Lower levels of TRAF1 in Brodmann's area 24, but not 46, in bipolar disorders are not detectable in major depressive disorders.

INTRODUCTION: Multiple lines of research implicate inflammation-related pathways in the molecular pathology of mood disorders, with our data suggesting a critical role for aberrant cortical tumour necrosis factor α (TNF)-signaling in the molecular pathology of bipolar disorders (BPD) and major depressive disorders (MDD). METHODS: To extend our understanding of changes in TNF-signaling pathways in mood disorders we used Western blotting to measure levels of tumour necrosis factor receptor associated factor 1 (TRAF1) and transmembrane TNF receptor superfamily member 1B (tmTNFRSF1B) in Brodmann's areas (BA) 24 and 46 from people with BPD and MDD. These proteins are key rate-limiting components within TNF-signaling pathways. RESULTS: Compared to controls, there were higher levels of TRAF1 of large effect size (η = 0.19, Cohen's d = 0.97) in BA 24, but not BA 46, from people with BPD. Levels of TRAF1 were not altered in MDD and levels of tmTNFRSF1B were not altered in either disorder. LIMITATIONS: The cases studied had been treated with psychotropic drugs prior to death which is an unresolvable study confound. Cohort sizes are relatively small but not untypical of postmortem CNS studies. CONCLUSIONS: To facilitate post-synaptic signaling, TRAF1 is known to associate with tmTNFRSF1B after that receptor takes its activated conformation which occurs predominantly after it binds to transmembrane TNF (tmTNF). Simultaneously, when tmTNFRSF1B binds to tmTNF reverse signaling through tmTNF is activated. Hence our findings in BA 24 argues that bidirectional TNF-signaling may be an important component of the molecular pathology of BPD.

Sex differences in schizophrenia, bipolar disorder, and post-traumatic stress disorder: Are gonadal hormones the link?

In this review, we describe the sex differences in prevalence, onset, symptom profiles, and disease outcome that are evident in schizophrenia, bipolar disorder, and post-traumatic stress disorder. Women with schizophrenia tend to exhibit less disease impairment than men. By contrast, women with post-traumatic stress disorder are more affected than men. The most likely candidates to explain these sex differences are gonadal hormones. This review details the clinical evidence that oestradiol and progesterone are dysregulated in these psychiatric disorders. Notably, existing data on oestradiol, and to a lesser extent, progesterone, suggest that low levels of these hormones may increase the risk of disease development and worsen symptom severity. We argue that future studies require a more inclusive, considered analysis of gonadal steroid hormones and the intricacies of the interactions between them, with methodological rigour applied, to enhance our understanding of the roles of steroid hormones in psychiatric disorders. LINKED ARTICLES: This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc.