Psychoneuroendocrinology of Psychosis Disorders

The etiopathological mechanisms underlying psychotic disorders remain to be fully elucidated in their complexity. The broadly accepted dopaminergic hypothesis appears to be just the downstream effect of several pathophysiological processes, involving other neurotransmission systems, such as the serotonergic, glutamatergic and GABAergic systems. A vast body of research on psychosis suggests that dysregulated excitation/inhibition balance in the hippocampal structure might lead to midbrain hyper-dopaminergic tone, through polysynaptic projection pathways to the midbrain/striatum. Hormones have profound effects on other neurotransmission systems, as well as on the hippocampal structure and function. Several anecdotal cases of new onset psychosis have been described, commencing following hormonal, especially thyroidal storms, and remitting with the treatment for the endocrine unbalance. Epidemiological evidence proposes that the psychosis prevalence is higher among patients affected by endocrinological conditions, e.g., hypothyroidism. Also, autoimmune encephalopathies associated with the presence of intrathecal thyroid autoantibodies, may present psychotic symptoms, possibly mimicking schizophrenia. Hormones can interact with the central nervous system either genomically, via binding to nuclear receptors and modulating the expression of thousands of genes, or non-genomically, via binding to membrane receptors and modulating downstream signaling cascades. Glucocorticoids and thyroid hormones emerged as crucial factors in regulating adult neurogenesis in the subgranular zone of the hippocampal dentate gyrus. Therefore, perturbations of their function, caused by primary endocrinological conditions, as well as by exposure to chronic stress or to endocrine disruptors, induce long-lasting reductions in neurogenesis and plasticity, which ultimately result in the cognitive impairments observed in patients suffering from psychotic disorders. The hippocampus is also a target of neuropeptides, such as oxytocin and vasopressin. Oxytocin has an important role in the maturation of neural circuits during the pre- and peri-natal period, and, later in life, in the protection of hippocampal plasticity from the effects of stress. From the behavioural point of view, these neuropeptides are involved in functions which map on to common psychotic symptoms, in particular in the social cognition domain. Interestingly, exogenous delivery of oxytocin and vasopressin is currently under investigation as a novel therapeutic approach in psychosis. Recently, a novel branch of thyroid hormone signaling has been discovered, consisting of thyronamines, mainly the 3-iodothyronamine, and its receptor, the trace amine-associated receptor 1 (TAAR1). Rare missense single nucleotide variants have been found to be significantly enriched in a cohort of schizophrenic patients. Furthermore, synthetic TAAR1-selective agonists showed antipsychotic-like effects in murine models of positive and cognitive symptoms of schizophrenia.

This Research Topic presents recent advances in the role of hormonal systems in the etiopathology of psychotic disorders. We encourage contributions that address:
- how endocrine alterations - endocrine disorders, chronic stress, pollutants acting as endocrine disruptors - may impact the pathophysiological mechanisms leading to psychosis onset
- how the exogenous manipulation of endocrine systems may provide novel useful tools in the treatment of psychotic disorders.

Contributions to Research Topic can be either original research papers or review articles. It is intended that this collection will provide important knowledge into the pathophysiological and therapeutic implications of the hormonal balance in psychotic disorders.