🧵What are the differences between Ketamine and Memantine - 🚨1/7

Both are NMDA antagonists - But with different clinical effects.

Here’s why 👇 1/ Receptor selectivity

-Memantine → preferentially blocks extrasynaptic NMDARs (excitotoxic signalling)

-Ketamine → blocks synaptic + extrasynaptic NMDARs

- Ketamine is non-selective (muscarinic, monoaminergic, opioid effects → psychotomimetic profile)

🧵A process in cancer may hold clues for psychiatry. 🚨1/10

Let’s talk about the Warburg Effect 👇 1/ In cancer, one of the earliest changes isn’t a mass or a tumour.

It’s a metabolic shift.

Despite oxygen being available, ~70–80% of cancers switch from efficient mitochondrial respiration to aerobic glycolysis.

This is the Warburg effect first described over a century ago.

🧵Is treatment response to Stimulants ‘mis’...leading to ADHD misdiagnoses? Pathomodal vs Physiomodal? 🚨1/15

Vyvanse has now overtaken Ozempic as the most prescribed agent in Australia.

That fact alone should make us pause. 🚨 1/ Prof Michael Berk has just published an important editorial in the British Journal of Psychiatry that articulates something many clinicians feel but rarely name.

It’s about treatment response and how it quietly shapes diagnosis

🧵Antidepressants don’t act on a unitary construct called “misery”.🚨1/11

They act on various systems.

Fear.
Salience.
Reward.
Cognition.
Pain.
Inflammation.
Arousal.
Behavioural activation…..etc

That distinction matters.

Let me explain 👇

https://twitter.com/stimimi/status/2010247051133759708

1/ These medications are multifaceted in their mechanisms of action that allow the pharmacologist to target specific domains.

Like Metformin, GLP-1 agonists, SGLT2 inhibitors, etc, we've moved away from 'antidiabetics' to greater nuance.

So let's look at 'Antidepressants' and the various MOAs

🧵The Comeback. “ADHD is a circadian rhythm disorder” is trending. Is it? 🚨1/12

Useful lens? Yes. ( Good on @NTFabiano and @BrandonLuuMD in highlighting it)

Complete model? No.

Back in 2019, Bijlenga, Vollebregt, Kooij & Arns asked the question directly: is it time to redefine ADHD? -Based on circadian system dysfunction

Here is how to conceptualise it 👇 1/ Sleep problems in ADHD are heterogeneous.

Delayed sleep phase is common in ADHD. ( a focus on the ‘clock’)

But “ADHD sleep” is not one thing.

You can have:

-delayed phase
-sleep-onset insomnia
-fragmented sleep
-RLS/PLMS
-parasomnias
-REM dysregulation / nightmares
-sleep-disordered breathing
…
Different mechanisms.

Different interventions.

🧵Six suggestions for clinicians about diagnosis (whether or not DSM-6 changes) 🚨1/9

DSM committees focus on labels - creation, modification and omission.

But there are six diagnostic habits clinicians can adopt now that materially change practice and remain a constant. 👇

https://twitter.com/awaisaftab/status/1991656715901964436

1️⃣ Treat diagnosis as a process, not an endpoint

Diagnostic work is iterative hypothesis-testing, not a one-step assignment of a label.

Move deliberately through: history → diagnostic hierarchy → formulation → only then, if useful, a categorical diagnosis.

🧵 When the Brain Mistakes Its Own Voice 🚨1/17 ( long thread - but worth it 😁)

A 2025 EEG study found that in schizophrenia, inner speech isn’t suppressed - it’s amplified. 🔥

In ‘healthy’ brains, inner speech ‘quiets’ the auditory system.

In schizophrenia, it amplifies it - the brain reacts as if someone else is speaking.

Why does that happen?

And what does it teach us about treating psychosis?

Let’s unpack what this means for clinical practice 👇

TL;DR:
The disrupted inner speech suppression response shows how integration between self and other breaks down in schizophrenia.

Understanding this isn’t academic ; it’s central to how we use neuroscience, pharmacology, and learning to restore that integration in clinical practice….. 1/ Psychosis isn’t just about voices or dopamine.

