甲状腺功能与抑郁障碍关系的研究
摘要
甲状腺功能异常与抑郁障碍密切相关,甲状腺功能亢进或减退都可导致抑郁障碍；甲减与抑郁症具有相似的临床表现,两者都可引起认知障碍。甲状腺功能异常引发抑郁障碍的机制尚不完全清楚,为探讨甲状腺功能与抑郁障碍的关系我们进行了以下研究：
1、在动物实验部分采用旷野试验及蔗糖试验评价甲状腺功能减退大鼠的行为改变,18F-FDG micro PET显像评价脑葡萄糖代谢的变化,分析行为表现与特定脑区代谢活性的关系。结果发现,甲减大鼠体重、蔗糖偏好度、旷野实验中排便粒数和直立跨格数明显低于对照组：双侧尾状核/豆状核、扣带回皮质、伏隔核、额叶联合部及运动皮质葡萄糖代谢减低,尾状核/豆状核及伏隔核代谢变化与蔗糖偏好度变化显著相关。
2、131I治疗后出现亚临床甲减的患者中抑郁症的发病率(23.5%)显著高于甲状腺功能正常者(7.3%)；对亚临床甲减组中TSH超过10mIU/L的部分患者用左旋甲状腺素进行治疗,结果HAMD得分显著降低,说明替代治疗可使这部分患者受益。
3、选择临床确诊的Graves'病患者,通过量表评分及临床资料分析,探讨甲亢伴发抑郁、焦虑的危险因素,并对SF-36量表在甲亢患者中的适用性进行评价。结果表明,FT3、FT4、TRAb和眼症是Graves'病伴发抑郁的危险因素,FT3、心率和甲状腺肿大是Graves’病伴发焦虑的危险因素；SF-36量表能准确反映甲亢患者的生存质量。
4、用SPECT脑血流显像评价抑郁及甲减患者局部脑血流变化,用Go/No go实验评价认知功能。结果发现抑郁患者双侧尾状核、右侧扣带回血流显著降低,甲减患者双侧前额叶、中央前回、中央后回、海马、顶上小叶及扣带回血流显著降低。两组HAMD得分均显著高于对照组,抑郁组HAMD得分与双侧扣带回及尾状核相对rCBF显著负相关,而甲减组HAMD得分与扣带回相对rCBF显著负相关；抑郁及甲减患者均存在认知障碍,抑郁组Go/No go认知试验正确率与前额叶皮质相对rCBF显著正相关,甲减组Go/No go认知试验正确率与前额叶及海马相对rCBF显著正相关。
结论：甲减大鼠脑局部葡萄糖代谢降低,代谢异常与抑郁症状密切相关,甲状腺激素缺乏通过影响边缘系统的功能导致抑郁障碍；甲减与抑郁均引起局部脑血流异常,两者存在部分重叠,甲减与抑郁患者的情感、认知障碍具有相似的神经机制；亚临床甲减增加了抑郁症的发病率,甲状腺激素替代治疗能够改善亚临床甲减患者的抑郁症状；FT3、FT4、TRAb和眼症是Graves'病伴发抑郁的危险因素,FT3、心率和甲状腺肿大是Graves'病伴发焦虑的危险因素,SF-36量表能准确反映甲亢患者的生存质量。
Thyroid dysfunction is closely related to depressive disorder, both hyperthyroidism and hypothyroidism can lead to depressive disorder; hypothyroidism and depression have similar clinical manifestations, both of them can cause cognitive defects. The mechanism under which thyroid disfunction leads to depressive disorder is still unclear, the following study was performed in order to explore the relationship between thyroid function and depressive disorder:
1. The open field test and sucrose preference test were performed to evaluate the behavioural changes of the hypothyroid rats, F-FDG micro PET imaging was conducted to evaluate the changes in glucose metabolism of the brain, and the relationship between the behavioural manifestations and the brain metabolism were analyzed. Body weight, sucrose preference, feces boli and rearing in the open field test decreased significantly in the hypothyroid rats compared to the control rats; the glucose metabolism decreased bilaterally and significantly in caudate/putamen, cortex cingulate, nucleus accumbens, cortex frontal association and cortex motor in the hypothyriod rats; the metabolic changes in caudate/putamen and nucleus accumbens correlated significantly with changes in sucrose preference.
