Investigation of risk factors contributing to mania development with antidepressant treatment in patients with early onset bipolar disorder

Objective: Early onset Bipolar disorder (BPD) is associated with a severe disease course and poor prognosis. Although the occurrence of BPD is 60% below the age of 20, the course of the disease is approximately 2 times more severe in children with prepubertal-onset BPD compared to those with postpubertal-onset BPD. Accordingly, it has become important to identify the factors that initiate BPD in the child and adolescent patient group. The most important finding proven among these factors is the history of BPD in the family. In addition, the development of Mania (ATOM) with Antidepressant Treatment is also considered as an important risk factor, and it is seen that antidepressant drug-induced BPB is conceptualized as a symptom of bipolar disorder in DSM 5. The biological factors that lead to the development of ATOM in the pediatric and adolescent patient group have not been investigated before, and in this project, it is aimed to find a biological predictor that causes this situation by evaluating the hypothalamo-pituitary axes. Method: In this study, patients aged 9-18 years who applied to the Child and Adolescent Psychiatry Outpatient Clinic of Dokuz Eylül University Medical Faculty Hospital and diagnosed with BPD and major depressive disorder were included. The patients were chosen to be divided into 2 groups. These groups are; It was named ATOM and Unipolar Depression, and a total of 60 patients were enrolled. Global Assessment Scale for Children and Childhood Trauma Scale were applied to these cases.The puberty and general developmental stages of the patients included in the study by Dokuz Eylül University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology were performed. Thyroid hormone levels and thyroid autoantibodies levels were measured to evaluate the hypothalamic-pituitary-thyroid axis. In the evaluation of the hypothalamic-pituitary-gonadal axis including sex steroids, a detailed puberty examination was performed and the blood levels of hormones associated with puberty (FSH, LH, Total Testosterone, Serum Estradiol, DHEA-S) were determined. Results: As risk factors identified in ATOM formation; autoimmune thyroid disease (OR = 3.6; 95% CI: 1.1-12.2; p = 0.035), history of accompanying panic disorder (OR = 10.9; 95% CI: 1.9-62.6; p = 0.007), postpartum depression (OR = 5.5 ; 95% CI: 1.6-18.5; p = 0.005) and autoimmune thyroid disease (OR = 3.6; 95% CI: 1.1- 11.1; p = 0.022). It was shown that sexual (p = 0.001) and physical abuse (p = 0.049) scores were significantly higher in the ATOM group. When the age of onset of pubic hair was examined, it was found that it started at a younger age in patients in the ATOM group (p = 0.001). In addition, in gonadal steroid levels, when the ATOM group was compared with the Unipolar Depression group by gender, it was found that total testosterone (p = 0.020) and DHEA-S (p = 0.035) levels were significantly higher in the female gender group, whereas only DHEA-S (p = 0.029) levels were found to be significantly higher in male gender group. Conclusion: It is thought that anti-TPO antibodies and imbalances in hormones associated with puberty play a role in the formation of the ATOM phenotype. There is a need for randomized controlled studies in samples with different sociodemographic characteristics, including evaluation of autoimmune thyroid disease and puberty before antidepressant treatment, especially in risky groups.