🧵The Stability Paradox in BPD: Why Attention-Seeking Is Not What You Think 🚨

Most misunderstand attention-seeking in BPD.

It’s not (always) conscious manipulation- often a deeply automatised habit shaped by implicit memory, predictive coding, and reward prediction errors (RPEs)

Let's break it down 👇 1/14 1/ Can you remember a time you trusted someone or something-only to realise it wasn’t true?

-A friendship that let you down?
-An exam you thought you’d ace but didn’t?
- A betrayal that left you questioning everything?

-That pain.
-The sinking feeling.
-The moment of shock.

🧵Lithium & Long-Term Risks: What You Need to Know 🚨

Lithium remains the gold standard for bipolar disorder (BD), but what are the risks for thyroid dysfunction and chronic kidney disease (CKD)?

And at what lithium levels do these risks emerge? 1/ 1/ A cohort study (2025) of patients with BD in Hong Kong (n=7,029) analysed the risk of hypothyroidism, hyperthyroidism, and CKD associated with lithium vs. other mood stabilisers.

The Paradox of BPD – When Diagnosis Becomes a Barrier to Care. 🚨 1/13

Borderline Personality Disorder (BPD) is a disorder of paradox.
Is the way we diagnose and treat it paradoxical, too?

Let's explore 👇 1/ A/ Prof Sandra Sulzer interviewed 22 clinicians in a 2015 study to understand how BPD patients are perceived.

7 psychiatrists, 8 psychologists, 5 Licensed Clinical Social Workers (LCSW’s), and 2 BPD activists.

Her findings? BPD is not just seen as difficult- it is often functionally demedicalized.

🧵The Unique Receptor Pharmacology of Clozapine: Acetylcholine in Focus 🧵 1/ 9

Let’s break it down. 👇 (From Morrison et al., 2025) 1/ Most antipsychotics antagonise muscarinic receptors.

Clozapine? It’s different.

It exhibits partial agonism at M4, while its metabolite norclozapine is a potent M1 agonist.

Could this be key to its unique clinical effects?

🧵Are you in the mood for a journal club?
Does Cannabis Cause Schizophrenia? 🚨

I've just finished an 8-hour teaching session on Critical Appraisal for Registrars on the wkend and am in the mood to jump into critical analysis.

Let’s break it down. 1/12 👇 1️⃣A population-based retrospective cohort study in Ontario, Canada, examined the Population Attributable Risk Fraction (PARF) of schizophrenia associated with Cannabis Use Disorder (CUD) over 17 years (2006–2022).

Does it meet Bradford Hill’s causality criteria?

🧵What Can RFK Jr. Teach Us About Pharmacology? 💊

Let’s explore Methylene Blue ( MB) 1/9 1/ Methylene Blue

The internet is abuzz speculating about Robert Francis Kennedy Jr adding Methylene blue to his drink.

MB is being ‘promoted’ for its health benefits-enhancing mitochondrial function, improving mood, and enhancing cognitive performance.

But could its benefits ( including the downstream mitochondrial effects) be likely tied to its MAO inhibition, which is often underplayed?

🧵ADHD & Evolution – An Adaptation or a Mismatch? 1/ 10 👇 1/ ADHD: An Evolutionary Advantage in the Wrong Era?

ADHD is, as the diagnosis states, framed as a disorder, but what if the traits that define it- impulsivity, hyperactivity, distractibility, and novelty-seeking- were once an adaptation?

What if these traits weren’t inherently dysfunctional but rather context-dependent, shaped by evolutionary pressures that made them advantageous in one environment yet challenging in another?

* Understanding ADHD through this lens doesn’t mean minimising the struggles it creates today. 🚨

Instead, it offers a broader perspective.

Let’s explore ADHD through an evolutionary lens.

🧵Antidepressants are no better than placebo – is this true? 1/8

Let’s break this down. 👇 1/ “Antidepressants only improve depression by 2 points!” Sounds damning, right?

Writes Moncrieff et al 👇

“Mean differences between antidepressants and placebo reported in meta-analyses of the Food and Drug Administration data set have ranged from 1.80 to 2.56 points on the widely used Hamilton rating scale for depression (HAM-D) [4], with effect sizes (d) ranging from 0.31 to 0.32”

🧵"Nothing in biology makes sense except in the light of evolution." – Theodosius Dobzhansky

What can Darwin teach us about mental health? 👇1/11 1/ I read this fascinating paper recently published - below is a summary : 👇

Evolutionary medicine views diseases not just as malfunctions but as outcomes of trade-offs, constraints, and mismatches shaped by natural selection.

“Despite being fit for the function that they carry out, adaptations are far from representing the ideal device that an engineer would design to solve a specific problem.

Instead, they are a "patch-work" of previously, reproductively speaking, successful intermediates, each intermediate with similar or different functions from the current one (Dawkins, 2016). “

SSRIs: A Double-Edged Sword? The Bleeding & Clotting Paradox 🧵 1/7

https://twitter.com/drkeithsiau/status/1886187875043065965

1/ SSRIs & Bleeding Risk 🩸

SSRIs inhibit serotonin uptake into platelets, depleting platelet serotonin stores by >80% (e.g., paroxetine).

Since 99% of blood serotonin is stored in platelets, this leads to impaired platelet aggregation, increasing the risk of bleeding diathesis.

This risk is exacerbated with concurrent NSAIDs and anticoagulant use.

Caution in elderly as well.

🧵Insulin Resistance & Psychiatry - We knew it then ; What's changed? 1/11 1/ We knew this in 2008. In my paper on antipsychotic-induced weight gain, I highlighted the role of metformin & topiramate in addressing metabolic dysfunction.

