Inflammation subtypes in psychosis and their relationships with genetic risk for psychiatric and cardiometabolic disorders

Zhang, Lusi; Lizano, Paulo; Guo, Bin; Xu, Yanxun; Rubin, Leah H.; Hill, S. Kristian; Alliey‐Rodriguez, Ney; Lee, Adam M.; Wu, Baolin; Keedy, Sarah K.; Tamminga, Carol A.; Pearlson, Godfrey D.; Clementz, Brett A.; Keshavan, Matcheri S.; Gershon, Elliot S.; Sweeney, John A.; Bishop, Jeffrey R.

doi:10.1016/j.bbih.2022.100459

Cited by 11 publications

(7 citation statements)

References 59 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent work has identified subgroups based on comprehensive assessment of inflammatory/immune markers [41][42][43][44][45]. These studies have consistently identified two inflammatory subtypes, with a higher frequency of SMI and healthy controls (HC) in the high and low subtype, respectively.…”

Section: Introductionmentioning

confidence: 99%

Inflammation and cognition in severe mental illness: patterns of covariation and subgroups

et al. 2022

View full text Add to dashboard Cite

A potential relationship between dysregulation of immune/inflammatory pathways and cognitive impairment has been suggested in severe mental illnesses (SMI), such as schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, multivariate relationships between peripheral inflammatory/immune-related markers and cognitive domains are unclear, and many studies do not account for inter-individual variance in both cognitive functioning and inflammatory/immune status. This study aimed to investigate covariance patterns between inflammatory/immune-related markers and cognitive domains and further elucidate heterogeneity in a large SMI and healthy control (HC) cohort (SZ = 343, BD = 289, HC = 770). We applied canonical correlation analysis (CCA) to identify modes of maximum covariation between a comprehensive selection of cognitive domains and inflammatory/immune markers. We found that poor verbal learning and psychomotor processing speed was associated with higher levels of interleukin-18 system cytokines and beta defensin 2, reflecting enhanced activation of innate immunity, a pattern augmented in SMI compared to HC. Applying hierarchical clustering on covariance patterns identified by the CCA revealed a high cognition—low immune dysregulation subgroup with predominantly HC (24% SZ, 45% BD, 74% HC) and a low cognition—high immune dysregulation subgroup predominantly consisting of SMI patients (76% SZ, 55% BD, 26% HC). These subgroups differed in IQ, years of education, age, CRP, BMI (all groups), level of functioning, symptoms and defined daily dose (DDD) of antipsychotics (SMI cohort). Our findings suggest a link between cognitive impairment and innate immune dysregulation in a subset of individuals with severe mental illness.

show abstract

Section: Introductionmentioning

confidence: 99%

Inflammation and cognition in severe mental illness: patterns of covariation and subgroups

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Similar to findings on cognitive subgroups (Bora et al, 2023;Cowman et al, 2021;Lewandowski, 2020;Wenzel et al, 2023Wenzel et al, , 2021, the higher-inflammation subtype is associated with more adverse neurobiological and clinical outcomes, and is associated with lower cognitive functioning (Boerrigter et al, 2017;Fillman et al, 2016;Lizano et al, 2023Lizano et al, , 2020Millett et al, 2021;Nettis et al, 2019;Zhang et al, 2022). A common observation is that a larger proportion of individuals with SMI compared to control participants, belong to a higherinflammation subtype (Boerrigter et al, 2017;Fillman et al, 2016;Lizano et al, 2020).…”

Section: Introductionmentioning

confidence: 78%

Longitudinal course of inflammatory-cognitive subgroups across first treatment severe mental illness and healthy controls

