2025 Volume 72 Issue 11 Pages 1175-1187
Adult-onset hypothyroidism has long been recognized as a reversible cause of cognitive impairment. However, recent studies have shown that it is associated with structural brain alterations besides functional alterations, particularly in the hippocampus and prefrontal cortex. Neurophysiological and molecular studies have demonstrated that hypothyroidism impairs synaptic plasticity, disrupts neurotransmitter signaling, and promotes neuroinflammation, leading to learning and memory impairments. The condition also affects adult neurogenesis, particularly in the hippocampal dentate gyrus. Moreover, hypothyroidism has been linked to psychiatric disorders, including depression and anxiety, through its influence on the plasticity of the amygdala. In addition, adult-onset hypothyroidism contributes to cerebellar ataxia and peripheral neuropathy, impacting motor coordination and sensory processing. Since we come to know that adult-onset hypothyroidism in part causes irreversible changes in brain structure, prompt treatment is crucial. Furthermore, in addition to thyroid field, recent studies suggest a potential of thyroid hormone treatment beyond the thyroid disorders, such as neurodegenerative and cognitive/psychiatric disorders. This review highlights the critical role of THs in maintaining neural function and explores their therapeutic potential in addressing neurological and psychiatric conditions.
Adult-onset hypothyroidism is a common endocrine disorder characterized by a deficiency in thyroid hormones (THs: thyroxine, T4 and triiodothyronine, T3) [1]. Since they are important regulators of metabolism and have widespread effects on the body [2, 3], it causes various systemic symptoms including fatigue, constipation, intolerance to cold, weight gain, hair loss, dry skin, and hoarseness. In addition, various neurological symptoms may occur, affecting both the central and peripheral nervous systems. These neurological symptoms are often part of other clinical signs of hypothyroidism but can also appear independently as the primary symptom. Many of these symptoms can improve, either partially or completely, with TH treatment [4].
To understand the neurological symptoms of hypothyroidism, it is essential to recognize that TH undergoes specific transport and metabolic pathways, particularly in the central nervous system (CNS), before exerting its effects on target organs and cells. Generally, TH is produced in the thyroid gland, transported via TH transporters, metabolized by deiodinases, and ultimately binds to nuclear TH receptors (TRs) to exert its effects. Primarily, it regulates gene transcription and induces various physiological functions [5]. Outside the brain, TH regulates metabolic processes such as protein synthesis, lipid metabolism, and heat production, and it is also essential for maintaining cardiovascular health and normal growth [6-8].
In the brain, TH plays a crucial role in development and function, influencing neuronal differentiation, synaptic plasticity, and overall cognitive function [9]. To enter the CNS, TH must cross the blood-brain barrier (BBB) via specific transporters, such as monocarboxylate transporter (MCT) 8 and organic anion transporter (OATP) 1C1. The BBB are twined around by astrocytes which also express TH transporters at endfeet in close contact with the endothelial cells. THs first enter astrocytes through those transporters and T4 is converted into T3 by type 2 deiodinase (DIO2). Subsequently, T3 is transported into its primary target cells, including neurons and maturing oligodendrocytes [10], however, the transporter that mediates T3 efflux from the astrocytes has not been identified. T3 is then taken up into axons via clathrin-dependent endosomes/non-degradative lysosomes (NDLs) and transported retrogradely along microtubules to be delivered to the nucleus [11]. Finally, T3 is inactivated by type 3 deiodinase (DIO3), which is highly expressed in neurons.
In a hypothyroid rat brain, the expression level of Dio3 was decreased, causing an increase in T3 levels in synaptosomes [12, 13]. This suggests that the maintenance of TH homeostasis in the brain is regulated independently of circulating TH levels. Within the CNS, TH influences various processes, including neuronal migration, growth, differentiation, and signal transduction [14].
The effects of TH on the nervous system differ between the developmental and adult stages. In particular, TH deficiency during the fetal and neonatal periods is a hallmark of congenital hypothyroidism (previously known as cretinism), which leads to irreversible consequences if left untreated in the early stages. Newborn mass screening programs have been implemented in many countries, allowing the early identification of most infants with congenital hypothyroidism [15]. During this critical period, TH plays a key role in regulating gene expressions essential for neurogenesis, neuronal growth, and neural circuit formation. Its deficiency can cause irreversible neurodevelopmental disorders, often resulting in severe intellectual disability and motor impairments [16]. On the other hand, TH deficiency after adolescence has been associated with cognitive dysfunction and memory impairment resembling dementia, as well as reduced mental activity similar to depression. These findings indicate that TH continues to play an essential role in maintaining neurological function in the mature CNS. Nevertheless, the knowledge about adult-onset hypothyroidism is very limited compared to developmental hypothyroidism.
