Thyroid, brain and mood modulation in affective disorder: insights from molecular research and functional brain imaging.
ABSTRACT The efficacy resulting from adjunctive use of supraphysiological doses of levothyroxine has emerged as a promising approach to therapy and prophylaxis for refractory mood disorders. Most patients with mood disorders who receive treatment with supraphysiological doses of levothyroxine have normal peripheral thyroid hormone levels, and also respond differently to the hormone and tolerate it better than healthy individuals and patients with primary thyroid diseases. Progress in molecular and functional brain imaging techniques has provided a new understanding of these phenomena, illuminating the relationship between thyroid function, mood modulation and behavior. Thyroid hormones are widely distributed in the brain and have a multitude of effects on the central nervous system. Notably many of the limbic system structures where thyroid hormone receptors are prevalent have been implicated in the pathogenesis of mood disorders. The influence of the thyroid system on neurotransmitters (particularly serotonin and norepinephrine), which putatively play a major role in the regulation of mood and behavior, may contribute to the mechanisms of mood modulation. Recent functional brain imaging studies using positron emission tomography (PET) with [ (18)F]-fluorodeoxyglucose demonstrated that thyroid hormone treatment with levothyroxine affects regional brain metabolism in patients with hypothyroidism and bipolar disorder. Theses studies confirm that thyroid hormones are active in modulating metabolic function in the mature adult brain, and provide intriging neuroanatomic clues that may guide future research.
SourceAvailable from: Agata Orzechowska[Show abstract] [Hide abstract]
ABSTRACT: The clinical implications of thyroid hormones in depression have been studied extensively and still remains disputable. Supplementation of thyroid hormones is considered to augment and accelerate antidepressant treatment. Studies on the role of thyroid hormones in depression deliver contradictory results. Here we assess theirs impact on depression severity and final clinical outcome in patients with major depression. Thyrotropin, free thyroxine (FT4), and free triiodothyronine (FT3) concentrations were measured with automated quantitative enzyme immunoassay. Depression severity and final clinical outcome were rated with 17-itemic Hamilton Rating Scale for Depression [HDRS(17)] and Clinical Global Impression Scales for severity and for improvement (CGIs, CGIi). FT3 and FT4 concentrations were significantly positively correlated with clinical improvement evaluated with CGIi (R = 0.38, P = 0.012; R = 0.33, P = 0.034, respectively). There was a significant correlation between FT4 concentrations and depression severity assessed in HDRS(17) (R = 0.31, P = 0.047). Male patients presented significantly higher FT3 serum levels (Z = 2.34, P = 0.018) and significantly greater clinical improvement (Z = 2.36, P = 0.018) when compared to female patients. We conclude that free thyroid hormones concentrations are associated with depression severity and have an impact on final clinical outcome. It can be more efficient to augment and accelerate the treatment of major depressive disorder with triiodothyronine instead of levothyroxine because of individual differences in thyroid hormones metabolism.Molecular Biology Reports 01/2014; 41(4). DOI:10.1007/s11033-014-3097-6 · 1.96 Impact Factor
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ABSTRACT: Hypothyroidism leads to somatic, neuropsychological, and psychiatric changes that are similar to depression. The mechanisms underlying the behavioral abnormalities in adult onset hypothyroidism remain ambiguous. Hypothyroidism was induced in adult male Wistar rats by the maintenance of 0.05% propylthiouracil (PTU) in drinking water for five weeks (hypothyroid group; HP group); control rats (CON group) received an equivalent amount of water. The open field and sucrose preference tests were employed, and the link between behavioral changes and brain glucose metabolism was evaluated using micro positron emission tomography imaging. The open field test revealed slightly decreased locomotor activity and significantly reduced rearing and defecation in the hypothyroid group. Hypothyroid rats were also characterized by decreased body weight, sucrose preference, and relative sucrose intake compared to control rats. Hypothyroidism induced reduced brain glucose metabolism in the bilateral motor cortex, the caudate putamen, the cortex cingulate, the nucleus accumbens, and the frontal association cortex. A decreased sucrose preference was positively correlated with metabolic glucose changes in the caudate putamen and the nucleus accumbens. The results indicate that the activity pattern in adult onset hypothyroidism is different from the activity pattern when hypothyroidism is induced in the developmental period of the central nervous system. Decreased sucrose preference in hypothyroid rats may be attributed to anhedonia. Furthermore, these findings suggest there may be a common mechanism underlying adult onset hypothyroidism and depression.Behavioural Brain Research 06/2014; 271. DOI:10.1016/j.bbr.2014.06.019 · 3.39 Impact Factor
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ABSTRACT: Background & objectives: Abnormalities in thyroid hormonal status is common in major psychiatric disorders. Although the relevance of thyroid dysfunction to bipolar disorder is well-recognized, yet the association between thyroid dysfunction and schizophrenia-spectrum disorders is under-emphasized. The aim of this study was to examine and compare the rates of abnormal thyroid hormonal status in patients with schizophrenia-spectrum disorders and mood disorders in an inpatient tertiary care general hospital psychiatry unit. Methods: This was a retrospective hospital-based study on 468 inpatient samples. Data on serum thyroid stimulating hormone (TSH), T3 (triiodothyroxine), T4 (L-thyroxine), free unbound fractions of T3 and T4 (FT3 and FT4) were obtained from records of 343 patients, 18 patients were anti-TPO (anti thyroid peroxidase antibody) positive. The rates of abnormal thyroid hormonal status were compared using the chi square test. Results: Abnormal thyroid hormonal status in general, and presence of hypothyroidism and hyperthyroidism, in particular were seen in 29.3, 25.17 and 4.08 per cent patients with schizophrenia spectrum disorders, respectively. These were comparable to the rates in patients with mood disorders (23.24, 21.62 and 1.62%, respectively). Eleven of the 18 patients with antiTPO positivity had a schizophrenia-spectrum disorder. There were no gender differences. Interpretation & conclusions: Thyroid dysfunction was present in patients with schizophrenia-spectrum disorder as well as mood disorders. Autoimmune thyroid disease was more commonly seen in patients with schizophrenia-spectrum disorders compared to mood disorders. The findings reiterate the relevance of screening patients with schizophrenia-spectrum disorders for abnormal thyroid hormonal status.The Indian Journal of Medical Research 12/2013; 138(6):888-93. · 1.66 Impact Factor