Psychodynamic psychotherapy is built on 2 core processes.

Take one away, and therapy may not progress.

Here are those 2 processes and how they apply in practice: 🧵👇

(scroll through to see number 2) 1/ Attachment

The connection between therapist and patient.

In psychodynamic psychotherapy, it is this therapist-patient bond that forms the foundation of the entire therapeutic process.

Without enough connection, mentalisation has less room to develop.

Gabapentin and pregabalin are often described as “GABA-like.”

But clinically, that can be misleading.

They do not act by binding to GABA receptors.

To understand their role in psychiatry, let's start with what gabapentinoids actually do. 🧵👇 Despite their structural similarity to GABA, gabapentin and pregabalin do not bind to GABA-A or GABA-B receptors.

Their main target is the α2δ subunit, especially α2δ-1, of voltage-gated calcium channels.

Psychiatric disorders are not explained by genetic vulnerability alone.

Stress, trauma, substance use, nutrition, infection, and medication can also shape gene expression.

That is where epigenetics becomes clinically relevant. 🧵👇 Let’s start with the definition.

Epigenetics refers to changes in gene activity and expression that occur without changing the DNA sequence itself.

The genetic code may stay the same.

But how that code is read can change.

Methylphenidate is not simply “a stimulant.”

Its clinical effect depends on how dopamine and noradrenaline are increased, released, sustained, and worn off.

That is where formulation choice becomes clinically important. 🧵👇 Methylphenidate blocks the reuptake of:

* dopamine via DAT
* noradrenaline via NAT

This increases dopamine and noradrenaline in the synaptic cleft, supporting dopaminergic and noradrenergic transmission.

It’s not just: 

“Is psychosis improving?”

It’s also:

“Is the patient returning to daily life?”

Clinical care often focuses on reducing psychosis.

But recovery also means rebuilding function. 🧵👇 This is the recovery gap in schizophrenia.

Positive symptoms may improve:

* hallucinations
* delusions
* thought disorder

But the patient may still struggle with motivation, expression, social connection, and goal-directed behaviour.

Depression is not one biological pathway.

For some patients, monoamines may be only part of the story.

Here’s how new developments in the biology of depression are reshaping antidepressant treatment: 🧵👇 For decades, antidepressants have largely targeted monoamine systems:

* serotonin
* noradrenaline
* dopamine

This model changed depression care.

But it also left major gaps:

* delayed onset
* treatment resistance
* tolerability problems
* incomplete response

Guanfacine and clonidine are often grouped together as alpha-2 agonists.

But that shared mechanism doesn’t make them clinically interchangeable.

So the question is not simply:

“Which one should I prescribe?”

It is:

“What symptom or problem am I trying to address?” 🧵👇 Both medications can be useful in ADHD when stimulants are:

* unsuitable
* not tolerated
* ineffective
* only partly effective

They can be used as monotherapy or as adjunctive agents.

But their clinical fit is not the same.

Psychiatric labels are useful.

But in complex presentations, they often don’t explain enough.

The better clinical question is not only:

“What diagnosis fits?”

But:

“Which neural circuit is driving the presentation?” 🧵👇 This is where the Tripartite Model of Fronto-Striato-Limbic Circuits becomes useful.

Rather than organising symptoms only by diagnosis, it helps clinicians map symptoms onto 3 core loops:

1. Affective loop
2. Cognitive loop
3. Motor loop

Not all PTSD reflects the same neurobiological pattern.

Some presentations are predominantly hyperaroused. Others are predominantly dissociative. 

This distinction has direct clinical implications:🧵👇 Around 13–30% of individuals with PTSD meet criteria for the dissociative subtype.

So treating all PTSD as one neurobiological pattern risks clinical oversimplification.

This suggests that hyperaroused and dissociative PTSD may reflect different underlying regulatory patterns.

Schizophrenia is often framed through the mesolimbic dopamine model.

But recent neuroimaging suggests dopaminergic dysfunction may be more pronounced in the dorsal striatum than previously emphasised.

