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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: 2.17). 12/2003; 36 Suppl 3(Suppl 3):S215-21. DOI: 10.1055/s-2003-45133
Source: PubMed

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.

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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). "
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    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.
    Archives italiennes de biologie 03/2013; 151(1):1474. · 1.42 Impact Factor
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    • "Despite the evidence that THs affect brain function in adults, the underlying molecular mechanisms remain poorly understood [14]. It is known that THs action is mediated by nuclear receptors that are widely distributed throughout the brain and influences several neurotransmitters (serotonin, norepinephrine, GABA and glutamate) [15]. Furthermore, studies in rodents showed that hypothyroidism disrupts inhibitory and excitatory neurotransmission , synaptic plasticity and learning and memory [16] [17] [14].However, these results need to be confirmed in hypothyroid patients. "
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    ABSTRACT: Despite clinical evidences that hypothyroidism is often associated with cognitive dysfunction, affective disorders and psychosis, the effects of thyroid hormone deficiency on the adult brain have been largely unexplored. We investigated the hypothesis that hypothyroidism might affect cortical excitability and modulates inhibitory and excitatory cortical circuits by using Transcranial Magnetic Stimulation. Cortical excitability was probed in 10 patients with overt hypothyroidism and 10 age-matched healthy controls. We tested motor thresholds and corticospinal excitability, cortical silent period and peripheral silent period, short interval intracortical inhibition, intracortical facilitation. Patients were evaluated at the time of diagnosis, as well as after 3 and 6 months replacement therapy with l-thyroxin. At baseline, patients showed decreased cortical excitability, with increased resting and active motor threshold and decreased steepness of the motor evoked potential recruitment curves. These changes were paralleled by longer cortical silent period and decreased short interval intracortical inhibition. After 3 months replacement therapy, all the parameters but short interval intracortical inhibition were restored to normal values. Short interval intracortical inhibition returned to normal values only after 6 months of replacement therapy. Thyroid hormones are needed to modulate cortical excitability and cortical inhibitory circuits in adults.
    Journal of the Neurological Sciences 04/2008; 266(1-2):38-43. DOI:10.1016/j.jns.2007.08.031 · 2.26 Impact Factor
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