This is so, so well-articulated.

I’ve spent 15 years challenging a flawed explanation for an infant’s death. Credit to The New Yorker for patient investigative journalism that corrected the record when institutions did not.

Does early autonomic burden in prodromal Parkinson’s disease predict later cognitive (thinking) impairment? Martinez Nunez and colleagues describe in a new paper in Movement Disorders how early autonomic symptoms in prodromal Parkinson’s disease may be linked to later cognitive (thinking) decline.

I'm starting a thread on misunderstandings about the role of APOE in Alzheimer's disease / dementia, from the POV of epidemiology / statistical genetics. I will add to this sporadically over time...

#endalz #episky #medsky

I lost my job, my kids have measles, and Trump's personal Gestapo is randomly executing American citizens. But at least now there won't be any non-binary characters on the new Paw Patrol spin-off.

Chinese whispers, genetic edition. This is a fascinating reminder that "genetic determination", at the level of organism behaviour, is not just about the genome inherited in the zygote, but about millions/billions of cells, each with a prob unique take on that foundational genome, working together.

Evoke trial of @novonordisk’s #semaglutide for AD fails to slow progression:
www.sciencemediacentre.org/expert-react...

A second large #GLP1 agonist trial in neurodegeneration with another disappointing result.

Why isn’t the promise (& hype) of observational data translating to trials?

This does feel like a major crossing of the Rubicon – the world's best-funded and in many ways most powerful public health agency is now actively pushing disinformation.

I know there's a *lot* going on to care about at the moment, but this one really is significant, and matters well beyond the US.

Academics in Assyria in the 7th c BC complain that admin is preventing them from doing research and teaching

Effort choices are sensitive to prior learning Motivated behaviour relies on both learning and effort-based decision-making, yet these processes are often studied in isolation. We developed a novel paradigm combining probabilistic associative lear...

My first post into the bsky void, the first preprint of my PhD! A novel task to bridge learning and effort decision-making.

Of course, we find that effort choice is sensitive to prior learning, but this integration of beliefs into action is affected by anhedonia.

doi.org/10.1101/2025...

The effects of antidepressants on cardiometabolic and other physiological parameters: a systematic review and network meta-analysis We found strong evidence that antidepressants differ markedly in their physiological effects, particularly for cardiometabolic parameters. Treatment guidelines should be updated to reflect differences...

Fascinating and clinically important new paper. It highlights both reassuring and concerning findings on the cardiometabolic effects of #antidepressants.

Should post-initiation monitoring focus more on #metabolic changes than QTc?

www.thelancet.com/journals/lan...

Genetics of human handedness: microtubules and beyond Handedness (i.e., the preference to use either the left or the right hand for fine motor tasks) is a widely investigated trait. Handedness heritability is consistently estimated to be 25%. After decad...

Great review on The Genetics of Human Handedness: Microtubules and Beyond www.cell.com/trends/genet... - handedness is such an interesting phenotype!

Out today at Neuron, our experiments show that frontal cortical representation of economic variables is jointly determined by spatial organization and downstream
connectivity of neurons, revealing a structured, multi-scale code for economic variables. www.cell.com/neuron/fullt...

1/ To explore or to exploit? I’m excited to share my new preprint with @tobiasuhauser.bsky.social and @micahgallen.com, correlating variations in cortical microstructures with individual differences in exploration-exploitation behaviours, using a gamified task! 🧵 www.biorxiv.org/content/10.1...

Really interesting work by Bakhurin and colleagues challenging the reward prediction error hypothesis of dopamine:
www.nature.com/articles/s41...
I love this figure which both echoes and undermines the famous figure from Schultz et al. (1997).

Israeli Forces Kill 198 Palestinians in Gaza Over Three Days - News From Antiwar.com Israeli attacks have killed at least 198 Palestinians and wounded 786 in the Gaza Strip over 72 hours, according to death toll updates released by Gaza's Health Ministry, as Israel continues its US-ba...

“Israeli Forces Kill 198 Palestinians in Gaza Over Three Days”

It’s a genocide. Daily endless massacres, largely ignored in the West.

