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Association of elevated levels of peripheral complement components with cortical thinning and impaired logical memory in drug-naive patients with first-episode schizophrenia.

ABSTRACT: Schizophrenia has been linked to polymorphism in genes encoding components of the complement system, and hyperactive complement activity has been linked to immune dysfunction in schizophrenia patients. Whether and how specific complement components influence brain structure and cognition in the disease is unclear. Here we compared 52 drug-naïve patients with first-episode schizophrenia and 52 healthy controls in terms of levels of peripheral complement factors, cortical thickness (CT), logical memory and psychotic symptoms. We also explored the relationship between complement factors with CT, cognition and psychotic symptoms. Patients showed significantly higher levels of C1q, C4, factor B, factor H, and properdin in plasma. Among patients, higher levels of C3 in plasma were associated with worse memory recall, while higher levels of C4, factor B and factor H were associated with thinner sensory cortex. These findings link dysregulation of specific complement components to abnormal brain structure and cognition in schizophrenia.

SUBMITTER: Yu H

PROVIDER: S-EPMC10630449 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Association of elevated levels of peripheral complement components with cortical thinning and impaired logical memory in drug-naïve patients with first-episode schizophrenia.

Yu Hua H Ni Peiyan P Tian Yang Y Zhao Liansheng L Li Mingli M Li Xiaojing X Wei Wei W Wei Jinxue J Wang Qiang Q Guo Wanjun W Deng Wei W Ma Xiaohong X Coid Jeremy J Li Tao T

Schizophrenia (Heidelberg, Germany) 20231107 1

Schizophrenia has been linked to polymorphism in genes encoding components of the complement system, and hyperactive complement activity has been linked to immune dysfunction in schizophrenia patients. Whether and how specific complement components influence brain structure and cognition in the disease is unclear. Here we compared 52 drug-naïve patients with first-episode schizophrenia and 52 healthy controls in terms of levels of peripheral complement factors, cortical thickness (CT), logical m ...[more]

PMID: 37935744

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Project description:Impaired insight into illness is a common element of schizophrenia that contributes to treatment nonadherence and negative clinical outcomes. Previous studies suggest that impaired insight may arise from brain abnormalities. However, interpretations of these findings are limited due to small sample sizes and inclusion of patients with a narrow range of illness severity and insight deficits. In a large sample of patients with schizophrenia, the majority of which were designated as treatment-resistant, we investigated the associations between impaired insight and cortical thickness and subcortical volumes. A total of 94 adult participants with a schizophrenia spectrum disorder were included. Fifty-six patients (60%) had treatment-resistant schizophrenia. The core domains of insight were assessed with the VAGUS insight into psychosis scale. We obtained 3T MRI T1-weighted images, which were analysed using CIVET and MAGeT-Brain. Whole-brain vertex-wise analyses revealed impaired insight, as measured by VAGUS average scores, was related to cortical thinning in left frontotemporoparietal regions. The same analysis in treatment-resistant patients showed thinning in the same regions, even after controlling for age, sex, illness severity, and chlorpromazine antipsychotic dose equivalents. No association was found in non-treatment-resistant patients. Region-of-interest analyses revealed impaired general illness awareness was associated with cortical thinning in the left supramarginal gyrus when controlling for covariates. Reduced right and left thalamic volumes were associated with VAGUS symptom attribution and awareness of negative consequences subscale scores, respectively, but not after correction for multiple testing. Our results suggest impaired insight into illness is related to cortical thinning in left frontotemporoparietal regions in patients with schizophrenia, particularly those with treatment resistance where insight deficits may be more chronic.

