Morning Rounds: September 7-14
Key Takeaways
- Assortative mating increased prevalence of any psychiatric disorder by 1.8% and inflated parent-offspring heritability estimates by 12.5% versus random mating in Danish registry simulations.
- Partner similarity was highest for schizophrenia, ADHD, ASD, and substance use disorder, while cross-disorder correlations diminished after excluding comorbidity, underscoring comorbidity as a major confounder.
Catch up on last week's news in psychiatry.
Clinical Research
Nonrandom Mating Inflates Psychiatric Disorder Prevalence and Heritability, Danish Cohort Finds
A population-based cohort study of more than 4.2 million Danish residents found that partner similarity for psychiatric disorders substantially inflates the prevalence and heritability of mental illness across generations.1 Investigators calculated tetrachoric parental correlations across 10 major psychiatric illness classes, finding the strongest within-disorder correlations for schizophrenia, attention-deficit hyperactivity disorder, autism spectrum disorder, and substance use disorder, and the weakest for generalized anxiety disorder.¹ Permutation-based simulations comparing observed data with a randomly mated population showed nonrandom mating increased the prevalence of any psychiatric disorder by 1.8% and parent-offspring heritability by 12.5% relative to random mating.1 Much of the observed cross-disorder correlation attenuated after excluding individuals with psychiatric comorbidities, suggesting comorbidity drives a substantial share of the apparent cross-disorder partner resemblance. For prescribers, the findings reinforce that a psychiatric history in both parents meaningfully concentrates familial risk beyond additive genetic inheritance, information that may inform family-based risk counseling and early identification in offspring.
Lower ACE Protein Levels Identified as Potential Biomarker for Treatment-Resistant Psychosis
A cross-sectional study of 200 individuals found that angiotensin-converting enzyme (ACE) protein levels were significantly lower in both cerebrospinal fluid and serum among patients with early-stage psychosis compared with healthy controls.2 Serum ACE protein levels were lower still in patients with treatment-resistant psychosis than in those without treatment resistance, though canonical enzymatic activity did not differ between the two patient subgroups.2 Higher ACE genetic burden for schizophrenia correlated with lower ACE protein levels but not with enzymatic activity, pointing to a noncanonical, nonenzymatic mechanism linking the ACE gene to psychosis pathology. The 122 patients with early-stage psychosis were aged 13 to 35 years, with onset within the prior 2 years, addressing a population in which objective biomarkers remain scarce.
Pharmaceutical Updates
Phase 3 Data Show Oveporexton Improves Wakefulness, Cataplexy, and Quality of Life in Narcolepsy Type 1
Full results from the FirstLight and RadiantLight phase 3 trials show that oveporexton (Orzeyful), an oral orexin receptor 2 agonist, produced statistically significant improvements over placebo across all 14 measured endpoints in patients with narcolepsy type 1.3 Median weekly cataplexy rates fell 79.0% to 88.8% with oveporexton compared with 27.7% to 39.1% with placebo at week 12, with benefits apparent at the earliest assessed time point and sustained through 12 weeks in both studies.3 More than 70% of treated participants reached the mildest severity tier on the Narcolepsy Severity Scale, and nearly all treated participants reported improvement on the Patient Global Impression of Change scale. The most common treatment-emergent adverse events were insomnia, urinary urgency, urinary frequency, and excessive saliva, most of which were mild to moderate and resolved without medical intervention.
Single-Dose DT120 ODT Meets Primary Endpoint in Phase 3 Panorama Study of Generalized Anxiety Disorder
Definium Therapeutics announced positive topline results from Panorama, its second phase 3 study of DT120 (lysergide) orally disintegrating tablet in adults with generalized anxiety disorder, marking the company's third positive phase 3 readout for the drug.4 The trial randomized 245 participants with a Hamilton Anxiety Rating Scale (HAM-A) score of 20 or higher to a single dose of DT120 ODT 100 µg, 50 µg, or placebo, with change in HAM-A total score at week 12 as the primary endpoint.4 Participants receiving the 100-µg dose showed a least-squares mean improvement of 9.8 points versus 4.7 points with placebo at week 12, a difference of 5.1 points (P < 0.0001), with clinical activity emerging by day 2 and sustained through the 12-week double-blind period. DT120 ODT was generally well tolerated, with no new safety signals, including no suicidality signal, and similar discontinuation rates across dose groups.
Policy & Legislation
State Funding for Suicide Prevention and Crisis Services Increases 6x From 2021 to 2026
A cross-sectional study examining every enacted state budget from fiscal years 2021 through 2026 found that per-capita state funding for suicide prevention and crisis services rose roughly 6-fold over the period, though allocations varied widely by state.5 Investigators identified 1150 budget line items explicitly dedicated to suicide prevention and crisis infrastructure across 306 state-year budget observations, totaling more than $7.2 billion spent nationally over the study period.5 States that had enacted 988 telecom fee legislation allocated more than twice the per-capita funding of states without such fees ($7.73 vs $3.13), and a greater share of their total budgets, supporting telecom fees as a scalable financing mechanism for crisis infrastructure. Notably, funding levels were not associated with a state's suicide mortality rate, indicating that higher clinical need did not reliably translate into higher budget allocations.
References
1. Dehkordi SR, Meijsen J, Waples R, et al.
2. Yang K, Longo L, Di Carlo P, et al.
3. Dauvilliers Y, Mignot E, Antczak J, et al.
4. Definium Therapeutics announces positive topline results from phase 3 Panorama study of DT120 ODT in generalized anxiety disorder. Press release. September 14, 2026. Accessed September 14, 2026.
5. Purtle J, Weiss M, McBain RK, et al.