Yet, despite clear recommendations, monitoring rates remain poor. Has much changed?

🧵IPSRT: The Bridge Between Psychodynamic Therapy and Neurobiology in BPAD 1/11

Here is how I use this integration in psychoeducation in BPAD

*Lithium has the best evidence for prophylaxis and acute Rx of mania.

This post is aimed at showing how a psychodynamic and neurobiological understanding can enhance treatment. 1/ Interpersonal and social rhythm therapy (IPSRT) is an evidence-based treatment for Bipolar Affective Disorder (BPAD)

BPAD is shaped by both neurobiological rhythms and interpersonal dynamics influenced by early life experiences. (Approximately 30% to 50% of individuals with BPAD have experienced traumatic events in childhood.)

IPSRT bridges these two worlds.

*(the unconscious doesn't tend to be overtly discussed or applied in IPSRT, but we as clinicians can use this understanding to enhance Rx)

🧵ADHD meds & Raynaud’s Syndrome: Should we be monitoring? 1/10

Findings from a systematic review 👇 1/ What is Raynaud’s Syndrome (RS)?

RS is a peripheral vasculopathy causing impaired blood flow to extremities, leading to skin discolouration (pallor, cyanosis, erythema) and increased sensitivity to cold.

🧵 What is Borderline Personality Disorder (BPD)?

Here's how I conceptualise it: 👇 1/8 1/ BPD is best understood as a condition where developmental, neurobiological, and psychodynamic processes intersect.

At its core, unmet developmental needs or unresolved demands act as a chronic allostatic load on the individual.

🧵 The Leaky Umbrella: Critiquing the Serotonin & Depression Review 1/11

The Umbrella review in 2023 drew a lot of attention-
However, did you know how leaky the Umbrella was? ☔️

Let's find out 👇 1/11 1/ Methodological Weaknesses: An Inconsistent Umbrella

Combining different study types:

-The review mixed meta-analyses, systematic reviews, and primary studies inconsistently, making effect size comparisons unreliable.

-Overlapping data excluded: The authors avoided synthesising overlapping studies yet failed to use standard umbrella review methods to address this.

-Arbitrary scoring: They inconsistently applied a "modified GRADE" system, post-protocol.

For example: Confounding effects of antidepressants were considered only for positive outcomes, not negative ones. Established biomarkers were excluded arbitrarily, e.g., Yatham et al.’s imaging study.

A flawed methodological base leads to unreliable conclusions.
@sameerjauhar

🧵Pramipexole for Treatment-Resistant Bipolar Depression (TRBD)

Findings from an RCT 👇 1/6 1/ Study Design

A multi-centre RCT including 39 participants aged ≥18 with TRBD (failure to respond to or tolerate ≥2 of quetiapine, olanzapine, lamotrigine, or lurasidone).

Participants were randomized 1:1 to pramipexole (max 2.5 mg/day) or placebo alongside mood stabilisers.

🧵Sleep Deprivation & The Descent Into Psychosis 🚨

Ever wondered what happens when the Brain stays awake too long? 1/9

Let's explore 👇 1/ A systematic review of 476 studies (21 eligible) explored what happens to healthy individuals when deprived of sleep.

Duration of sleep loss ranged between 24 hours and 11 nights (total 760 participants; average 72–92 hours without sleep).

🧵 1/ 6 Sleep as a proxy for cognitive and emotional regulation.

REM sleep in particular plays an important role in emotional memory processing.

REM sleep, however, should be differentiated into

1. Restless REM sleep
2. Restful REM sleep

Following are implications of Restless REM sleep 👇 2/ Restless REM sleep interferes with emotional memory processing; if persistent, these adverse consequences may have a long-lasting impact on brain function.

👉The Frontoparietal network (FPN), which is the alerting network and the default mode network (DMN) activated during tasks that do not need significant attention, i.e. resting state, e.g. mind wandering, abstraction (DMN), are affected by sleep deprivation.

🧵The Neurobiology of Depression

1/8

“A unified theory of depression conceptualises MDD as a matrix of genetic, epigenetic, and environmental factors that interact with personality vulnerabilities that predispose an individual to information processing biases, stress reactivity, and belief formation that precipitate pathophysiological mechanisms across molecular, cellular, circuit, and behavioural levels.” 2/ Abnormalities in Monoamine Neurotransmission

👉Neurotransmitters are all interrelated and do not operate in isolation.

👉For example there are 14 different serotonin receptors that modulate other neurotransmitters via heteroreceptors.

👉Serotonin neurotransmission plays a role in emotional regulation and cognition. ( there is more but this is one example)

👉Similarly glutamatergic neurotransmission is involved in LTP and memory consolidation

👉Therefore, in the context of antidepressant drugs, their potential efficacy relies on the drug interacting with different monoamines and the interactions between sympathetic nervous, immune, and endocrine systems. [Leonard 2001]

🧵1/8 What if some of the most significant PTSD symptoms stem from experiences the DSM doesn’t even consider as triggers? 🚨👇

#PTSD #Trauma 2/ PTSD is often defined by the DSM as a response to life-threatening events, but emerging research reveals that 3 categories of events excluded from this definition-are strongly associated with PTSD symptoms.

🧵1/8 My Predictions for the Future of Psychiatry - 2025 and beyond 🚀👇 1/ Breaking Silos: Integration as the Next Frontier

👉The largest strides in psychiatry will emerge by recognising the brain’s role in top-down modulation of multiple organ systems, uniting disciplines like psychoneuroimmunology, psychoneuroendocrinology, behavioural sciences etc

👉This will dismantle outdated mind-body dichotomies, allowing us to see the brain, mind, and body as an interconnected whole.