Is Autoimmune Thyroiditis Part of the Genetic Vulnerability (or an Endophenotype) for Bipolar Disorder?

University of Groningen, Groningen, Groningen, Netherlands
Biological Psychiatry (Impact Factor: 10.26). 08/2007; 62(2):135-40. DOI: 10.1016/j.biopsych.2006.08.041
Source: PubMed


Both genetic and environmental factors are involved in the etiology of bipolar disorder; however, biological markers for the transmission of the bipolar genotype ("endophenotypes") have not been found. Autoimmune thyroiditis with raised levels of thyroperoxidase antibodies (TPO-Abs) is related to bipolar disorder and may be such an endophenotype. This study was intended to examine whether autoimmune thyroiditis is related to the disease itself, to the (genetic) vulnerability to develop bipolar disorder, or both.
Blood was collected from 22 monozygotic (MZ) and 29 dizygotic (DZ) bipolar twins and 35 healthy matched control twins to determine TPO-Abs.
The TPO-Abs were positive in 27% of the bipolar index twins, 29% of the monozygotic bipolar cotwins, 27% of the monozygotic nonbipolar cotwins, 25% of the dizygotic bipolar cotwins, 17% of the dizygotic nonbipolar cotwins, and in 16% of the control twins. Repeated measures analysis of covariance on log-transformed absolute TPO-Abs values revealed significantly increased mean TPO-Abs levels in discordant twin pairs as compared with healthy twin pairs, whereas no difference was found between bipolar patients and their (discordant) nonbipolar cotwins.
This study shows that autoimmune thyroiditis is related not only to bipolar disorder itself but also to the genetic vulnerability to develop the disorder. Autoimmune thyroiditis, with TPO-Abs as marker, is a possible endophenotype for bipolar disorder.

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    • "This theory is supported by findings of higher frequencies of comorbid autoimmune diseases, aberrant cytokine concentrations (e.g. tumor necrosis factor alpha, interleukin 4) and elevated inflammation-related gene expression in circulating monocytes and T cell activation (Drexhage et al., 2011; Munkholm et al., 2013; Padmos et al., 2008; Vonk et al., 2007). The corticolimbic theory is based on many studies demonstrating an overall hyperactivation of "
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    ABSTRACT: Background: The hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipolar I disorder (BD-I) patients versus healthy controls (HC) with magnetic resonance imaging (MRI) and spectroscopy (MRS). We post-hoc investigated whether hippocampal volume and hippocampal metabolites were associated with microglial activation and explored if potential illness modifying factors affected these hippocampal measurements and whether these were associated with experienced mood and functioning. Material and methods: Twenty-two BD-I patients and twenty-four HCs were included in the analyses. All subjects underwent psychiatric interviews as well as an MRI scan, including a T1 scan and PRESS magnetic resonance spectroscopy (MRS). Volumetric analysis was performed with Freesurfer. MRS quantification was performed with LCModel. A subgroup of 14 patients and 11 HCs also uderwent a succesfull [(11)C]-(R)- PK11195 neuroinflammation positron emission tomography scan. Results: In contrast to our hypothesis, hippocampal volumes were not decreased in patients compared to HC after correcting for individual whole-brain volume variations. We demonstrated decreased N-acetylaspartate (NAA) + N-acetyl-aspartyl-glutamate (NAAG) and Creatine (Cr) + Phosphocreatine (PCr) concentrations in the left hippocampus. In the explorative analyses in the left hippocampus we identified positive associations between microglial activation and the NAA+NAAG concentration, between alcohol use and NAA+NAAG concentration, between microglial activation and the depression score and a negative relation between Cr+PCr concentration and experienced occupational disability. Duration of illness associated positively with volume bilaterally. Conclusion: Compared to HCs, the decreased NAA+NAAG concentration in the left hippocampus of BD-I patients suggests a decreased neuronal integrity in this region. In addition we found a positive relation between microglial activation and neuronal integrity in vivo, corresponding to a differentiated microglial function where some microglia induce apoptosis while others stimulate neurogenesis.
    Brain Behavior and Immunity 09/2015; DOI:10.1016/j.bbi.2015.09.004 · 5.89 Impact Factor
    • "This finding was confirmed in a Dutch study (Oomen et al., 1996) particularly in patients with rapid cycling of bipolar disorders. Moreover a twin study indicated that AIT is associated with a genetic vulnerability to develop a bipolar disorder, i.e. it could be an endophenotype of the bipolar disorder (Vonk et al., 2007). Also it was shown that female offspring of bipolar parents have an increased risk to develop AIT (Hillegers et al., 2007). "
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    ABSTRACT: Hashimoto’s thyroiditis (HT) is the most frequent cause of hypothyroidism in areas with sufficient iodine intake. While the impact of thyroid function on mood and cognition is well known, only in the recent years, an increasing number of studies report on the association of HT with cognitive and affective disturbances also in the euthyroid state. Recent imaging studies have shown that these impairments are accompanied by altered brain perfusion, in particular, in the frontal lobe and a reduced grey matter density in the left inferior gyrus frontalis. Brain function abnormalities in euthyroid patients with HT may be subtle and only detected by specific testing or even severe as it is the case in the rare neuropsychiatric disorder Hashimoto’s encephalopathy (HE). The good response to glucocorticoids in patients with HE indicates an autoimmune origin. In line with this, the cognitive deficits and the high psycho-social burden in euthyroid HT patients without apparent signs of encephalopathy appear to be associated with anti-thyroid peroxidase auto-antibody (TPO Abs) levels. Though in-vitro studies showing binding of TPO Abs to human cerebellar astrocytes point to a potential direct role of TPO Abs in the pathogenesis of brain abnormalities in HT patients, TPO Abs may function only as a marker of an autoimmune disorder of the central nervous system. In line with this, anti-central nervous system auto-antibodies (CNS Abs) which are markedly increased in patients with HT disturb myelinogenesis in-vitro and, therefore, may impair myelin sheath integrity. In addition, in HT patients, production of monocyte- and T-lymphocyte-derived cytokines is also markedly increased which may negatively affect multiple neurotransmitters and, consequently, diverse brain neurocircuits.
    Brain Behavior and Immunity 10/2014; 41(14). DOI:10.1016/j.bbi.2014.03.008 · 5.89 Impact Factor
    • "There is a significant correlation between family history of mood disorder in first degree relatives and patients having hypothyroidism. This may suggest a possible genetic connection, perhaps an inherited vulnerability as indicated by a genetic study in the Chinese population.[17] In another study of the female offspring of bipolar parents, children of parents with bipolar disorder were found to be more vulnerable to develop thyroid autoimmunity, independently of their vulnerability to develop psychiatric disorders.[18] "
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    ABSTRACT: Hypothalamic-pituitary-thyroid axis dysfunction in the pathophysiology of bipolar disorder has received less attention as compared with that in depressive disorder.
    Indian Journal of Psychological Medicine 04/2014; 36(2):125-8. DOI:10.4103/0253-7176.130966
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