Associations between cognitive functioning and thyroid axis hormones in individuals with anxiety and mood disorders

Background: Thyroid axis hormones, such as free triiodothyronine (fT3), free thyroxine (fT4), and thyrotropin (TSH) are associated with mental disorders, especially with depression and anxiety [1, 2]. These hormones have been associated with worse cognitive functioning in individuals with coronary artery disease [3]. Cognitive dysfunction is prevalent in individuals with anxiety and mood disorders (AMD) [4, 5], however, the associations between these variables have not been studied in individuals with AMD. Therefore, the aim of our study was to investigate the correlation between fT3, fT4, the fT3/fT4 ratio, TSH and cognitive functioning in individuals with AMD. Methods: One hundred and ninety-two (age 39±12 years; 21% men and 79% women) individuals attending a Stress-related disorders day care unit of the Palanga Hospital at Neuroscience Institute of the Lithuanian University of Health Sciences, took part in this cross-sectional study. Diagnoses of AMD were established using the Mini-International Neuropsychiatric Interview. Cognitive tests were completed in order to assess cognitive functioning. Participants completed Digit Span Test to assess auditory attention and Trail Making Test (TMT) A and B to assess their perceptual speed, task-switching and executive control characteristics. Venous blood samples were drawn for evaluation of fT3, fT4, and TSH. Blood was centrifuged and serum was stored frozen at -70˚C. Serum levels of fT3, fT4, and TSH were analysed using an automated enzyme immunoassay analyser. Depression symptoms were measured with the Patient Health Questionnaire-9 (PHQ-9), anxiety symptoms were measured with the Generalized Anxiety Disorder-7 (GAD-7). For statistical analyses, univariate regression analysis was used to examine unadjusted associations of fT3, fT4, TSH, and fT3/fT4 with scores on cognitive functioning tests. Then, multivariable regression analyses were performed to determine if fT3, fT4, TSH, and fT3/fT4 remained significantly associated with cognitive functioning after adjusting for age, sex, education, depression and anxiety symptoms, smoking, and current medication use. Results: In individuals with AMD, univariate regression analyses showed that fT3 had a negative correlation with TMT Part A (b=-0.206; p=0.004), and Part B (b=-0.145; p=0.046); however, these associations were not significant in multivariable analyses after adjusting for age, sex, education, depression and anxiety symptoms, smoking, and current medication use. A univariate regression analyses also showed a negative correlation between fT4 and TMT Part A (b=-0.210; p=0.004), as well as Part B (b=-0.152; p=0.036). These associations were significant even after controlling them for aforementioned confounding factors (b=-0.192; p=0.006; b=-0.151; p=0.036 respectively). Conclusions: Overall, in individuals with AMD, lower fT4 concentrations were associated with slower perceptual speed and worsened task-switching abilities independent of socio-demographic characteristics, clinical factors as well as depression and anxiety symptoms. The results show the importance of thyroid hormones on cognitive functions in individuals with AMD. Particularly lower fT4 could be a potential biomarker of impaired cognitive functioning in individuals with AMD.