Investigation the relationship between the development of bipolar disorder and VEGF, IGF-1 and FGF-2 in patients with autism spectrum disorder

Background and Aim: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that begins in childhood and characterized with social deficits and limited, repetitive behaviors and interests. ASD can often coexist with other psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), anxiety disorders, and mood disorders. Co-occurring mood problems have a significant impact on the quality of life of patients with ASD. Therefore, accurate detection of bipolar disorder (BD) in patients with ASD may provide a more targeted treatment and improve the level of function and quality of life of patients. However, accurate diagnosis of comorbid disorders in young people with ASD has been difficult due to significant overlap in symptom presentation, diagnostic shadowing, problems with conformity of standard diagnostic criteria, and lack of phenomenological data. The etiological pathways of mood disorders in patients with ASD include genetic, cognitive, social/behavioral systems and physiological/neurobiological mechanisms interacting with each other. When the literature is investigated multiple neurotrophic and/or growth factor systems such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2, nerve growth factor (NGF), insulin-like growth factor (IGF)-1 etc. appear to play a key role in neuroplasticity, and dysfunction of neurotrophic/growth factor systems appears to play a critical role in the pathophysiology and treatment of mood disorders. Therefore, detecting the relationship between the development of BD and VEGF, IGF-1 and FGF-2 factors in patients with ASD may provide important contributions to the pathophysiology, diagnosis and treatment of the disorder. Method: The study consisted of two groups, the case group and the control group. 40 participants who were diagnosed with ASD and BD according to DSM-5 diagnostic criteria were included in the case group, and 40 participants who were diagnosed with ASD according to DSM-5 diagnostic criteria but were not diagnosed with mood disorders were included in the control group. The case group and control group were similar in terms of age and gender. Sociodemographic data form was used to evaluate the clinical and sociodemographic characteristics of the study sample. In order to determine psychiatric disorders Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (KSADS-PL) was performed. The Childhood Autism Rating Scale was used to ascertain the ASD severity. Behavioral problems and sleep disturbances were assessed in accordance with the Aberrant Behavior Checklist and the Sleep Disturbance Scale for Children. The school-related issues section of the Children's Quality of Life Scale was used to assess quality of life. Additionly, the Clinical Global Impression Scale and the Children's Clinical Global Assesment Scale were used to evaluate the clinical features of the case group. Approximately 5-8 ml of venous blood was collected from both groups. Serum samples were evaluated by ELISA method and VEGF, IGF-1 and FGF-2 levels were measured. Results: Serum VEGF and FGF-2 levels of the case group were found to be significantly higher than the serum levels of the control group (p=0.002, p=0.021, respectively). Although there was no difference in serum IGF-1 levels between the two groups, IGF-1 levels were negatively correlated with the severity of BD and positively correlated with the number of BD episodes in the case group. It is observed that the more increment in the serum VEGF levels was correlated with lower age of initial diagnosis of BD. The CGAS scores of the cases and serum FGF-2 levels were negatively correlated. No correlation was found between factor levels and ASD severity, problematic behaviors, sleep disorders and quality of life. Conclusion: The data in this study suggest that the difference in serum VEGF and FGF-2 levels may be related to the etiopathogenesis of BD development in children with ASD. VEGF and FGF-2 may be a potential biomarker for detecting BD development in children with ASD. Further researches with larger samples are needed. Keywords: Autism Spectrum Disorder, bipolar disorder, mood disorder, VEGF, IGF-1, FGF-2, biomarker