Familial confounding in the associations between maternal health and autism - Nature Medicine Using national registry data from Denmark, 30 maternal diagnoses linked to offspring autism were identified with most associations attributable to family-level factors rather than direct causal effects of maternal diagnoses.

Familial confounding in the associations between maternal health and autism www.nature.com/articles/s41... - drawing causal conclusions from observational studies is not a good idea

BlueSky friends, forgive me for not posting much on here. I'm standing for President of the RCPsych in the elections next March. I'm still speaking and listening to friends and colleagues about what is important, but you can learn about what I would do if successful here: www.profrobhoward.com

Implications for the field:
🔹 We found no evidence that mAb therapies increase depression risk in AD/PD.
🔹 Neuropsychiatric outcomes are rarely included in disease-modifying therapy trials.
🔹 Without proper measurement, we risk missing both potential benefits and harms.

Our meta-analysis found no significant difference in risk of depression with mAb therapy vs placebo (log risk ratio −0.24, 95% CI −0.52 to 0.04, p=0.09).

However, most trials excluded participants with depression at baseline and included no depression measures.

From 3000 studies we identified 13 RCTs (👥 8,603 participants: 4,690 treatment, 3,913 placebo)

All reported depression incidence as an adverse event.
‼️ *But* NONE assessed change in depressive symptom severity with mood scales.

Why does this matter?
#Depression is common (40% of pts), disabling & tough to treat in AD/PD.

Monoclonal antibodies (like lecanemab, donanemab etc) target pathological proteins (eg amyloid) but also trigger inflammatory & vascular changes—all mechanisms linked to depression.

Sage Journals: Discover world-class research Subscription and open access journals from Sage, the world's leading independent academic publisher.

New paper out in @journal_ad (led by Guy Gitlin-Leigh). @profrobhoward.bsky.social

We conducted the first systematic review + meta-analysis on whether monoclonal antibody therapies for #Alzheimer’s (AD) & #Parkinson’s (PD) affect risk of depression.
Link:

journals.sagepub.com/doi/10.1177/...

🚨Our preprint is online!🚨

www.biorxiv.org/content/10.1...

How do #dopamine neurons perform the key calculations in reinforcement #learning?

Read on to find out more! 🧵

Predictive Modelling of Depression Treatment Response using Individual Symptoms and Latent Factors Machine learning models have increasingly been used to identify predictors of treatment response in depression, and it is hoped that they may eventually help with clinical decision making. However, th...

Excited to share this new preprint on the Predictive Modelling of Depression Treatment Response using Individual Symptoms and Latent Factors with @clairegillan.bsky.social fresh up on @medrxivpreprint.bsky.social www.medrxiv.org/content/10.1...

Transitions in dynamical regime and neural mode during perceptual decisions - Nature Simultaneous recordings were made of hundreds of neurons in the rat frontal cortex and striatum, showing that decision commitment involves a rapid, coordinated transition in dynamical regime and neura...

How does the brain decide? 🧠

Our new @nature.com paper shows that neural activity switches from an 'evidence gathering' to a 'commitment' state at a precise moment we call nTc.

After nTc, new evidence is ignored, revealing a neural marker for the instant when the mind is made up.

rdcu.be/eGUrv

The studies I’m thinking of ⬇️. Any others?

jamanetwork.com/journals/jam...

www.thelancet.com/journals/lan...

Pretty sure the only large blinded RCTs of #GLP-1 agonists in psychiatry/neurology have been in #schizophrenia and #Parkinson’s disease—both found no core symptomatic benefit.

Fantastic drugs for metabolic health, but current trial evidence for broader neuro/psych use sadly isn’t promising.

‘Maintaining share of #NHS spend on mental health, will be critical although it fell last year and will again this year. It likely will continue to do so over the next 3years. I hope I am wrong.’

Worrying times for NHS #mentalhealth care which barely featured in the 10yr plan…

In #DeepBrainStimulation

the two major developments across the last decade have been

1. Adaptive DBS and
2. Connectomic DBS

In a @natrevneurol.nature.com article with @julianneumann.bsky.social, we ask:

Could the two be united into a common framework?

www.nature.com/articles/s41...

A 🧵