That distinction matters clinically. Here’s why: 🧵👇 The dorsal striatum is not just a motor structure.

Its associative striatal region acts as an integrative hub linking cortical, limbic, and motor systems.

So dysfunction here can affect not only psychosis, but also cognition, action selection, and behaviour.

Autoimmune Encephalitis (AE) is a relatively rare neuroinflammatory disorder.

However, what makes AE so hard for clinicians to spot isn't just its rarity.

Rather, it is that it can look psychiatric early.

To avoid misdiagnosis, here’s a 3-point AE diagnostic criteria clinicians should know:🧵👇 AE diagnosis can be considered when all three of the following criteria are met.

1/ Subacute Onset

The first criterion is a subacute onset, defined as a rapid progression over less than 3 months.

Clinically, this may present as:

- working memory deficits or short-term memory loss
- altered mental status
- psychiatric symptoms

The key signal is not just symptom type, but how quickly the syndrome evolves.

Schizophrenia is often conceptualised across 3 domains:

- Reality distortion: delusions and hallucinations

- Disorganisation: formal thought disorder, disorganised behaviour, inappropriate affect 

- Negative symptoms: alogia, avolition, anhedonia, asociality

But this framework doesn’t fully capture clinical complexity.

Here are 3 additional features that remain clinically relevant in schizophrenia, even if they are not specific to it alone:🧵👇

(Click through to see all 3 additional clinically relevant features) 1/ Catatonia

Catatonia is a psychomotor syndrome that can occur in schizophrenia.

Catatonic stupor may be a recognisable presentation, but immobility, mutism, staring, and rigidity are also described clinical signs.

Although DSM frameworks have reclassified catatonia from a core feature of schizophrenia to a specifier across several disorders, it remains clinically relevant and still manifests in around 9% of schizophrenia cases. (Solmt et. al., 2018)

Why do some patients not improve, despite the “right” medication?

Because prescribing is not purely biological…

It is not only metabolised by the body.
it is also filtered through trust, ambivalence, and transference.

To minimise avoidable treatment limitations, here are 7 psychodynamic principles in pharmacotherapy every clinician should understand 🧵👇 1/ Avoid the Mind–Body Split

Psychopharmacology and psychotherapy are not separate.

Medication acts on biology…

But the mind shapes how it is experienced, tolerated, and adhered to.

Addiction is not just about reward.

It reflects predictable dysfunction across brain systems governing behaviour, learning, and control.

Here are 5 core neurobiological processes underlying addiction and relapse: 🧵👇

(Click through to see all 5) 1/ Reward & Motivation

Chronic substance use floods the brain with dopamine, eventually downregulating D2 receptors.

This structurally shifts the brain from "liking" the drug (hedonic pleasure) to intensely "wanting" it (incentive salience).

The biological urge to use becomes overpowering, even when the substance ceases to provide actual pleasure.

Educating patients that the craving they feel is a structural reflex, not a reflection of character, relieves guilt and contextualises relapse.

More than 50% of patients with schizophrenia smoke tobacco. [Fond et al 2017]; [Dickerson et al 2018]; [Oluwoye et al 2019]

Despite heavily substantiated nicotine-induced metabolic and pharmacokinetic risks, this number refuses to drop.

This raises the question: “What does nicotine do that makes this specific patient population so uniquely dependent on it?”

Here’s a neurobiological breakdown of nicotine dependence in schizophrenic patients clinicians should know: 🧵👇 The Intrinsic Receptor Deficit

In the general population, chronic smoking leads to an upregulation of α4β2 nicotinic receptors.

In schizophrenia, this compensatory upregulation is impaired.

This suggests an intrinsic defect in the nicotinic receptor system. 

Theoretically, for schizophrenia patients, smoking is an attempt to achieve receptor saturation to overcome this deficit, though it rarely leads to sustained cognitive improvement.

Depression is not a single, uniform brain pattern.

