Poster #S58 SERUM LEVELS OF INNATE IMMUNE RESPONSE MARKERS CCL22, CXCL1 AND APOLIPOPROTEIN A1 ALTERED IN FIRST-EPISODE PSYCHOSIS ASSOCIATE WITH WHITE MATTER VOLUME AND INTEGRITY

Background: Reductions in the volume of brain white matter are a common feature in schizophrenia and bipolar disorder while the association between white matter and polygenic schizophrenia-related risk is unclear. To look at the intermediate state between health and the full-blown disorder, we investigated this aspect in groups of patients before and after the onset of psychosis. Methods: On a 3 Tesla scanner, total and regional white matter volumes were investigated by structural magnetic resonance imaging (MRI) in the following groups: 37 at-risk mental state patients (ARMS), including 30 with no transition to psychosis (ARMS-NT) and 7 with a transition to psychosis (ARMS-T) pooled with 25 first episode psychosis (FEP) patients. These T1-weighted images were automatically processed with the FreeSurfer software and compared with an odds-ratio-weighted polygenic schizophrenia-related risk score (PSRS) based on the publicly available top white matter single-nucleotide polymorphisms. Results: We found no association, only a trend, between PSRS and white matter volume over all groups (β = 0.24, p = 0.07, 95% confidence interval = [-0.02 – 0.49]). However, a higher PSRS was significantly associated with a higher probability of being assigned to the ARMS-T + FEP group rather than to the ARMS-NT group (β = 0.70, p = 0.02, 95% confidence interval = [0.14 – 1.33]); there was no such association with white matter volume. Additionally, a positive association was found between PSRS and the Brief Psychiatric Rating Scale (BPRS) total score for the pooled ARMS-NT/ARMS-T+FEP sample and for the ARMS-T + FEP group also, but none for the ARMS-NT group only. Conclusion: These findings suggest that at-risk mental state patients with a transition and first-episode psychosis patients have a higher genetic risk for schizophrenia than at-risk mental state patients with no transition to psychosis; this risk was associated with psychopathological symptoms. Further analyses may allow polygenic schizophrenia-related risk scores to be used as biomarkers to predict psychosis.

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Duration of prodromal phase and severity of volumetric abnormalities in first-episode psychosis

The British Journal of Psychiatry ◽

10.1192/bjp.191.51.s123 ◽

2007 ◽

Vol 191 (S51) ◽

pp. s123-s127 ◽

Cited By ~ 27

Author(s):

Julia Lappin ◽

Paola Dazzan ◽

Kevin Morgan ◽

Craig Morgan ◽

Xavier Chitnis ◽

...

Keyword(s):

White Matter ◽

Medical Records ◽

Grey Matter ◽

Insular Cortex ◽

First Episode Psychosis ◽

First Episode ◽

Voxel Based Morphometry ◽

White Matter Volume ◽

Prodromal Phase ◽

Episode Psychosis

BackgroundFirst-episode psychosis is typically preceded by a prodrome in which there is deterioration in global and social functioningAimsTo examine whether the duration of the prodromal phase influences grey and white matter volumes at the onset of psychosisMethodsEighty-two people were scanned using magnetic resonance imaging when they developed a first episode of psychosis. The duration of the prodromal phase was estimated from detailed interviews and medical records. Voxel-based morphometry was used to assess neuroanatomical abnormalitiesResultsA long prodromal phase was associated with smaller grey matter volumes in the cingulate, frontal and left insular cortex, and with less white matter volume bilaterally in the superior longitudinal and uncinate fasciculi and the cingulumConclusionsThe severity of volumetric abnormalities in first-episode psychosis was greater in those with a long prodrome

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Role of glia in prefrontal white matter abnormalities in first episode psychosis or mania detected by diffusion tensor spectroscopy

Schizophrenia Research ◽

10.1016/j.schres.2019.05.018 ◽

2019 ◽

Vol 209 ◽

pp. 64-71 ◽

Cited By ~ 5

Author(s):

Kathryn E. Lewandowski ◽

Fei Du ◽

Xiaoying Fan ◽

Xi Chen ◽

Polly Huynh ◽

...

Keyword(s):

White Matter ◽

Diffusion Tensor ◽

First Episode Psychosis ◽

First Episode ◽

White Matter Abnormalities ◽

Episode Psychosis

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VARIATION IN GREY MATTER VOLUME WITH DEGREE OF INSIGHT IN FIRST EPISODE PSYCHOSIS AND CHRONIC SCHIZOPHRENIA

Schizophrenia Research ◽

10.1016/j.schres.2010.02.589 ◽

2010 ◽

Vol 117 (2-3) ◽

pp. 340

Author(s):

J. McFarland ◽

D. Cannon ◽

H. Schmidt ◽

M. Ahmed ◽

S. Hehir ◽

...

