Transcriptional level of inflammation markers associates with short-term brain structural changes in first-episode schizophrenia

Abstract

Background Inflammation has been implicated in the pathology of schizophrenia and may cause neuronal cell death and dendrite loss. Neuroimaging studies have highlighted longitudinal brain structural changes in patients with schizophrenia, yet it is unclear whether this is related to inflammation. We aim to address this question, by relating brain structural changes with the transcriptional profile of inflammation markers in the early stage of schizophrenia. Methods Thirty-eight patients with first-episode schizophrenia and 51 healthy controls were included. High-resolution T1-weighted magnetic resonance imaging (MRI) and clinical assessments were performed at baseline and 2 ~ 6 months follow-up for all subjects. Changes in the brain structure were analyzed using surface-based morphological analysis and correlated with the expression of immune cells-related gene sets of interest reported by previous reviews. Transcriptional data were retrieved from the Allen Human Brain Atlas. Furthermore, we examined the brain structural changes and peripheral inflammation markers in association with behavioral symptoms and cognitive functioning in patients. Results Patients exhibited accelerated cortical thickness decrease in the left frontal cortices, less decrease or an increase in the superior parietal lobule and right lateral occipital lobe, and increased volume in the bilateral pallidum, compared with controls. Changes in cortical thickness correlated with the transcriptional level of monocyte across cortical regions in patients (r = 0.54, p < 0.01), but not in controls (r = − 0.05, p = 0.76). In addition, cortical thickness change in the left superior parietal lobule positively correlated with changes in digital span-backward test scores in patients. Conclusions Patients with schizophrenia exhibit regional-specific cortical thickness changes in the prefrontal and parietooccipital cortices, which is related to their cognitive impairment. Inflammation may be an important factor contributing to cortical thinning in first-episode schizophrenia. Our findings suggest that the immunity-brain-behavior association may play a crucial role in the pathogenesis of schizophrenia.

Childhood maltreatment influences adult brain structure through its effects on immune, metabolic, and psychosocial factors

“…On the other hand, immuno-metabolic dysregulation is expected to primarily affect brain structure through inflammatory processes triggered by obesity ( 91 ) which have the capacity to exert widespread cortical effects ( 34 ). Our findings of regional variation in increases or decreases of MRI-derived measures of gray matter structure mediated by the immuno-metabolic pathway coincide with previous studies independently linking immune ( 68 , 92 ) and metabolic dysregulation ( 93 ) to macroscopic brain structure. This suggests that inflammatory processes capable of modulating brain structure have consequences for neuronal health that vary on a region-by-region basis.…”

Hematological and inflammatory markers in Han Chinese patients with drug-free schizophrenia: relationship with symptom severity

“…Increased peripheral monocytes may suggest activation of microglia in central nervous system (43). As a type of macrophage, activated microglia interferes with neuronal development and disrupts the function of neuronal circuits in the brain (44).For example, Cui et al (45) found that high transcript levels of monocyte genes across cortical regions were associated with cortical thinning in patients with psychosis by a high-resolution T1-weighted structural image, while cortical thickness could reflect neurodevelopmental status. Third, our study found that lymphocytes significantly decreased in patients but did not correlate with the total score of BPRS.…”

Relationship between plasma TNF-α levels and agitation symptoms in first episode patients with schizophrenia

“…All patients were prescribed antipsychotic medications without delay upon admission, which may affect inflammatory cytokine levels. However, the usage duration of all patients was less than two weeks and was not enough to exert the therapeutic effect [ 10 , 11 ]. Moreover, there is no observed correlation between CPZ and TNF-α level( p = 0.855), suggesting that the impact of antipsychotic medications on our findings was likely minimal.…”

“…The ethical approval number is 2022-15 Research. The inclusion criteria were as follows: (1) diagnosis of schizophrenia confirmed by two psychiatrists based on the Structured Clinical Interview for DSM-IV (SCID); (2) age 15–55 years old; (3) previous antipsychotic exposure did not exceed 2 weeks [ 10 , 11 ]; and (4) total disease duration ≤ 60 months. The exclusion criteria were the following: (1) other psychiatric disorders meeting DSM-IV Axis I diagnosis; (2) co-morbidity of acute, unstable, and/or significant untreated medical illnesses; (3) documented disease of the central nervous system (CNS); (4) history of chronic inflammation, autoimmune disorder, or severe allergy; (5) pregnancy or breastfeeding state; (6) dependence on alcohol or illicit drugs; (7) use of non-steroid anti-inflammatory drugs within the previous 4 weeks; and (8) no capacity to understand the study and provide written informed consent.…”