Monday, October 5, 2026

The AI Psych Brief

🔬 Section 1

Psychiatric Research Article

Changes in Genetic Contributions to ASD and ADHD by Year of Diagnosis

LaBianca S, Lousdal ML, Dybdahl Krebs M, et al.; Schork AJ (iPSYCH Study Consortium and the Autism Spectrum Disorder Working Group of the Psychiatric Genomics Consortium) · JAMA Psychiatry · September 2026

Diagnoses of ADHD and autism have climbed steeply for decades, and the argument has always been whether that reflects a real rise in risk or a change in who gets the label. This Danish cohort study used the iPSYCH2015 case-cohort to look at the polygenic scores of 17,071 people diagnosed with ASD and 20,111 diagnosed with ADHD between 1994 and 2016, asking whether the genetic profile of a newly diagnosed person shifted with calendar year.

It did, and in one direction: people diagnosed more recently carried less genetic loading. Per 10-year increase in diagnosis year, the mean ADHD polygenic score among ADHD cases fell by 0.06 SD, and the ASD score among ASD cases fell by 0.07 SD, with parallel declines in scores for other disorders such as bipolar disorder and schizophrenia. The authors compared these trends against simulated scenarios and found the pattern fit best with broadening diagnostic criteria, not with a new environmental risk factor driving more cases.

💡 Why it matters

The patient diagnosed today is, on average, genetically milder than the patients in the older trials that built the evidence base, so effect sizes and prognosis from 1990s cohorts may not transfer cleanly. It is also a useful, data-based answer for families who ask whether there is an ADHD or autism "epidemic."

Read the paper → doi:10.1001/jamapsychiatry.2026.1450

📚 Section 2

Landmark Study

Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder

Foa EB, Liebowitz MR, Kozak MJ, Davies S, Campeas R, Franklin ME, Huppert JD, Kjernisted K, Rowan V, Schmidt AB, Simpson HB, Tu X · American Journal of Psychiatry · January 2005

Landmark study from *50 Studies Every Psychiatrist Should Know*. By the early 2000s both serotonin reuptake inhibitors and exposure with ritual prevention (EX/RP) were established for OCD, but nobody had tested them head-to-head, or together, in one blinded trial. Foa, Liebowitz and colleagues randomized 122 adult outpatients across three sites (one expert in pharmacotherapy, one in EX/RP, one in both) to intensive EX/RP, clomipramine up to 250 mg/day, the combination, or pill placebo. EX/RP was delivered intensively for 4 weeks, followed by eight weekly maintenance sessions; clomipramine ran 12 weeks.

At week 12 every active arm beat placebo. EX/RP alone did not differ from the combination, and both beat clomipramine alone. Response rates (intent-to-treat / completer) were 62% / 86% for EX/RP, 70% / 79% for the combination, 42% / 48% for clomipramine, and 8% / 10% for placebo.

💡 Why it matters

The core finding has held up: guidelines still name CBT with exposure and response prevention as a first-line OCD treatment, and later SRI-augmentation trials from the same group again favored EX/RP over adding an antipsychotic. Note the gap between the EX/RP intent-to-treat and completer rates; the treatment is powerful for patients who stay, so engagement and dropout prevention are part of prescribing it.

Read the paper → doi:10.1176/appi.ajp.162.1.151

💊 Section 3

Psychiatric Fact

Clomipramine's metabolite works against what you're prescribing it for

Clomipramine is the most serotonergic tricyclic, but it is demethylated (mainly via CYP1A2, 2C19 and 3A4) to desmethylclomipramine, a largely noradrenergic reuptake inhibitor with a longer half-life. At steady state the metabolite often exceeds the parent, so a patient on a "serotonergic" drug can be carrying mostly a noradrenergic one, with the anticholinergic and cardiac burden that comes with it. That is the rationale behind the old trick of adding low-dose fluvoxamine: its CYP1A2 and 2C19 inhibition shifts the ratio back toward the parent. The same inhibition can multiply total tricyclic exposure, so this is never done blind. Order a combined clomipramine + desmethylclomipramine level and an ECG before and after, and treat a rising combined level (many clinicians aim to stay below roughly 500 ng/mL) or a widening QRS as a stop sign. The label's 250 mg/day ceiling is a seizure-risk ceiling, and a CYP inhibitor can push a patient past it without any dose change.

🛋️ Section 4

Psychotherapy Teaching Pearl

Termination reopens every earlier separation — set the date early and watch what comes back

Termination is not the administrative end of a treatment; it is often its last and most informative phase. Announcing an ending reactivates how the patient has handled every earlier loss: a parent who left, a move, a friendship dropped before it could drop them. Symptoms that had quieted can return, the patient may devalue the work ("none of this really helped"), miss sessions to end on their own terms, or become conspicuously cheerful. These are not signs the treatment failed; they are the patient's characteristic way of managing separation, now happening live and in the room. That is why setting the date well in advance, often months ahead in longer work, matters: it leaves time to recognize the pattern and work through it rather than act it out. The therapist's own reactions (relief, guilt, an urge to extend) belong in the formulation too.

🗒️ Vignette

A 30-year-old man in year two of weekly dynamic therapy, seen by a graduating resident, starts arriving late after the June end date is set in February. He says the sessions have "gotten repetitive" and asks whether he could simply stop in April. The resident's first impulse is to accept, since the patient is doing well. Instead she notices the pattern and ties it to his history: "You told me that when your father moved out, you were the one who stopped calling first. I wonder if leaving here early is a way of making sure you do the leaving this time, so you don't have to feel left." He is quiet, then angry that she is "making it a thing." The following week he arrives on time and, for the first time, talks about missing his father. The move was to name the enactment as it formed rather than grant the early exit or argue for staying.