Sleep isn’t just “off.”

The locus coeruleus (LC), the brain’s noradrenaline hub, stays active in a patterned way, shaping when we sleep deeply, dream, or wake too easily. (Osorio-Forero 2022)

Here’s why it matters clinically.

1/11🧵 Classic view: LC goes quiet at night.

Revised view: it’s state-dependent.

• NREM: activity is low but rhythmic.
• REM: LC neurons are almost completely silent.

2/11🧵

How Can Dissociation Exacerbate PTSD?

Most view dissociation as a secondary trauma symptom.

However, clinical data suggests it is a maladaptive state that actively increases PTSD severity by denying the brain the opportunity to process traumatic memories (Ozer et al. 2003)

Rather than a temporary homeostatic pause, dissociation is a state of emotional over-modulation linked to poorer prognoses and higher risks of self-harm or suicide.

Here’s a breakdown of how dissociation exacerbates PTSD👇🧵 Dissociation in PTSD is often associated with the emotional overmodulation subtype (PTSD+DS).

In this phenotype, neuroimaging models describe increased top-down regulation of limbic reactivity by medial prefrontal regions, sometimes referred to as the corticolimbic inhibition model (Lanius et al., 2010).

This means traumatic reminders may trigger not hyperarousal, but instead a detached shutdown state, reducing defensive emotional engagement.

Why Is Psychotherapy Often Limited During Active Addiction?

Psychotherapy is essential in addiction care, but during active substance use or acute withdrawal, the brain may be in a state where higher-order cognitive engagement is biologically constrained.

Addiction is not simply a disorder of 'insight'.

It is a disorder of neurocircuitry.

Here’s the neuroscience behind why treatment sequencing matters: 🧵👇 Addiction Impairs Prefrontal Control (“Hypofrontality”)

Chronic substance use is associated with structural and functional disruption in prefrontal regions responsible for:

 • executive function
 • inhibitory control
 • decision-making
 • salience regulation

Imaging studies show reduced metabolic activity in the OFC, ACC, and DLPFC in addiction.

This state is often described as hypofrontality, a compromised capacity for sustained top-down regulation.

Can Smoking Compromise Antipsychotic Efficacy in Schizophrenia?

The interaction between smoking and schizophrenia is complex and multifaceted, with patients consistently showing higher rates of tobacco smoking and heavy nicotine dependence.

One important consideration is the influence smoking has on the CYP450 system.

🧵👇 The isoenzyme CYP1A2 is highly induced by smoking tobacco.

CYP1A2 is the main enzyme involved in the metabolism of the antipsychotics clozapine and olanzapine.

Why Does Sleep Therapy Often Fall Short in ADHD?

Traditionally, sleep issues in ADHD are viewed as the result of poor sleep hygiene.

However, clinical data suggests these disturbances are intrinsic, biologically wired into the ADHD phenotype via clock gene polymorphisms (Bijlenga et al., 2019).

This renders sleep therapy often insufficient, as it ignores the underlying pathophysiological drivers of the ADHD sleep phenotype.

Here’s a breakdown of why sleep therapy often falls short in ADHD:🧵👇 The reason why standard sleep therapy falls short often begins with ADHD's "intrinsic" biological clock.

Sleep issues in ADHD are tied to clock gene polymorphisms (e.g., CLOCK, PER2) that set the internal timer to a later zone.

This chronobiological mismatch causes a 1.5–2 hour delay in Dim Light Melatonin Onset (DLMO), resulting in a biological "jet lag" that persists daily.

Standard "early to bed" advice may fail because the biological "sleep gate" is physically closed until much later.

Why Do Some PTSD Patients “Explode” With Hyperarousal While Some "Implode" Into Dissociative Detachment?

Traditionally, PTSD is viewed through a lens of sympathetic hyperactivity.

However, clinical data suggests that while 70% of PTSD patients manifest hyperarousal, the other 30% respond with dissociative detachment (Lanius et al., 2006).

