Psychosis symptoms following aberrant immunity in the brain

Ozaki, Akitoshi; Yamawaki, Yoshio; Ohtsuki, Gen

doi:10.4103/1673-5374.293148

Cited by 10 publications

(7 citation statements)

References 13 publications

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“…However, considering the evidence on acute and chronic inflammation discussed above, an inflammatory‐mediated alteration to the cerebellum appears credible. Inflammatory‐related alterations to the cerebellum have previously been associated with psychomotor slowing or lethargy 24,28,29 . Consistent with this evidence, we found significant associations between the increased exchange rate in the cerebellum and decreased vigor.…”

Section: Discussionsupporting

confidence: 89%

“…Inflammatory-related alterations to the cerebellum have previously been associated with psychomotor slowing or lethargy. 24,28,29 Consistent with this evidence, we found significant associations between the increased exchange rate in the cerebellum and decreased vigor. These associations were not observed in the placebo condition, suggesting that the effect on vigor was uniquely mediated by inflammation.…”

Section: Increased Exchange Rate In the Cerebellumsupporting

confidence: 87%

“…The principal finding of the current study is an inflammatory‐mediated increase in MT exchange rate in the white matter of the cerebellum. The cerebellum is well‐known for its role in motor coordination and learning, although studies have also linked the cerebellum to inflammation and psychiatric symptoms 24–26 . Rats administered lipopolysaccharide (LPS) have demonstrated elevated inflammatory markers in the cerebellum alongside increases in depressive‐like behaviors 27,28 .…”

Section: Discussionmentioning

confidence: 99%

“…The cerebellum is wellknown for its role in motor coordination and learning, although studies have also linked the cerebellum to inflammation and psychiatric symptoms. [24][25][26] Rats administered lipopolysaccharide (LPS) have demonstrated elevated inflammatory markers in the cerebellum alongside increases in depressive-like behaviors. 27,28 One postulated mechanism is that TNF-α, released from activated microglia, induces hyperexcitability of the cerebellum via Purkinje cells, resulting in psychomotor slowing and behavioral abnormalities.…”

Section: Increased Exchange Rate In the Cerebellummentioning

confidence: 99%

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Detection of Neuroinflammation Induced by Typhoid Vaccine Using Quantitative Magnetization Transfer MR: A Randomized Crossover Study

Morgan

Smith

et al. 2023

Magnetic Resonance Imaging

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BackgroundThe role of neuroinflammation in psychiatric disorders is not well‐elucidated. A noninvasive technique sensitive to low‐level neuroinflammation may improve understanding of the pathophysiology of these conditions.PurposeTo test the ability of quantitative magnetization transfer (QMT) MR at 3 T for detection of low‐level neuroinflammation induced by typhoid vaccine within a clinically reasonable scan time.Study TypeRandomized, crossover, placebo‐controlled.SubjectsTwenty healthy volunteers (10 males; median age 34 years).Field Strength/SequenceMagnetization prepared rapid gradient‐echo and MT‐weighted 3D fast low‐angle shot sequences at 3 T.AssessmentParticipants were randomized to either vaccine or placebo first with imaging, then after a washout period received the converse with a second set of imaging. MT imaging, scan time, and blood‐based inflammatory marker concentrations were assessed pre‐ and post‐vaccine and placebo. Mood was assessed hourly using the Profile of Mood States questionnaire. QMT parameter maps, including the exchange rate from bound to free pool (kba) were generated using a two‐pool model and then segmented into tissue type.Statistical TestsVoxel‐wise permutation‐based analysis examined inflammatory‐related alterations of QMT parameters. The threshold‐free cluster enhancement method with family‐wise error was used to correct voxel‐wise results for multiple comparisons. Region of interest averages were fed into mixed models and Bonferroni corrected. Spearman correlations assessed the relationship between mood scores and QMT parameters. Results were considered significant if corrected P < 0.05.ResultsScan time for the MT‐weighted acquisition was approximately 11 minutes. Blood‐based analysis showed higher IL‐6 concentrations post‐vaccine compared to post‐placebo. Voxel‐wise analysis found three clusters indicating an inflammatory‐mediated increase in kba in cerebellar white matter. Cerebellar kba for white matter was negatively associated with vigor post‐vaccine but not post‐placebo.Data ConclusionThis study suggested that QMT at 3 T may show some sensitivity to low‐level neuroinflammation. Further studies are needed to assess the viability of QMT for use in inflammatory‐based disorders.Evidence Level1Technical EfficacyStage 2

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Section: Discussionsupporting

confidence: 89%

Section: Increased Exchange Rate In the Cerebellumsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Increased Exchange Rate In the Cerebellummentioning

confidence: 99%

See 2 more Smart Citations

Detection of Neuroinflammation Induced by Typhoid Vaccine Using Quantitative Magnetization Transfer MR: A Randomized Crossover Study

Morgan

Smith

et al. 2023

Magnetic Resonance Imaging

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“…Cumulative immune activation by both infectious and social defeating stress enhances the risk for schizophrenia [1][2][3][4][5] . A disease-biased heterogeneity of microglia in the brain is regarded as one of the promising mechanisms of mental disorders, as well as neurodegenerative diseases [6][7][8] . While changes in microglial morphology and transcript expression have been argued in the observations of postmortem brains with psychiatric disorders and translational animals, it is unclear how alterations of microglial characteristics and their reactivity are related to neural and cognitive dysfunctions.…”

Section: Main Textmentioning

confidence: 99%

Maternal immune activation and peripubertal stress synergistically produce reactive microglia and confine cerebellar cognitive function.

Ohtsuki,

Hikosaka,

Parvez

et al. 2024

Preprint

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The functional alteration of microglia emerges in the brains exposed to extrinsic stress insults during early development. Pathophysiological findings of psychiatric disorders such as schizophrenia and autism implied a localized deficit of the cerebellum. However, the link between microglia reactivity and cerebellar dysfunction is missing. Here, we investigated the developmental immune environment of translational mouse models that combine two risk factors: maternal infection and repeated social defeat stress (i.e., 2HIT). We found synergy of inflammatory stress insults produced reactive microglia, specifically in the cerebellum in both sexes. The microglial proliferation correlated with the Purkinje neuron loss in 2HIT mice. Highly multiplexed imaging-mass-cytometry demonstrated a TREM2-positive population of stress-associated microglia in the cerebellum. Single-cell-proteomic clustering revealed IL-6- and TGFβ-signaling association with microglial cell transition. Purkinje cells reduced excitability, cerebellum-involved brain-wide functional dysconnectivity, and behavioral anomalies underpin the cerebellar cognitive dysfunctions in 2HIT animals, ameliorated by cerebellum-specific microglia replacement.

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Towards a Unified Account of Aberrant Salience in Psychosis: Proximate and Evolutionary Mechanisms

Savva,

Griffin,

Abed

2024

Evolutionary Psychological Science

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Psychosis symptoms following aberrant immunity in the brain

Cited by 10 publications

References 13 publications

Detection of Neuroinflammation Induced by Typhoid Vaccine Using Quantitative Magnetization Transfer MR: A Randomized Crossover Study

Detection of Neuroinflammation Induced by Typhoid Vaccine Using Quantitative Magnetization Transfer MR: A Randomized Crossover Study

Maternal immune activation and peripubertal stress synergistically produce reactive microglia and confine cerebellar cognitive function.

Towards a Unified Account of Aberrant Salience in Psychosis: Proximate and Evolutionary Mechanisms

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