Project description:IntroductionSymptoms of schizophrenia are closely related to aberrant language comprehension and production. Macroscopic brain changes seen in some patients with schizophrenia are suspected to relate to impaired language production, but this is yet to be reliably characterized. Since heterogeneity in language dysfunctions, as well as brain structure, is suspected in schizophrenia, we aimed to first seek patient subgroups with different neurobiological signatures and then quantify linguistic indices that capture the symptoms of "negative formal thought disorder" (i.e., fluency, cohesion, and complexity of language production).MethodsAtlas-based cortical thickness values (obtained with a 7T MRI scanner) of 66 patients with first-episode psychosis and 36 healthy controls were analyzed with hierarchical clustering algorithms to produce neuroanatomical subtypes. We then examined the generated subtypes and investigated the quantitative differences in MRS-based glutamate levels [in the dorsal anterior cingulate cortex (dACC)] as well as in three aspects of language production features: fluency, syntactic complexity, and lexical cohesion.ResultsTwo neuroanatomical subtypes among patients were observed, one with near-normal cortical thickness patterns while the other with widespread cortical thinning. Compared to the subgroup of patients with relatively normal cortical thickness patterns, the subgroup with widespread cortical thinning was older, with higher glutamate concentration in dACC and produced speech with reduced mean length of T-units (complexity) and lower repeats of content words (lexical cohesion), despite being equally fluent (number of words).ConclusionWe characterized a patient subgroup with thinner cortex in first-episode psychosis. This subgroup, identifiable through macroscopic changes, is also distinguishable in terms of neurochemistry (frontal glutamate) and language behavior (complexity and cohesion of speech). This study supports the hypothesis that glutamate-mediated cortical thinning may contribute to a phenotype that is detectable using the tools of computational linguistics in schizophrenia.

Project description:BackgroundThe elevated prolactin levels in first-episode drug-naïve (FEDN) schizophrenia patients may correlate with long-term stress caused by childhood trauma. This study aimed to assess the relationship between elevated prolactin levels and childhood trauma in FEDN schizophrenia patients, while also considering sex differences.MethodsUtilizing a cross-sectional design, the study involved 88 FEDN schizophrenia patients and 76 healthy controls (HCs). Evaluations encompassed measuring prolactin levels in peripheral blood and assessing mental health using the Positive and Negative Syndrome Scale (PANSS), the Childhood Trauma Questionnaire - Short Form (CTQ-SF), as well as evaluating resilience with the Connor-Davidson Resilience Scale (CD-RISC), perceived social support with the Perceived Social Support Scale (PSSS), and demographic characteristics to control for confounding factors. A mediation model was constructed using the RMediation package of the R software.MethodsThe results suggested prolactin levels in FEDN schizophrenia patients were higher than in HCs(t=-9.938, p = 0.000). Group classification (HCs vs. FEDN schizophrenia patients) (t = 9.291, p = 0.000) and sex (t = 3.282, p = 0.001) were influential factors for prolactin levels. Elevated prolactin(OR = 1.007, p = 0.000), along with higher scores for childhood emotional(OR = 1.469, p = 0.006)andsexual abuse(OR = 1.592, p = 0.018) and lower social support(OR = 0.946, p = 0.026), were associated with the onset of schizophrenia. Positive correlations were found between prolactin levels and childhood emotional (r = 0.268, p = 0.002) /sexual abuse(r = 0.264, p = 0.002), with no sex differences. No significant relationship was observed between prolactin levels and PANSS scores. Mediation analysis revealed that childhood emotional abuse (95% CI: [0.059 ~ 0.293]) and sexual abuse (95% CI: [0.086 ~ 0.439]) had significant indirect effects on schizophrenia, mediated by elevated prolactin levels.ConclusionThese findings suggest that childhood trauma may be associated with the onset of schizophrenia by influencing prolactin levels, highlighting the complex interplay between hormonal disruptions and early-life stress in the development of schizophrenia.

Dataset Information

Association of elevated levels of peripheral complement components with cortical thinning and impaired logical memory in drug-naive patients with first-episode schizophrenia.

Publications

Association of elevated levels of peripheral complement components with cortical thinning and impaired logical memory in drug-naïve patients with first-episode schizophrenia.

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