French Society for Biological Psychiatry and Neuropsychopharmacology and French-speaking Marcé Society guidelines for the management of mood disorders in women before, during, and after pregnancy.

PURPOSE: The French Society for Biological Psychiatry and Neuropsychopharmacology and the French-speaking Marcé Society have joined forces to establish expert recommendations on the prescription of psychotropic drugs before, during, and after pregnancy in women with major depressive disorder (MDD) and bipolar disorder (BD). METHODS: To elaborate recommendations, we used the RAND/UCLA Appropriateness Method, which combines scientific evidence and expert clinicians' opinions. A written survey was completed by 48 psychiatrists, who have expertise in the management of mood disorders and/or in perinatal psychiatry. Key recommendations are provided by the scientific committee based on data analysis and interpretation of the results of the survey. RESULTS: The recommendations address the following three areas that are deemed essential in women with mood disorders, with an emphasis on screening, treatment options, and monitoring: (i) management of mood disorders in women of childbearing age, (ii) management during pregnancy, (iii) management during the post-partum period. As first-line strategies, experts recommend treating mood symptoms during pregnancy and maintaining a pharmacological treatment, even in euthymic or stabilized patients. First-line options include only medications with no teratogenic risk, and during breastfeeding, only medications without evidence of adverse effects in nursing infants. CONCLUSION: The expert consensus guidelines will help facilitate treatment decisions for clinicians in the daily assessment and management of mood disorders in women of childbearing age, during pregnancy, and in the post-partum period.

Nuclear HMGB1 protects from nonalcoholic fatty liver disease through negative regulation of liver X receptor.

Dysregulations of lipid metabolism in the liver may trigger steatosis progression, leading to potentially severe clinical consequences such as nonalcoholic fatty liver diseases (NAFLDs). Molecular mechanisms underlying liver lipogenesis are very complex and fine-tuned by chromatin dynamics and multiple key transcription factors. Here, we demonstrate that the nuclear factor HMGB1 acts as a strong repressor of liver lipogenesis. Mice with liver-specific Hmgb1 deficiency display exacerbated liver steatosis, while Hmgb1-overexpressing mice exhibited a protection from fatty liver progression when subjected to nutritional stress. Global transcriptome and functional analysis revealed that the deletion of Hmgb1 gene enhances LXRα and PPARγ activity. HMGB1 repression is not mediated through nucleosome landscape reorganization but rather via a preferential DNA occupation in a region carrying genes regulated by LXRα and PPARγ. Together, these findings suggest that hepatocellular HMGB1 protects from liver steatosis development. HMGB1 may constitute a new attractive option to therapeutically target the LXRα-PPARγ axis during NAFLD.

Macrophage-derived HMGB1 is dispensable for tissue fibrogenesis.

Alarmins and damage-associated molecular patterns (DAMPs) are powerful inflammatory mediators, capable of initiating and maintaining sterile inflammation during acute or chronic tissue injury. Recent evidence suggests that alarmins/DAMPs may also trigger tissue regeneration and repair, suggesting a potential contribution to tissue fibrogenesis. High mobility group B1 (HMGB1), a bona fide alarmin/DAMP, may be released passively by necrotic cells or actively secreted by innate immune cells. Macrophages can release large amounts of HMGB1 and play a key role in wound healing and regeneration processes. Here, we hypothesized that macrophages may be a key source of HMGB1 and thereby contribute to wound healing and fibrogenesis. Surprisingly, cell-specific deletion approaches, demonstrated that macrophage-derived HMGB1 is not involved in tissue fibrogenesis in multiple organs with different underlying pathologies. Compared to control HMGB1Flox mice, mice with macrophage-specific HMGB1 deletion (HMGB1ΔMac) do not display any modification of fibrogenesis in the liver after CCL4 or thioacetamide treatment and bile duct ligation; in the kidney following unilateral ureter obstruction; and in the heart after transverse aortic constriction. Of note, even under thermoneutral housing, known to exacerbate inflammation and fibrosis features, HMGB1ΔMac mice do not show impairment of fibrogenesis. In conclusion, our study clearly establishes that macrophage-derived HMGB1 does not contribute to tissue repair and fibrogenesis.