Keyword(s):

Grey Matter ◽

Chronic Schizophrenia ◽

First Episode Psychosis ◽

First Episode ◽

Grey Matter Volume ◽

Matter Volume ◽

Episode Psychosis

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White Matter Microstructural Abnormalities in the Broca’s-Wernicke’s-Putamen “Hoffman Hallucination Circuit” and Auditory Transcallosal Fibers in First-Episode Psychosis With Auditory Hallucinations

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa105 ◽

2020 ◽

Author(s):

Dean F Salisbury ◽

Yiming Wang ◽

Fang-Cheng Yeh ◽

Brian A Coffman

Keyword(s):

White Matter ◽

Left Hemisphere ◽

Structural Integrity ◽

Right Hemisphere ◽

First Episode Psychosis ◽

Auditory Hallucinations ◽

First Episode ◽

Psychotic Episode ◽

Arcuate Fasciculus ◽

Episode Psychosis

Abstract Background Functional connectivity abnormalities between Broca’s and Wernicke’s areas and the putamen revealed by functional magnetic resonance imaging (fMRI) are related to auditory hallucinations (AH). In long-term schizophrenia, reduced white matter structural integrity revealed by diffusion imaging in left arcuate fasciculus (connecting Broca’s and Wernicke’s areas) is likely related to AH. The structural integrity of connections with putamen and their relation to AH are unknown. Little is known about this relationship in first-episode psychosis (FEP), although auditory transcallosal connections were reported to play a role. White matter in the Broca’s-Wernicke’s-putamen language-related circuit and auditory transcallosal fibers was examined to investigate associations with AH in FEP. Methods White matter connectivity was measured in 40 FEP and 32 matched HC using generalized fractional anisotropy (gFA) derived from diffusion spectrum imaging (DSI). Results FEP and HC did not differ in gFA in any fiber bundle. In FEP, AH severity was significantly inversely related to gFA in auditory transcallosal fibers and left arcuate fasciculus. Although the right hemisphere arcuate fasciculus-AH association did not attain significance, the left and right arcuate fasciculus associations were not significantly different. Conclusions Despite overall normal gFA in FEP, AH severity was significantly related to gFA in transcallosal auditory fibers and the left hemisphere connection between Broca’s and Wernicke’s areas. Other bilateral tracts’ gFA were weakly associated with AH. At the first psychotic episode, AH are more robustly associated with left hemisphere arcuate fasciculus and interhemispheric auditory fibers microstructural deficits, likely reflecting mistiming of information flow between language-related cortical centers.

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Innate Immune Cells and C-Reactive Protein in Acute First-Episode Psychosis and Schizophrenia: Relationship to Psychopathology and Treatment

Schizophrenia Bulletin ◽

10.1093/schbul/sbz068 ◽

2019 ◽

Cited By ~ 2

Author(s):

Johann Steiner ◽

Thomas Frodl ◽

Kolja Schiltz ◽

Henrik Dobrowolny ◽

Roland Jacobs ◽

...

Keyword(s):

Innate Immunity ◽

First Episode Psychosis ◽

Innate Immune ◽

First Episode ◽

Antipsychotic Treatment ◽

C Reactive Protein ◽

Activation Markers ◽

Reactive Protein ◽

Immune System Activation ◽

Episode Psychosis

Abstract Innate immunity has been linked to initiation of Alzheimer’s disease and multiple sclerosis. Moreover, risk of first-episode psychosis (FEP) and schizophrenia (Sz) is increased after various infections in predisposed individuals. Thus, we hypothesized an analogous role of innate immunity with increased C-reactive protein (CRP) in non-affective psychosis. Differential blood count, CRP, neutrophil and monocyte–macrophage activation markers, cortisol and psychotic symptoms (Positive and Negative Syndrome Scale [PANSS]) were assessed in controls (n = 294) and acutely ill unmedicated FEP (n = 129) and Sz (n = 124) patients at baseline and after 6 weeks treatment. Neutrophils, monocytes, and CRP were increased in patients vs controls at baseline (P < .001), and neutrophil and monocyte counts correlated positively with activation markers. Eosinophils were lower at baseline in FEP (P < .001) and Sz (P = .021) vs controls. Differences in neutrophils (P = .023), eosinophils (P < .001), and CRP (P < .001) were also present when controlling for smoking and cortisol, and partially remitted after antipsychotic treatment. FEP patients with high neutrophils (P = .048) or monocytes (P = .021) had higher PANSS-P scores at baseline but similar disease course. CRP correlated with PANSS-P at baseline (ρ = 0.204, P = .012). Improvement of positive symptoms after treatment correlated with declining neutrophils (ρ = 0.186, P = .015) or CRP (ρ = 0.237, P = .002) and rising eosinophils (ρ = −0.161, P = .036). In FEP, normalization of neutrophils (ρ = −0.231, P = .029) and eosinophils (ρ = 0.209, P = .048) correlated with drug dosage. In conclusion, innate immune system activation correlated with PANSS-P, supporting the immune hypothesis of psychosis. Neutrophil and monocyte counts and CRP levels may be useful markers of disease acuity, severity, and treatment response.

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Neuroactive Steroids in First-Episode Psychosis: A Role for Progesterone?

Schizophrenia Research and Treatment ◽

10.1155/2016/1942828 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Martino Belvederi Murri ◽

Flaminia Fanelli ◽

Uberto Pagotto ◽

Elena Bonora ◽

Federico Triolo ◽

...

Keyword(s):

Psychotic Disorders ◽

Serum Levels ◽

First Episode Psychosis ◽

Neuroactive Steroids ◽

First Episode ◽

Positive Symptoms ◽

Symptom Dimensions ◽

Episode Psychosis ◽

Male Patients ◽

And Gender

Neuroactive steroids may play a role in the pathophysiology of psychotic disorders, but few studies examined this issue. We compared serum levels of cortisol, testosterone, dehydroepiandrosterone, and progesterone between a representative sample of first-episode psychosis (FEP) patients and age- and gender-matched healthy subjects. Furthermore, we analyzed the associations between neuroactive steroids levels and the severity of psychotic symptom dimensions. Male patients had lower levels of progesterone than controls (p=0.03). Progesterone levels were inversely associated with the severity of positive symptoms (p=0.007). Consistent with preclinical findings, results suggest that progesterone might have a role in the pathophysiology of psychotic disorders.

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