Biological Psychiatry最新文献

After decades of limited progress in depression treatment, recent advancements have sparked renewed interest in developing novel antidepressants, particularly rapid-acting antidepressants (RAADs). Despite these promising developments, there remains a significant gap in research on bipolar depression. While several antipsychotics have been investigated for their efficacy in bipolar depression due to the reduced risk of mania induction, research on RAADs, such as (es)ketamine, remains scarce despite their demonstrated safety and effectiveness. This review gives an overview of current developments in RAADs in the context of bipolar disorder. Both published studies as well as phase II, III and IV studies on bipolar depression (based on clinicaltrials.gov) are reviewed in this work. The following RAAD substance classes have been or are currently investigated as possible treatments for bipolar depression: NMDA antagonists and indirect AMPA agonists (ketamine, esketamine, riluzole, felbamate), GABA-A activators or positive allosteric modulators (zuranolone, pregnenolone, PEA), psychedelics (psilocybin, 5-MeO-DMT), muscarine receptor antagonists (scopolamine), and kappa-opioid receptor antagonists (navacaprant). Other than the well-established efficacy and safety of (es)ketamine in treating bipolar depression, there has been little research effort in the treatment of bipolar depression. Recent research into RAADs demonstrates the growing field of novel mechanisms of action in the pharmacological treatment of bipolar depression. However, there is an urgent need for well-controlled clinical studies on RAADs in bipolar depression to expand treatment options and improve outcomes for millions of affected individuals worldwide.

Anorexia nervosa (AN) is an eating disorder for which the underlying aetiology remains mostly uncharacterised. Large-scale genetic studies of AN suggest a relationship between AN liability and cardiometabolic traits, such as lipid and glycaemic biology, which may reveal novel treatment targets through pharmacological or nutritional interventions. However, the role of body mass index (BMI) in the diagnosis of AN presents a challenge in the interpretation of these genetic studies. Specifically, BMI is a heritable trait with a genetic architecture that is related to cardiometabolic traits. This becomes particularly salient with the emergence of an "atypical" AN diagnosis whereby individuals display behaviours consistent with AN, but their BMI remains within normal or higher ranges. In this review, we outline the evidence from genetic studies that support a role of cardiometabolic traits in risk for AN, as well as the unmet need to study cardiometabolic factors in atypical AN. The influence of selection for individuals with low BMI, particularly from large, international studies that rely on cohorts that used older diagnostic criteria, will be discussed, along with efforts from the literature to disentangle these relationships. We conclude that there is at least some evidence that genetic susceptibility to lower BMI may impact the inferred cardiometabolic relationships with AN genetic liability; however, there remains genetic support for a role of metabolic factors in AN risk beyond what is directly attributable to weight related diagnostic considerations alone. Finally, we provide recommendations for future genetic studies exploring cardiometabolic traits across the spectrum of eating disorders.