Thyroid hormones are crucial during development and in the adult brain. Of interest, fluctuations in the levels of thyroid hormones at various times during development and throughout life can impact on psychiatric disease manifestation and response to treatment. Here we review research on thyroid function assessment in schizophrenia, relating interrelations between the pituitary-thyroid axis and major neurosignaling systems involved in schizophrenia’s pathophysiology. These include the serotonergic, dopaminergic, glutamatergic, and GABAergic networks, as well as myelination and inflammatory processes. The available evidence supports that thyroid hormones deregulation is a common feature in schizophrenia and that the implications of thyroid hormones homeostasis in the fine-tuning of crucial brain networks warrants further research. 1. Introduction In 1888 a report by the Committee of the Clinical Society of London explored the association of hypothyroidism with psychosis [1]. Not surprisingly, given the essential role of thyroid hormones for mammalian brain development, the effect of thyroid hormones (THs) in the modulation of affective illness and behavior continues to be an avenue of research in the pathophysiology of mood disorders [2–12]. Complementarily, research has revealed the TH modulation of crucial brain neurotransmitter systems [12–15] including the dopaminergic, serotonergic, glutamatergic, and GABAergic networks [14, 16–20]. As elaborated on throughout this paper, the misregulation of these pathways, as well as the participation of myelination and of cytokines, is of particular relevance in the schizophrenic brain [18, 21–23]. Schizophrenia is one of the most severe psychiatric disorders with an estimated prevalence of 0.7–1.0% in the population worldwide. It often runs a chronic and debilitating course, with many patients responding poorly to medication and suffering frequent and disrupting relapses. Furthermore, it is accompanied by a great social cost in terms of productivity loss and treatment-related expenses [21]. Its core features include cognitive impairment, delusions, hallucinations, altered volition and emotional reactivity and disorganized behavior. It is now clear that the heterogeneity and complexity of schizophrenia is both at the clinical and aetiological levels and that this complex disorder arises from the interaction of a range of deviant genetic traits and environmental “insults,” which may begin to act in the prenatal period [21]. The clear understanding of schizophrenia’s molecular mechanism(s) is elusive, and no
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