This subtype of PTSD portrays a distinct neural phenotype characterised by emotional over-modulation.

Here's a breakdown of this neurobiological divergence: 🧵👇 The classic hyperarousal PTSD phenotype represents emotional under-modulation.

Neurobiologically, this manifests as a failure of cortical inhibition.

Upon threat exposure, the amygdala (threat detection) and insula (interoception) become hyperactive.

Crucially, the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC) fail to exert top-down inhibitory control over these limbic structures, resulting in overwhelming emotional and sympathetic flooding.

How Can Obstructive Sleep Apnoea (OSA) Exacerbate ADHD?

While often treated as distinct comorbidities, the relationship between OSA and ADHD is bidirectional and synergistic.

Research indicates that sleep-disordered breathing significantly worsen the core symptoms of ADHD, particularly inattention and irritability.

This occurs because OSA triggers repeated micro-arousals, preventing the brain from reaching restorative sleep stages.

Here’s a breakdown of OSA-ADHD’s pathophysiological interplay:🧵👇 The mechanism of OSA-induced ADHD exacerbation is driven by severe sleep fragmentation.

In OSA, repeated airway collapse forces the brain to exit deep sleep to resume breathing.

Each collapse triggers a micro-arousal that resets the sleep cycle resulting in chronic deprivation of restorative sleep, leading to prefrontal cortex (PFC) dysfunction.

This fragmentation directly impairs the neural circuits required for executive function and sustained attention the following day.

Why Does Withdrawal Induce Hyperkatifeia not just Anhedonia?

In treating addiction, most focus on mitigating withdrawal-induced Anhedonia—the loss of pleasure.

However, clinical data suggests chronic substance use triggers a shift toward Hyperkatifeia, an increase in the intensity of negative emotional states.

Instead of a simple loss of pleasure, the brain becomes hyper-sensitised to emotional distress and physical pain.

Here's a breakdown of this maladaptive stress adaptation of addiction:🧵👇 The shift from Anhedonia to Hyperkatifeia is driven by a "Between-System" neuroadaptation.

While the reward system (Ventral Striatum) becomes desensitised, the Brain Stress Systems (Extended Amygdala) become pathologically overactive.

In withdrawal, the brain doesn't just lose its positive reinforcement state; it upregulates the Corticotropin-Releasing Factor (CRF) and Dynorphin systems to create an active, agonising state of dysphoria that demands immediate relief.

Borderline Personality Disorder (BPD) is an inherently heterogeneous condition, characterised by profound emotional dysregulation and unstable interpersonal patterns.

To assist clinicians in deciphering this complexity, BPD symptoms are often classified into four distinct clinical phenotypes.

Building on the classifications shown in the diagram, here is a deeper breakdown of the symptomatic drivers clinicians must be familiar with: 1. Interpersonal Instability:

Patients frequently exhibit patterns of unstable and conflicted relationships, alternating between intense over-involvement and abrupt social withdrawal.

This instability is often driven by dichotomous thinking—or "splitting"—where others are perceived as either entirely supportive or entirely rejecting.

These volatile cycles are typically rooted in a pervasive fear of abandonment and heightened sensitivity to perceived rejection.

Why is Borderline Personality Disorder (BPD) in Women Misdiagnosed as Bipolar Type 2 (BDII)?

Traditionally, intense affective instability in women is reflexively labelled as Bipolar Disorder.

However, clinical data suggests that a significant subset of patients with BPD are misdiagnosed with BDII—a figure that skews higher in women due to gendered diagnostic bias.

Here's a breakdown of why BPD in women gets misdiagnosed as BDII: 👇🧵 Misdiagnosing BPD as BDII in women starts when "affective instability" is misinterpreted.

BDII: Mood shifts are "autonomous" and episodic, lasting days regardless of external events.