The present review focuses on four major neurological symptoms following adult-onset hypothyroidism—cognitive impairment, psychiatric disorders, cerebellar ataxia, and neuropathy (excluding myxedema coma, Hashimoto’s encephalopathy, and myopathy, as shown in Fig. 1). We summarize the mechanisms that have been elucidated using animal models. Finally, based on these research findings, we discuss the potential therapeutic applications of TH and its analogs in neurological disorders that are not primarily thyroid-related.
The table summarizes the neurological symptoms often seen in adult hypothyroid patients, the characteristics, and the supporting epidemiological data with the references.
Since the 1970s, adult-onset hypothyroidism has been recognized as one of the medical conditions that can cause reversible cognitive impairment [17]. Today, it is listed in dementia guidelines worldwide as a condition that should be distinguished as a treatable cause of dementia [18-21]. Meanwhile, a recent systematic review found no causal relationship between subclinical hypothyroidism (SCH) and cognitive impairment [22]. Also, there have been an individual participant data analysis and a systematic review using a meta-analysis reporting no association between overt hypothyroidism and cognitive deficits [23, 24]. Meanwhile, there are some cases of overt hypothyroidism to be associated with cognitive dysfunction, and its impact increases with age, which highlights the necessity of regular thyroid function screening as yet, particularly in older individuals [22, 25]. Further epidemiological data are expected for understanding the correlation between hypothyroidism and cognitive impairment.
Although it has yet to come to the consensus in the recent epidemiological data, a number of reports from both basic and clinical research have revealed the effects of hypothyroidism on brain function. Patients with hypothyroidism exhibit various structural and functional changes in the brain. In particular, a reduction in hippocampal volume has been observed [26]. Additionally, functional Magnetic Resonance Imaging (fMRI) studies have demonstrated decreased activity in the medial prefrontal cortex, posterior cingulate cortex, and left inferior parietal lobule during memory processing [27]. Furthermore, positron emission tomography (PET) using 18F-fluorodeoxyglucose has revealed decreased glucose metabolism in the bilateral amygdala, hippocampus, perigenual anterior cingulate cortex (ACC), left subgenual ACC, and right posterior cingulate cortex [28]. These findings suggest that hypothyroidism affects cognitive function and mental state, emphasizing the importance of proper diagnosis and treatment.
In animal model study, adult-onset hypothyroid rats [29-34] and mice [35-39] have been extensively studied because they exhibit cognitive dysfunction similar to humans. Many studies have focused on the hippocampus, a key brain region involved in memory storage and retrieval [40]. Morphological changes observed in hypothyroid rats include a reduction in the granular layer volume accompanied by a decrease in the number of granule cells [41]. In the CA1 region of the hippocampus, a decrease in the number of pyramidal cells has been reported [42]. Additionally, hypothyroidism induced neuronal apoptosis in the CA3 region, whereas TH administration has been found to exert neuroprotective effects [43]. This is consistent with findings that hypothyroidism increases DNA damage in the CNS [44]. Moreover, hippocampal neuronal damage has been suggested to be caused by glutamate excitotoxicity [45]. Hypothyroidism also induced microglial dysfunction, promoting neuroinflammation and abnormalities in glia-neuron communication [46-48]. Furthermore, such pathological condition may be associated with hippocampal apoptosis through autophagy [49].
