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BackgroundDysregulation of immunity, such as levels of inflammatory factors, has been regarded as a sign of schizophrenia. Changes in cytokine levels are not only described in the early onset of disease, but also observed in ultra-high risk (UHR) individuals. This study aimed to investigate the potential of cytokines as biomarkers for psychotic disorders and in individuals at UHR of developing a psychotic disorder in the future.MethodsThe Luminex liquid chip technology was used to detect the concentrations of Interferon-gamma (INF-γ), Interleukin (IL)-2, Interleukin (IL)-4, Interleukin (IL)-6, Interleukin (IL)-17, Interleukin-1beta (IL-1β), and Tumor Necrosis Factor-beta (TNF-β) in the plasma of all subjects. Meanwhile, the plasma level of Tumor Necrosis Factor-Alpha (TNF-α) was measured with the enzyme-linked immunosorbent assay (ELISA) kits. Then, the levels of these cytokines were compared among patients with Drug-naïve first-episode schizophrenia (FES; n = 40), UHR population (UHR; n = 49), and healthy controls (HCs; n = 30). Baseline cytokine levels were compared among UHR individuals who later transitioned (UHR-T; n = 14), those who did not transition (UHR-NT; n = 35), and HCs (n = 30).ResultsOur analysis results showed that IL-1β levels were significantly higher in UHR group than HC group (p = 0.015). Meanwhile, TNF-α concentration was significantly increased in FES group compared with HC group (p = 0.027). IL-17 (p = 0.04) and TNF-β (p = 0.008) levels were significantly higher in UHR-T group compared with UHR-NT group.ConclusionIn conclusion, our findings suggest that the immuno-inflammatory activation level is increased in the early stage of psychosis before psychotic conversion and the Drug-naïve FES. IL-1β and TNF-α are the representatives of the specific biomarkers for UHR and FES, respectively. IL-17 and TNF-β may be the potential selective predictive biomarkers for future transition in UHR individuals.

BackgroundIndividuals who experience the prodromal phase of schizophrenia (SCZ), a common and complex psychiatric disorder, are referred to as ultra-high-risk (UHR) individuals. Short-chain fatty acid (SCFA) is imperative in the microbiota-gut-brain axis and brain function. Accumulating amount of evidence shows the connections between psychiatric disorders and SCFAs. This study aims to explore the underlying roles SCFAs play in SCZ by investigating the association of alterations in SCFAs concentrations with common cognitive functions in both the SCZ and UHR populations.MethodsThe study recruited 59 SCZ patients (including 15 participants converted from the UHR group), 51 UHR participants, and 40 healthy controls (HC) within a complete follow-up of 2 years. Results of cognitive functions, which were assessed by utilizing HVLT-R and TMT, and serum concentrations of SCFAs were obtained for all participants and for UHR individuals at the time of their conversion to SCZ.ResultsFifteen UHR participants converted to SCZ within a 2-year follow-up. Valeric acid concentration levels were lower in both the baseline of UHR individuals whom later converted to SCZ (p = 0.046) and SCZ patients (p = 0.036) than the HC group. Additionally, there were lower concentrations of caproic acid in the baseline of UHR individuals whom later transitioned to SCZ (p = 0.019) and the UHR group (p = 0.016) than the HC group. Furthermore, the caproic acid levels in the UHR group are significantly positively correlated with immediate memory (r = 0.355, p = 0.011) and negatively correlated with TMT-B (r = -0.366, p = 0.009). Significant differences in levels of acetic acid, butyric acid and isovaleric acid were absent among the three groups and in UHR individuals before and after transition to SCZ.ConclusionOur study suggests that alterations in concentrations of SCFAs may be associated with the pathogenesis and the cognitive impairment of schizophrenia. Further researches are warranted to explore this association. The clinical implications of our findings were discussed.

Positive symptoms are marked features of schizophrenia, and emerging evidence has suggested that abnormalities of the brain network underlying these symptoms may play a crucial role in the pathophysiology of the disease. We constructed two brain functional networks based on the positive and negative correlations between positive symptom scores and brain connectivity in drug-naive patients with first-episode schizophrenia (FES, n = 45) by using a machine-learning approach (connectome-based predictive modeling, CPM). The accuracy of the model was r = 0.47 (p = 0.002). The positively and negatively associated network strengths were then compared among FES subjects, individuals at genetic high risk (GHR, n = 41) for schizophrenia, and healthy controls (HCs, n = 48). The results indicated that the positively associated network contained more cross-subnetwork connections (96.02% of 176 edges), with a focus on the default-mode network (DMN)-salience network (SN) and the DMN-frontoparietal task control (FPT) network. The negatively associated network had fewer cross-subnetwork connections (71.79% of 117 edges) and focused on the sensory/somatomotor hand (SMH)-Cingulo opercular task control (COTC) network, the DMN, and the visual network with significantly decreased connectivity in the COTC-SMH network in FES (FES < GHR, p = 0.01; FES < HC, p = 0.01). Additionally, the connectivity strengths of the right supplementary motor area (SMA) (p < 0.001) and the right precentral gyrus (p < 0.0001) were reduced in FES. To the best of our knowledge, this is the first study to generate two brain networks associated with positive symptoms by utilizing CPM in FES. Abnormal segregation, interactions of brain subnetworks, and impaired SMA might lead to salience attribution abnormalities and, thus, as a result, induce positive symptoms in schizophrenia.

The glutamatergic system has previously been shown to be involved in the pathophysiology of schizophrenia and the mechanisms of action of antipsychotic treatment. The present study aimed to investigate the relationship between the levels of glutamate (Glu) or Glu/total creatine (Glu/Cr+PCr) in the anterior cingulate cortex (ACC) and psychiatric symptoms as well as the response to antipsychotic treatment. We performed proton magnetic resonance spectroscopy (1H–MRS) to measure Glu and Glu/Cr+PCr in the ACC of 35 drug-naïve first-episode schizophrenia (FES) patients and 40 well-matched healthy controls (HCs). After scanning, we treated the patients with risperidone for eight weeks. Remission status was based on the Positive and Negative Syndrome Scale (PANSS) scores at week 8. At baseline, there were no significant differences in the levels of Glu or Glu/Cr+PCr in the ACC between drug-naïve FES patients and HCs. Lower baseline levels of Glu/Cr+PCr but not Glu in the ACC were associated with more severe negative symptoms of schizophrenia. Compared to the remission group (RM), the non-remission group (NRM) had lower baseline ACC Glu levels (P < 0.05). Our results suggest that ACC Glu levels may be related to the severity of symptoms in the early stages of schizophrenia and therefore may be a marker with which to evaluate the treatment effect of antipsychotics in schizophrenia patients.