BPD: Shifts are "hyper-reactive," triggered by interpersonal stress or perceived rejection.

Clinicians reflexively mistake the BPD's "reactive high" for hypomania, when it is actually an attachment-based survival reflex to avoid abandonment, not a spontaneous metabolic cycle seen in BDII.

Are "Feelings" and "Emotions" the Same Thing?

Linguistically, we use these terms interchangeably, assuming the difference is merely semantics.

However, studies revealed that they are distinct physiological events occurring in two different "theatres" (Damasio, 2003).

• Emotion = Theatre of the Body (unconscious physiological arousal)

• Feeling = Theatre of the Mind (conscious interpretation)

Here’s the neurobiological breakdown of the distinction between the two and why it matters clinically: 👇🧵 The Neural Substrate of “Emotion”

An emotion is a pre-conscious biological reflex.

It is an immediate physiological response to a "competent stimulus" (a threat or reward) before awareness sets in.

• The Amygdala detects the stimulus

• The Hypothalamus orchestrates the hormonal release

•  The body acts

All of this occurs milliseconds before the "mind" even knows what it “feels.”

Example: You jump back from a snake-like shape before you consciously identify it as a stick.

The emotion is the action.

How Do Brain Functions Differ in Patients With Autism Spectrum Disorder (ASD)?

ASD involves complex neurobiological shifts across distinct functional domains.

While once viewed as a simple behavioural “deficit,” studies revealed a pattern of atypical connectivity and structural organisation that alters how the brain processes social and sensory data.

Meaning, the ASD brain follows a unique computational logic rather than a "broken" one.

Here’s a breakdown of the neurobiological substrate of ASD: 👇🧵 The Connectivity Paradox

ASD is characterised by a "disconnection syndrome" in how the brain organises information. 

This stems from an imbalance where local neural circuits are over-developed at the expense of global integration.

• Long-range under-connectivity: Reduced communication between the frontal and posterior regions.

• Local over-connectivity: Excessive neural density in sensory zones.

This explains why patients excel at details but struggle with global behavioural integration.

There are no ‘silver bullets’ in psychiatry…

Knowing that a treatment exists is not the same as knowing when to use it, how to explain it, or where it fits in a patient’s journey.

Here are 10 clinical insights from The Academy to take into 2026 🧵👇

(Prof Michael Berk) (Prof David Barton) 1. Formulation is not reflective writing, it is the architecture of care.

Formulation must directly guide what you do next and why. If a formulation cannot be operationalised into a management plan, monitoring strategy, and review points, it has failed its primary clinical function.

Are women more vulnerable to anxiety and depression than men?

Statistics show women are 2x as likely to develop anxiety and depression than men.

Some attribute this disparity to gendered societal strain.

However, neuroscience reveals the female brain is simply biologically wired that way: primed for vigilance, having denser stress receptors that consolidate threat data more intensely than the male equivalent.

Here’s a breakdown of the neurobiological differences 👇🧵 The Female CRF Substrate

While cortisol is responsible for stress response, the ‘driver’ of heightened vigilance in women is the Corticotrophin-Releasing Factor (CRF), the primary regulator of the body's stress system.

Research shows that female brains possess a significantly higher density of CRF receptors in the amygdala (the brain's fear centre).

This structural density causes stress signals to bind more intensely, making fear responses harder to extinguish even after the threat is gone.

Is Depression a “Mental” or a “Metabolic” Disorder?

For decades, depression has been framed as a disorder of neurotransmitters.
Low serotonin. Faulty signalling. Chemical imbalance.

But for a clinically meaningful subset of patients, the primary driver may sit upstream of neurotransmission.

The 'problem' isn’t the signal.
It's the energy required to generate it.

Here’s how brain insulin resistance (BIR) can drive a hypometabolic depressive state 👇🧵 The brain is metabolically demanding.

• ~2% of body weight
• ~20% of total glucose consumption

Neuronal function is tightly coupled to ATP availability.

