Mood disorders remain a major public health concern worldwide. Monoaminergic hypotheses of pathophysiology of bipolar and major depressive disorders have led to the development of monoamine transporter-inhibiting antidepressants for the treatment of major depression and have contributed to the expanded indications of atypical antipsychotics for the treatment of bipolar disorders. In spite of psychopharmacological progress, current pharmacotherapy according to the monoaminergic hypothesis alone is insufficient to improve or prevent mood disorders. Recent approval of esketamine for treatment of treatment-resistant depression has attracted attention in psychopharmacology as a glutamatergic hypothesis of the pathophysiology of mood disorders. On the other hand, in the last decade, accumulated findings regarding the pathomechanisms of mood disorders emphasised that functional abnormalities of tripartite synaptic transmission play important roles in the pathophysiology of mood disorders. At first glance, the enhancement of astroglial connexin seems to contribute to antidepressant and mood-stabilising effects, but in reality, antidepressive and mood-stabilising actions are mediated by more complicated interactions associated with the astroglial gap junction and hemichannel. Indeed, several depressive mood-inducing stress stimulations suppress connexin43 expression and astroglial gap junction function, but enhance astroglial hemichannel activity. On the other hand, monoamine transporter-inhibiting antidepressants suppress astroglial hemichannel activity and enhance astroglial gap junction function, whereas several non-antidepressant mood stabilisers activate astroglial hemichannel activity. Based on preclinical findings, in this review, we summarise the effects of antidepressants, mood-stabilising antipsychotics, and anticonvulsants on astroglial connexin, and then, to establish a novel strategy for treatment of mood disorders, we reveal the current progress in psychopharmacology, changing the question from “what has been revealed?” to “what should be clarified?”.
Pre-emptive kidney transplantation (PEKT) is considered one of the most effective types of kidney replacement therapies to improve the quality of life (QOL) and physical prognosis of patients with end-stage renal disease (ESRD). In Japan, living-donor kidney transplantation is a common therapeutic option for patients undergoing dialyses (PDKT). Moreover, during shared decision-making in kidney replacement therapy, the medical staff of the multidisciplinary kidney team often provide educational consultation programmes according to the QOL and sociopsychological status of the ESRD patient. In Japan, the majority of kidney donations are provided by living family members. However, neither the psychosocial status of donors associated with the decision-making of kidney donations nor the interactions of the psychosocial status between donors and recipients have been clarified in the literature. In response to this gap, the present study determined the QOL, mood and anxiety status of donors and recipients at kidney transplantation decision-making between PEKT and PDKT. Deterioration of the recipient’s QOL associated with “role physical” shifted the decision-making to PEKT, whereas deterioration of QOL associated with “role emotional” and “social functioning” of the recipients shifted the decision-making to PDKT. Furthermore, increased tension/anxiety and depressive mood contributed to choosing PDKT, but increased confusion was dominantly observed in PEKT recipients. These direct impact factors for decision-making were secondarily regulated by the trait anxiety of the recipients. Unlike the recipients, the donors’ QOL associated with vitality contributed to choosing PDKT, whereas the physical and mental health of the donors shifted the decision-making to PEKT. Interestingly, we also detected the typical features of PEKT donors, who showed higher tolerability against the trait anxiety of reactive tension/anxiety than PDKT donors. These results suggest that choosing between either PEKT or PDKT is likely achieved through the proactive support of family members as candidate donors, rather than the recipients. Furthermore, PDKT is possibly facilitated by an enrichment of the life–work–family balance of the donors. Therefore, multidisciplinary kidney teams should be aware of the familial psychodynamics between patients with ESRD and their family members during the shared decision-making process by continuing the educational consultation programmes for the kidney-replacement-therapy decision-making process.
The authors wish to make the following corrections to this paper [...]
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