Robert Y. Chen Profile picture
PGY-3 @UW Psychiatry. Prev MD-PhD @WUSTL. Biomarker and drug discovery for psychiatry, starting with Schizophrenia. Dog Daddy x2 to Taro and Azuki.
Oct 23 7 tweets 3 min read
🚨 Is ketamine effective for treating depression when tested in a trial that actually controls for confounders?

You be the judge:
» 3 point difference on MADRS vs control
» MADRS is a 60 point scale

How to reconcile this landmark study published yesterday in JAMA Psych 🧵Image 💉What to know about ketamine for depression

Ketamine has time and time again shown to be effective for treating depression:
✅ Treatment-resistance
✅ Bipolar depression
✅ Suicidality ↓Source: https://journals.sagepub.com/doi/10.1177/10398562251328805
Oct 9 6 tweets 3 min read
🚨 The older the sperm, the more likely it is to cause autism

Sequencing sperm using nearly error-free sequencing → measure % sperm carrying disease-causing mutations:

2% at age 30 → 4.5% at 70

Most were autism genes

New paper in @Nature today 🧵https://www.nature.com/articles/s41586-025-09448-3#Fig3 👴 Why does parental age matter?

• Spermatogonial stem cells produce millions of sperm daily, with a mutation rate 5–20x lower than other cells.
• Driver mutations in these cells can clonally expand, increasing their presence in sperm and potentially passing to offspring.
• Prior studies linked 13 genes to developmental disorders, but new tech (NanoSeq) now allows broader exploration.

x.com/KeithSakata/st…
Oct 2 7 tweets 4 min read
🚨 The FIRST RCT of antipsychotic discontinuation was published YESTERDAY.

Do antipsychotics in patients with first-episode psychosis actually improve long-term outcomes?

In short:

NO

But it's nuanced.

Here's what you need to know about this landmark paper in JAMA Psych🧵https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2839607 🤔 To Continue or Taper?

Antipsychotics (APs) are a staple of preventing relapse in Schizophrenia, but long-term studies are mixed.

Wunderlink et al. (% with functional recovery):
» Continue: 17.6%
» Discontinue or dose reduce (DRD): 40.4%

Chen et al. (% patients with poor outcomes):
» Continue: 21%
» DRD: 39%

Neither study was a randomized controlled trialSource: Source: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/1707650?utm_campaign=articlePDF&utm_medium=articlePDFlink&utm_source=articlePDF&utm_content=jamapsychiatry.2025.2525
Sep 27 8 tweets 5 min read
🌤️ Cognitive Behavioral Therapy

You hear it all the time.

But what is it actually?

And why is it so effective?

Therapy is shrouded with mystical know-how that doesn't need to be complicated.

Here are the five core concepts you need to know to start CBT right now 🧵Meta-analysis of CBT modalities compared to care as usual or waiting list. Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC6583673/ 📐 The Cognitive Triangle

The core idea of CBT is the Cognitive Triangle:

An event happens that triggers us → what happens?
• Automatic thoughts ♻️Emotions ♻️Behaviors

CBT is the process of recognizing this cycle → breaking it → leveraging itImage
Sep 14 6 tweets 3 min read
🚨 Cannabis was once thought harmless, with boundless benefits.

But since 2005 to today:
» Cannabis use disorder: ↑500%
» Psychosis not otherwise specified: ↑84%
» Schizophrenia: ↓27%..??

Explaining the paradox of this study of 13 MILLION people published this year 🧵Source: JAMA Network Open. 2025;8(2):e2457868. doi:10.1001/jamanetworkopen.2024.57868 📔 Schizophrenia is diagnosed based on the DSM-5 criteria

» Positive symptoms: psychosis, delusions, disorganization
» Negative symptoms: alogia, avolition, emotional blunting

Crucially, Criterion E states: "not attributable to the physiological effects of a substance"Source: https://www.psychdb.com/psychosis/schizophrenia-scz
Aug 11 11 tweets 6 min read
🚨Should we put Lithium in the water supply?🚨

Microdosing Lithium may protect against Alzheimer's disease.

But not just any Lithium - a very specific form of a Lithium salt.

Here's what you need to know about the @Nature paper the anti-aging community is talking about 👇Image 💊Lithium was an accident

In the 1940s, an Australian psychiatrist John Cade accidentally discovered anti-manic properties of Lithium.

He had this theory that bipolar disorder could be transmitted via toxins in the urine.

So, he took urine from patients with mania and injected them into guinea pigs.

The guinea pigs died.

He realized that what was killing the mice was the highly concentrated uric acid that was crystallizing into urate. At that time, it was well known that Lithium could help dissolve urate crystals.

So, John Cade tried the experiment again, this time adding Lithium to the patients' urine before injecting into guinea pigs.

The result? The guinea pigs got sleepy.

John Cade interpreted these results to mean that Lithium might have calming or anti-manic properties.

After first testing Lithium on himself, he then trialed it in 10 manic patients, leading to the landmark discovery of Lithium as an anti-manic medication.

Definitely some cowboy psychiatry...Image
Nov 11, 2020 10 tweets 8 min read
How do the hundreds of genetic risk-factors for #Schizophrenia actually lead to disease? New work medrxiv.org/content/10.110… from @manoliskellis illuminates the #SingleCell landscape of #Brains from patients with #Schizophrenia and their healthy counterparts🔬🧠🧵1/10 Combining single-nuclear RNA-Seq @10xGenomics, barcode #ing, and multi-level cell-state decomposition, first author Brad Ruzicka et al. identify 20 cell types in the prefrontal cortex of 24 patients with #Schizophrenia and 24 controls 2/10
Nov 8, 2020 11 tweets 6 min read
Why is it becoming harder to #remember things you have recently read? New work nature.com/articles/s4158… out in @nature from Anthony Wagner's group @Stanford explore how multi-media #multitasking impacts a specific axis of #attention that in turn, impacts our #memory📱🧠🧵1/11 Image When we're reading a book and simultaneously checking our #twitter or #finsta feeds, we're not actually multitasking - we're task-switching! We switch our focus from one goal to another, interrupting our train of thought and scattering our #attention 2/11 Image