Thyroid, Brain and Mood Modulation in Affective Disorder: Insights from Molecular Research and Functional Brain Imaging
Department of Psychiatry and Psychotherapy, Charité - University Medicine Berlin, Campus Charité-Mitte (CCM), Berlin, Germany.Pharmacopsychiatry (Impact Factor: 1.85). 12/2003; 36 Suppl 3(Suppl 3):S215-21. DOI: 10.1055/s-2003-45133
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.
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- "The effect of thyroid hormones in the brain and specifically in the monoaminergic, serotoninergic or neuromodulator systems has been found to be relevant (Bauer et al., 2003, 2008; Chakrabarti, 2011). Thyroid hormones play a critical role in the metabolic activity of the adult brain, and thyroid disease could be related to certain neuropsychiatric manifestations (Bauer et al., 2008). "
ABSTRACT: Background: Among the biological factors associated with the development and outcomes in Bipolar Disorder Type I (BD-I), previous studies have highlighted the involvement of both thyroid function and/or auto-immunity, proposing a thyroid endophenotype. The objective of this study was to determine the presence of thyroid alterations in BD-I and their first-degree relatives (FDR). Methodology: Unselected, cross-sectional case-control study with parallel analysis of individuals affected by BD-I (239), their FD-R (131), and 108 healthy controls. Thyroidal functional abnormalities (TSH and free T4) and thyroidal antibodies (thyroglobulin and thyroperoxidase antibodies) were studied. Assessments were carried out in parallel. The sample was described using arithmetic means, standard deviations, percentages and ranges. Chi-square, Student-t tests, ANOVA and Pearson correlation coefficients were used when indicated. Results: BD-I on actual and/or ever treated with lithium showed significant thyroidal functional abnormalities as compared to their FD-R and healthy controls. This BD-I subgroup showed a significant greater proportion of subjects suffering from subclinical hypothyroidism (22%). The role of gender/lithium interactions was relevant. The groups did not show differences in terms of positivization of thyroidal antibodies. Limitations: The crosssectional design and the lack of determination of dietary iodine deficiencies and/or thyroidal ecographical controls may be a drawback. Conclusions: The present study supports previous findings on the effect of lithium treatment on thyroidal functional, but did not support previous findings related to a familial association or endophenotype. In addition, the present study did not support a familial aggregation of thyroidal antibodies positivization in pedegrees of BD-I.
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- "The association between thyroid dysfunction and mood disorders is well recognized. The prevalence of mood and anxiety disorders is higher in patients with thyroid dysfunction1, thyroid status predicts treatment response in major depression and bipolar disorder2, augmentation with thyroid hormone has therapeutic efficacy in treatment-resistant depression3, and additionally, thyroid hormone receptors are localized to limbic structures implicated in regulation of mood4. The nature of the association between thyroid dysfunction and schizophrenia-spectrum disorders has, however, not been well studied. "
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.
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- "In particular, adult patients affected with overt hypothyroidism, typically show deficits in various cognitive abilities (i.e. attention , memory, executive functions etc.), altered mood (depression or anxiety) (Dugbartey, 1998; Bauer and Whybrow, 2001; Bernal, 2002; Simon et al., 2002; Bauer et al., 2003; Davis and Tremont, 2007) and also Alzheimer's disease-like manifestations (memory loss, confusion, slowness, paranoid depression, hallucinations ) (Whybrow et al., 1969). Besides, some studies (Osterweil et al., 1992; Haggerty et al., 1993; Monzani et al., 1993; Baldini et al., 1997; Kalmijn et al., 2000; Zhu et al., 2006; Samuels, 2008) have suggested that subtle deficits in specific cognitive domains as well as affective disorders may exist also in the condition of subclinical hypothyroidism (SH), a peculiar preclinical condition , frequent especially in women, with a prevalence between 2% and 20% in the adult population (Wilson and Curry Jr. 2005; for a review see Biondi and Cooper, 2008). "
ABSTRACT: There is evidence of an association between thyroid hormones (TH) alterations and mental dysfunctions related to procedural and working memory functions, but the physiological link between these domains is still under debate, also for the presence of age as a confounding factor. Thus, we investigated the TH tuning of cerebral functions in young females affected by the borderline condition of subclinical hypothyroidism (SH) and in euthyroid females of the same age. The experiment consisted in the characterization of the affective state and cognitive abilities of the subjects by means of specific neuropsychological questionnaires, and of brain activity (EEG) in resting state and during the passive viewing of emotional video-clips. We found that SH had i) increased anxiety for Physical Danger; ii) better scores for both Mental Control and no-working-memory-related functions; iii) association between anxiety for Physical Danger and fT4 levels. Thus, in young adults, SH increases inward attention and paradoxically improves some cognitive functions. In addition, self-assessed questionnaires showed that SH had a greater susceptibility to unpleasant emotional stimulation. As for EEG data, SH compared to controls showed: i) reduction of alpha activity and of gamma left lateralization in resting state; ii) increased, and lateralized to the right, beta2 activity during stimulations. Both results indicated that SH have higher levels of arousal and greater susceptibility to negative emotion than controls. In conclusion, our study indicates that minimal changes in TH levels produce subtle but well-defined mental changes, thus encouraging further studies for the prediction of pathology evolution.
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