It’s a failure of the brain to distinguish self-generated from external signals. ( one component)

The efference copy normally tells us,

“That sound, that thought, that movement 👉it’s mine.”

When it fails, the brain misattributes internal activity to the outside world.

Clinically, change isn’t all-or-none - it’s about modulation, calibration, and meaning.

🧵What If Psychiatry ( and Neurology) Begins in the Retina? 👁️🚨

They say the eye is the window to the world BUT what if it’s the window to the brain itself.

Stay with me, this one’s a ride. 1/15 👇#WCP25 #WCP2025 1/At #WCP25 Attended a talk by Prof Tomas Paus and this one theme stood out - the retina.

Not the cortex or neurotransmitters we often discuss, but the eye itself as the starting point of cortical organisation and neurodevelopment.

🧵ADHD - Mimic and Mimicked. 🚨
Sitting for an ADHD discussion session

My insights 💡👇

ADHD presentations, like many conditions in psychiatry, are heterogeneous. 1/5

#WCP25 #WCP2025 1/ What we often call “ADHD” is a cluster of domains -

1. Cognition
2. Activity
3. Reward sensitivity
4. Behavioural activation and inhibition
5. The fight/flight system
6. Sleep circuits.

3+4+5 are part of the affective system ( Yes Emotional and Affective Regulation is core - yet strikingly absent in ADHD diagnostic scales / tools! ) 🚨

Others modulate 3,4 and 5 #WCP25 #WCP2025

🧵 Behavioural Addictions: Neuroscience, Habits & Unmet Needs 🚨1/8

Prof Henrietta Bowden-Jones spoke today on behavioural addictions- gambling, gaming, porn use …..

She emphasised the importance of neuroscience, noting how it remains “neglected.”

That’s precisely the issue. My thoughts 👇
#WCP25 #WCP2025

1/ As a psychiatrist who work in addiction psychiatry - Understanding neuroscience is crucial because the brain doesn’t label behaviours as gambling or porn.

It consolidates habits through the same reward-based learning mechanisms - prediction, reward, error, repetition.

#WCP25 #WCP2025

🧵Prof Martinotti speaking on the role of D3 receptor partial agonism in substance use in SCZ. #WCP25 1/3

Third generation antipsychotics - Partial agonists can play an important role in substance related psychosis.

Third generation APs can facilitate this treatment process by enhancing PFC function and reward related mechanisms.

My thoughts 👇1/3
1/ Role of D3 receptors #WCP25 #WCP2025

🧵Finished a busy series - 7.5 hours on Depression 🚨1/11
Here are 5 Maxims that guide how to manage depression in real life.

For GPs & psychiatrists alike.

And the Aha 💡 moments from participants which is what inspires me .. 👇 1/ Maxim 1: Define the depression

Is this a mild, single-domain case (low mood, anxiety)…

Or is it a multi-domain depression affecting activity, cognition, and emotion?

👉 If you don’t ask, you’ll miss the type.

👉“Hats off for your persistence for getting to bottom of the case. Very inspirational.”

In clinical practice persistence is about identifying barriers to improvement by taking a broader lens and seeing depression as a heterogenous construct.

🚨Depression vs Cholesterol: Which Matters More After a Heart Attack? 1/10

After a myocardial infarction, our focus is on LDL, BP, HbA1c ( rightly so)

But one silent factor predicts death more than obesity or cholesterol🚨

What if the real key to survival lay in something psychiatry knows best👇 2/ That factor is Depression and exhaustion (DEEX)

The DEEX subscale from the von Zerssen checklist measures 8 simple symptoms:

-Irritability
-Fatigue
-Tiredness
-Inner tension
-Loss of energy
-Difficulty concentrating
-Nervousness
-Anxiety

Looks ‘psychological.’

But the outcomes aren’t.

🧵STAR*D and the Cost of Neglecting Phenomenology in Depression 🚨1/11

Finished a talk for GPs on 👉Depression and its forms – over 300 registrations.

Today was about spotting the various forms of depression.

Patients come with signals.

Our role is to see the wrapper around those signals - is it embedded within a wider construct?

