Rapid communication Expression and differential response to haloperidol treatment of Cyclon/CCDC86 mRNA in schizophrenia patients Trifon Chervenkov a , Rinaldo Shishkov b , Anton B. Tonchev c,⇑ a Laboratory of Immunology, University Hospital ‘‘St. Marina’’, Varna, Bulgaria b Department of Psychiatry and Medical Psychology, Medical University – Varna, Varna, Bulgaria c Department of Anatomy, Histology and Embryology, Medical University – Varna, Varna, Bulgaria article info Article history: Received 19 December 2012 Received in revised form 23 January 2013 Accepted 13 February 2013 Available online 21 February 2013 Keywords: Schizophrenia Cyclon/CCDC68 Leukocytes Treatment Clustering abstract A gene known as Cyclon (cytokine-induced protein with coiled-coil domain) or CCDC86 (coiled-coil domain-containing protein 86) is known for its expression in leukocytes in mice, where it regulates the immune response. We investigated whether Cyclon/CCDC68 is expressed in leukocytes of schizophre- nia patients and whether it might be used as a biological marker for the disease endophenotype segre- gation. We examined the level of mRNA of Cyclon/CCDC68 in white blood cells obtained from schizophrenia patients in relapse and remission as well as in healthy controls. The mRNA of Cyclon/ CCDC68 was expressed by white blood cells of both schizophrenia patients and healthy controls. There was a dichotomous change in the levels of Cyclon/CCDC68 of relapsed patients before and after treatment. High Cyclon/CCDC68 levels were associated with a recent disease and presence of psychotic symptoms, while low levels were associated with a long duration of the disease and an absence of psychotic symp- toms. These data indicate that Cyclon/CCDC68 levels correlate with the clinical presentation of relapsed schizophrenia. Cyclon/CCDC68 might be involved in the immune system disturbances observed in schizophrenia. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction Schizophrenia is a severe psychiatric disorder involving approx- imately 1% of the population worldwide. Diagnosis is based on an array of symptoms generally referred to as ‘‘positive’’ (e.g. delu- sions and auditory hallucinations) and ‘‘negative’’ (e.g. emotional flattening and motivational deficits) (Insel, 2010; Tandon et al., 2010). The symptoms typically start in early adulthood and even- tually impair both the social and occupational integration of the subjects. Over a century after the investigations on the mecha- nisms of schizophrenia had begun, the neurobiological basis of the disease remains obscure. Heterogeneity of schizophrenic symptoms probably reflects heterogeneity in the underlying path- ological mechanisms (Bray et al., 2010). A number of investigations suggest a link between schizophre- nia and the cytokine interleukin-3 (IL-3) (Chen et al., 2007; Chen and Kendler, 2008). Both IL-3 itself (Sirota et al., 1995; Xiu et al., 2008) and its receptors (Sun et al., 2008, 2009; Chen et al., 2011) have been associated with the disease. However, the mechanisms that mediate this involvement are poorly understood. A gene known as Cyclon (cytokine-induced protein with coiled-coil do- main) or CCDC86 (coiled-coil domain-containing protein 86) is strongly induced by IL-3 in hematopoietic cell lines (Hoshino and Fujii, 2007) and acts downstream of IL-3 signaling. It was also found that Cyclon/CCDC86 was induced by T-cell receptor activa- tion (Saint Fleur et al., 2009) and that it induces the expression of the death receptor CD95/Fas as part of the activation-induced cell death (AICD) phenomenon. Multiple immune system distur- bances are known to occur in schizophrenia (Müller and Schwarz, 2010; Steiner et al., 2010; Müller et al., 2012). Whether Cyclon/ CCDC86 could be involved in these processes is currently unknown. Here we studied this issue and found a differential expression pattern of the gene Cyclon/CCDC86 in relapsed schizophrenia pa- tients prior to treatment. Whereas schizophrenia patients with high Cyclon/CCDC86 expression were characterized by a recent diagnosis of disease and presence of psychotic symptoms, low lev- els were associated with an absence of psychotic symptoms and a long duration of the disease. Further, we followed up the Cyclon/ CCDC86 expression after the treatment has yielded a clinically rel- evant remission of the disease. 2. Patients and methods 2.1. Patients Twenty-one patients (11 male with mean age 34.1 ± 12.1 years, 10 female with mean age 28.8 ± 7.8 years; range of age 0197-0186/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neuint.2013.02.017 ⇑ Corresponding author. Tel.: +359 52 677 082; fax: +359 52 650 019. E-mail address: anton.tonchev@mu-varna.bg (A.B. Tonchev). Neurochemistry International 62 (2013) 870–872 Contents lists available at SciVerse ScienceDirect Neurochemistry International journal homepage: www.elsevier.com/locate/nci