Differences in inflammatory marker profiles and cognitive functioning between deficit and nondeficit schizophrenia

Wang, Dandan; Wang, Yewei; Chen, Yan; Li, Yu; Wu, Zenan; Liu, Ruimei; Ren, Jun; Fang, Xinyu; Zhang, Chen

doi:10.3389/fimmu.2022.958972

Cited by 9 publications

(9 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results also showed that CRP and C3 may be the independent risk factor positive symptoms in schizophrenia. This is line with previous studies ( 24 ).…”

Section: Discussionsupporting

confidence: 94%

Effects of olanzapine on anhedonia in schizophrenia: mediated by complement factor H

et al. 2023

Self Cite

View full text Add to dashboard Cite

BackgroundAnhedonia is a trans-diagnostic symptom in schizophrenia and MDD. Our recent work indicated that increased plasma level of complement factor H (CFH) is associated with anhedonia in major depressive disorder. This study hypothesized that CFH is likely to be a biomarker of anhedonia in schizophrenia.MethodsA 12-week prospective study is performed to observe the effects of olanzapine on anhedonia and CFH. We used the Chinese version of Snaith-Hamilton Pleasure Scale (SHAPS) to evaluate anhedonic phenotype in patients with schizophrenia. Plasma levels of C-reactive protein (CRP), C3, C4 and CFH were measured.ResultsOf the recruited 152 samples, patients with anhedonia were found in 99/152 (65.13%). Patients with anhedonia had notably higher PANSS negative subscores, SHAPS total score and higher level of plasma CFH than those without anhedonia (Ps<0.05). Stepwise multivariate linear regression analysis showed that increasing level of plasma CFH was a risk factor for SHAPS total score (β = 0.18, p = 0.03). Of the 99 patients with anhedonia, 74 completed the 12-week follow-up. We observed significantly reduced scores of PANSS, SHAPS and decreased plasma CFH level, when the patients completed this study. The change of SHAPS total score is positively correlated with the level of CFH decrease (p = 0.02).ConclusionOur results implied that plasma CFH levels may be a biomarker for anhedonia in schizophrenia, and the effect of olanzapine on treating anhedonia is through decreasing plasma CFH levels.

show abstract

“…Our results also showed that CRP and C3 may be the independent risk factor positive symptoms in schizophrenia. This is line with previous studies ( 24 ).…”

Section: Discussionsupporting

confidence: 94%

Effects of olanzapine on anhedonia in schizophrenia: mediated by complement factor H

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…While both dopamine and serotonin contribute to positive and negative symptoms, a dysfunctional dopaminergic signaling pathway is reported to play a dominant role in positive symptoms, and the serotonergic signaling pathway is linked with negative, cognition and mood-related symptoms [50][51][52] . In addition, neuroinflammation via pro-inflammatory cytokines contributes to the disease pathophysiology emanating from immune responses or infection [4][5][6][7] . This pathology notably appears in deficit schizophrenia 7 and with negative symptoms, specifically motivational deficits 4 .…”

Section: Studies Provide Insight To Activity On Modelled Behaviors Of...mentioning

confidence: 99%

“…In addition, neuroinflammation via pro-inflammatory cytokines contributes to the disease pathophysiology emanating from immune responses or infection [4][5][6][7] . This pathology notably appears in deficit schizophrenia 7 and with negative symptoms, specifically motivational deficits 4 . Heterogeneity in the cluster of symptoms and their severities among schizophrenia patients exist.…”

Section: Studies Provide Insight To Activity On Modelled Behaviors Of...mentioning

confidence: 99%

“…IL-4, IL-6, TNF-α, INF-γ) seen in the blood and cerebrospinal fluid of patients with this disorder is of particular interest [4][5][6] . Many of these are pro-inflammatory cytokines 4,7 . This presentation appears in deficit schizophrenia 7 and with negative symptoms, specifically motivational deficits 4 .…”

Section: Introductionmentioning

confidence: 99%

“…Many of these are pro-inflammatory cytokines 4,7 . This presentation appears in deficit schizophrenia 7 and with negative symptoms, specifically motivational deficits 4 . Thus, key dopamine and serotonin receptors serve as primary upstream targets for the pharmacological treatment of schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Brilaroxazine (RP5063), a Novel Serotonin-Dopamine Stabilizer, Displays Antipsychotic Efficacy in Rodents

