Up to 60% of individuals with schizophrenia experience persistent negative symptoms (Correll C & Schooler N et al., 2020).

These symptoms contribute more to functional impairment than positive symptoms and are often under-recognised in clinical settings.

Let’s explore the neurobiology, diagnostic challenges, and treatment strategies that guide clinician care in managing negative symptoms. 🧵👇 Defining Negative Symptoms

Negative symptoms represent deficits in normal functioning and are classified into:

• Avolition

• Anhedonia

• Asociality

• Alogia

• Blunted affect

They are distinct from depression or cognitive impairment and require targeted assessment.

Catatonia occurs in 9–17% of patients with acute psychiatric illness and is associated with serious medical complications if not promptly treated.

It is seen across mood disorders, psychotic conditions, and general medical illnesses, not only schizophrenia.

Here’s what clinicians should know about its identification, underlying circuitry, and treatment.🧵👇 Clinical Features of Catatonia

Catatonia presents with motor, behavioural, and affective abnormalities.

Key signs include stupor, mutism, waxy flexibility, echolalia, echopraxia, posturing, negativism, and grimacing.

Both withdrawal and agitation may occur within the same episode.

Psych Scene Tip: Consider catatonia in the differential for any patient presenting with unexplained motor changes or unresponsiveness.

In the SHIP study, three-quarters of individuals with psychosis were overweight or obese (Galletly et al., 2012).

Obesity is not a side effect but a comorbid condition that compounds cardiovascular, metabolic, and psychiatric burdens.

Here’s what clinicians need to know about the pathophysiology and management of weight gain in psychiatry. 🧵👇 Hypothalamic Circuits of Appetite Regulation

The arcuate nucleus (ARC) integrates peripheral signals (ghrelin, leptin, insulin) to modulate appetite:

• AGRP/NPY neurons → stimulate food intake

• POMC/CART neurons → suppress appetite

Disruption of this balance leads to hyperphagia and weight gain.

Up to 73% of children and 67% of adults with Attention-Deficit/Hyperactivity Disorder (ADHD) report clinically significant sleep disturbances.

These impair attention, emotion regulation, and behaviour, often misattributed to core ADHD pathology.

Continue reading to understand the neurobiology, diagnostic complexity, and management strategies guiding clinical care.🧵👇 Four Clinical Pathways Linking ADHD and Sleep

1. ADHD causes sleep disturbance

2. Sleep problems mimic or aggravate ADHD

3. Shared psychosocial or developmental confounders

4. Common neurobiological origin

This model frames how symptoms and causality may overlap.

In a Swedish cohort of bipolar patients, 26% of those on lithium met the criteria for hypercalcemia (Meehan et al., 2017).

Despite known associations between lithium and calcium dysregulation, routine monitoring remains inconsistent.

Here’s what clinicians need to know about prevalence, pathophysiology, and treatment strategies. 👇🧵 Prevalence and Risk Comparison

Hypercalcemia occurred in:

• 26% of bipolar patients on lithium

• 1.4% of bipolar patients not on lithium

• 2.9% of the general population controls

Lithium-treated patients had 13-fold higher odds of hypercalcemia after adjusting for age, gender, and diagnosis.

A 59-year-old woman with no prior psychiatric history presented with severe depressive symptoms, nihilistic delusions, and poor insight.

She required inpatient admission due to suicidality and functional decline.

Let’s examine this case and its imaging to highlight the diagnostic and management considerations. 🧵👇 Clinical Features on Admission

• Profound psychomotor retardation

• Delusions of organ failure and being dead

• Anhedonia, insomnia, and self-neglect

• Non-responsiveness to verbal prompts

Initial diagnosis: Major depressive disorder with psychotic features (mood-congruent).

In the STAR*D study, patients with melancholic features had higher illness severity, greater suicide risk, and a 24% lower chance of remission compared to those with non-melancholic depression (McGrath et al., 2008).

Despite distinct profiles, melancholic and psychotic subtypes are often misclassified.

Let’s take a look at how to identify melancholic and psychotic depression, understand their neurobiology, and apply evidence-based strategies for management. 🧵👇 Clinical Features of Melancholic Depression

• Marked psychomotor disturbance

• Diurnal variation (worse in mornings)

• Anhedonia and reduced reactivity

• Cognitive slowing

• Profound guilt and self-reproach

These patients are often less responsive to psychotherapy and standard SSRIs.

Is Amygdala Reactivity a Familial Risk Factor for PTSD?

