Differential Diagnosis & Clinical Reasoning – What Are We Really Seeing?

Case 1, Episode 4:

I think my professors are plotting against me. I hear whispers through the vents. It’s like the world’s changed, and no one told me.

Sarah’s words are vivid, disturbing, and yet not uncommon.
In Episode 3, we stepped back and conducted a full psychiatric assessment that revealed a rich, complex picture:

• A young adult under stress

• A fragile identity unraveling

• Possible psychotic features emerging

• Substance use, disrupted sleep, and isolation as compounding factors

 Now comes the clinical art: What’s actually going on?

And more importantly: How do we figure it out without guessing, or labeling too soon?

Welcome to the Differential Diagnosis Process
The Goal of Differential Diagnosis[1]
You’re not just trying to name the problem; you’re trying to understand the mechanism behind the symptoms.

Think of symptoms as signals.

Diagnosis gives us a working model for how those signals are generated, and how to intervene.

The Top Four Diagnostic Pathways in Sarah’s Case
Let’s examine the most likely diagnostic categories and how to think through each[2]:

1. Primary Psychotic Disorder (e.g., Schizophrenia, Schizophreniform)
Why It’s Possible:

• Paranoid delusions

• Auditory hallucinations

• Social withdrawal

• Flattened affect 

What You’d Expect to See:

• Onset in late adolescence or early adulthood

• No prominent mood symptoms

• Progressively declining function over at least 6 months

• Poor insight and disorganized thinking

What to Look For:

• Family history of schizophrenia

• Negative symptoms: apathy, alogia, avolition

• Formal thought disorder (loose associations, tangentiality)

2. Mood Disorder with Psychotic Features (Bipolar I, Major Depression with Psychosis)

Why It’s Possible:

• Sarah reports mood instability, identity collapse, and sleep disturbance

• College onset aligns with typical bipolar spectrum onset

What You’d Expect to See:

• Psychotic symptoms that occur only during mood episodes

• Manic or depressive features (elevated mood, grandiosity, or suicidal ideation)

• Full return to baseline between episodes

What to Ask About:

• Past episodes of elevated energy, risky behavior, pressured speech

• Cyclical mood changes

• Family history of mood disorders

3. Substance/Medication-Induced Psychotic Disorder

Why It’s Possible:

• She’s using unprescribed Adderall, drinking large amounts of caffeine, and sleeping only[3] 2–3 hours/night

• Symptoms worsened after lifestyle changes

What You’d Expect to See:

• Temporal connection between substance use and symptom onset

• Symptoms resolve with abstinence and rest

• Lack of progression or residual impairment once substance is cleared

How to Assess:

• Urine tox screen

• Clear timeline of symptom vs. substance use

• Sleep and nutrition restoration trial

4. Trauma-Related Disorders (PTSD, Dissociative Disorder)[4]

Why It’s Possible:

• Sarah describes detachment, feeling watched, identity confusion

• Childhood instability and cultural stigma may suggest unspoken trauma

What You’d Expect to See:

• Flashbacks, hypervigilance, startle response

• Dissociation (depersonalization, derealization)

• Avoidance of triggers 

What to Explore Gently:

• Has she ever experienced something deeply frightening, shaming, or violating?

• What memories feel “out of time”?

• What does she fear most right now?

The Red Flags of Diagnostic Anchoring
Be mindful of jumping too quickly to a single diagnosis based on a standout symptom.

For example:

• Hearing whispers? Must be schizophrenia.

• Took Adderall? Must be stimulant-induced psychosis.

• Isolated and paranoid? Must be trauma related.

The truth?
It could be all of the above.
Or none. 

That’s why we hold multiple possibilities in mind while we observe, gather data, and let the story unfold.

What Else Should We Do Now?
Here’s a working diagnostic strategy:

1. Order labs and tox screen (TSH, CBC, CMP, B12, folate, urine tox)

2. Collect collateral (family, professors, roommates if possible)

3. Continue observation over time: do symptoms persist, evolve, resolve?

4. Try non-pharmacological stabilization first:

• Sleep hygiene

• Nutrition

• Psychoeducation

• Supportive contact

Only then do we move toward diagnosis-based interventions with confidence.

Coming Up Next: Episode 5 – Algorithmic Treatment Planning
Once we’ve narrowed the differentials and stabilized the basics, we begin building a treatment plan—but not just a list of medications.

We’ll walk through:

• A decision tree model: If this doesn’t work, then what?

• How to prioritize needs based on Maslow and symptom severity

• When to initiate medication, therapy, or crisis intervention

• How to sequence care for long-term stabilization

Reflective Prompt for You
What’s the most common diagnostic trap you see in your practice?
Where do you find yourself jumping too quickly—or hesitating too long? 
Let’s normalize the complexity of diagnostic reasoning. Share this episode, or comment with your own reflections.

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References

[1] Brito, Maria Cristina, Alberto Bentinjane, and Thomas Dietlein. "1. Definition, classification, differential diagnosis." Childhood glaucoma 9 (2013): 1.

[2] Oosterhuis, H. J. G. H. "Diagnosis and differential diagnosis." Myasthenia gravis. CRC Press, 2019. 203-234.

[3] Wilson, Lorna, et al. "Clinical characteristics of primary psychotic disorders with concurrent substance abuse and substance-induced psychotic disorders: A systematic review." Schizophrenia research 197 (2018): 78-86.

[4] Howlett, Jonathon R., and Murray B. Stein. "Prevention of trauma and stressor-related disorders: a review." Neuropsychopharmacology 41.1 (2016): 357-369.