Opparounds

The Typology of Common Psychiatric Disorders as Depicted by Genetic Maps: A Study Based on Swedish Population-Based Registers

Kendler KS, Ohlsson H, Amstadter AB, Sundquist J, Sundquist K · World Psychiatry · May 2026

Using Swedish national registers, the authors built a two-dimensional "genetic map" for 12 major psychiatric and substance use disorders, with axes defined by family genetic risk for major depression and for drug use disorder — plotting where each disorder sits on a continuum from purely internalizing to purely externalizing genetic liability, rather than assuming DSM categories are genetically discrete groups.

Disorders separated into two broad clusters: an internalizing group with moderate depression-liability and low drug-use-liability, and an externalizing group with substantial genetic loading on both axes. The maps also shifted informatively by sex, age at onset, and recurrence — earlier-onset, more recurrent cases of the same DSM diagnosis sat further out on the genetic-risk map, closer to a "core" form of the disorder.

Read the paper →  doi:10.1002/wps.70074

Suicidality at Epilepsy Diagnosis and Future Treatment Resistance in Adults With Focal Epilepsy

Barnard SN, French JA, Chen Z, et al, for the Human Epilepsy Project Investigators · JAMA Neurology · March 2026

In this prospective, international, multicenter cohort (the Human Epilepsy Project), 347 adults with newly diagnosed focal epilepsy completed the Columbia-Suicide Severity Rating Scale within four months of starting their first antiseizure medication and were followed for up to six years for development of drug-resistant epilepsy, defined as failure of two adequate antiseizure drug trials to control seizures.

Suicidality present at diagnosis — before years of accumulated seizures, medication trials, or psychosocial burden could plausibly explain it — was associated with more than double the risk of later treatment resistance (relative risk 2.02, 95% CI 1.32-3.09), independent of comorbid mood or anxiety disorder.

Read the paper →  doi:10.1001/jamaneurol.2026.0204

Modafinil quietly outruns half your other prescriptions

Modafinil and armodafinil aren't just mild, stimulant-adjacent wakefulness agents — they're moderate-to-strong inducers of CYP3A4, and unlike most enzyme induction clinicians reflexively screen for, this one has a specific, high-stakes blind spot: hormonal contraception. Modafinil accelerates ethinyl estradiol metabolism enough to meaningfully raise contraceptive failure risk, and the effect persists for about a month after the drug is stopped, because enzyme induction (new protein synthesis) resolves slower than the drug itself clears — so timing modafinil around a cycle doesn't sidestep the interaction.

The same induction lowers levels of other 3A4 substrates a psychiatric patient is likely to be taking: quetiapine XR, triazolo-benzodiazepines like alprazolam and midazolam, and buspirone can all lose potency with no dose change to explain why. Anyone starting modafinil for antidepressant-augmentation of fatigue, or for clozapine-associated sedation, needs a contraception conversation and a medication reconciliation — not just a wakefulness check-in at follow-up.

Guided discovery only works if you don't already know the destination

Socratic questioning gets taught as CBT's signature move, but in practice it degrades into something closer to cross-examination: the therapist has already identified the "correct" reframe and asks a chain of leading questions until the patient arrives at it — persuasion wearing a question mark. Guided discovery is the real technique, and it only counts as guided discovery if the therapist is genuinely uncertain what the patient will find when a belief gets examined — the questions have to come from curiosity about the patient's actual evidence and logic, not from the therapist's hypothesis about what the answer should be.

The tell is what happens when the patient's answer surprises you: if you catch yourself steering back toward your original formulation, you were doing interrogation, not discovery — and the patient can usually feel the difference even when they can't name it.