A recent fMRI study in identical twins revealed heightened amygdala response to ambiguous facial expressions in both PTSD patients and their trauma-unexposed twins. (Hinojosa, et al, 2022)

Let’s explore the implications of this finding for clinical psychiatry. 🧵👇 Twin fMRI Methodology

Researchers examined monozygotic twin pairs discordant for trauma exposure using fMRI.

Participants viewed emotionally ambiguous stimuli (e.g., surprised faces).

Results:

• Both PTSD patients and their unexposed co-twins showed increased amygdala activation

• Control pairs did not show this pattern

This may indicate a familial trait marker for PTSD vulnerability.

Up to 80% of individuals with Autism Spectrum Disorder (ASD) show ADHD symptoms, and up to 50% of those with ADHD meet ASD criteria (Lau-Zhu et al., 2019).

DSM-5 formally recognised co-diagnosis, reshaping how we assess, manage, and support neurodevelopmental overlap.

Let’s examine the neurobiological overlap, diagnostic complexities, and treatment considerations driving clinical care. 🧵👇 Symptom Overlap and Diagnostic Challenges

• Inattention and distractibility

• Emotional dysregulation

• Executive dysfunction

• Social and communication difficulties

Overlap can obscure dual diagnosis, especially in females who may mask symptoms.

Psych Scene Tip: Always screen for dual traits in ADHD and ASD assessments.

Hypersalivation affects 30–80% of patients on clozapine. One study reported a rate as high as 91%.
(Maher et al., 2016)

This adverse effect is often under-recognised, yet can significantly impair quality of life and lead to non-adherence.

Let’s examine the pathophysiology and treatment of clozapine-induced hypersalivation (CIH). 🧵👇 Why It Matters

Daytime drooling is among the top three adverse effects reported by clozapine users.

It can cause:

• Social withdrawal

• Low self-esteem

• Insomnia

• Aspiration risk

Psych Scene Tip: Addressing hypersalivation early can improve adherence and outcomes.

Life expectancy is reduced by 18.7 years for men and 16.3 years for women with schizophrenia, primarily due to physical health comorbidities (Morgan et al., 2016).

Cardiometabolic disease is a major contributor to excess mortality, yet remains frequently under-recognised and undertreated.

Here’s what clinicians need to know about prevention, monitoring, and clinical management. 🧵👇 Cardiometabolic Risk Profile

Schizophrenia is associated with a higher burden of cardiovascular risk factors.

• Increased smoking, obesity, inactivity

• Higher rates of diabetes, hypertension, dyslipidaemia

• Life expectancy shortened by 15–20 years
(Galletly et al., 2016; Mitchell et al., 2013)

💡 Psych Scene Tip: Address physical health early—mortality risk is not only psychiatric.

Cariprazine is a third-generation antipsychotic with D3-preferring D3/D2 partial agonism and 5-HT1A partial agonism. (Kiss et al., 2019)

Its unique receptor profile is associated with improved motivation, mood, and cognitive functioning.

Here’s what clinicians need to know about its mechanism, pharmacokinetics, and clinical application. 🧵👇 Mechanism of Action Overview

Cariprazine's receptor activity includes:

• Partial agonism at D3 and D2 receptors

• Partial agonism at 5-HT1A receptors

• Antagonism at 5-HT2A receptors

D3 receptor affinity is believed to contribute to improvements in negative symptoms and cognitive function.

Clozapine-induced constipation (CIC) is common, with prevalence estimates ranging from 30–60% (Attard et al., 2019).

Clozapine-induced gastrointestinal hypomotility (CIGH) is even more prevalent, affecting up to 73% of users, and carries a significantly higher risk of fatal outcomes.

Let’s look at how to identify, prevent, and manage this potentially life-threatening complication. 🧵👇
Prevalence & Mortality

• Constipation in trials: ~14%

• Real-world CIC prevalence: 30–60%

• CIGH prevalence: up to 73%

• Case fatality: 18–28% in reported series

Unlike agranulocytosis, the risk of CIGH persists across all phases of clozapine treatment.

Up to 60% of methamphetamine users in inpatient settings present with psychotic features.

Methamphetamine-associated psychosis (MAP) is often under-recognised or misdiagnosed, yet it carries significant implications for long-term psychiatric risk.