The neurophysiological basis of learning and memory involves synaptic plasticity in the hippocampus, particularly long-term potentiation (LTP) [50, 51]. LTP in hippocampal neurons of rats has been shown to be closely related to THs [52]. Hypothyroid rats exhibit impaired LTP associated with alterations in the expression of cAMP response element binding protein (CREB), extracellular signal-regulated kinase (ERK) 1/2, calcium/calmodulin-dependent protein kinase (CaMK) IV, and brain-derived neurotrophic factor (BDNF), which can be normalized by T4 supplementation [29-33, 53, 54]. Additionally, hypothyroidism leads to a decrease in phosphoinositide 3-kinase, (PI3K)/ Ak strain transforming (Akt) signaling, potentially contributing to impaired metaplastic regulation of LTP, which may underlie learning and cognitive deficits [55]. As the outcome of hippocampal plasticity hugely affects the neuronal projection to the other brain regions, it comes inevitable to discuss cognitive impairments at the circuit level. Hypothyroid mice displayed memory and learning deficits together with the reduced acetylcholinesterase activity in various brain regions including hippocampus [56-58]. The altered expression of synaptic proteins such as synaptotagmin 1, Munc-18, and the SNARE complex, along with reduced acetylcholine content and activity, were observed in both hippocampal neurons of hypothyroid rats [59-61] and the prefrontal cortex (PFC), where abnormalities in synaptic structures and myelin sheaths have been reported [62, 63]. In the dorsal hippocampus-medial prefrontal cortex (mPFC) pathway, both short- and long-term synaptic plasticity are impaired, but TH supplementation can restore these functions [64].
The effects of TH on synaptic function are not limited to classical genomic regulation but also involve non-genomic pathways that modulate the phosphorylation of synapse-related proteins [65]. TH also affects energy metabolism in the CNS. In hypothyroid rats, decreased mitochondrial metabolism has been observed in the hippocampus and the entire brain, suggesting an abnormality in energy metabolism [66, 67]. Additionally, increased hydrolysis of ATP, ADP, and AMP has been observed in the hippocampus and cortex, affecting adenine nucleotide-mediated responses [68]. These findings indicate that THs regulate synaptic plasticity and neural signaling in the hippocampus and other brain regions through both genomic and non-genomic mechanisms, thereby playing a crucial role in cognitive function and learning.
In the hippocampus of hypothyroid rats, abnormalities in the degradation pathway of amyloid precursor protein (APP) have been found, leading to increased amyloid production and accumulation of amyloid β peptides [69]. This suggests that hypothyroidism may increase the risk of amyloid deposition with aging [36]. In aged mice, hypothyroidism induces spatial memory impairment and reduces brain weight [36]. The timing of hypothyroidism onset affects different task-dependent memory functions [35], suggesting that aging has a synergistic effect on hypothyroidism. Recent studies have also reported influences outside the CNS. In aging Alzheimer’s disease model mice, hypothyroidism increases exosomal transport of ApoE4 from the liver to the brain, affecting cognitive function and inducing depressive- and anxiety-like behaviors [70]. These findings highlight the close relationship between TH action and dementia. Furthermore, in a drug-induced Alzheimer’s disease model, TH administration has been shown to exert neuroprotective effects [71], suggesting that THs could be a potential therapeutic strategy for dementia.
Neurogenesis in adulthood is related to memory, learning, and social behavior, and its regulation partly depends on TH [72, 73]. In the vertebrate brain, neural stem cells (NSCs) generate both neurons and glial cells. In the adult mammalian brain, NSCs are mainly found in the subventricular zone (SVZ) around the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). These NSCs generally remain in a quiescent state [74].
In the SVZ of mice, insufficient TH signaling, particularly through TRα, reduces NSC and progenitor cell proliferation and inhibits cell cycle progression [75]. In contrast, in the SGZ of rats, TH deficiency decreases progenitor cell survival but does not affect cell proliferation in the granule cell layer [76-78]. Specifically, the proliferation of type 1, type 2b, and type 3 cells is not affected by hypothyroidism, whereas early non-proliferating cells and immature granular neurons are significantly reduced. These changes are accompanied by decreased brain-derived neurotrophic factor (BDNF) expression in the DG of the rat hippocampus [78]. Similar findings have been observed in mice, where THs target type 2b and type 3 hippocampal progenitor cells, promoting neurogenesis. This suggests that TH-mediated transcriptional regulation controls the neuronal differentiation of adult hippocampal progenitor cells [79].
The effects of hypothyroidism on adult neural stem cells can be reversed by TH supplementation. However, this recovery is not observed with 3-iodothyronamine (T1AM), a derivative of THs [76, 80]. In mice with a specific deletion of MCT8 in adult neural stem cells, decreased expression of the cell cycle inhibitor P27KIP1, reduced differentiation of neuroblasts, and impaired generation of new granule cell neurons were observed. This indicates that TH signaling plays both a cell-autonomous role in adult hippocampal neurogenesis and a non-cell-autonomous role in the early stages of cell proliferation [81]. These findings suggest that neurogenesis in the adult brain is strictly regulated by THs. Further research is needed to explore their relationship with cognitive function and psychiatric disorders.
