🧵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.

🧵1/ Immuno-Metabolic Depression: The Overlooked Subtype? 🚨

Key points :

👉20-30% of people with depression experience significant immuno-metabolic dysregulation.

This subtype, is marked by:

1️⃣ Atypical, energy-related symptoms: hypersomnia, fatigue, hyperphagia, and anhedonia.

2️⃣ Systemic low-grade inflammation: elevated C-reactive protein, cytokines, and glycoprotein acetyls.

3️⃣ Metabolic abnormalities: obesity, dyslipidaemia, and insulin/leptin resistance.

🔍 Individuals with this profile face higher risks of cardiometabolic diseases and may respond poorly to standard antidepressants.

Treatment options :

1️⃣Antidepressants and their anti inflammatory effects ( when matched to certain markers)

2️⃣Anti inflammatory and lipid lowering agents

3️⃣Exercise

4️⃣Nutritional interventions
#depression #inflammation #metabolism 2/ “The etiological and phenotypic heterogeneity of depression is large. A more homogenous biology-based classification of depression could progress towards the promise of precision psychiatry rather than ‘one size fits all’ approaches.”

Paper 👉 thelancet.com/journals/lanep…

🧵 1/10 Understanding Chronic Emptiness in Borderline Personality Disorder (BPD) 🚨

Insights from a qualitative study 👇 1/ What is chronic emptiness in Borderline Personality Disorder (BPD)?

It’s more than sadness or loneliness; participants in studies describe it as a sense of nothingness and numbness.

A pervasive disconnection from self and others leaves individuals feeling unfulfilled and purposeless.

👉"Numb. It reminds me of a dead leg, kind of. Like, the sensation of the fuzziness is there."

👉"It’s like being in a dark room. And you’re just sitting in the middle of a completely dark room. And there’s nothing."

1/10 ADHD and Sleep 🚨

Grab a ☕ (or skip it if it’s late!), and let’s discuss the intricate relationship between ADHD and Sleep ✅

AND Why Sleep in ADHD is a crucial piece of the puzzle!👇

#SleepScience 2/ Sleep and wakefulness are evolved systems separating processes that would conflict if simultaneous.

Process C (Circadian): Regulated by retinal cells affecting dopamine and melatonin. Blue light disrupts melatonin, highlighting the role of sleep hygiene.

Process S (Homeostatic): Driven by adenosine accumulation during wakefulness, creating sleep pressure.

ADHD disrupts both processes- but there’s more to the story.

1/11 🧵 Exploring Complexity in Science: Stress, Diabetes, and the Interplay of Systems

What should clinicians know? 👇 2/ Complexity science helps us navigate uncertainty-not by providing absolute answers but by highlighting interconnected, non-linear relationships.

Stress and diabetes is an excellent example of how causality unfolds across time and systems. Let's explore.👇

🧵1/6 The ‘ADHD brain’ 🧠

"I get bored easily."

"I’m easily distracted."

Why do stimuli grab the brain’s attention so easily in ADHD? 👇

Let’s explore the neuroscientific principles 👇 1/ This is tied to the salience network, which mediates arousal and reward.

In ADHD, this network struggles to regulate what’s salient (important).

Reward and arousal become key players. Here's how 👇

🧵1/5 What do we know about the Neuroscience of Love? ❤️

Let’s explore 👇

https://twitter.com/drmarkhyman/status/1870503496551715064

1/ Love and Immune System Regulation ❤️

Study:
Over 2 years, researchers profiled immune cell gene expression in 47 women in romantic relationships.

Key findings:

👉Up-regulation of Type I interferon genes (enhancing antiviral immune responses via dendritic cells).

👉Down-regulation of neutrophil-related α-defensin genes (modulating innate immunity).

These effects occurred independently of illness, social isolation, or sexual activity.

Clinical Relevance:

👉Understanding how emotions modulate immune responses opens new avenues for psychosomatic medicine. - Affective Immunology

👉 Social relationships are associated with beneficial outcomes in inflammatory conditions

“People who have supportive close relationships have lower levels of systemic inflammation compared to people who have cold, unsupportive, conflict-ridden relationships.”

🧵1/14 Is C-PTSD replacing BPD ?

Why is BPD having to look over its shoulder ? 🚨

Let’s explore this shift 👇 2/ The growing recognition of complex PTSD (C-PTSD) highlights the longstanding limitations in how borderline personality disorder (BPD) has been conceptualised-particularly its neglect of :

1.Biological

2.Neurodevelopmental factors.

Predicting Parkinson's Disease : Early Clues That Matter 🚨🚨

Key messages :

1. Men with constipation, REM sleep behaviour disorder (RBD), and hyposmia have a 23x higher risk of developing Parkinson’s Disease (PD) within 3 years.

2. A probability of prodromal PD ≥0.8 predicts a 21x higher risk of PD diagnosis. ( probability of prodromal PD based on the Movement Disorders Society (MDS) research criteria)

3. Combining key non-motor symptoms provides stronger predictive power than individual symptoms.

4. Screening these signs may help identify individuals for early intervention and PD prevention trials. Study 👉 onlinelibrary.wiley.com/doi/10.1002/an…

🧵1/ Amygdala Functioning in ASD 🚨
The amygdala in patients with ASD has been associated with abnormal face processing. 2/ Although not yet fully understood, it is postulated that the failure of the amygdala to develop during the early stages of neurodevelopment may mediate amygdala habituation in ASD (i.e., amygdala responsiveness to repeated presentation of stimuli). [Tam et al., 2017]

Three important phenomena are linked to social communication difficulties: 👇

🧵1/ Is ADHD Management Missing the Bigger Picture?

A new study sheds light on the benefits and limitations of current treatments for ADHD 👇 2/ A systematic review and network meta-analysis (NMA) evaluated the comparative benefits and harms of pharmacological and non-pharmacological interventions for adults with ADHD.