Association of altered thyroid hormones and neurometabolism to cognitive dysfunction in unmedicated bipolar II depression

Abstract

BackgroundThe underlying mechanism of cognitive impairment in bipolar II depression (BD II) remains unclear. Studies show disturbances of the hypothalamus-pituitary-thyroid (HPT) axis are suspected of correlating to brain neurometabolic alterations and cognitive deficits in psychiatric disorders. While, the nature of their inter-relationships in BD II depression remain enigmatic. Methods106 patients with unmedicated BD II depression and 100 healthy controls underwent cognitive function assessment using Trail Making Test, Part-A (TMT-A), Digit Symbol Substitution Test (DSST), and Semantic Verbal Fluency testing (SVF). Of those, 69 patients and 53 healthy controls had serum thyroid hormone levels measured including free tri-iodothyronine (FT3), total tri-iodothyronine (TT3), free thyroxin (FT4), total thyroxin (TT4) and thyroid-stimulating hormone (TSH). Additionally, 79 of the patients and 76 of the healthy controls underwent proton magnetic resonance spectroscopy (H-MRS) to obtain ratios of N-acetyl aspartate to creatine (NAA/Cr) and choline-containing compounds to creatine (Cho/Cr) in the prefrontal cortex (PFC), anterior cingulate cortex (ACC) and thalamus. Finally, association and multiple regression analysis were conducted to investigate their inter-relationships. ResultsPatients with BD II depression showed significantly lower DSST and verbal fluency scores and longer completion time of TMT-A than did healthy controls. The FT3, TT3, and TSH levels of the BD cohort significantly decreased, while their FT4 levels increased. We also found significantly lower NAA/Cr ratios in the PFC and higher NAA/Cr ratios in the left thalamus of patients with BD II depression than in healthy controls. Furthermore, association analysis showed that increased FT4 negatively correlated to DSST and SVF, while increased FT4 correlation significantly with increasing TSH and DSST. Multiple regression analyses revealed relationships between TSH and NAA in the left PFC and the left thalamus, while correlating to SVF testing within the BD II depression cohort. ConclusionsOur results demonstrate coinciding thyroid hormone abnormalities, cognitive dysfunction, and neurometabolic alterations of the PFC-thalamic circuitry occur in an early course of BD II depression. Further understanding of the interaction between thyroid-stimulating hormone and NAA/Cr of PFC-thalamic circuitry may shed light on the etiology of associated cognitive impairment.