Thyroid Function in Drug-Naïve Bipolar Disorder

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RESEARCH UPDATE

CASE VIGNETTE

“Ms Lena” is a 60-year-old African-American female with a 20-year history of bipolar I disorder. Her most recent episode featured depression without psychosis, and she is seen for monthly outpatient visits. She had a history of thyroid dysfunction and had a thyroidectomy at age 25 years. She currently takes 175 mcg levothyroxine for thyroid replacement. She has had no psychiatric hospitalizations in the past 15 years, but has chronic, mild depression. She took lithium briefly in the past, but her current psychotropic medications include risperidone and oxcarbazepine. Her most recent thyroid function was notable for elevated TSH (10.67 mcIU/mL), but normal free T4 (1.15 ng/dL) and T3 (0.64 ng/mL). As her psychiatrist, do you think changes in her thyroid function tests are associated with changes in mood state?

Fluctuations in mood state in bipolar disorder may be spontaneous or associated with psychological and/or pharmacologic factors. Lithium, along with key treatment option for bipolar disorder, is known to affect thyroid function.¹ Low thyroid function may be associated with bipolar depression.² Hospitalized patients with bipolar depression and low baseline thyroid-stimulating hormone (TSH) levels are more likely to switch to mania.³ Thyroid dysfunction is also associated with poorer treatment response in bipolar disorder.⁴

The Current Study

Zhao and colleagues⁵ investigated thyroid function in drug-naïve patients with bipolar disorder, considering effects of current mood state. They recruited inpatients from the West China Hospital from December 2018 to December 2019. Indices of thyroid function included TSH, free and total T3 and T4 (FT3, TT3, FT4, and TT4), as well as the rate of thyroid hormone secretion.

Inclusion criteria were that participants must be aged 18 to 65 years and drug-naïve before hospitalization, with a discharge diagnosis of ICD-10 bipolar disorder. Exclusion criteria were psychiatric comorbidity, serious physical illness, autoimmune disorders, pregnancy or lactation, and history of thyroid disease. Symptoms were assessed with the Montgomery-Asberg Depression Scale (MADRS) and the Young Mania Rating Scale (YMRS). Data were analyzed with ANOVA or χ2 tests.

The authors included 291 patients (136 with mania, 128 with depression, and 27 with mixed). The mean participant age was 27 years, the mean illness duration was 6.7 years, and 48% were male. Subjects were further subgrouped based on severity of mania or depression, and the presence or absence of psychosis. There were no significant differences in age, sex, education, or other demographic variables by the main diagnostic subgroups (mania, depression, and mixed). There were no differences in TSH, TT3, TT4, and FT4 by diagnostic subgroups.

However, there were significant differences in FT3 levels among the diagnostic subgroups, with higher levels in mania versus depression (mean 8.1 versus 4.3 pmol/L). Concomitantly, there was also difference in the incidence of increased rate of thyroid hormone secretion in mania versus depression (20.6 versus 1.6%). Finally, there was a difference in the incidence in the total abnormality rate of thyroid hormone secretion in mania versus depression (69.9 versus 45.3%). There was a small but significant correlation between FT3 levels and YMRS total score in patients with bipolar mania (r=0.18). By contrast, there were no correlations between symptoms and FT3 levels in patients with bipolar mixed or depression.

Study Conclusions

The authors concluded that in drug-naïve patients with bipolar mania, FT3 levels are higher, and rates of abnormal thyroid hormone secretion are higher than in patients with bipolar depression. FT3 levels were significantly positively correlated with the severity of mania.

The primary study strength was that subjects were drug-naïve, which means findings are independent of the effects of psychotropic medications. Study limitations included the cross-sectional design and assessment of thyroid indices at a single time point, which precluded inferences regarding causality. The authors also did not screen for thyroid autoantibodies. The small number of subjects in the bipolar mixed subgroup also limited statistical power for between-group comparisons.

The Bottom Line

There is evidence for more severe thyroid axis dysfunction in patients with bipolar mania versus depression. Thyroid hormone levels may contribute to mood changes in bipolar disorder, which should be assessed in prospective studies. Primary prevention, screening, and treatment efforts are needed for this patient population to mitigate increased cardiovascular disease morbidity and mortality.

Dr. Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric Times^TM. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.

References

1. McKnight RF, Adida M, Budge K, et al. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379(9817):721-728.

2. Szuba MP, Amsterdam JD, Fernando AT 3rd, et al. Rapid antidepressant response after nocturnal TRH administration in patients with bipolar type I and bipolar type II major depression [published correction appears in J Clin Psychopharmacol. 2005 Dec;25(6):538. Fernando, Antonio T 3rd [added]; Gary, Keith A [added]; Whybrow, Peter C [added]; Winokur, Andrew [added]]. J Clin Psychopharmacol. 2005;25(4):325-330.

3. Bottlender R, Rudolf D, Strauss A, Möller HJ. Are low basal serum levels of the thyroid stimulating hormone (b-TSH) a risk factor for switches into states of expansive syndromes (known in Germany as "maniform syndromes" in bipolar I depression? Pharmacopsychiatry. 2000;33(2):75-77.

4. Cole DP, Thase ME, Mallinger AG, et al. Slower treatment response in bipolar depression predicted by lower pretreatment thyroid function. Am J Psychiatry. 2002;159(1):116-121.

5. Zhao S, Zhang X, Zhou Y, et al. Comparison of thyroid function in different emotional states of drug-naïve patients with bipolar disorder. BMC Endocr Disord. 2021;21(1):210.