Harry Costello
@drharrycostello.bsky.social
Academic neuropsychiatrist | MD PhD | Clinical Lecturer @UCLPsychiatry | Mood, Motivation & Neurodegeneration | Aspiring apiarist
Pinned
Impaired reward sensitivity in Parkinson's depression is unresponsive to dopamine treatment
Depression in Parkinson’s disease is common and disabling, and often includes motivational symptoms such as apathy and anhedonia. Costello et al. show that
doi.org
Delighted our ( @jonroiser.bsky.social @profrobhoward.bsky.social) paper is now out in @brain1878.bsky.social ! 🎉🧠
We show that #Parkinson's #depression may stem from a reduction in reward sensitivity that is unresponsive to dopaminergic medication:
🔗 doi.org/10.1093/brai...
🧵⬇️
We show that #Parkinson's #depression may stem from a reduction in reward sensitivity that is unresponsive to dopaminergic medication:
🔗 doi.org/10.1093/brai...
🧵⬇️
Reposted by Harry Costello
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.
One for the heredity scolds: construct a multi-tissue GRM where people
are differentially related to themselves.
www.nature.com/articles/d41...
are differentially related to themselves.
www.nature.com/articles/d41...
We are all mosaics: vast genetic diversity found between cells in a single person
Technical advances allow researchers to trace the genetic changes that occur over time.
www.nature.com
November 30, 2025 at 8:00 PM
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?
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?
November 24, 2025 at 5:35 PM
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?
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?
Reposted by Harry Costello
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.
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.
The CDC website now disseminates disinformation about vaccines, claiming erroneously that infant vaccines might cause autism, when we know conclusively that they do not. It is difficult to overstate just how dangerous this is. www.cdc.gov/vaccine-safe...
November 20, 2025 at 2:03 PM
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.
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.
Reposted by Harry Costello
Academics in Assyria in the 7th c BC complain that admin is preventing them from doing research and teaching
November 3, 2025 at 10:04 AM
Academics in Assyria in the 7th c BC complain that admin is preventing them from doing research and teaching
Reposted by Harry Costello
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...
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...
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...
doi.org
August 1, 2025 at 10:00 AM
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...
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...
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...
Should post-initiation monitoring focus more on #metabolic changes than QTc?
www.thelancet.com/journals/lan...
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...
www.thelancet.com
October 22, 2025 at 11:37 AM
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...
Should post-initiation monitoring focus more on #metabolic changes than QTc?
www.thelancet.com/journals/lan...
Reposted by Harry Costello
Great review on The Genetics of Human Handedness: Microtubules and Beyond www.cell.com/trends/genet... - handedness is such an interesting phenotype!
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...
www.cell.com
October 16, 2025 at 6:12 PM
Great review on The Genetics of Human Handedness: Microtubules and Beyond www.cell.com/trends/genet... - handedness is such an interesting phenotype!
Reposted by Harry Costello
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...
connectivity of neurons, revealing a structured, multi-scale code for economic variables. www.cell.com/neuron/fullt...
October 16, 2025 at 3:00 PM
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...
connectivity of neurons, revealing a structured, multi-scale code for economic variables. www.cell.com/neuron/fullt...
Reposted by Harry Costello
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...
October 15, 2025 at 11:57 AM
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...
Reposted by Harry Costello
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).
www.nature.com/articles/s41...
I love this figure which both echoes and undermines the famous figure from Schultz et al. (1997).
October 14, 2025 at 11:05 AM
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).
www.nature.com/articles/s41...
I love this figure which both echoes and undermines the famous figure from Schultz et al. (1997).
Reposted by Harry Costello
“Israeli Forces Kill 198 Palestinians in Gaza Over Three Days”
It’s a genocide. Daily endless massacres, largely ignored in the West.
It’s a genocide. Daily endless massacres, largely ignored in the West.
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...
news.antiwar.com
September 29, 2025 at 3:42 AM
“Israeli Forces Kill 198 Palestinians in Gaza Over Three Days”
It’s a genocide. Daily endless massacres, largely ignored in the West.
It’s a genocide. Daily endless massacres, largely ignored in the West.
Reposted by Harry Costello
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
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.
www.nature.com
September 24, 2025 at 7:12 PM
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
Reposted by Harry Costello
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
ProfRobHoward
www.profrobhoward.com
September 21, 2025 at 3:06 PM
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.
🔹 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.
September 22, 2025 at 7:58 AM
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.
🔹 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.
However, most trials excluded participants with depression at baseline and included no depression measures.
September 22, 2025 at 7:58 AM
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.
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.
All reported depression incidence as an adverse event.
‼️ *But* NONE assessed change in depressive symptom severity with mood scales.
September 22, 2025 at 7:58 AM
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.
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.
#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.
September 22, 2025 at 7:58 AM
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.
#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.
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/...
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/...
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journals.sagepub.com
September 22, 2025 at 7:58 AM
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/...
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/...
Reposted by Harry Costello
🚨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! 🧵
www.biorxiv.org/content/10.1...
How do #dopamine neurons perform the key calculations in reinforcement #learning?
Read on to find out more! 🧵
September 19, 2025 at 1:05 PM
🚨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! 🧵
www.biorxiv.org/content/10.1...
How do #dopamine neurons perform the key calculations in reinforcement #learning?
Read on to find out more! 🧵
Reposted by Harry Costello
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...
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...
www.medrxiv.org
September 19, 2025 at 11:58 AM
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...
Reposted by Harry Costello
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
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
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...
www.nature.com
September 17, 2025 at 8:12 PM
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
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...
jamanetwork.com/journals/jam...
www.thelancet.com/journals/lan...
September 13, 2025 at 7:58 PM
The studies I’m thinking of ⬇️. Any others?
jamanetwork.com/journals/jam...
www.thelancet.com/journals/lan...
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.
Fantastic drugs for metabolic health, but current trial evidence for broader neuro/psych use sadly isn’t promising.
We know GLP-1 drugs reduce brain inflammation. But I didn't anticipate bipolar disorder as a possible indication in the future
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Glucagon-like Peptide-1 receptor agonists as emerging therapeutics in bipolar disorder: a narrative review of preclinical and clinical evidence - Molecular Psychiatry
Molecular Psychiatry - Glucagon-like Peptide-1 receptor agonists as emerging therapeutics in bipolar disorder: a narrative review of preclinical and clinical evidence
www.nature.com
September 13, 2025 at 7:58 PM
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.
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…
Worrying times for NHS #mentalhealth care which barely featured in the 10yr plan…
National mental health director Claire Murdoch resigns with immediate effect claiming political pressure for a new person...her resignation letter....👀
September 12, 2025 at 11:44 AM
‘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…
Worrying times for NHS #mentalhealth care which barely featured in the 10yr plan…
Reposted by Harry Costello
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 🧵
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 🧵
September 3, 2025 at 7:59 PM
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 🧵
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 🧵