C-Reactive Protein: Higher During Acute Psychotic Episodes and Related to Cortical Thickness in Schizophrenia and Healthy Controls

There is increasing evidence for the role of inflammation in schizophrenia, yet the stability of increased peripheral inflammation in acute psychosis and the degree to which peripheral inflammation relates to cortical thickness, a measure of the degree of neuropathology, are unknown. In independent samples, we assessed the peripheral inflammation marker C-reactive protein (CRP) to determine the extent to which: (1) CRP was elevated and stable across admissions for acute psychosis, (2) cognition, daily function and symptom severity are characteristic of chronically ill patients with schizophrenia displaying elevated CRP, and (3) CRP levels predict cortical thickness. Study 1 assessed peripheral CRP (primary outcome) and other blood measures in 174/280 people with acute psychosis while Study 2 assessed peripheral CRP, cognition and cortical thickness (primary outcomes), symptoms, and daily function in 85/97 chronically ill patients with schizophrenia and 71/87 healthy controls. In acute psychosis, CRP and neutrophil-to-lymphocyte ratio were significantly elevated relative to a normal cutoff (with 59.8% of patients having elevated CRP) which remained elevated across admissions. CRP was significantly elevated in 43% of chronically ill patients with schizophrenia compared to 20% in controls. Elevated CRP patients displayed significantly worse working memory and CRP was inversely correlated with cortical thickness in frontal, insula, and temporal brain regions. This work supports the role of inflammation in psychotic illnesses and suggests that use of peripheral markers (e.g., CRP) in conjunction with diagnosis could be used to identify patients with more cortical neuropathology and cognitive deficits

Experimental and meta-analytic evidence that source variability of misinformation does not increase eyewitness suggestibility independently of repetition of misinformation

Considerable evidence has shown that repeating the same misinformation increases its influence (i.e., repetition effects). However, very little research has examined whether having multiple witnesses present misinformation relative to one witness (i.e., source variability) increases the influence of misinformation. In two experiments, we orthogonally manipulated repetition and source variability. Experiment 1 used written interview transcripts to deliver misinformation and showed that repetition increased eyewitness suggestibility, but source variability did not. In Experiment 2, we increased source saliency by delivering the misinformation to participants via videos instead of written interviews, such that each witness was visibly and audibly distinct. Despite this stronger manipulation, there was no effect of source variability in Experiment 2. In addition, we reported a meta-analysis (k = 19) for the repeated misinformation effect and a small-scale meta-analysis (k = 8) for the source variability effect. Results from these meta-analyses were consistent with the results of our individual experiments. Altogether, our results suggest that participants respond based on retrieval fluency rather than source-specifying information.This article is published as O’Donnell R, Chan JCK, Foster JL and Garry M (2023) Experimental and meta-analytic evidence that source variability of misinformation does not increase eyewitness suggestibility independently of repetition of misinformation. Front. Psychol. 14:1201674. doi: 10.3389/fpsyg.2023.1201674. Posted with permission.© 2023 O’Donnell, Chan, Foster and Garry. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms

Emotion regulation in schizophrenia: Affective, social and clinical correlates of suppression and reappraisal

Individuals can exert considerable control over their experience and expression of emotion by applying different regulatory strategies such as reappraisal and suppression. However, although it has been suggested that blunted affect in schizophrenia, characterized by markedly reduced emotion expressivity alongside apparently normal emotion experience, may reflect overuse of suppression, no study to date has assessed self-reported use of these different emotion regulatory strategies in relation to this disorder. In the present study, 41 individuals with schizophrenia and 38 control participants completed a self-report measure that differentiated between use of suppression and reappraisal. Symptom severity and various aspects of cognitive and psychosocial functioning were also assessed. Relative to controls, individuals with schizophrenia did not differ with regard to their reported use of suppression and reappraisal, and reported use of both strategies was unrelated to clinical ratings of blunted affect. However, whereas (lower) use of reappraisal was associated with greater social function impairment for both groups, only for controls was (greater) use of suppression associated with reduced social functioning. Implications for understanding blunted affect and social dysfunction in schizophrenia are discussed

Emotion dysregulation in schizophrenia: Reduced amplification of emotional expression is associated with emotional blunting

A prominent emotional disturbance in schizophrenia is clinically evident in blunted affect, often observed as reduced emotional expressivity alongside the individual's report of normal or heightened emotional experience. It has been suggested that this disjunction between the experience and expression of emotion may reflect problems with the regulation of emotional expression. The present study thus set out to examine the capacity to engage in particular emotion regulatory strategies, and specifically, the ability to amplify the emotional expression of an experienced emotion ('amplification') or suppress the emotional expression of an experienced emotion ('suppression') whilst watching film clips selected to elicit amusement. Twenty nine participants with schizophrenia and 30 demographically matched non-clinical controls were asked to watch three different amusing film clips, whilst engaging in different regulatory strategies. The results indicate that participants with schizophrenia have difficulties with the amplification (but not suppression) of emotion expressive behavior. These difficulties are significantly correlated with total negative symptoms experienced, particularly emotional blunting