That’s where the answers lie. 👇 1/ STAR*D is often described as a pragmatic trial.

But here’s the paradox
It wasn’t truly pragmatic.

Here is a key fact 👇

Nearly half the sample had anxious depression - overlapping with melancholic, mixed, and psychotic features.

What the trial did was treat every depression the same - the opposite of what real-world practice demands.

STAR*D was a perfect example of what happens when phenomenology is ignored.

🧵Medications in Borderline Personality Disorder (BPD)🚨1/15

A common belief persists: “medications don’t work in BPD.”

This false split 👉psychotherapy vs. pharmacology👉prevents optimal outcomes.

Here’s why that view is misleading, and how to think differently. 👇

#BPD #medications #psychiatry 1/ Psychotherapy is essential in BPD.

No question.

But dismissing medications outright ignores neurobiology.

Patients with BPD often carry comorbid psychiatric and physical conditions.

Emotional dysregulation is not split from biological processes underpinning it

Leaving those untreated means leaving suffering unaddressed.

🧵Difficult-to-Treat Depression: What’s Resistant- and What’s Misunderstood?🚨1/14

In psychiatry, we often label complex cases as treatment-resistant.

But that term suggests the illness is the problem.

What if the issue lies in how we think-not just what we treat?

Let’s shift from labels to clinical reasoning. 👇 1/ Depression is frequently reduced to sadness or low mood.

But these symptoms, while common, are not central to every presentation.

Instead, depression involves dysfunction across three core domains:

Activity, Cognition, and Emotional Hedonics (ACE)

🧵Clonidine vs Zopiclone in Sleep and Pain - Who’s the Winner ? 🚨1/7

Zopiclone - A z drug acting via allosteric modulation at GABA-A receptor

Clonidine - an Alpha-2 agonist .

Let’s explore 👇1/7 1/ Clonidine is an alpha 2 agonist.

-α2A (tonic) = stabilises attention, calms hyperarousal

-Presynaptic α2 = reduces noradrenaline release

🧵It’s Not All GLP-1: Why Psychiatrists Shouldn’t Forget Metformin 🚨1/7

GLP-1 agonists are getting all the hype in psychiatry.

But we shouldn’t forget metformin -less dramatic upfront, but still effective long-term in many patients.

Here’s why psychiatrists should look closer 👇 1/ Metformin’s relevance in psychiatry goes beyond glucose control.

It acts on:

1. Peripheral insulin sensitivity → improves glycaemia

2. AMPK activation → ↓ systemic inflammation & oxidative stress

3. Brain insulin resistance (BIR) → a mechanism now linked to psychosis, mood disorders & treatment resistance

🧵New JAMA paper: GLP-1 agonists show metabolic benefits in psychiatric patients. 🚨1/7

Weight ↓ | HbA1c ↓ | QoL ↑ | No adverse MH outcomes.

The question isn’t if these work.

It’s whether we implement them in psychiatry. 👇 1/ For over a decade, psychiatry has recognised the metabolic burden of antipsychotics.

We’ve known about

-Metformin
-Topiramate

And now:

-GLP-1 receptor agonists (Semaglutide, Liraglutide, Tirzepatide etc )

The data keep coming.

Yet metabolic outcomes?…

🧵Psychiatry as a Scapegoat-And the Mirror We’d Rather Not Face 🚨1/11

‘Psychiatry isn’t real medicine.’
‘Psychiatry medicalises normal life.’
‘Psychiatry is pseudoscience.’
‘Psychiatry is dangerous.’
‘Psychiatry is built on lies’

Psychiatry is the perfect object of projection.

Let’s explore 👇 1/ For physicians

It is where bias, feelings of helplesness, the medically unexplained (and uncertain) and inadequate (MH) training are displaced.

A refuge that protects the ego against the threat of incompetence,
while clinging to the false comfort of the mind–body split.

🧵What Doctors Do When the Evidence Runs Out 🚨

Evidence-based medicine is the mantra.

But what happens when there’s no evidence?👇1/9 1/ Prof David Isaacs & Dr Dominic Fitzgerald wrote a tongue-in-cheek classic categorising how clinicians actually make decisions.