Altered thyroid function and neurometabolic features provide clues to understand the comorbidity of bipolar II depression and obsessive-compulsive disorder

Abstract

Bipolar disorder (BD) is highly comorbid with obsessive-compulsive disorder (OCD), leading to poor treatment outcome and prognosis. However, the neurobiological mechanisms underlying BD comorbid with OCD remain poorly understood. To address it, we recruited 69 untreated patients with bipolar II depression, including 35 comorbid with OCD (BD-II-Depression-OCD) and 34 without OCD (BD-II-Depression-nonOCD), and 38 healthy controls (HC). Serum thyroid hormones levels and neurometabolic ratios, including N-acetyl aspartate (NAA), choline-containing compounds (Cho), and creatine (Cr), were detected to explore the neuroendocrine and neurometabolic mechanisms of BD-II-Depression-OCD comorbidity. Multivariate logistic regression and restricted cubic spline analyses were performed to identify influential factors for comorbidity and their nonlinear relationships with symptom severity. Our results revealed that patients with BD-II-Depression-OCD demonstrated reduced thyroid-stimulating hormone (TSH) levels, decreased NAA/Cr in the left prefrontal white matter (PWM), and increased Cho/Cr in the right PWM compared to patients without comorbidity. These parameters demonstrated diagnostic potential for distinguishing BD-II-Depression-OCD comorbidity. Furthermore, nonlinear associations were observed between obsessive-compulsive symptom severity and both serum TSH levels and right PWM Cho/Cr ratios among patients with comorbidity. In conclusion, BD-II-Depression-OCD comorbidity is characterized by distinct thyroid dysfunction and neurometabolic alterations. Disruptions in serum TSH levels and bilateral PWM neurometabolism may represent potential mechanisms underlying BD-II-Depression-OCD comorbidity.