From Personality Traits And Interleukin Levels To Genetic Markers Of Mood Disorders Spectrum In Adolescents And Young Adults

Background Data in literature support the inflammation component in Bipolar disorder (BD). Stress may induce inflammatory changes in the immune system by activating the hypothalamic-pituitary-adrenal (HPA) axis. Recent studies confirmed that genetically determined personality traits are responsible for personal resources of stress resistance and thus they can play an important role in bipolar disorder development especially in young patients. There is no doubt that BD is a complex mental illness with a relevant genetic component. However, previously used strategies to identify genetic biomarkers have not produced the expected results. Actually there is no biological markers that can help to early diagnose and effective pharmacotherapy especially in adolescents and young adults. GWAS skip genes with relatively little impact on the disease. They prevent therefore identify genes in psychiatric disorders with cumulative polygenic inheritance and epigenetics influences. That's why we made an attempt to reverse the methods by “from candidate gene to protein” to “from protein to candidate gene” with regard to personality traits. Methods 33 patients (aged 12-24), with a diagnosis MD meeting spectrum BD criteria, were included to this study. Participants were assessed by using structured diagnostic interviews according to ICD-10 and DSM-IV and completed the Temperament and Character Inventory (TCI). The evaluation was conducted in the state of severity of the symptoms (visit 0) and after reaching the stabilize mood (visit K). We studied a panel of 6 cytokines (IL-1β, 2, 4, 6, 8 and 10), known to interact with BD. Serum concentrations of all these molecules were measured using the commercial available DIAplex kit. The genes selection for analyzes includes multi-level approach with use of the own results of personality traits measure and cytokines level obtained in patients with BD spectrum from Polish population as well as databases and pathway analysis using in silico tools. Results Comparing the results of patients at 0 to K no significant differences in cytokine serum levels were observed. Correlation analysis showed a significant higher IL-8 serum levels in non-depressed vs depressed patients (p=0.017) as well as higher concentration of IL-6 in young adults (18>years) compared to teenagers (p=0.030). Patients at 0 obtained higher score in Harm Avoidance (HA) dimension (P=.023). Correlation analysis of cytokine serum concentration and main dimension of personality traits showed significant positive relationship between IL-2 and persistence (P) (p=0.017) as well as negative relationship between IL-6 and Self Transcendence (ST) (p=0.035). Discussion Obtained results indicates that interesting candidate genes to association study may be IL-2,6 and 8. However most promising connector of all analyzed traits in analyzed group is IL-6. In silico analyses according to i.e. gene prospector and other free available data bases confirms that IL-6 is strong candidate gene for association analysis including gene expression in the lymphocytes of patients with bipolar disorder. IL-6 is able to activate HPA axis and is involved in the development of despair-like behaviors triggered by inflammation. The single nucleotide polymorphism (SNP) rs1800795 (-174 G/C) and rs1800796 ( 572G>C) known from inflammatory autoimmune disease were not analyzed in bipolar disorder. Preliminary results suggest that proposed approach should be used in reanalysis on a larger study group to enable genotyping and association analysis.