Factors related to prenatal depression among hospitalized high-risk pregnant women in South Korea: a cross-sectional study focused on resilience, pregnancy stress, and marital satisfaction.

Schizophrenia is a complex, chronic mental health condition associated with a substantial burden on patients and their families [,]. Schizophrenia symptoms vary and include positive symptoms (delusions, hallucinations and disorganized behavior); negative symptoms (flattened affect, social isolation); and cognitive impairment [,]. It affects approximately 23.1 million people globally and results in 15.1 million disability-adjusted life years [], making it a leading cause of mental-disorder-associated disability [,]. Approximately 1.2% of US adults meet the criteria for a schizophrenia-spectrum disorder [], and US adults with schizophrenia are 3.5-times more likely to die prematurely than the general population []. American Psychiatric Association guidelines recommend a patient-centric approach involving pharmacological and nonpharmacological treatments, with current standard of care centering around first-generation (FGA) and second-generation (SGA) antipsychotics targeting dopamine receptors []. Although effective at treating positive symptoms, FGAs can exacerbate negative symptoms, do not improve cognition, and result in well-known drug-induced movement disorders including extrapyramidal side effects (such as dystonia, parkinsonism and tardive dyskinesia) []. While SGAs have a reduced likelihood of extrapyramidal symptoms and tardive dyskinesia, they are associated with metabolic adverse events (AEs) such as weight gain and metabolic syndrome (including glucose and lipid abnormalities) []. The range of AEs resulting from these drugs' action on dopaminergic receptors leads to low treatment tolerability, poor adherence and subsequent symptom relapses [,]. There is therefore a need for treatment options with novel modes of action, better safety profiles and improved clinical outcomes. Several pharmacological approaches have been researched, including targeting muscarinic receptors, trace amine-associated receptor 1 (TAAR1), serotonin 5-HT1A and 5-HT2A receptors and glycine transporter 1 []. However, few candidates have demonstrated efficacy in clinical trials including adults with schizophrenia, and only one of these has received US FDA approval []. In September 2024 the FDA approved xanomeline/trospium chloride (KarXT) [] based on efficacy and safety data from three double-blind, placebo-controlled trials: EMERGENT-1/-2/-3 []. Xanomeline is an agonist of M and M muscarinic receptors that crosses the blood–brain barrier, while trospium chloride is a nonselective, peripherally restricted muscarinic receptor antagonist []. Xanomeline is thought to ameliorate psychotic symptoms by indirectly modulating neurotransmitter levels including dopamine, gamma-aminobutyric acid and glutamate [], whereas trospium chloride mitigates the peripheral cholinergic (especially gastrointestinal) side effects of xanomeline.