The association between hypothyroidism and psychiatric symptoms, such as depression, anxiety, and mood disorders, has been widely reported across different age groups [82-90]. Even asymptomatic patients with SCH were associated with depression [91-93], recommending thyroid function testing when psychiatric symptoms appear. However, since major depressive disorder (MDD) is often associated with autoimmune thyroiditis [94], it is important to consider that these symptoms may not be solely attributed to the direct effects of THs.
Studies using animal models have also investigated the relationship between hypothyroidism and depressive-like behaviors, but results have been inconsistent. Hypothyroid mice exhibit increased anxiety-like behavior, reduced locomotor activity, and memory and learning deficits, similar to humans [56]. In rats, depressive-like behavior has been observed and is reversible with TH replacement therapy [95, 96]. In the brain, increased serotonin and 5-HIAA levels suggest a potential role in the pathophysiology of depression [97]. However, other studies have reported that hypothyroidism not only induces depressive tendencies but also reduces anxiety-like behavior while causing decreased serotonin (5-HT) levels and increased BDNF levels in the hippocampus [34, 98, 99]. These discrepancies are likely due to differences in animal species and experimental conditions.
The amygdala plays a key role in emotional regulation, potentially leading to changes in anxiety and stress responses. In hypothyroid rats, corticosterone signaling in the amygdala is enhanced, increasing vulnerability to fear and emotional memory [100]. In mice, local THs in the amygdala act as crucial regulators of plasticity related to fear memory [101]. These findings suggest that hypothyroidism influences the function of the amygdala. Moreover, THs may regulate striatal function in a multifaceted manner, which could have beneficial effects on bipolar disorder. The previous study has reported that TH deficiency affects the expression of genes involved in signal transduction and circadian rhythm regulation in the striatum [102].
Recent studies using rats have provided further insights. Hypothyroidism has been shown to exert different effects between hypothyroid Wistar rats and Wistar-Kyoto (WKY) rats, which are used as depression models. In hypothyroid rats, LTP in the DG is reduced, while basal excitatory transmission is increased. In WKY rats, LTP reduction is observed in both the DG and CA1 regions of the hippocampus. Regarding short-term plasticity, both hypothyroid and WKY rats show decreased paired-pulse ratio (PPR) in the CA1 region [103]. In depression models associated with hypothyroidism, combined therapy with serotonin-norepinephrine reuptake inhibitors (SNRIs) and L-T4 was more effective in improving metabolic parameters, synaptic plasticity, and markers related to cellular damage than monotherapy [104]. These findings suggest that hypothyroidism influences psychiatric symptoms and neurophysiological changes. However, further research is needed to clarify the underlying mechanisms and individual differences.
Additionally, chronic social stress model rats exhibit transient hypothyroidism [105], indicating that stress itself may impact the hypothalamic-pituitary-thyroid (HPT) axis. Therefore, the effects of stress on thyroid function should also be considered.
The cerebellum has long been known as a brain region responsible for coordinating movement and motor learning. As numerous studies have shown that THs are crucial for cerebellar development [106], children with untreated congenital hypothyroidism often exhibit cognitive and motor dysfunction as they grow [15]. On the other hand, in cases of adult-onset hypothyroidism, some patients have developed symptoms related to motor behavior such as gait ataxia and impaired motor coordination [107, 108]. Some cases include limb ataxia which is represented by clumsiness, intention tremor, and dysmetria, and dysarthria [109-111]. Treatment of the hypothyroid condition resulted in the improvement or complete resolution of these cerebellar symptoms [109, 111-114]. However, the effects on the cerebellum and potential mechanisms in adult-onset hypothyroidism are less understood compared to congenital hypothyroidism. This chapter will present findings on the effects of adult-onset hypothyroidism on the cerebellum, based on limited literature of both human and mouse models.
The synaptic plasticity in cerebellar transmission between parallel fibers, which are axonal extensions from granule cells, and Purkinje cells plays a crucial role in controlling motor behavior [115]. Specifically, long-term depression (LTD) at parallel fiber–Purkinje cell synapses plays a key role in motor coordination and learning [116-118]. We have previously examined the LTD expression in two different adult-onset hypothyroid mouse models. The first one underwent hypothyroidism only in Purkinje cells following the adeno-associated virus (AAV) delivery of a dominant-negative TR gene constructed with a Purkinje cell-specific promotor gene [119]. This model displayed any anomalies neither in the LTD expression nor motor behavior assessed by ladder walking test [119, 120]. The second model, a conventional propylthiouracil (PTU) – induced hypothyroid model, expressed impaired motor coordination on the ladder together with LTP rather than LTD (Fig. 2). The subtraction indicates that the cerebellar circuits consisting of various neurons including Purkinje cells may be targeted in an adult-onset hypothyroidism. However, no further investigations on motor deficits in adult-onset hypothyroid mice have been conducted so far, leaving the underlying mechanisms unclear. Further research is needed to distinguish these effects from those caused by developmental hypothyroidism.
Adult-onset hypothyroid mice displayed the impaired motor coordination in the ladder walking task [120]. In their cerebellum, the long-term depression (LTD) was inhibited and long-term potentiation (LTP) was instead induced [119].
About 50% of adult-onset hypothyroidism patients experience sensory abnormalities, including pain [121, 122]. These patients show reduced amplitude and/or conduction velocity in peripheral nerve conduction tests [121, 123, 124], suggesting axonal and myelin damage. Peripheral neuropathy caused by hypothyroidism is generally reversible with TH replacement therapy, and symptoms often improve [125]. Additionally, recent reports indicate that the primary cause of sensory abnormalities is often mononeuropathy, such as carpal tunnel syndrome [123, 126]. With advancements in diagnostic techniques, cases of untreated thyroid dysfunction over extended periods have decreased, making it less common for polyneuropathy to progress to a severity that causes sensory abnormalities.
There have been limited number of animal model studies investigating the pathophysiology of peripheral neuropathy induced by hypothyroidism. In thyroidectomized rats, abnormalities were observed in Brainstem Auditory Evoked Potentials (BAEP), a test for both peripheral and central nervous function. However, these abnormalities were normalized following T4 treatment [127]. Additionally, a study reported that hypothyroid mice exhibited increased thermal sensitivity in the periphery due to an imbalance between excitatory and inhibitory neuronal activities in the anterior cingulate cortex (ACC) [128]. We have also contributed to elucidating part of the underlying mechanism (Fig. 3). A mouse model of adult-onset hypothyroidism exhibited mechanical hypersensitivity, which was improved upon normalization of thyroid function. While no pathological changes were observed in the sciatic nerve, electrophysiological analysis revealed a tendency for shortened latency under continuous stimulation of Aδ fibers compared to healthy controls, suggesting relative hyperexcitability. Furthermore, a reduction in voltage-gated potassium channel subfamily A (Kv1.1) in the sciatic nerve was identified as one of the causes of peripheral nerve hyperexcitability. It may owe the reversibility of symptoms to the absence of structural abnormalities which led to the normalization of TH levels [129]. Recently, a study using systemic knockout mice for TH transporters reported no electrophysiological or morphological abnormalities in the sciatic nerve, despite the presence of these transporters in the nerve [130]. THs play a crucial role in oligodendrocyte maturation and myelination during neural development [131]. In adult hypothyroid rats, abnormalities in myelin formation and compaction were observed in the CNS, leading to disorganized wrapping of oligodendrocytes around axons [132, 133]. However, their effects on the peripheral nervous system remain unclear, highlighting the need for further research in this area.
Adult-onset hypothyroid mice displayed hypersensitivity to noxious stimuli, which could be a part of neuropathy. Their peripheral nerves were hyperexcited following the reduction of voltage-gated potassium channels (Kv1.1) and latency to firing [129].
