Levels of fibroblast growth factor-2 (FGF-2) and fibroblast growth factor-9 (FGF-9) in bipolar disorder

Bipolar Disorder (BD) is a chronic psychiatric illness characterized by episodic mood disturbances—including manic, hypomanic, depressive, or mixed episodes—with either symptom-free intervals or the presence of subthreshold symptoms between acute episodes. Interest in the role of Fibroblast Growth Factors (FGFs) in mood disorders began more than a decade ago, based on observations in postmortem human brain samples. Since then, a growing body of evidence from both human studies and animal models has suggested that the FGF family may be involved in the pathogenesis of various neuropsychiatric disorders. This study aimed to compare serum FGF-2 and FGF-9 levels in patients with BD under follow-up and in healthy controls and to evaluate whether these molecules may serve as biomarkers for mood episodes (manic or depressive) in BD. A total of 121 patients diagnosed with BD according to DSM-5 diagnostic criteria (47 euthymic, 37 manic, and 37 depressive) who presented to the Psychiatry Clinic and Outpatient Unit of Akdeniz University Faculty of Medicine were included in the study. Additionally, 67 healthy controls with similar sociodemographic characteristics were recruited. A sociodemographic data form, the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Structured Clinical Interview for DSM-5 Disorders – Clinical Version were administered. Peripheral blood samples were collected from all participants after an 8-12 hours of fasting period for the assessment of serum FGF-2 and FGF-9 levels. The mean age of patients was 41.11±12.05 years, and that of healthy controls was 41.12±9.18 years. Women comprised 55.4% of the patient group and 58.2% of the control group. FGF-2 levels in the acute episode group (manic + depressive) were significantly lower than those in both the euthymic group and the control group; however, no significant difference was observed between the euthymic and control groups. FGF-9 levels were significantly lower in the acute episode group compared to the euthymic group, but the difference compared to the control group, although lower, was not statistically significant. No significant difference was found between the euthymic and control groups. FGF-2 and FGF-9 levels were similar between manic and depressive subgroups. In the ROC analysis for the acute episode group (mania + depression), the cut-off value for FGF-2 was determined as ≤26.83 pg/mL, with a sensitivity of 56.8%, specificity of 74.6%, positive predictive value of 71.2%, negative predictive value of 61.0%, and an area under the curve ± standard error of 0.646±0.046. For FGF-9, the cut-off value was ≤24.15 pg/mL, with a sensitivity of 71.6%, specificity of 50.7%, positive predictive value of 61.6%, negative predictive value of 61.8%, and an area under the curve ± standard error of 0.599±0.048. In conclusion, FGF-2 and FGF-9 may be potential biomarkers for identifying manic or depressive episodes in BD, particularly at specific cut-off points for predicting acute episodes. This study is the first to evaluate FGF-2 and FGF-9 concurrently in a BD sample, and further research is warranted to clarify the role of FGFs in the etiology of bipolar disorder. Keywords: Bipolar Disorder, Mood Disorder, Fibroblast Growth Factor (FGF), FGF-2, FGF-9