Sæther,

Ueland,

Haatveit

et al. 2024

Preprint

View full text Add to dashboard Cite

Background While inflammation is associated with cognitive impairment in severe mental illnesses (SMI), there is substantial heterogeneity and evidence of transdiagnostic subgroups across schizophrenia (SZ) and bipolar (BD) spectrum disorders. There is however, limited knowledge about the longitudinal course of this relationship. Methods Systemic inflammation (C-Reactive Protein, CRP) and cognition (nine cognitive domains) was measured from baseline to 1 year follow-up in first treatment SZ and BD (n=221), and healthy controls (HC, n=220). Linear mixed models were used to evaluate longitudinal changes separately in CRP and cognitive domains specific to diagnostic status (SZ, BD, HC). Hierarchical clustering was applied on the entire sample to investigate the longitudinal course of transdiagnostic inflammatory-cognitive subgroups. Results There were no case-control differences or change in CRP from baseline to follow-up. We confirm previous observations of case-control differences in cognition at both time-points and domain specific stability/improvement over time regardless of diagnostic status. We identified transdiagnostic inflammatory-cognitive subgroups at baseline with differing demographics and clinical severity. Despite improvement in cognition, symptoms and functioning, the higher inflammation-lower cognition subgroup (75% SZ; 48% BD; 38% HC) had sustained inflammation and lower cognition, more symptoms, and lower functioning (SMI only) at follow-up. This was in comparison to a lower inflammation-higher cognition subgroup (25% SZ, 52% BD, 62% HC), where SMI participants showed cognitive functioning at HC level with a positive clinical course. Conclusions Our findings support heterogenous and transdiagnostic inflammatory-cognitive subgroups that are stable over time, and may benefit from targeted interventions.

show abstract

“…Choroid plexus (ChP), the principal source of CSF production and vital structure of the blood-CSF barrier, serves as an immunological barrier regulating the trafficking of immune cells entry into the central nervous system 2 . Recent interest regarding the ChP in schizophrenia has been stimulated by increased understandings of interactions between immune activation and brain dysfunction 3 – 5 . Transcriptome sequencing of the ChP in schizophrenia has shown predominantly upregulated gene expression related to immune function and inflammation compared with healthy individuals 6 .…”

Section: Introductionmentioning

confidence: 99%

Choroid plexus volume enlargement in first-episode antipsychotic-naïve schizophrenia

Zeng,

Zhang,

Tang

et al. 2024

Schizophr

Self Cite

View full text Add to dashboard Cite

Investigation of the choroid plexus in schizophrenia has seen growing interest due to its role in the interaction between neuroinflammation and brain dysfunction. Most previous studies included treated and long-term ill patients, while antipsychotics and illness course might both affect the choroid plexus. Here, we recruited first-episode antipsychotic-naïve schizophrenia patients, performed high-resolution structural brain scan and manually extracted choroid plexus volume. Choroid plexus volume was compared between patients and healthy controls after controlling for age, sex and intracranial volume. Age and sex effects were examined on choroid plexus volume in patient and healthy control groups respectively. In patients, we also examined the correlation of choroid plexus volume with volume measures of cortical and subcortical gray matter, white matter, lateral ventricular as well as symptom severity and cognitive function. Schizophrenia patients showed significantly enlarged choroid plexus volume compared with healthy controls. Choroid plexus volume was positively correlated with age in only patient group and we found significantly larger choroid plexus volumes in males than females in both patient and healthy control groups, while the sex effects did not differ between groups. Choroid plexus volume was only found correlated with lateral ventricular volume among the brain volume measures. No significant correlation between choroid plexus volume and clinical ratings or cognitive performance was observed. Without potential confounding effects of pharmacotherapy or illness course, our findings indicated the enlargement of choroid plexus in schizophrenia might be an enduring trait for schizophrenia.

show abstract

Inflammation subtypes in psychosis and their relationships with genetic risk for psychiatric and cardiometabolic disorders

Cited by 11 publications

References 59 publications

Inflammation and cognition in severe mental illness: patterns of covariation and subgroups

Inflammation and cognition in severe mental illness: patterns of covariation and subgroups

Longitudinal course of inflammatory-cognitive subgroups across first treatment severe mental illness and healthy controls

Choroid plexus volume enlargement in first-episode antipsychotic-naïve schizophrenia

Contact Info

Product

Resources

About