IntroductionSchizophrenia is conceptualized as a disorder of brain network dysconnectivity, yet relationships between neural alterations, cognitive deficits, and genetic risk remain unclear.MethodsWe examined 86 participants: schizophrenia patients (SCZ), unaffected siblings (SCZ-SIB), healthy controls (CON), and control siblings (CON-SIB). We used a multiscale graph-theoretic analysis of task-based fMRI during N-back working memory and unsupervised clinical-cognitive clustering.ResultsWe found that reduced cerebellum-sensorimotor (CER-SM) and cerebellum-cingulo-opercular (CER-CO) connectivity during the 1-back condition robustly discriminated SCZ from CON (AUC = 0.89). Critically, these dysconnectivity patterns were linked to clinical state, present in SCZ vs. SCZ-SIB but absent in SCZ-SIB vs. CON-SIB, suggesting illness expression rather than familial risk. Unsupervised clustering revealed three data-driven subtypes with distinct cognitive- symptomatic profiles: subtype 1 with relative preservation of verbal abilities (predominantly controls), subtype 2 with marked fluid cognitive impairment (enriched in SCZ), and subtype 3 with intermediate performance with working memory sparing (mixed composition). Cerebellar-cortical hypoconnectivity showed graded alignment across these profiles.DiscussionThese findings demonstrate that cerebellar dysconnectivity is most detectable under moderate cognitive load, tracks with clinical state, and covaries with transdiagnostic cognitive profiles, advancing circuit-based understanding of schizophrenia heterogeneity.
Minimal life by computer
Nature Biotechnology, Published online: 07 April 2026; doi:10.1038/s41587-026-03110-7
Progress toward a true virtual cell will depend on uniting AI’s pattern-finding power with the causal rigor of mechanistic models.
Zodasiran for cholesterol and triglyceride lowering in patients with hyperlipidemia: final report of phase 1 basket trial
Nature Medicine, Published online: 07 April 2026; doi:10.1038/s41591-026-04307-8
In a phase 1 basket trial, the small interfering RNA zodasiran, targeting ANGPTL3, lowered triglycerides in patients with severe hypertriglyceridemia and lowered both triglycerides and low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolemia.
Methylome-Wide Association Study of Obsessive-Compulsive Disorder
Obsessive-compulsive disorder (OCD) is a debilitating psychiatric condition influenced by both genetic and environmental risk factors. Epigenetic modifications, such as DNA methylation, may offer insights into biologically meaningful differences associated with the disorder.
Neural circuits encode prior knowledge of temporal statistics
Nature Neuroscience, Published online: 07 April 2026; doi:10.1038/s41593-026-02255-7
This study shows that cerebellar circuits learn and encode prior probabilities of event timing. Cell-type-specific neural activity reflects environmental statistics and guides predictive motor behavior, providing support for neural Bayesian inference.
Digital Health Coffee Time Briefing ☕
Today’s briefing features a saliva-based pregnancy test called the Lollipop and a healthcare-focused AI interpreter app.
Rolling out the FDP and AVT at scale
In this episode at Rewired 2026, Will Monaghan discusses rolling out the federated data platform and ambient voice technology at scale.
STAT+: Merck’s experimental HIV prevention pill could be made for less than $5 a year, researchers say
An experimental HIV prevention pill being developed by Merck could be mass produced for less than $5 per patient a year according to a new analysis. Advocates argue the low cost means the company should find it easier to license the drug so that low- and middle-income countries can gain easy access.
The pill, dubbed MK 8527, is currently undergoing a pair of late-stage clinical trials that are expected to determine whether the medicine can lower HIV transmission when given to people at high risk of infection. The results are due in the latter half of 2027, according to separate postings on ClinicalTrials.gov.
Already, the pill is generating considerable interest after Merck released mid-stage results last summer showing its drug holds promise. In addition to being safe and effective, the study found it could protect against infection, a form of prevention known as pre-exposure prophylaxis or PrEP, within 24 hours after being taken. Merck noted the pill works in a novel way.
A star scientist showed that better genetics lessons could reduce racism. It was the death knell for his career
Every year, the Genetics Society of America bestows the Elizabeth W. Jones Award for Excellence in Education, recognizing someone who has helped the public better understand the science of DNA. It’s understood to be a lifetime achievement award; past recipients tend toward retirement age with decades of work behind them and stacks of textbooks to their names.
When this year’s winner, Brian Donovan, was announced at the end of February, many geneticists and science educators found it hard to celebrate the news. Not because he’s undeserving of the honor. Far from it. But because it seemed to confirm what many feared: that Donovan’s incandescent research career was over before it had barely begun.
STAT+: FDA backs proposals to entice pharma companies to test, make drugs domestically
WASHINGTON — The Food and Drug Administration used the president’s budget to propose policies aimed at encouraging domestic development and manufacturing of drugs.
FDA Commissioner Marty Makary has said the agency needs “giant, big ideas” to counter China’s dominance in early-stage clinical development of drugs. Among the FDA’s ideas are proposals to make it easier to run early-stage trials in the U.S. and to hand an advantage to U.S.-based generics manufacturers.
The Trump administration has been using a variety of policy levers to try and bring drug manufacturing to the U.S. For example, many of the brand drugmakers that struck deals to lower U.S. prices also promised to increase domestic manufacturing, under the threat of tariffs.