Changes in Inflammatory Markers in Clinical High Risk of Developing Psychosis

Abstract

<b><i>Introduction:</i></b> Immune alterations are associated with the progression of psychosis. However, there are few studies designed to longitudinally measure inflammatory biomarkers during psychotic episodes. We aimed to assess changes in biomarkers from the prodromal phase to psychotic episodes in individuals with clinical high risk (CHR) of psychosis and compare converters and non-converters to psychosis as well as healthy controls (HCs). <b><i>Methods:</i></b> We enrolled 394 individuals with CHR and 100 HCs. A total of 263 individuals with CHR completed the 1-year follow-up, and 47 had converted to psychosis. Interleukin (IL)-1β, 2, 6, 8, 10, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor levels were measured at baseline and 1 year after completion of the clinical assessment. <b><i>Results:</i></b> The baseline serum levels of IL-10, IL-2, and IL-6 were significantly lower in the conversion group than in the non-conversion group (IL-10, <i>p</i> = 0.010; IL-2, <i>p</i> = 0.023; IL-6, <i>p</i> = 0.012) and HC (IL-6: <i>p</i> = 0.034). Self-controlled comparisons showed that IL-2 changed significantly (<i>p</i> = 0.028), and IL-6 levels tended toward significance (<i>p</i> = 0.088) in the conversion group. In the non-conversion group, serum levels of TNF-α (<i>p</i> = 0.017) and VEGF (<i>p</i> = 0.037) changed significantly. Repeated measures analysis of variance revealed a significant time effect related to TNF-α (<i>F</i> = 4.502, <i>p</i> = 0.037, effect size (η<sup>2</sup>) = 0.051), a group effect related to IL-1β (<i>F</i> = 4.590, <i>p</i> = 0.036, η<sup>2</sup> = 0.062), and IL-2 (<i>F</i> = 7.521, <i>p</i> = 0.011, η<sup>2</sup> = 0.212), but no time × group effect. <b><i>Discussion:</i></b> Alterations in the serum levels of inflammatory cytokines were found to precede the first episode of psychosis in the CHR population, particularly for those who later converted to psychosis. Longitudinal analysis supports the varied roles of cytokines in individuals with CHR with later psychotic conversion or non-conversion outcomes.

Comprehensive review of multidimensional biomarkers in the ShangHai At Risk for Psychosis (SHARP) program for early psychosis identification

“…The occurrence and development of psychosis is not only a change in behavioral appearance or brain function but also a characteristic change in the characteristics of immunoinflammatory markers in the early stage. The SHARP team 29,34,35 found that the imbalance of The results suggest that antipsychotic drugs should not be used prematurely in the at-risk population 27,28,40 as they are only valuable for <15% of the CHR population of a certain subtype [41][42][43] ; it is necessary to carry out individualized new intervention technologies for CHR subtypes of different biological dimensions. 3 Approximately 30% of the CHR population may recover naturally without intervention, and a large proportion of CHR are teenagers.…”

“…The occurrence and development of psychosis is not only a change in behavioral appearance or brain function but also a characteristic change in the characteristics of immunoinflammatory markers in the early stage. The SHARP team 29 , 34 , 35 found that the imbalance of inflammation (CD4 + T helper cell [Th] 1/Th2 cytokine imbalance) was related to psychotic attack in the CHR outcome after studying the balance of inflammatory factors in the peripheral serum of the CHR population. The baseline serum Th1 inflammatory factor concentration in the CHR‐C group was significantly reduced, and can be considered a form of immune deactivation, resulting in a lower Th1/Th2 ratio than that in the CHR‐NC and HC groups.…”

Association between serum cytokines and timeframe for conversion from clinical high‐risk to psychosis

“…In the context of neuropsychiatric disorders such as psychosis, there is growing evidence to indicate a pivotal role for inflammation in the pathogenesis of psychotic onset. [1][2][3] Neuroinflammation is characterized by the activation and proliferation of glial cells, 4,5 particularly microglia and astrocytes, within the central nervous system, which triggers an inflammatory response in the brain. 5 Under abnormal conditions, such as in brain disease, microglia transition from a "resting" state to an "activated" state, releasing proinflammatory cytokines like interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α.…”

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“…The levels of interleukin factors appear to be associated with the course of the disease and the severity of symptoms. Patients with elevated levels of IL-6, IL-8, and IL-4 tend to have a longer duration of illness and longer hospital stays (17,18). Moreover, higher levels of IL-6, IL-1b, IL-33, and IL-17 are associated with more severe positive symptoms (19)(20)(21)(22).…”