The AI Psych Brief

Angiotensin-Converting Enzyme in Patients With Early-Stage Psychosis

Kun Yang, Luisa Longo, Pasquale Di Carlo, Max Lam, Ruoyu Wang, et al. · JAMA Psychiatry · September 2026

Johns Hopkins investigators measured angiotensin-converting enzyme (ACE) in 122 patients aged 13 to 35 within two years of psychosis onset and 78 healthy controls. ACE protein was clearly lower in patients in both cerebrospinal fluid (Cohen d = -1.16) and serum (d = -0.92), and the two compartments tracked each other (r = 0.34).

A higher ACE-linked polygenic burden for schizophrenia predicted lower ACE protein, but not lower enzymatic activity - the canonical renin-angiotensin function was intact. Patients with treatment-resistant psychosis had lower serum ACE protein than responders (d = -0.50), again without any difference in enzyme activity. This is a cross-sectional, single-centre sample, so it shows association, not mechanism or a usable test.

Read the paper →  doi:10.1001/jamapsychiatry.2026.2588

Neonatal Abstinence Syndrome after Methadone or Buprenorphine Exposure (the MOTHER trial)

Hendrée E. Jones, Karol Kaltenbach, Sarah H. Heil, Susan M. Stine, Mara G. Coyle, Amelia M. Arria, Kevin E. O'Grady, Peter Selby, Peter R. Martin, Gabriele Fischer · New England Journal of Medicine · December 2010

MOTHER randomized 175 pregnant women with opioid dependence at eight international sites to buprenorphine or methadone in a double-blind, double-dummy, flexible-dosing design, with comprehensive prenatal care in both arms. Before it, methadone was the only recommended option in pregnancy and buprenorphine was largely untested.

Among the 131 infants whose mothers stayed on study drug to delivery, buprenorphine-exposed neonates needed far less morphine (mean 1.1 mg vs 10.4 mg), had shorter hospital stays (10.0 vs 17.5 days) and shorter NAS treatment (4.1 vs 9.9 days). The proportion of infants needing any NAS treatment, peak NAS score and head circumference did not differ significantly, nor did maternal or neonatal adverse events. The catch: 33% of women on buprenorphine stopped treatment versus 18% on methadone, a difference that was not statistically significant but was clinically noticeable.

Read the paper →  doi:10.1056/NEJMoa1005359

Varenicline is the strongest quit aid in psychiatric patients, and EAGLES is why the boxed warning came off

The 2009 boxed warning for neuropsychiatric events kept varenicline away from exactly the patients who smoke most. EAGLES (Anthenelli et al., Lancet 2016) randomized about 8,000 smokers - half with a psychiatric diagnosis - to varenicline, bupropion, nicotine patch or placebo. In the psychiatric cohort, moderate-to-severe neuropsychiatric events ran about 5-7% in all four arms, placebo included, with no significant excess for varenicline or bupropion; the FDA removed the boxed warning in December 2016.

Varenicline also produced the highest abstinence of any arm in both cohorts. Two practical points follow: it is the default first choice in stable depression, bipolar disorder and schizophrenia, and quitting itself matters pharmacologically - stopping smoking removes CYP1A2 induction, so clozapine and olanzapine levels need watching whichever quit aid you choose.

When a patient gets worse right after getting better, look at what the improvement cost them

Freud named the negative therapeutic reaction for patients who worsen precisely when the work goes well - a good interpretation, a hopeful session or a real gain is followed by symptom flare, lateness or a wish to quit. The useful clinical stance is to treat the timing as the finding. Improvement can carry an unbearable meaning: unconscious guilt (I do not deserve relief, or getting well abandons a damaged parent), envy of the therapist who helped (your success is my humiliation), or loss of a masochistic tie that has organized the patient's identity. Reassurance or a medication change in that moment usually confirms the patient's fear that only symptoms keep them connected. The technical move is to link the deterioration to the preceding gain, out loud and without accusation, and wonder what getting better threatened.