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Purpose: Early life adversity is associated with both metabolic impairment and depression in adulthood, as well as with poorer responses to antidepressant medications. It is not yet known whether individual differences in sensitivity to antidiabetic medications could also be related to early life adversity. We examined whether a history of early life adversity affected the observed changes in metabolic function and depressive symptoms in a randomized trial of pioglitazone for augmentation of standard treatments for depression., Purpose: Early life adversity is associated with both metabolic impairment and depression in adulthood, as well as with poorer responses to antidepressant medications. It is not yet known whether individual differences in sensitivity to antidiabetic medications could also be related to early life adversity. We examined whether a history of early life adversity affected the observed changes in metabolic function and depressive symptoms in a randomized trial of pioglitazone for augmentation of standard treatments for depression., Findings: We found that early life adversity significantly impaired the metabolic response to pioglitazone. Effects on depressive symptoms did not reach significance, but nonetheless suggested that pioglitazone could mitigate the depressant effects of childhood adversity, only among those insulin resistant at baseline., Conclusions: We conclude that a history of early life adversity may impair the body's ability to respond to insulin sensitizing pharmacotherapy, and furthermore that its contribution to resistant depression may function in part via the generation of an insulin resistant phenotype., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

This study aims to summarize the current state of knowledge regarding approaches to treatment-resistant depression in pregnancy and the postpartum period and to develop algorithms for ante- and postnatal management in cases of refractory major depression. PubMed, Scopus, Google Scholar, and the Cochrane Library databases were searched without temporal restriction. Search terms included pregnancy and depression, perinatal depression, postnatal depression, treatment resistance and depression, antipsychotics and pregnancy, antidepressants and pregnancy, and mood stabilizers and pregnancy. Abstracts were reviewed for relevance, and further articles were obtained from bibliographic citations. There is a significant subpopulation of patients in pregnancy and postpartum whose depressive symptoms do not respond to first-line treatments. No research studies have focused specifically on this population. Data extracted from studies on women with depressive symptoms in pregnancy suggest that in the absence of evidence on which to base clinical decisions, many are receiving combinations of psychotherapeutic medications that have not been specifically studied for use in pregnancy. Antidepressant use in pregnancy is well studied, but studies specifically addressing the case of the patient who does not respond to first-line treatments are absent. Research in this area is urgently needed. The authors review a number of possible therapeutic approaches to treatment-resistant depression in pregnancy and the postpartum period.