Jiang QH, Gong WD. Correlation analyse between thyroid hormone levels and severity of schizophrenia symptoms. World J Psychiatry 2025; 15(1): 100880 [DOI: 10.5498/wjp.v15.i1.100880]
Corresponding Author of This Article
Wei-Dong Gong, Breast Tumor Surgical Outpatient, Hengyang Central Hospital, No. 12 Yancheng Road, Hengyang 421000, Hunan Province, China. 18274781070@163.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Author contributions: Jiang QH designed the experiments, performed the experiments, and analyzed the data; Gong WD wrote the paper, revised it, and organized the data.
Institutional review board statement: The study was reviewed and approved by the Hengyang Central Hospital Institutional Review Board.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data related to this paper can be obtained from the author on reasonable grounds.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Received: September 6, 2024 Revised: October 18, 2024 Accepted: November 21, 2024 Published online: January 19, 2025 Processing time: 103 Days and 1.2 Hours
Abstract
BACKGROUND
The imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia, especially thyroid hormones.
AIM
To study the relationship between triiodothyronine (T3), thyroxine (T4), free T3 (FT3), free T4 (FT4), thyroid stimulating hormone (TSH) and schizophrenia.
METHODS
In this study, 100 schizophrenia patients were selected from our hospital between April 2022 and April 2024. Their clinical data were analyzed retrospectively. Based on the Positive and Negative Syndrome Scale (PANSS) score, patients were divided into mild (1-3 points, n = 39), moderate (4 points, n = 45), and severe groups (5-7 points, n = 16). Additionally, 55 healthy individuals served as a control group. Venous blood samples were collected to measure T3, T4, FT3, FT4, TSH, and cortisol concentrations, analyzing their relationship with PANSS scores.
RESULTS
The serum levels of T3, FT3, FT4, TSH and cortisol in the schizophrenia group were lower than those in the control group (P < 0.05). With the increase of the severity of the disease, the concentrations of T3 and T4 decreased, while the concentrations of TSH and cortisol increased (P < 0.05). The concentrations of TSH and cortisol were positively correlated with the PANSS score, while T3 and T4 were negatively correlated with the PANSS score (P < 0.05). The receiver operating characteristic curve results showed that T3, T4, TSH, and cortisol had good efficacy in the diagnosis of schizophrenia. Logistic results showed that decreased T3 level, decreased T4 level, decreased TSH level and increased cortisol level may be independent risk factors for schizophrenia.
CONCLUSION
Thyroid hormone levels are associated with the severity of schizophrenia symptoms, which can provide new solutions for the diagnosis and treatment of schizophrenia.
Core Tip: Previous studies have confirmed that hormone imbalance is closely related to the occurrence and progression of schizophrenia, especially thyroid hormone. However, the relationship between thyroid hormone and schizophrenia symptoms is still unknown at this stage. Based on this, this study conducted a retrospective analyse to explore the correlation between thyroid hormone levels and the severity of schizophrenia.
Citation: Jiang QH, Gong WD. Correlation analyse between thyroid hormone levels and severity of schizophrenia symptoms. World J Psychiatry 2025; 15(1): 100880
Schizophrenia is a clinical syndrome whose pathogenesis has not been fully elucidated, it is currently believed to be related to genetic susceptibility genes and environmental factors, the disease affects about 1% of the world’s population[1,2]. In recent years, the prevalence of schizophrenia has increased year by year, and it is more common in young and middle-aged people. Patients often show cognitive symptoms, negative symptoms and positive symptoms[3,4]. As the disease progresses, about 50% of schizophrenia patients will develop mental disability and then lose their ability to work[5]. Schizophrenia has a long course and is difficult to cure. After the onset of the disease, patients may be accompanied by hallucinations, confusion, behavioral disorders and other manifestations. In severe cases, they may even harm others or self-harm or commit suicide, which is very harmful and affects social stability[6,7]. Gibson et al[8] pointed out that the imbalance of hormone levels in the body is closely related to the occurrence and progression of schizophrenia, especially thyroid hormones. Thyroid hormones can induce tissue metabolism, promote protein conversion and generate energy in the body, and participate in the regulation of central nervous system development. Excessive increase in their release can enhance nerve excitability, ultimately leading to symptoms such as insomnia and tachycardia[9,10]. Some literature points out that excessive increase in thyroid hormones in the body is related to the risk of suicide in schizophrenia patients, and can directly cause depression or violence, especially triiodothyronine (T3) and thyroxine (T4). Surveys and studies have shown that about 40% of schizophrenia patients have abnormal thyroid function[11,12]. In this way, the role of thyroid hormone levels in schizophrenia is particularly important. However, the relationship between thyroid hormones and schizophrenia symptoms remains unknown at this stage[13]. Based on this, this study conducted a retrospective analyse to explore the association between thyroid hormone levels and the severity of schizophrenia.