For a long time, THs and their related compounds have been used exclusively for treating conditions associated with TH deficiency or impaired action, such as hypothyroidism and TH cell membrane transport defect. However, in recent years, attention has shifted toward the physiological effects of THs themselves, leading to their exploration as treatments for non-thyroid-related diseases. For example, Resmetirom, a liver- and TRβ-selective thyromimetic, was recently approved by the U.S. Food and Drug Administration (FDA) as the first treatment for metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH) [134]. It has been well established that reduced TH levels in the liver contribute to lipotoxicity, inflammation, and fibrosis, thereby increasing the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) [3, 135]. Clinical trials have demonstrated that TH administration improves liver metabolic disorders, highlighting the therapeutic potential of Resmetirom and other thyromimetics in this field. Several clinical trials evaluating liver-specific thyromimetics are currently underway [135]. The application of THs and thyromimetics for diseases beyond thyroid disorders is also expanding into the field of CNS diseases. Recent findings suggest that behavioral and systemic metabolic changes induced by TH fluctuations result from synaptic plasticity driven by direct modulation of cell-specific transcription programs in the brain [133]. This evidence strongly supports the view that thyromimetics may serve as promising therapeutic agents for targeting the nervous system.
As mentioned in the previous section, hypothyroidism is known to cause depressive symptoms, which can be alleviated with TH replacement therapy [90]. Additionally, studies have reported that the administration of T3 or L-T4 as an adjunct to antidepressant therapy can enhance or potentiate the effects of certain psychiatric medications, particularly in patients with treatment-resistant depression or those requiring augmentation therapy [90, 136]. The neuroenhancing effects of THs have also been demonstrated in basic research. For instance, in rats, T3 enhances the downregulation of cortical 5-HT2A receptors induced by chronic administration of tricyclic antidepressants [137]. Notably, this effect is absent with T3 monotherapy, suggesting that T3 specifically modulates long-term adaptive changes occurring at the postsynaptic level in serotonergic neurotransmission. These findings further support the potential of THs as a novel treatment option for neurological disorders.
However, two major challenges must be addressed in utilizing THs for non-thyroid disorders. The first is their “off-target effects,” as THs can act on multiple organs beyond the intended target. In particular, the presence of the BBB makes it difficult to achieve therapeutic concentration of THs in the brain. The second challenge is that even if THs reach the brain, they do not distribute evenly across all brain regions. In L-T4 therapy, the conversion of T4 to T3 is regulated in a cell-specific manner via DIO2, resulting in region-specific sensitivity to THs [138]. Similarly, triiodothyroacetic acid (TRIAC), synthetic analog of TH, has been reported to exhibit differential sensitivity across brain regions [139]. A potential solution to the first issue has already been proposed. Researchers have developed an amide prodrug targeting fatty-acid amide hydrolase (FAAH), an enzyme abundantly expressed in the CNS. This prodrug exhibits exceptionally high CNS penetration while minimizing peripheral physiological effects as a nuclear receptor modulator [140, 141]. Currently, a selective TRβ agonist, ABX-002, which is a methyl amide prodrug, is undergoing phase II clinical trials for bipolar disorder depression and major depressive disorder, with further updates eagerly awaited [142, 143].
In addition to depression, THs and their analogs are being explored in animal models and clinical research for conditions such as multiple sclerosis [144], traumatic brain injury [145], and stroke [146]. These findings indicate that THs and their analogs have potential applications beyond thyroid diseases, extending to a wide range of disorders, including CNS diseases. With continued research and clinical trials, the potential of THs as a novel therapeutic strategy is expected to expand further.
THs play an essential role in cognitive function, mood regulation, motor function, and neuroprotection. Hypothyroidism disrupts neural circuits, impairs synaptic plasticity, and contributes to neuroinflammation, affecting memory, learning, motor coordination, and emotional regulation (Graphical Abstract). While TH replacement therapy effectively reverses many of these deficits, further research is needed to explore its full therapeutic potential in neurodegenerative and psychiatric disorders. Particularly, as stated in the previous sections, hypothyroidism might cause structural alterations in brain, some of which may be irreversible. Thus, prompt treatment to normalize thyroid status may be crucial.
The emerging role of THs in promoting neurogenesis and modulating neurotransmitter systems highlights their significance in brain health. Future studies should focus on optimizing TH-based treatments and understanding their mechanisms of action by utilizing time-, brain region-, and cell-specific model animals to develop novel therapeutic strategies for cognitive impairment, mood disorders, and neurological diseases.
This work was supported by Japan Endocrine Society (JES) Grant for Promising Investigator to IA.
None of the authors have any potential conflicts of interest associated with this research. Noriyuki Koibuchi is a member of Endocrine Journal’s Editorial Board.
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