Haptoglobin in ultra-high risk of psychosis - findings from the longitudinal youth at risk study (LYRIKS)

• Main Authors: Yee, Jie Yin, Chow, Si Qing, Lim, Keane, Goh, Wilson, Sng, Judy, Lee, Tih-Shin, Lee, Jimmy
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Biological sciences; Calgary Depression Scale; Global Assessment of Functioning
• Online Access: https://hdl.handle.net/10356/164048
• Institution: Nanyang Technological University

The role of immune dysregulation in mental disorders is not new and has been investigated in acute psychosis, schizophrenia, depression, bipolar disorder, and post-traumatic stress disorder (Çakici et al., 2020; Debnath et al., 2021; Karanikas et al., 2021). Smith and Maes (1995) proposed the monocyte and T-lymphocyte theory of schizophrenia, which hypothesised activation of macrophages and T-lymphocytes in psychosis (Smith and Maes, 1995). Early findings focused on measurements of protein levels of commonly studied immune markers in individuals with schizophrenia (Müller et al., 1999; Neelamekam et al., 2014). These are supported by recent reports on immune inflammatory processes in peripheral blood and brain on a larger network of immune markers, and association studies on various stages of psychosis (Maes et al., 1994, 1997; Goldsmith et al., 2016; van Kesteren et al., 2017). While there is evidence for dysregulation of immune markers in first-episode psychosis, chronic schizophrenia, and treatment-resistance schizophrenia, only two studies reported higher plasma IL-6 levels in individuals at ultra-high risk of psychosis (UHR) and in those who converted to psychosis (Stojanovic et al., 2014; Zeni-Graiff et al., 2016). Much of the focus has been on the various cytokines with scant work done on acute phase proteins (APP) in mental disorders. Studied APP in schizophrenia include haptoglobin (Hp), fibrinogen, complement component 3, C4, alpha-1 antitrypsin, alpha-2 macroglobulin, alpha 1-acid-glycoprotein, hemopexin, and C-reactive protein (Wong et al., 1996; Maes et al., 1997; Morera et al., 2007; Wan et al., 2007; Yee et al., 2017). From the available but limited literature, these APP were understood to have anti-inflammatory properties through different mechanisms such as regulating production of cytokines and promoting DNA repair mechanisms (Gruys et al., 2005). Hp, a positive APP member, rises in serum levels in presence of inflammation. It prevents iron loss and renal damage by binding strongly to free haemoglobin. Hp also has anti-bacterial properties and can bind to receptors on cell membranes of leukocytes (Wassell, 2000). Hp has been reported to be elevated in first-episode psychosis and schizophrenia and was associated with depression and excitement symptoms on the Positive and Negative Syndrome Scale (PANSS) (Seal and Eist, 1966; Bock et al., 1971; Maes et al., 1997; Yang et al., 2006; Wan et al., 2007; Yee et al., 2017). To date, there has been no published study on Hp in individuals at UHR, which will provide insights into the role inflammation-immune processes have on the etiopathogenesis of psychosis. The present study seeks to (1) extend findings from a previous report on elevated Hp gene expression level in first-episode psychosis into individuals at UHR (Yee et al., 2017), (2) examine the association of Hp gene expression level with symptom severity and transition to psychosis, and (3) explore Hp gene polymorphisms in UHR.