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Session 4 – Depression

Welcome to Session 4 of NPiP!

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Despite being one of the most common psychiatric illnesses – and one of the oldest areas of biological psychiatry research – current treatment of depression still falls short. According to the World Health Organization, depression remains the leading cause of disability worldwide. More than 40,000 people die from suicide annually in the United States alone.

This may finally be changing. Over the past 15-20 years, cutting-edge research has led to new models for understanding and for treating depression. We no longer talk about a “chemical imbalance.” Modern perspectives include circuit-based approaches and the neurotrophic model. Crucially, these ideas are translating into new approaches for treatment – with numerous early successes. Dig in to today’s self-study resources to learn what’s going on and then join your pod to dive into What To Say When Patients Ask!

Learning resources

Brief commentaries

Article (5 pages): Reshaping the Depressed Brain: A Focus on Synaptic Health –This piece brings together our understanding of how different treatments of depression may share a common mechanism of action. If you’re looking for a single, accessible source with a contemporary biological perspective on depression, this is it.  


Article (4 pages): Changing the Way We Think About (and With) Antidepressans – How do medications for depression actually work? Do they really take 4 to 6 weeks? If you’ve ever prescribed an SSRI (or ever intend to), this is a must-read.


Article (5 pages): The Habenula: Darkness, Disappointment, and Depression – If you’ve ever wondered “What the hell is the habenula?!?!” (and let’s be honest – who hasn’t had that thought?), this piece is for you. Read this to discover what Karl Deisseroth and other cutting-edge researchers are so excited about.

Additional multimedia

A handful of “This ‘Stuff’ Is Really Cool” (TSIRC) talks highlighting different contemporary perspectives on depression.


Video (08:25 long): “Sad Synapses” – a classic talk bringing to life the neurotrophic model of depression. Seriously – you need to understand this – it’s at the heart of everything.


Video (09:34 long): “Simple Logic” – expanding on the themes from “Sad Synapses,” a beautiful elaboration of how this ought to look in clinical practice.


Video (09:03 long): “The Neuroscience of Kafka” – for anyone who’s struggled with hospital bureaucracy or some other personal version of a “PC Load Letter” error, this talk is for you. A brilliant summary of the role of cognitive biases in depression. Another must-watch!


Video (09:22 long): “Computational Approaches to Psychiatric Illnesses” – from Pokémon to primates, a whole new way to think about depression. (This is the TSIRC companion to the habenula column referenced above.)


Video (09:55 long): “The Hedgehog and the Virus” – Bradford Martins explores the neurobiological effects of social isolation in the context of the COVID-19 pandemic.


Videos (5 parts): ECT is one of the most effective treatments in all of medicine. But… how does it work? Check out this collection of mini-videos from Dr. Sarah Lisanby, Director of the NIMH Division of Translational Research.

What to Say When Patients Ask

  • The “What To Say” (WTS) framework gives participants the chance to practice incorporating cutting-edge neuroscience findings into our everyday clinical encounters. Each session begins by asking participants to imagine how they might answer some of the common questions that patients bring to us in our clinical practice. Then you’ll read and discuss a brief clinical commentary designed to bring to life one core concept in modern neuroscience. Then return to the role-play to see how you might use this perspective to better answer the patient’s initial questions.
  • What to Say: The Electrochemical Brain: Lessons from The Bell Jar and Interventional Psychiatry – A piece that touches on historical treatments and perspectives on depression before introducing an emerging branch of medicine: interventional psychiatry. Work through the exercises and role plays with your pod. Then read the Clinical Commentary Article here. Then review the answer key.

At the end of Session 4, you should be able to:

  • Describe the neurotrophic model of depression. 
  • Describe a circuit-based model of depression (including answering the question: What the hell is the habenula?!?!).
  • Describe what early changes occur with antidepressant medication treatment (i.e. in the first 1-2 weeks) and how they might be relevant to both clinical practice and research.
  • Describe in patient-centered language how ECT works.
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