MATERIALS AND METHODS
Study subjects
Taking thyroid stimulating hormone (TSH) level as the main index, based on previous experience and relevant literature, the standard deviation σ is expected to be 4.63, requiring a two-sided test, α is 0.05, and the allowable error δ is 1. The sample size is calculated according to the following formula (Figure 1). The sample size n = 83 can be obtained. Considering the 20% loss to follow-up rate, this study needs to include at least 100 patients as study subjects. In this study, 100 schizophrenia patients were selected from Hengyang Central Hospital as the schizophrenia group between April 2022 and April 2024, and their clinical data were retrieved and retrospectively studied. Another 55 healthy people were selected as the control group.
Inclusion criteria: (1) All patients met the relevant diagnostic criteria for schizophrenia[14]; (2) All patients were diagnosed using magnetic resonance brain structural imaging technology; (3) All patients had complete clinical data available in our hospital; and (4) All patients had normal intellectual development and were first-episode psychosis patients.
Exclusion criteria: (1) Patients with a history of exposure to psychoactive substances; (2) Patients with a history of drug or alcohol abuse; (3) Patients with a history of electroconvulsive therapy; (4) Patients with brain lesions; and (5) Patients with a history of thyroid dysfunction or treatment with T4.
Specimen collection
Venous blood was collected from both the schizophrenia group and the control group in the early morning of the next day after entering the study using sterile vacuum blood collection tubes. After collecting 4-5 mL, the blood was left to stand in a natural state for 30 minutes, and then centrifuged to obtain the supernatant for storage for subsequent testing.
Thyroid hormone measurement
AIA-CL2400 fully automatic chemiluminescence immunoassay analyzer (provided by Shanghai Tosoh Biotechnology Co., Ltd.) was used to measure the concentrations of T3, T4, free T3 (FT3), free T4 (FT4), TSH and cortisol in the schizophrenia group and the control group.
Statistical analysis
The study data were processed by SPSS 22.0 statistical software. The Shapiro-Wilk method was used to test the normal distribution of the measurement data. The measurement data that met the normal distribution were expressed in the form of (mean ± SD). The inter-group comparison was obtained by two-tailed t test. The counting data were expressed in the form of [n (%)], and the results were obtained by χ2 test. The receiver operating characteristic curve was used to analyze the diagnostic efficacy of serum T3, T4, FT3, FT4, TSH, and cortisol in schizophrenia. Logistic regression model was used to analyze the independent risk factors affecting schizophrenia. P < 0.05 was considered statistically significant.
RESULTS
General information
The final study included 55 healthy subjects and 100 schizophrenia patients. The 100 schizophrenia patients were divided into mild group (1-3 points, n = 39), moderate group (4 points, n = 45) and severe group (5-7 points, n = 16) according to the Positive and Negative Syndrome Scale (PANSS) score. The general data of the subjects included in each group were analyzed, and there was no significant difference in age, gender, and smoking rate among the groups (P > 0.05) in Table 1.
Thyroid hormone concentrations in schizophrenia group and control group
The serum T3 (2.04 ± 0.53), T4 (118.66 ± 17.44), FT3 (4.60 ± 0.50), FT4 (16.51 ± 2.20), TSH (3.10 ± 0.90), and cortisol (3.23 ± 0.09) levels in the control group were all within the normal range, but the serum T3 (1.77 ± 0.58), T4 (98.78 ± 16.30), FT3 (4.35 ± 0.60), FT4 (13.40 ± 2.19), TSH (2.08 ± 0.85), and cortisol (6.50 ± 1.30) levels in the schizophrenia group were lower than those in the control group (P < 0.05) in Table 2.
Table 2 Comparison of thyroid hormone levels (mean ± SD).
Grouping
T3 (nmol/L)
T4 (nmol/L)
FT3 (pmol/L)
FT4 (pmol/L)
TSH (mIU/L)
Cortisol (mmol/L)
Control group (n = 55)
2.04 ± 0.53
118.66 ± 17.44
4.60 ± 0.50
16.51 ± 2.20
3.10 ± 0.90
3.23 ± 0.09
Schizophrenia group (n = 100)
1.77 ± 0.58
98.78 ± 16.30
4.35 ± 0.60
13.40 ± 2.19
2.08 ± 0.85
6.50 ± 1.30
t
2.856
7.086
2.783
8.442
7.002
25.066
P value
0.005
< 0.001
0.006
< 0.001
< 0.001
< 0.001
Serum thyroid hormone concentration in patients with different degrees of schizophrenia
There was no difference in the concentrations of FT3 and FT4 among the mild, moderate and severe groups (P > 0.05); however, there were differences in T3, T4, TSH, cortisol and PANSS scores among the three groups. With the increase in the severity of the disease, the concentrations of T3 and T4 decreased, while the concentrations of TSH and cortisol increased (P < 0.05) in Table 3.