It does not present the same way in every patient.

Sometimes it appears as rumination.
Sometimes as cognitive dysfunction.
Sometimes as emotional over-reactivity.

So how do we make sense of what’s happening beneath the surface? There is a structured way to approach this.

Here is a clinical breakdown of the Triple Network Model, a framework for understanding functional brain changes in depression 🧵👇 The Triple Network Model frames depression as dysregulation within and between three major functional brain systems.

Rather than locating the disorder in one isolated region, it conceptualises depression as a disturbance in large-scale network organisation.

This gives clinicians a more structured way to think about why depressive presentations can differ so markedly.

PTSD treatment is not just about reducing symptoms.

The other half of the clinical equation is about interrupting the mechanisms that make the brain increasingly reactive over time.

To do so, there are 2 clinical PTSD concepts clinicians must take into full consideration in treatment planning: 🧵👇 PTSD develops through a combination of psychological and biological mechanisms.

This dual foundation also means that effective treatment must address both sides of the disorder, often integrating psychotherapy with pharmacotherapy.

This is where the following concepts come in, illustrating exactly what is happening in the dysregulated brain, helping clinicians align their intervention strategies with the underlying pathology.

For decades, Major Depressive Disorder (MDD) has been clinically framed primarily through mood symptoms.

However, recent clinical studies have described a potential emerging biotype of MDD whose core pathology leans more towards cognition than just mood symptoms.

Here are 5 key clinical insights clinicians need to know about this emerging cognitive MDD biotype:🧵👇 Cognition has long been recognised as part of MDD, with impairments in areas such as attention, working memory, and processing speed already linked to poorer function and poorer treatment outcomes.

Even so, MDD remained primarily organised around mood symptoms, with cognitive dysfunction often treated as secondary rather than defining.

This emerging cognitive biotype shifts that framing by suggesting that, in some patients, cognition may be more central to the pathology itself.

Addiction vulnerability is heritable.

While often framed as a brain reward-system dysfunction, clinical studies suggest that genetic factors are estimated to account for around 40-60% of addiction risk, with inherited vulnerability contributing to susceptibility. [Volkow et al., 2019]

This raises the next question: How does inherited risk translate into biological vulnerability, and what does that mean in clinical practice?🧵👇 The Polygenic Architecture of Vulnerability

What is inherited is not addiction itself, but vulnerability.

This vulnerability is polygenic: multiple variants, especially in dopamine and glutamate systems, increase susceptibility.

In effect, what is inherited may be a reward-system profile prone to dysregulated reinforcement.

This may explain why some individuals show greater neurobiological vulnerability even before substance exposure.

Around 70% of adults globally experience at least one traumatic event, with a proportion of individuals subsequently developing PTSD. [Benjet et al., 2016]

However, standard clinical approaches to PTSD remain largely binary: patients either meet the symptom checklist, or they don't. 

But what if underlying pathological processes begin long before the DSM checklist is met? 

To bridge this gap, here’s a 5-stage clinical staging approach to PTSD clinicians can apply in practice:🧵👇 Stage 0: Trauma Exposed & Asymptomatic

Before clinical diagnosis, neurobiological changes associated with trauma exposure may begin to emerge. 

Trauma exposure has been associated with alterations in glucocorticoid receptor sensitivity, circadian regulation, and amygdala reactivity. 

Clinically, individuals may exhibit transient attention bias and deficits in extinction learning.

This is the "watch-and-wait" phase, where early resilience strategies may be highly beneficial.

Depression is often treated as a single disorder.

But clinically, not all depression is the same.

Different subtypes have distinct symptom profiles, biology, and treatment responses.

Here are 3 key depressive subtypes clinicians should recognise 👇🧵 In clinical practice, depressive presentations can show distinct subtype patterns that carry different treatment implications.

Recognising these patterns helps clinicians move beyond a generic diagnosis of major depressive disorder and toward a more targeted formulation.

Three commonly recognised depressive subtypes include: