🧵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.

❌ Why We’ve Got Prescribing Exercise All Wrong 🚨1/10

There’s endless debate about “exercise” in mental health.

This evidence shows movement helps depression.

However, it doesn’t mean that medications or CBT aren’t useful.

The key is movement - matched to the right time, for the right person.

The aim is to get the brain moving!

So rather than say “go exercise, it’s good for you,”

👉 Here’s how I actually prescribe it 👇 1/10 1/ When I “prescribe exercise,” I’m not asking patients to suddenly become gym junkies.

The real target isn’t exercise. ❌

It’s movement. ✅

Because movement → cognition → emotional regulation.

🧵Could this single image help us understand PSSD? 🚨 1/14

PSSD - Post-SSRI Sexual Dysfunction can follow SSRIs, finasteride (PFS) or isotretinoin.

It’s often discussed as a peripheral problem.

But the genitals have a huge cortical footprint, deeply connected to emotion and salience networks.

Could functional brain changes be a key part of the puzzle?

Let’s explore 👇

*image from Dr Khaldoon Al Saee presentation on the Academy on The Neuroscience of Pain
#PSSD 1/ In the sensory homunculus, the genitals take up huge cortical real estate.

That’s not about anatomy size -it’s about sensitivity and signal importance.

🧵The Brain as a Predictive Organ: Why You Think You Know More Than You (may) Do 🚨1/10

You think you know it.

Wrong.

Your brain predicts that you know, SO you can feel like you know it.

Read it again

This is not a trick.

It’s the fundamental operating system of the brain-boxy connection

Diagram from article : Sammons M et al, Brain-body physiology: Local, reflex, and central communication. Cell. 2024 👇1/11 1/ The brain is an organ of prediction.

It doesn’t just react to reality - it rehearses it.

Prediction gives the body a head start.

A sense of certainty = reduced arousal = sense of the world

It’s why you salivate before food touches your lips.

🧵Vortioxetine in SSRI-Resistant OCD – Early Clinical Signals 🚨1/4

Study :

-64 adults with DSM-5 OCD
-SSRI non-responders
-Vortioxetine monotherapy ≥20 mg/day
-≥8 weeks treatment

👉Primary outcome: Y-BOCS

👉Secondary: HAM-D, HAM-A, adverse events

Results 👇1/4 1/ Results:

- 39.1% met responder criteria (≥25% ↓ Y-BOCS)

-Y-BOCS ⬇️from 27.1 → 20.7

-HAM-D and HAM-A improved significantly

-Most common SEs: nausea (29.7%), sedation (18.8%)

-No serious adverse events

🧵When Patients Feel Harmed by Treatment - Is There More to the Story? 🚨 1/21

This will get backlash.

It’s not about denying harm.

It’s about understanding how harm is experienced, amplified, encoded, and communicated and

how that understanding can help people move forward in a world that’s flawed and uncertain.

1/21👇 1/You’ve heard stories like:

“I was harmed by antidepressants.”
“These medications ruined my life.”
“I’m a shell of who I used to be.”

These experiences are real and often tragic.

But to truly understand them, we need to look beyond pharmacology - into personality, pain, and developmental templates.

🧵 Protracted SSRI Withdrawal and the Problem of Causality 🚨1/11

Much of the debate around “protracted SSRI withdrawal” stems from a misunderstanding of causality.

Let’s explore it using Rothman’s model: causality consists of

1️⃣Necessary causes
2️⃣Sufficient causes
3️⃣Component causes

Let’s apply it directly to this debate 👇1/11 1/ Necessary Cause = A cause that must be present for the outcome to occur.

In protracted SSRI withdrawal, the SSRI itself is a necessary cause.

You cannot have SSRI withdrawal without prior SSRI use.

But necessary ≠ sufficient.

🧵SSRI Withdrawal Is Real But So Are Other Possibilities 🚨1/11

This slide shows the withdrawal (discontinuation) symptoms from SSRIs-based on the Horowitz & Taylor paper (2019).

It’s a helpful summary. Right?

But now imagine this:

Someone stops their SSRI... and these symptoms continue for months or even years.

Protracted withdrawal? Easy ? Not quite 👇 1/ Protracted withdrawal.

It sounds clear, right?

But what actually makes it “protracted withdrawal”?

Let’s think clinically.