Insulin signalling in the brain modulates energy utilisation, synaptic plasticity, and neuronal firing efficiency.

In brain insulin resistance (BIR), this signalling is blunted.

PTSD isn’t just about what happened.

It’s also about who it happened to, biologically.

Around 30–40% of PTSD risk is heritable, interacting with trauma exposure.

Here’s how genes, brain markers, and epigenetics shape vulnerability, and how this matters in clinic👇🧵 Most people exposed to trauma do not develop PTSD.

Conversely, similar trauma can lead to very different outcomes.

This variability is best explained by a Gene × Environment × Time model, not trauma severity alone.

What does sleep dysregulation have to do with ADHD?

At face value, ADHD and sleep dysregulation seem like two distinct, parallel issues: one about attention, the other about rest.

However, research indicates that roughly 80% of people with ADHD experience chronic sleep or circadian disturbance, suggesting a much tighter link than simple “comorbidity.”

Here’s how sleep dysregulation and ADHD form a feedback loop that most often overlook:👇🧵 Some often assume sleep issues in ADHD—such as delayed onset, bedtime resistance, and irregular sleep-wake patterns—are "behavioural," the result of poor routine or bedtime procrastination.

However, studies suggest said issues are “intrinsic,” biologically wired into the ADHD phenotype via clock gene polymorphisms (e.g., CLOCK, PER2). 

• The Reality: the internal clock is genetically set to a later time zone.

• The Result: a biological "jet lag" that persists daily

Why do some patients shift from casual drug use to chronic addiction?

Addiction is often framed as a moral choice, a simple lack of willpower.

However, clinically-speaking, it may reflect maladaptive changes in the brain, shifting drug use from “pleasure-seeking” to a dysregulated survival instinct.

Here are 4 key theories of addiction and how they translate into what you might see in practice👇🧵 1) Reward Deficiency Syndrome (RDS) Theory

Some brains are genetically ‘wired’ with ‘hypodopaminergic traits’ (low dopamine).

They don't use drugs to get "high," but to correct a deficit. 

The substance acts as a compensatory mechanism to stimulate an underactive reward system and feel "normal" (Blum et al., 1996).

Consciousness isn’t “generated” by the cortex alone…

Loss of cortical activity does not reliably eliminate conscious feeling, while disruption of the ARAS–thalamocortical axis almost always does.

Here’s how to use this distinction to avoid misdiagnosing delirium, catatonia, psychosis, or functional states 👇🧵 Consciousness has two separable components:

• Arousal – brainstem–hypothalamic systems that maintain wakefulness.

• Awareness – cortical integration enabling content, reportability, and meta-representation.

Anaesthesia, delirium, and severe encephalopathies often dissociate these systems.

Depression isn’t just “low mood”…

Converging cognitive and affective science shows consistent biases in information processing that shape how patients think, feel, and interpret the world.

Here are the core cognitive–affective biases in depression — and what clinicians need to know about each👇🧵 1. Residual Cognitive Symptoms

Even when mood improves, many patients experience residual cognitive symptoms.

These difficulties are robustly associated with and can predict daily functioning, work performance, and quality of life (Lam et al., 2014).

Clinical note: consider assessing cognition even after mood stabilises.

ADHD is often discussed in terms of inattention, impulsivity, and hyperactivity...

But one domain is consistently under-recognised in assessment and treatment:

Sleep.

Here’s how sleep and ADHD are connected and the 5 clinically effective sleep strategies every clinician should know 👇🧵 Sleep disturbances are the rule, not the exception, in ADHD.

82.6% of individuals with ADHD report lifetime sleep problems.

And this extends far beyond delayed sleep onset.

Common presentations include:

• delayed sleep–wake phase
• restless legs / PLMD
• sleep-disordered breathing
• parasomnias (e.g., night terrors)

These often predate the ADHD diagnosis.