Cortisol-dehydroepiandrosterone ratios are inversely associated with hippocampal and prefrontal brain volume in schizophrenia

While high levels of glucocorticoids are generally neuro-damaging, a related adrenal steroid, dehydroepiandrosterone (DHEA), has anti-glucocorticoid and neuroprotective properties. Previous work has shown increased circulating levels of DHEA and abnormal cortisol/DHEA ratios in people with schizophrenia, however reports are limited and their relationship to neuropathology is unclear. We performed the largest study to date to compare levels of serum DHEA and cortisol/DHEA ratios in people with schizophrenia and healthy controls, and investigated the extent to which cortisol/DHEA ratios predict brain volume. Serum cortisol and DHEA were assayed in 94 people with schizophrenia and 81 healthy controls. T1-weighted high-resolution anatomical scans were obtained using a 3 T Achieva scanner on a subset of 59 people with schizophrenia and 60 healthy controls. Imaging data were preprocessed and analyzed using SPM12. People with schizophrenia had significantly increased serum DHEA levels (p = 0.002), decreased cortisol/DHEA ratios (p = 0.02) and no difference in cortisol levels compared to healthy controls. Cortisol/DHEA ratios were inversely correlated with hippocampal (r = -0.33 p = 0.01) and dorsolateral prefrontal cortex (r = -0.30, p = 0.02) volumes in patients. Our findings suggest that the cortisol/DHEA ratio may be a molecular blood signature of hippocampal and cortical damage. These results further implicate the role of DHEA and hypothalamic-pituitary-adrenal axis dysfunction in the pathophysiology of schizophrenia

Adjunctive canakinumab reduces peripheral inflammation markers and improves positive symptoms in people with schizophrenia and inflammation: A randomized control trial.

BACKGROUND Clinical trials of anti-inflammatories in schizophrenia do not show clear and replicable benefits, possibly because patients were not recruited based on elevated inflammation status. Interleukin 1-beta (IL-1β) mRNA and protein levels are increased in serum, plasma, cerebrospinal fluid, and brain of some chronically ill patients with schizophrenia, first episode psychosis, and clinical high-risk samples. Canakinumab, an approved anti-IL-1β monoclonal antibody, interferes with the bioactivity of IL-1β and interrupts downstream signaling. However, the extent to which canakinumab reduces peripheral inflammation markers, such as, high sensitivity C-reactive protein (hsCRP) and symptom severity in schizophrenia patients with inflammation is unknown. TRIAL DESIGN We conducted a randomized, placebo-controlled, double-blind, parallel groups, 8-week trial of canakinumab in chronically ill patients with schizophrenia who had elevated peripheral inflammation. METHODS Twenty-seven patients with schizophrenia or schizoaffective disorder and elevated peripheral inflammation markers (IL-1β, IL-6, hsCRP and/or neutrophil to lymphocyte ratio: NLR) were randomized to a one-time, subcutaneous injection of canakinumab (150 mg) or placebo (normal saline) as an adjunctive antipsychotic treatment. Peripheral blood hsCRP, NLR, IL-1β, IL-6, IL-8 levels were measured at baseline (pre injection) and at 1-, 4- and 8-weeks post injection. Symptom severity was assessed at baseline and 4- and 8-weeks post injection. RESULTS Canakinumab significantly reduced peripheral hsCRP over time, F(3, 75) = 5.16, p = 0.003. Significant hsCRP reductions relative to baseline were detected only in the canakinumab group at weeks 1, 4 and 8 (p's = 0.0003, 0.000002, and 0.004, respectively). There were no significant hsCRP changes in the placebo group. Positive symptom severity scores were significantly reduced at week 8 (p = 0.02) in the canakinumab group and week 4 (p = 0.02) in the placebo group. The change in CRP between week 8 and baseline (b = 1.9, p = 0.0002) and between week 4 and baseline (b = 6.0, p = 0.001) were highly significant predictors of week 8 change in PANSS Positive Symptom severity scores. There were no significant changes in negative symptoms, general psychopathology or cognition in either group. Canakinumab was well tolerated and only 7 % discontinued. CONCLUSIONS Canakinumab quickly reduces peripheral hsCRP serum levels in patients with schizophrenia and inflammation; after 8 weeks of canakinumab treatment, the reductions in hsCRP are related to reduced positive symptom severity. Future studies should consider increased doses or longer-term treatment to confirm the potential benefits of adjunctive canakinumab in schizophrenia. Australian and New Zealand Clinical Trials Registry number: ACTRN12615000635561