Table 3 Comparison of serum thyroid hormone concentrations in each group (mean ± SD).
Correlation between thyroid hormone and PANSS score
Pearson correlation analyse of the correlation between thyroid hormone and PANSS score showed that the concentrations of FT3 and FT4 were not related to PANSS score (P > 0.05); TSH and cortisol concentrations were positively correlated with PANSS score, while T3 and T4 were negatively correlated with PANSS score (P < 0.05) in Table 4.
Table 4 Correlation between thyroid hormone and Positive and Negative Syndrome Scale score.
Thyroid hormone
PANSS score
r
P value
T3
-0.259
0.025
T4
-0.218
0.029
FT3
0.130
0.196
FT4
-0.049
0.631
TSH
0.215
0.032
FSH
0.315
0.019
Receiver operating characteristic curve analyse of related factors
The area under the curve of T3, T4, FT3, FT4, TSH, and cortisol were 0.749, 0.766, 0.545, 0.547, 0.890, 0.925, respectively. The optimal cutoff values were 1.68 nmol/L, 98.82 nmol/L, 4.49 pmol/L, 13.86 pmol/L, and 2.74 mIU/L, 5.88 mmol/L respectively. The sensitivities were 75.0%, 87.5%, 50.00%, 62.5%, 81.2%, and 81.2%, respectively. The specificities were 74.36%, 56.4%, 74.36%, 66.7%, 89.7%, and 89.7%, respectively. Among them, T3, T4, TSH, and cortisol had good efficacy in the diagnosis of schizophrenia in Table 5 and Figure 2.
Table 5 Receiver operating characteristic curve analyse of related factors.
Index
AUC
SE
95%CI
P value
Optimal cutoff value
Sensitivity (%)
Specificity (%)
T3
0.749
0.071
0.614-0.856
0.001
≤ 1.68
75.0
74.4
T4
0.766
0.070
0.632-0.870
< 0.001
≤ 98.82
87.5
56.4
FT3
0.545
0.093
0.405-0.680
0.628
> 4.49
50.0
74.36
FT4
0.547
0.092
0.407-0.682
0.608
> 13.86
62.5
66.7
TSH
0.890
0.051
0.777
0.958
> 2.74
81.2
89.7
Cortisol
0.925
0.038
0.821-0.978
< 0.001
> 5.88
81.3
89.7
Logistic multivariate analyse of factors affecting schizophrenia
T3, T4, FT3, FT4, and TSH in the Logistic regression model, it was found that decreased T3 levels [β = 0.616, odds ratio (OR) = 1.852, 95% confidence interval (CI): 1.526-2.652], decreased T4 levels (β = 0.506, OR = 1.658, 95%CI: 1.121-1.985), decreased TSH levels (β = 0.699, OR = 2.011, 95%CI: 1.781-2.698) and Increased cortisol levels (β = 0.511, OR = 1.523, 95%CI: 1.132-2.011) can all be used as independent risk factors for schizophrenia (Tables 6 and 7).
Table 7 Logistic multivariate analyse of factors affecting schizophrenia.
Index
β
SE
Wald
OR (95%CI)
P value
T3
-0.616
0.245
10.262
1.852 (1.526-2.652)
< 0.001
T4
-0.506
0.219
10.550
1.658 (1.121-1.985)
< 0.001
FT3
-0.227
0.277
2.958
1.255 (1.026-1.451)
0.152
FT4
-0.264
0.241
4.545
1.302 (1.114-1.534)
0.089
TSH
-0.699
0.271
9.518
2.011 (1.781-2.698)
< 0.001
Cortisol
0.511
0.230
9.825
1.523 (1.132-2.011)
< 0.001
DISCUSSION
Schizophrenia is a mental illness of unknown etiology. Brain structural lesions and neurological damage can lead to dysregulation of neurotransmitter release, inducing clinical symptoms such as apathy, delusions, and agitation. Some patients improve or recover after formal management intervention[15,16]; however, in most cases, patients have a very high risk of relapse after improvement, so long-term management intervention is still needed after improvement[17-19]. Sharif et al[20] used multivariate analyse to evaluate the relationship between schizophrenia symptoms and thyroid function and observed that schizophrenia patients were closely related to hypothyroidism. Gyllenberg et al[21] prospectively observed that hypothyroidism in pregnant women in the early and middle stages of pregnancy can significantly increase their risk of schizophrenia. In this case, the translation information provided by the mother can cause the offspring molecules and cells to deviate. In recent years, the incidence of schizophrenia has been increasing, so in-depth explanation of the relationship between the occurrence of this disease and thyroid hormone has gradually become a hot topic. This study observed that the serum T3, T4, FT3, FT4, TSH, and cortisol concentrations of the control group were all within the normal range, but the serum T3, T4, FT3, FT4, TSH, and cortisol concentrations of the schizophrenia group were lower than those of the control group. The results of this study indicate that thyroid function abnormalities occur in patients with schizophrenia accompanied by abnormal thyroid hormone concentrations. Accompanied by dysfunction of thalamocortical circuits. PANSS score is an important criterion for measuring the severity of schizophrenia. Therefore, this study grouped schizophrenia patients according to PANSS score and observed that there was no difference in FT3 and FT4 concentrations among the mild, moderate and severe groups, there were differences in T3, T4, TSH, cortisol, and PANSS scores among the