Bhat,

Adiey,

Bhat

et al. 2023

MRAJ

View full text Add to dashboard Cite

Introduction: Brilaroxazine (RP5063) displays high affinity for serotonin (5-HT) 1A/2A/2B/7 and dopamine (D) 2/3/4 and moderate affinity for D1, serotonin transporter (SERT), and nicotinic acetylcholine receptor, α4β2. These receptors are associated with multiple psychological disorders. Methods: The pre-clinical assessment involved three standard models emulating human schizophrenia symptoms. The apomorphine climbing test (Protais et al., 1976), in 5 groups of 10 NMRI mice, compared brilaroxazine (1, 3, and 10 mg/kg i.p.), haloperidol (0.5 mg/kg i.p.), and vehicle. The apomorphine-induced deficit in prepulse inhibition (PPI) (Geyer et al., 2001), in 5 groups of 15 Wistar rats, compared brilaroxazine (3, 10, and 30 mg/kg i.p.), haloperidol (1 mg/kg), and vehicle. The dizocilpine effect on locomotion, stereotypy, and rearing (Rung et al. 2005), in 6 groups of 10 Wistar rats, compared brilaroxazine (3, 10, and 30 mg/kg i.p.), olanzapine (6 mg/kg i.p.) and vehicle with (and without) induction. Results: Brilaroxazine decreased apomorphine-induced climbing across the 1, 3, and 10 mg/kg doses versus controls (p<0.001). This compound dose-dependently reversed the apomorphine-induced PPI effects- 10 mg/kg at 87 dB (p<0.05) and 30 mg/kg at all levels (p<0.01). In the dizocilpine-induced model, it decreased versus vehicle controls: (1) spontaneous locomotor activity by 15% (p<0.05, 3 mg/kg), 40% (p<0.001, 10 mg/kg) and 30% (p<0.01, 30 mg/kg); (2) induced locomotion by 25% (p<0.05, 3 mg/kg), 49% (p<0.01, 10 mg/kg), and 47% (p<0.01, 30 mg/kg), (3) stereotypy by 51% and 58% (p<0.001, 10- and 30-mg/kg, respectively), and rearing (only 10 mg/kg, NS). Conclusion: Brilaroxazine showed animal proof-of-concept activity by mitigating pharmacologically induced behaviors in rodents reflecting psychotic symptoms in humans.

show abstract

GABAergic and inflammatory changes in the frontal cortex following neonatal PCP plus isolation rearing, as a dual-hit neurodevelopmental model for schizophrenia

Cale,

Chauhan,

Cleaver

et al. 2024

Mol Neurobiol

View full text Add to dashboard Cite

The pathogenesis of schizophrenia begins in early neurodevelopment and leads to excitatory-inhibitory imbalance. It is therefore essential that preclinical models used to understand disease, select drug targets and evaluate novel therapeutics encompass similar neurochemical deficits. One approach to improved preclinical modelling incorporates dual-hit neurodevelopmental insults, like neonatal administration of phencyclidine (PCP, to disrupt development of glutamatergic circuitry) then post-weaning isolation (Iso, to mimic adolescent social stress). We recently showed that male Lister-hooded rats exposed to PCP-Iso exhibit reduced hippocampal expression of the GABA interneuron marker calbindin. The current study expanded on this by investigating changes to additional populations of GABAergic interneurons in frontal cortical and hippocampal tissue from the same animals (by immunohistochemistry) as well as levels of GABA itself (via ELISA). Because inflammatory changes are also implicated in schizophrenia, we performed additional immunohistochemical evaluations of Iba-1 positive microglia as well as ELISA analysis of IL-6 in the same brain regions. Single-hit isolation-reared and dual-hit PCP-Iso rats both showed reduced parvalbumin immunoreactivity in the prelimbic/infralimbic region of the frontal cortex. However, this was more widespread in PCP-Iso, extending to the medial/ventral and lateral/dorsolateral orbitofrontal cortices. Loss of GABAergic markers was accompanied by increased microglial activation in the medial/ventral orbitofrontal cortices of PCP-Iso, together with frontal cortical IL-6 elevations not seen following single-hit isolation rearing. These findings enhance the face validity of PCP-Iso, and we advocate the use of this preclinical model for future evaluation of novel therapeutics—especially those designed to normalise excitatory-inhibitory imbalance or reduce neuroinflammation.

show abstract

Differences in inflammatory marker profiles and cognitive functioning between deficit and nondeficit schizophrenia

Cited by 9 publications

References 58 publications

Effects of olanzapine on anhedonia in schizophrenia: mediated by complement factor H

Effects of olanzapine on anhedonia in schizophrenia: mediated by complement factor H

Brilaroxazine (RP5063), a Novel Serotonin-Dopamine Stabilizer, Displays Antipsychotic Efficacy in Rodents

GABAergic and inflammatory changes in the frontal cortex following neonatal PCP plus isolation rearing, as a dual-hit neurodevelopmental model for schizophrenia

Contact Info

Product

Resources

About