WEBVTT

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So we've struggled with the

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understanding of what is what

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we would call the pathophysiology

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of depression or other psychiatric

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disorders.

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What actually is malfunctioning in

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the brain that's leading to

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these disorders?

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The Nobel Prize was awarded

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about a hundred and twenty

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years ago for really

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the basic understanding of how

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individual cells, the neurons in

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the brain, actually communicate

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with each other through chemical

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impulses that are then translated

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to electrical stimuli.

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Since then, our understanding has

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evolved. We started to realize

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that these neurons are

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localized into nuclei, and then

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those nuclei form circuits the

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way they communicate with each

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other. And then those circuits

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actually form networks.

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So we're really starting to

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understand how the brain works

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as a

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very

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complex unit

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to regulate our emotions, our

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perceptions,

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our thoughts. We use the

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term neuroplasticity,

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which has become a big

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buzzword in the field.

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The ability for the cells

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in the brain to form

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new connections,

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to strengthen or weaken those

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connections.

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And we think there's some

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combination of those events

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that's leading to many of

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our psychiatric illnesses.

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The most common medications aren't

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always effective for depression

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even in combination with effective

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psychotherapy like cognitive behavioral therapy.

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And the greater number of

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medications

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that people try

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unfortunately

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the lower the likelihood that

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they'll have success.

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This has been

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a call for our field

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to figure out alternative ways

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to treat depression.

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To think outside the box

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to other neurotransmitters

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and other networks within the

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brain that may be involved

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in the pathophysiology

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of depression.

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Interventional psychiatry

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here at Yale includes

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treatment modalities

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such as rapid acting antidepressants

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such as ketamine or s

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ketamine,

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which we think

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works more in regards to

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the glutamate system and

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causes

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a myriad of downstream effects

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in terms

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of synaptic plasticity.

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This phenomenon

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where things that fire together

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wire together in the brain.

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It's really the idea

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that you're able to use

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both the neurochemistry

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and drugs such as ketamine

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that can do that, but

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also using

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treatments like electroconvulsive therapy or

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transcranial magnetic stimulation

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that have more of a

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direct effect on the electrical

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system in the brain.

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TMS is

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a non invasive form of

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neuromodulation.

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We're able to painlessly

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and

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safely

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target certain areas of the

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brain

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and induce what we call

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eddy currents,

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which are these small electrical

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currents that influence the activity

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of individual neurons.

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And when there are enough

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neurons

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collectively

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acting,

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it can cause downstream effects

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in terms of chemical release.

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So even though we're using

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the electrical

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manipulation,

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it's causing

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downstream

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chemical changes as well. So

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it's this idea of

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inducing some level of plasticity

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and then really trying to

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work through therapeutic techniques, through

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behavioral activation.

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We're trying to figure out

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the different mechanisms by which

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these illnesses occur

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and how we can individualize

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treatment on a clinical level

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for each individual patient.

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And that's where the basic

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neuroscience

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really

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allows us

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to grow and target treatments

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to be much more effective

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and and in this case,

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hopefully, much safer.

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The nice thing at the

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Yale Depression Research Program is

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it's a pretty broad range.

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We really try to do

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translational

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neuroscience

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work.

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We work very closely with

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colleagues in some of our

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own studies trying to

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what is

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underlying the pathophysiology

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of depression.

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But moving up, we also

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have real interest in studying

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the the actual clinical utility

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if we truly wanna optimize

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our treatments,

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it's not simply

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targeting a receptor or even

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targeting a circuit or a

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network.

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You really have to understand

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how

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that is interacting with what

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we call these contextual factors,

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all the other events that's

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going on in the environment

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in our lives.