot predict changes in cognitive performance and TLR4-activity. It also suggests that antipsychotic drug doses significantly affect TLR activity and its relationship with cognition. These effects are more pronounced on some domains than others. These findings open up new avenues for understanding the complex interplay between antipsychotic drugs, TLRs, and cognitive deficits in SZ.

Humans↗

PubMed2026

Examining the Relationship Between Physical Neglect, Inflammation and Anterior Cingulate Activation During Facial Emotion Recognition in Patients With Schizophrenia and Healthy Controls: A Functional Magnetic Resonance Imaging Study.

Physical neglect is associated with poorer cognitive functioning in patients with schizophrenia, including deficits in facial emotion recognition. Recent research by our group showed the relationship between physical neglect and facial emotion recognition is mediated by inflammation. While this mediation effect was observed at the level of behaviour, examining the relationship between physical neglect, inflammation and neural activation during facial emotion recognition would help confirm brain regions impacted and support behavioural findings, but these relationships are unclear. Two hundred twelve participants (52 patients with schizophrenia and 160 healthy controls) underwent functional magnetic resonance imaging while performing an established facial emotion recognition task and a subset completed the Childhood Trauma Questionnaire and provided blood samples outside of the scanner. Inflammation was measured using a latent variable that combined basal plasma levels of interleukin-6, tumour necrosis factor-alpha and C-reactive protein. The relationships between physical neglect, inflammation and neural activation were examined using multiple regression. Neither physical neglect nor inflammation predicted altered neural response during facial emotion recognition at p < 0.05, family-wise error corrected for multiple comparisons within an anterior cingulate region of interest, across the whole brain, in the whole sample or separately in patients or controls. Future research should examine relationships between physical neglect, inflammation and brain activation in larger samples, which may have sensitivity to detect smaller effects, and use tasks that require active recognition of emotions, in addition to passive viewing of faces, which might be associated with additional neural responses.

Humans↗

PubMed2026

Childhood Trauma and Frontoparietal Network Connectivity During Working Memory Task Performance in Individuals With Schizophrenia and Healthy Participants.

Schizophrenia is associated with altered frontoparietal connectivity, which supports higher-order cognition, including working memory. Childhood trauma has been linked to altered functional connectivity and reduced cognitive performance in individuals with schizophrenia and controls. Prior evidence suggests that trauma-related default mode dysconnectivity mediates the association between trauma and cognition. We hypothesised that childhood trauma would be associated with altered frontoparietal connectivity during a working memory task and that such connectivity changes would mediate the relationship between trauma and working memory. Childhood trauma, working memory and fMRI data were collected from individuals with schizophrenia or schizoaffective disorder (n = 38) and controls (n = 128). fMRI data were preprocessed in CONN, and seed-based connectivity analyses were performed for four frontoparietal seeds (bilateral dorsolateral prefrontal and posterior parietal cortices). Connectivity was contrasted across (a) diagnosis and (b) trauma severity. Moderated mediation analyses tested the associations between trauma, connectivity and working memory, with diagnosis as a moderator. Across all participants, higher physical neglect severity predicted poorer working memory performance. Stronger inverse connectivity between left dorsolateral prefrontal and frontal medial cortices predicted better working memory performance. As expected, patients showed widespread frontoparietal dysconnectivity relative to controls, but no differences in frontoparietal connectivity were observed across trauma severity groups. Frontoparietal connectivity did not mediate the association between trauma and working memory, although diagnosis moderated both the trauma-connectivity and connectivity-cognition associations. We conclude that, unlike previous evidence suggesting a mediating role for the default mode network, frontoparietal connectivity did not mediate the trauma-cognition association, possibly suggesting the unique significance of default mode network dysconnectivity in linking trauma to cognition in psychosis.

Humans↗