three groups. With the increase in the severity of the disease, the concentrations of T3 and T4 decreased, while the concentrations of TSH and cortisol increased, indicating that T3, T4, TSH, and cortisol concentrations are closely related to the severity of symptoms in patients with schizophrenia. This may be because patients with this disease usually have abnormal brain metabolism. If their brain vascular resistance increases, it can reduce brain blood flow, leading to cerebral ischemia, hypoxia, etc., and ultimately have an adverse effect on thyroid function[22,23]. In addition, patients with this disease have a large release of neurotransmitters such as dopamine in their brains, which can cause abnormal release of central neurotransmitters, endocrine system internal environment disorders, hinder the release of thyroid hormones, and thus affect the patient’s mood and cognitive function, ultimately leading to the occurrence of schizophrenia[24-28]. Huang et al[29] measured the serum concentration of 916 patients with schizophrenia and observed that the T3 concentration was reduced, which is also a population-specific risk factor for coronary artery calcification in schizophrenia. In addition, there is a mutually regulatory relationship between thyroid hormones and cortisol. High levels of cortisol may inhibit the synthesis and secretion of thyroid hormones, while changes in thyroid hormones may affect the secretion of cortisol. This interaction may play an important role in the pathological mechanism of schizophrenia. Studies have shown that thyroid hormones may affect the secretion of cortisol by regulating the hypothalamic-pituitary-adrenal axis. Conversely, elevated cortisol may further aggravate the symptoms of schizophrenia by affecting thyroid function[30]. Freuer and Meisinger[13] conducted a two-way two-sample Mendelian randomization experiment to explore the relationship between thyroid function and schizophrenia and found that increased TSH concentration can reduce the incidence of schizophrenia. However, Li et al[11] analyzed the serum FT3 and FT4 concentrations of 75 healthy subjects and 154 schizophrenia patients and found that the serum index concentrations of schizophrenia patients were reduced, and the FT3 and FT4 concentrations of patients with agitated behavior were even lower. In this study, the correlation between thyroid hormone and PANSS score was analyzed by Pearson correlation. It was observed that FT3 and FT4 concentrations were not related to PANSS score (P > 0.05); however, T3, T4, and TSH concentrations were positively correlated with PANSS score (P < 0.05), suggesting that thyroid hormone concentrations are associated with the severity of symptoms in patients with schizophrenia. This is due to the interaction between the brain and thyroid function, in which the brain can participate in regulating the release of thyroid hormones, and the thyroid can also negatively feedback to the brain. In addition, thyroid function can also be affected by psychological factors and emotions, so there is a certain correlation between the two[31-35]. This study also observed that the area under the curves of T3, T4, FT3, FT4, and TSH were 0.749, 0.766, 0.545, 0.547, and 0.890, respectively, and the optimal cutoff values were 1.68 nmol/L, 98.82 nmol/L, 4.49 pmol/L, 13.86 pmol/L, and 2.74 mIU/L, respectively, with sensitivities of 75.0%, 87.5%, 50.00%, 62.5%, and 81.2%, and specificities of 74.36%, 56.4%, 74.36%, 66.7%, and 89.7%, respectively. Among them, T3, T4, and TSH have good efficacy in the diagnosis of schizophrenia. And by incorporating T3, T4, FT3, FT4, and TSH into the Logistic regression model, it was found that decreased T3 levels, decreased T4 levels, and decreased TSH levels can all serve as independent risk factors affecting schizophrenia. Therefore, it is necessary to pay attention to the above risk factors.
CONCLUSION
Thyroid hormone levels are associated with the severity of schizophrenia symptoms, which can provide new solutions for the diagnosis and treatment of schizophrenia. The measurement of thyroid hormone levels can help doctors better understand the patient’s disease status and provide more targeted personalized treatment strategies for patients. Further study is needed on the pathological mechanism between abnormal thyroid function and schizophrenia in the future.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Psychiatry
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade B, Grade C
Novelty: Grade B, Grade C
Creativity or Innovation: Grade B, Grade C
Scientific Significance: Grade B, Grade C
P-Reviewer: Khalifeh H; Romm KF S-Editor: Wang JJ L-Editor: A P-Editor: Wang WB
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