In this study, 617 patients with bipolar disorder who had not been treated with drugs for at least three months before hospitalization were taken as the study objects, of which 442 were patients with manic episodes and 175 were with depressive episodes. There were no differences in general information such as gender, age, length of hospital stay, BMI, family history of mental illness and abnormal thyroid function rate among manic and depression patients who did not take drugs three months before hospitalization. Also, there was no difference in the distribution of emotional transition in different seasons. Only systolic/diastolic blood pressure in mania was higher than that in depression systolic/diastolic blood pressure. It is speculated that this may be related to the risk of irritability and high mood in patients with bipolar mania.
Our study found that T3 and FT3 in patients with mania were significantly higher than those in patients with depression, which was similar to the results of previous studies (Gordon et al. 1999; Weatherman 2007). Thyroid hormones (especially T3) are structurally similar to norepinephrine (NE) (Weatherman 2007). T3 is mainly concentrated in the nucleus and projection sites of the central NE energy system (Rozanov and Dratman 1996), which may be transmitted from the locus to its NE target through axonal transport (Gordon et al. 1999), thus increasing the activity of postsynaptic adrenergic activity (Whybrow and Prange 1981). NE plays an important role in the regulation of emotions, and excessive NE can lead to restlessness in patients. Thyroid hormone may also induce mania by enhancing the neurotransmission of 5-HT, especially by reducing the sensitivity of 5-HT1A autoreceptor in the nucleus raphe and increasing the sensitivity of 5-HT2 receptors (Bauer, Heinz, and Whybrow 2002). In conclusion, the hypothalamic-pituitary-thyroid axis and the neurotransmitter system share a common biosynthetic precursor, tyrosine (Weatherman 2007). At the same time, they all exist in key areas of the brain, and thyroid hormone receptors are widely distributed in the limbic system of the brain, which is related to the pathogenesis of emotional disorders, and the neurotransmitter system regulates emotions by regulating the activities of the limbic area and cortex (Bauer, Heinz, and Whybrow 2002). Therefore, thyroid hormone itself may act as a neurotransmitter or interact with the primary neurotransmitter system to influence the mood of patients (Bauer et al. 2008; Chakrabarti 2011; Zhang et al. 2015).
The results of this study showed that the TSH of male patients was significantly lower than that of female patients, and the FT3 and FT4 of male patients were significantly higher than those of female patients. The level of thyroid function in patients with bipolar disorder was different between genders, indicating gender differences in bipolar disorder. A number of related studies support this view (Arnold 2003; Barnes and Mitchell 2005; Bauer et al. 2014). It has been found that estrogen receptors and thyroid hormone receptors have associated DNA binding domain. Therefore, estrogen and thyroid receptors may bind competitively to specific DNA targets (DiPippo, Lindsay, and Powers 1995; Gantus et al. 2011), which may be the reason for gender differences in thyroid dysfunction in patients with bipolar disorder.
In this study, thyroid function was compared in patients with bipolar disorder before and after treatment. The patients were divided into lithium salt group and non-use lithium salt group. The results showed that after treatment, TSH was increased but T3, T4, FT3 and FT4 were decreased in both groups. There was a trend of hypothyroidism, which was similar to the results of the previous study (Frye et al. 2009). It is speculated that both lithium salt and antipsychotics may affect thyroid function. Some clinical studies support this view (Park et al. 2011; Suppes et al. 2009; Vedal et al. 2018). The possible mechanisms of lithium-induced hypothyroidism include: 1) lithium may inhibit TSH-induced iodine uptake, thereby reducing iodine biosynthesis and neonatal thyroid hormone formation (Urabe et al. 1991). 2) Lithium can stabilize thyroid microtubules, and thus affects the release of thyroid hormone (Bhattacharyya and Wolff 1976). 3) Lithium inhibits the conversion of thyroxine to nitrous oxide in peripheral and neuronal cells (Bagchi, Brown, and Mack 1978). 4) Lithium accumulates in the thyroid at a concentration three to four times its plasma concentration. The most common thyroid side effects of long-term lithium salt therapy are goiter and hypothyroidism (Kraszewska et al. 2014). Therefore, it is recommended to regularly detect thyroid function levels in the clinical treatment of bipolar disorder.
This study has the following limitations: 1. Since it is an observational study, the reason cannot be explained. 2. In this study, we did not have the control group with lithium salt monotherapy for bipolar disorder patients. Thus, it was not possible to determine whether lithium salt would affect thyroid function itself. 3. The sample size in this study was limited. Moreover, due to the small number of patients with bipolar mixing, they were not included in the study. 4. In this natural real-world study, the choice of laboratory testing and treatment was based on the doctor's decision in clinical practice, which may have the follow-up bias and treatment drug selection bias.