Here’s what clinicians need to know about its spectrum, symptom profiles, and overlap with primary psychotic disorders. 👇🧵 The Clinical Spectrum of MAP

Methamphetamine-associated psychosis can present in multiple ways:

• Transient psychosis during intoxication

• Subacute psychosis post-use

• Persistent psychosis with schizophrenia-like features

Symptoms may fluctuate with abstinence but in some 
cases, they persist beyond detox, mimicking primary psychosis.

ADHD TikTok content is growing but is it accurate?

A 2022 study published in The Canadian Journal of Psychiatry found that nearly 52% of ADHD-related TikTok videos were misleading.

Here’s what clinicians need to know about how ADHD social media content shapes public understanding and clinical conversations. 🧵👇 What the Data Shows

Researchers analysed 100 of the most-viewed ADHD TikTok videos.

Results:
• 52% were misleading
• 27% were useful
• 21% were neutral

Most misleading content was anecdotal and lacked alignment with clinical guidelines.
(Yeung et al., 2022)

D2 blockade isn’t the only way to manage psychosis.

Aripiprazole’s partial agonism at D2 receptors allows for targeted dopamine modulation—stabilising activity instead of shutting it down.

Here’s what clinicians need to know about its mechanism, receptor targets, and clinical applications​. 🧵👇 Partial Agonism and Dopamine Balance

Aripiprazole is a partial agonist at the dopamine D2 receptor. 

This means:

● In low-dopamine states, it increases dopaminergic tone

● In high-dopamine states, it reduces excessive activity

This bidirectional regulation helps minimise both positive and negative symptoms in schizophrenia.

A large multicentre study found that daily use of high-potency cannabis (THC >10%) is associated with up to a 5x increased risk of psychotic disorder, especially in genetically vulnerable individuals (Di Forti et al., 2019).

Modern strains contain higher THC and lower CBD, potentially increasing the risk of psychosis and cognitive impairment.

Let’s break down how cannabis, THC, and CBD influence psychosis and cognition. 🧵👇 CB1 & CB2 Receptors

The brain has a cannabinoid system with two key receptors:

● CB1 receptors → Located in the brain & CNS, involved in mood, memory, reward, and pain regulation.
● CB2 receptors → Found in immune cells & peripheral tissues, linked to inflammation & immunity.

THC binds to CB1 receptors, altering dopamine, GABA, and glutamate transmission—key pathways involved in psychosis and cognition.

What happens in the brain when therapeutic change occurs?

Reward prediction errors (RPEs)—mismatches between expected and actual outcomes—drive emotional learning and behavioural updates.

Here’s how this mechanism informs psychodynamic psychotherapy. 👇🧵 What Are Reward Prediction Errors (RPEs)?

An RPE is the brain’s signal that something unexpected occurred.

When reality violates our expectations, dopamine activity changes to prompt new learning.

This mechanism underpins how behaviours, emotions, and relational patterns are reinforced or challenged.
(Schultz, 2016)

Women are up to 4x more likely to develop hyperprolactinaemia while on antipsychotic treatment.

The consequences extend beyond hormonal changes—fractures, infertility, psychological burden, and increased breast cancer risk.

Here’s what you need to know about identifying, monitoring, and managing hyperprolactinaemia in clinical practice. 👇🧵 Why Women Are More Susceptible

Oestrogens contribute to prolactin elevation by:
• Increasing pituitary lactotroph responsiveness
• Reducing the inhibitory control of hypothalamic dopamine

This hormonal profile increases the likelihood of hyperprolactinaemia in women, particularly after puberty.

In a statin re-challenge trial, 90% of side effects also occurred during placebo treatment (Wood et al., 2020).

This nocebo effect—symptoms driven by expectation—can directly undermine medication adherence.

Let’s explore how placebo and nocebo responses influence psychiatric outcomes and clinical decision-making. 👇🧵 Placebo Responses Are Biologically Active

Placebo effects are mediated by endogenous opioids, dopamine, oxytocin, and endocannabinoids.

They can alter perception of pain, mood, fatigue, and motivation—core psychiatric domains (Colloca & Barsky, 2020).

Second-generation antipsychotics (SGAs) can double the risk of cardiovascular disease—and increase the risk of type 2 diabetes up to fivefold.

These risks contribute to a 15–20 year reduction in life expectancy in people with psychotic disorders.

Let’s explore the pathophysiology and clinical strategies for managing metabolic dysfunction in SGA use. 👇🧵 SGAs And The Burden Of Metabolic Syndrome

Metabolic syndrome occurs in up to 40–60% of patients with schizophrenia—especially those on SGAs.

It is associated with increased all-cause and cardiovascular mortality (De Hert et al., 2009).