2. Depression occured more frequently in patients with subclinical hypothyroidism (23.5%) after131I treatment than in euthyroid patients (7.3%). L-thyroxine treatment was performed in some patients with TSH level higher than10mlU/L in the subclinical hypothyroidism group, significant decrease in HAMD score was observed which demonstated the beneficial effects of substitutive treatment.
3. Scale evaluation and clinical data analysis were conducted in patients with Graves' diseae in an attempt to explore the risk factors of depression and anxiety in hyperthyroidism, usefulness of SF-36was evaluated in GD patients. Results showed that depression and anxiety were more prevalent in patients with Graves'disease, FT3, FT4, TRAb and eye symptoms were risk factors for depression, FT3, heart rate and thyroid swelling were risk factors for anxiety, SF-36was a suitable tool in the evaluation of life quality in GD patients.
4. Regional brain blood flow changes in patients with depression and hypothyroidsm were compared using SPECT, cognitive function was evaluated with Go/No go test. Relative rCBF decreased significantly in bilateral caudate and right cingulate for depressive patients and in bilateral prefrontal cortex, anterior central gyrus, posterior central gyrus, hippocampus, superior parietal lobule and cingulate for hypothyroid patients. Both depressive and hypothyroid patients had significant higher HAMD scores than contol patients, HAMD score in the depressive group correlated negatively with rCBF in bileteral cingulate and caudate, while HAMD score in the hypothyroid group correlated negatively with rCBF in bilateral cingulate; cognitive defects were observed in both depressive and hypothyroid groups, Go/No go score correlated positively with relative rCBF in prefrontal cortex in the depressive group, while correlated positively with prefrontal cortex and hippocampus in the hypothyroid group.
In conclusion, hypothyroidism can lead to decrease in regional brain glucose metabolism in rats, abnormal brain metabolism relates closely to depressive symptoms, thyroid hormone deficiency can influnce the function of emotional circuit which subsequently causes depressive disorder; both depression and hypothyroidism can lead to abnormality in regional brain blood flow, and some of the abnormal regions overlap in the two diseases which means similar neural mechanism underlies the mood and cognitive disorders in depressive and hypothyroid patients; subclinical hypothyroidism increases the incidence of depression, L-thyroxine substitution can improve the depressive symptoms in patients with subclinical hypothyroidism; FT3, FT4, TRAb and eye symptoms are risk factors of depression in Graves' disease, FT3, heart rate and thyroid swelling are risk factors of anxiety in Graves'disease, SF-36can reflect the life quality of patients with Graves" disease.
1、在动物实验部分采用旷野试验及蔗糖试验评价甲状腺功能减退大鼠的行为改变,18F-FDG micro PET显像评价脑葡萄糖代谢的变化,分析行为表现与特定脑区代谢活性的关系。结果发现,甲减大鼠体重、蔗糖偏好度、旷野实验中排便粒数和直立跨格数明显低于对照组：双侧尾状核/豆状核、扣带回皮质、伏隔核、额叶联合部及运动皮质葡萄糖代谢减低,尾状核/豆状核及伏隔核代谢变化与蔗糖偏好度变化显著相关。
2、131I治疗后出现亚临床甲减的患者中抑郁症的发病率(23.5%)显著高于甲状腺功能正常者(7.3%)；对亚临床甲减组中TSH超过10mIU/L的部分患者用左旋甲状腺素进行治疗,结果HAMD得分显著降低,说明替代治疗可使这部分患者受益。
3、选择临床确诊的Graves'病患者,通过量表评分及临床资料分析,探讨甲亢伴发抑郁、焦虑的危险因素,并对SF-36量表在甲亢患者中的适用性进行评价。结果表明,FT3、FT4、TRAb和眼症是Graves'病伴发抑郁的危险因素,FT3、心率和甲状腺肿大是Graves’病伴发焦虑的危险因素；SF-36量表能准确反映甲亢患者的生存质量。
4、用SPECT脑血流显像评价抑郁及甲减患者局部脑血流变化,用Go/No go实验评价认知功能。结果发现抑郁患者双侧尾状核、右侧扣带回血流显著降低,甲减患者双侧前额叶、中央前回、中央后回、海马、顶上小叶及扣带回血流显著降低。两组HAMD得分均显著高于对照组,抑郁组HAMD得分与双侧扣带回及尾状核相对rCBF显著负相关,而甲减组HAMD得分与扣带回相对rCBF显著负相关；抑郁及甲减患者均存在认知障碍,抑郁组Go/No go认知试验正确率与前额叶皮质相对rCBF显著正相关,甲减组Go/No go认知试验正确率与前额叶及海马相对rCBF显著正相关。
结论：甲减大鼠脑局部葡萄糖代谢降低,代谢异常与抑郁症状密切相关,甲状腺激素缺乏通过影响边缘系统的功能导致抑郁障碍；甲减与抑郁均引起局部脑血流异常,两者存在部分重叠,甲减与抑郁患者的情感、认知障碍具有相似的神经机制；亚临床甲减增加了抑郁症的发病率,甲状腺激素替代治疗能够改善亚临床甲减患者的抑郁症状；FT3、FT4、TRAb和眼症是Graves'病伴发抑郁的危险因素,FT3、心率和甲状腺肿大是Graves'病伴发焦虑的危险因素,SF-36量表能准确反映甲亢患者的生存质量。
Thyroid dysfunction is closely related to depressive disorder, both hyperthyroidism and hypothyroidism can lead to depressive disorder; hypothyroidism and depression have similar clinical manifestations, both of them can cause cognitive defects. The mechanism under which thyroid disfunction leads to depressive disorder is still unclear, the following study was performed in order to explore the relationship between thyroid function and depressive disorder:
1. The open field test and sucrose preference test were performed to evaluate the behavioural changes of the hypothyroid rats, F-FDG micro PET imaging was conducted to evaluate the changes in glucose metabolism of the brain, and the relationship between the behavioural manifestations and the brain metabolism were analyzed. Body weight, sucrose preference, feces boli and rearing in the open field test decreased significantly in the hypothyroid rats compared to the control rats; the glucose metabolism decreased bilaterally and significantly in caudate/putamen, cortex cingulate, nucleus accumbens, cortex frontal association and cortex motor in the hypothyriod rats; the metabolic changes in caudate/putamen and nucleus accumbens correlated significantly with changes in sucrose preference.
2. Depression occured more frequently in patients with subclinical hypothyroidism (23.5%) after131I treatment than in euthyroid patients (7.3%). L-thyroxine treatment was performed in some patients with TSH level higher than10mlU/L in the subclinical hypothyroidism group, significant decrease in HAMD score was observed which demonstated the beneficial effects of substitutive treatment.
3. Scale evaluation and clinical data analysis were conducted in patients with Graves' diseae in an attempt to explore the risk factors of depression and anxiety in hyperthyroidism, usefulness of SF-36was evaluated in GD patients. Results showed that depression and anxiety were more prevalent in patients with Graves'disease, FT3, FT4, TRAb and eye symptoms were risk factors for depression, FT3, heart rate and thyroid swelling were risk factors for anxiety, SF-36was a suitable tool in the evaluation of life quality in GD patients.
4. Regional brain blood flow changes in patients with depression and hypothyroidsm were compared using SPECT, cognitive function was evaluated with Go/No go test. Relative rCBF decreased significantly in bilateral caudate and right cingulate for depressive patients and in bilateral prefrontal cortex, anterior central gyrus, posterior central gyrus, hippocampus, superior parietal lobule and cingulate for hypothyroid patients. Both depressive and hypothyroid patients had significant higher HAMD scores than contol patients, HAMD score in the depressive group correlated negatively with rCBF in bileteral cingulate and caudate, while HAMD score in the hypothyroid group correlated negatively with rCBF in bilateral cingulate; cognitive defects were observed in both depressive and hypothyroid groups, Go/No go score correlated positively with relative rCBF in prefrontal cortex in the depressive group, while correlated positively with prefrontal cortex and hippocampus in the hypothyroid group.
In conclusion, hypothyroidism can lead to decrease in regional brain glucose metabolism in rats, abnormal brain metabolism relates closely to depressive symptoms, thyroid hormone deficiency can influnce the function of emotional circuit which subsequently causes depressive disorder; both depression and hypothyroidism can lead to abnormality in regional brain blood flow, and some of the abnormal regions overlap in the two diseases which means similar neural mechanism underlies the mood and cognitive disorders in depressive and hypothyroid patients; subclinical hypothyroidism increases the incidence of depression, L-thyroxine substitution can improve the depressive symptoms in patients with subclinical hypothyroidism; FT3, FT4, TRAb and eye symptoms are risk factors of depression in Graves' disease, FT3, heart rate and thyroid swelling are risk factors of anxiety in Graves'disease, SF-36can reflect the life quality of patients with Graves" disease.
引文
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