Treating Depression at Yale
March 16, 2026Transcript
- 00:05So we've struggled with the
- 00:07understanding of what is what
- 00:09we would call the pathophysiology
- 00:11of depression or other psychiatric
- 00:13disorders.
- 00:14What actually is malfunctioning in
- 00:16the brain that's leading to
- 00:18these disorders?
- 00:19The Nobel Prize was awarded
- 00:21about a hundred and twenty
- 00:22years ago for really
- 00:24the basic understanding of how
- 00:26individual cells, the neurons in
- 00:28the brain, actually communicate
- 00:30with each other through chemical
- 00:32impulses that are then translated
- 00:34to electrical stimuli.
- 00:36Since then, our understanding has
- 00:38evolved. We started to realize
- 00:40that these neurons are
- 00:42localized into nuclei, and then
- 00:44those nuclei form circuits the
- 00:45way they communicate with each
- 00:47other. And then those circuits
- 00:48actually form networks.
- 00:50So we're really starting to
- 00:51understand how the brain works
- 00:53as a
- 00:54very
- 00:55complex unit
- 00:57to regulate our emotions, our
- 00:59perceptions,
- 01:00our thoughts. We use the
- 01:01term neuroplasticity,
- 01:02which has become a big
- 01:04buzzword in the field.
- 01:06The ability for the cells
- 01:08in the brain to form
- 01:09new connections,
- 01:10to strengthen or weaken those
- 01:11connections.
- 01:13And we think there's some
- 01:14combination of those events
- 01:16that's leading to many of
- 01:17our psychiatric illnesses.
- 01:19The most common medications aren't
- 01:21always effective for depression
- 01:23even in combination with effective
- 01:25psychotherapy like cognitive behavioral therapy.
- 01:28And the greater number of
- 01:30medications
- 01:31that people try
- 01:33unfortunately
- 01:34the lower the likelihood that
- 01:35they'll have success.
- 01:37This has been
- 01:38a call for our field
- 01:40to figure out alternative ways
- 01:42to treat depression.
- 01:44To think outside the box
- 01:45to other neurotransmitters
- 01:47and other networks within the
- 01:49brain that may be involved
- 01:51in the pathophysiology
- 01:52of depression.
- 01:58Interventional psychiatry
- 02:00here at Yale includes
- 02:02treatment modalities
- 02:03such as rapid acting antidepressants
- 02:06such as ketamine or s
- 02:07ketamine,
- 02:08which we think
- 02:09works more in regards to
- 02:11the glutamate system and
- 02:14causes
- 02:16a myriad of downstream effects
- 02:19in terms
- 02:20of synaptic plasticity.
- 02:22This phenomenon
- 02:23where things that fire together
- 02:26wire together in the brain.
- 02:28It's really the idea
- 02:30that you're able to use
- 02:32both the neurochemistry
- 02:33and drugs such as ketamine
- 02:35that can do that, but
- 02:36also using
- 02:37treatments like electroconvulsive therapy or
- 02:40transcranial magnetic stimulation
- 02:42that have more of a
- 02:43direct effect on the electrical
- 02:45system in the brain.
- 02:47TMS is
- 02:48a non invasive form of
- 02:50neuromodulation.
- 02:52We're able to painlessly
- 02:54and
- 02:55safely
- 02:56target certain areas of the
- 02:58brain
- 02:59and induce what we call
- 03:00eddy currents,
- 03:01which are these small electrical
- 03:03currents that influence the activity
- 03:05of individual neurons.
- 03:07And when there are enough
- 03:08neurons
- 03:10collectively
- 03:10acting,
- 03:11it can cause downstream effects
- 03:14in terms of chemical release.
- 03:17So even though we're using
- 03:18the electrical
- 03:20manipulation,
- 03:21it's causing
- 03:23downstream
- 03:24chemical changes as well. So
- 03:25it's this idea of
- 03:27inducing some level of plasticity
- 03:29and then really trying to
- 03:32work through therapeutic techniques, through
- 03:35behavioral activation.
- 03:37We're trying to figure out
- 03:38the different mechanisms by which
- 03:39these illnesses occur
- 03:41and how we can individualize
- 03:43treatment on a clinical level
- 03:44for each individual patient.
- 03:46And that's where the basic
- 03:47neuroscience
- 03:48really
- 03:49allows us
- 03:50to grow and target treatments
- 03:52to be much more effective
- 03:53and and in this case,
- 03:55hopefully, much safer.
- 04:00The nice thing at the
- 04:01Yale Depression Research Program is
- 04:03it's a pretty broad range.
- 04:04We really try to do
- 04:06translational
- 04:08neuroscience
- 04:09work.
- 04:10We work very closely with
- 04:11colleagues in some of our
- 04:12own studies trying to
- 04:14what is
- 04:15underlying the pathophysiology
- 04:17of depression.
- 04:19But moving up, we also
- 04:20have real interest in studying
- 04:24the the actual clinical utility
- 04:26if we truly wanna optimize
- 04:28our treatments,
- 04:30it's not simply
- 04:32targeting a receptor or even
- 04:34targeting a circuit or a
- 04:36network.
- 04:37You really have to understand
- 04:38how
- 04:39that is interacting with what
- 04:41we call these contextual factors,
- 04:43all the other events that's
- 04:45going on in the environment
- 04:47in our lives.