Opparounds

Brain Morphology Mediators of the Association of Childhood Trauma With Bipolar Disorder: An International ENIGMA Bipolar Disorder Working Group Study

Tozzi L, Dauvermann MR, Corley E, et al · JAMA Psychiatry · June 2026

This cross-sectional case-control study pooled 19 international cohorts through the ENIGMA Bipolar Disorder Working Group, comparing 1,031 adults with bipolar disorder to 2,221 healthy controls. Childhood trauma severity, measured with the Childhood Trauma Questionnaire, was robustly associated with a bipolar diagnosis. The authors then tested whether 75 measures of brain morphology — cortical thickness, cortical surface area, and subcortical volume — mediated that association, using high-dimensional mediation analysis with permutation testing.

Despite the strength of the trauma-diagnosis link, structural brain differences explained less than 1% of it. The only statistically significant individual mediators were smaller hippocampal volume and thinner medial orbitofrontal and superior frontal cortex.

Read the paper →  doi:10.1001/jamapsychiatry.2026.1183

Effectiveness of Atypical Antipsychotic Drugs in Patients with Alzheimer's Disease (CATIE-AD)

Schneider LS, Tariot PN, Dagerman KS, et al, for the CATIE-AD Study Group · New England Journal of Medicine · October 2006

421 outpatients with Alzheimer's disease and psychosis, aggression, or agitation, across 42 U.S. sites, were randomized double-blind to olanzapine (mean dose 5.5 mg/day), quetiapine (mean dose 56.5 mg/day), risperidone, or placebo. The primary outcome was time to all-cause discontinuation of assigned treatment.

Time to discontinuation for any reason did not differ significantly across the four arms — because each active drug's efficacy advantage over placebo was offset by a higher rate of stopping for adverse effects: 24% for olanzapine, 18% for risperidone, 16% for quetiapine, versus 5% for placebo. Analyzed for lack of efficacy alone, risperidone and olanzapine markedly outlasted placebo and quetiapine (median 26.7 and 22.1 weeks respectively, versus about 9 weeks for the other two arms).

Read the paper →  doi:10.1056/NEJMoa061240

SSRI-induced SIADH is a clock, not just a dose

SSRI-induced SIADH isn't simply "more drug, more risk" — it's driven by 5-HT2C-mediated ADH release largely independent of dose, and its risk is front-loaded: the large majority of cases present in the first two to four weeks of treatment or right after a dose increase, then risk drops sharply. That timing should shape monitoring: check sodium at baseline and again around week 2 in anyone carrying the compounding risk factors — age over 65, a concurrent diuretic (especially a thiazide), low body weight, or a prior episode — rather than defaulting to a "recheck labs at three months" habit that misses the window when SIADH actually happens.

A sodium under 125 mmol/L, or any symptomatic hyponatremia (confusion, falls, seizure), means stop the SSRI and treat, not dose-reduce and recheck: this is a class effect tied to serotonergic tone at 5-HT2C, and it typically recurs on rechallenge with another SSRI or SNRI. The usual fix is switching to mirtazapine or bupropion, which carry minimal reported SIADH risk, rather than cycling through the same mechanism at a lower milligram number.

The selected fact turns noise into a session

Bion borrowed "selected fact" from the mathematician Poincaré to describe a specific moment in a session: you've been sitting with scattered, seemingly unrelated material — a complaint about a spouse, a missed appointment, an offhand joke — and then one fact arrives that suddenly organizes everything else into a coherent pattern, the way a hypothesis makes disparate data points look like they were always pointing the same direction. It isn't that you impose meaning on the material; the selected fact is discovered, not manufactured, and you know you've found it because the other elements click into place around it rather than being forced there.

The technical discipline is patience: tolerating the incoherence long enough — a version of what Bion calls negative capability — instead of prematurely organizing the material around the first plausible theme, which forecloses the real pattern before it can emerge.