Dr. Karl Deisseroth, M.D., Ph.D. (@KarlDeisseroth), is a Clinical Psychiatrist and scientist who directs a bioengineering research laboratory at Stanford University School of Medicine. His work aims to understand and develop treatments for disorders of the mind such as depression, attention deficit disorders (ADHD & ADD), autism, schizophrenia, anxiety, eating disorders, borderline personality, and obsessive-compulsive disorder.
In this episode of Huberman Lab, Dr. Huberman and Dr. Deisseroth discuss research progress in developing cures for mental health disease and break down how the brain works in a healthy state and with emotional distress.
Host: Andrew Huberman (@hubermanlab)
Book: Projections: A Story of Human Emotions by Karl Deisseroth
Neurologists use imaging to diagnose stroke, Alzheimer’s, brain damage, etc.
Psychiatry is built around diseases diagnosed with words that don’t appear on scans or neuroimaging
Future of mental health diagnoses: efforts are being made to look at brain waves and imaging but still has ways to go
What happens in the brain and psychiatric diseases is physical and measurables will likely be developed
Barriers to psychiatry: the stigma of mental health disorders prevents people from seeking treatment
Nuances in psychiatry: there is a difference between colloquial use of words and medical use of terminology
“You never really know what’s going on in the mind of another person.” – Dr. Karl Deisseroth
Sometimes other people observing someone is the best gauge of what’s happening in a person – e.g., husband may see that wife is sleeping more, eating less, and could be heading into depression
We actually know very little about the microcircuitry of the human brain
Cognitive-behavioral therapy is extremely beneficial in treating panic disorder
Successful medications: anti-psychotic medications for schizophrenia – and many medications used for the treatment of various mental health conditions
Electroconvulsive therapy is extremely effective in severe depression as long as administered safely and in a controlled environment
The most frustrating thing about electroconvulsive therapy is the lack of specificity – you’re causing a brain-wide seizure – but it works
Frustration in treatment: some of the most anti-psychotic drugs, therapies, and medications are the least specific and have the greatest side effects but have the best results
Vagus nerve stimulation: a way to get into the brain without going directly into the brain
  • FDA approved for depression but is dose-limited because it stimulates everything nearby in the neck
  • Physicians can turn up the intensity in real-time remotely or in-person
Some psychiatrists sample small doses of drugs to understand what patients feel and side effects
Frustrations: (1) psychiatrists don’t have the level of understanding that other fields of medicine have – it isn’t like cardiology with a clear understanding of biology and physiology; (2) symptoms vary across people
Need clearer understanding: most psychiatric treatments have been discovered serendipitously
  • Anti-depression drugs were first created to cure tuberculosis
Need to identify circuits and patterns of activity driving activity in “healthy” state versus “non-healthy” state – to allow treatment along the path in a targeted manner
In plants channelrhodopsins function as light-gated ion channels – when a light particle hits them, ions rush in the pore
The movement of ions across the membrane is how the human brain and neural code for on and off
Mechanism of channelrhodopsins spurred the new field of optogenetics
Optogenetics: control neurons with algae protons (channelrhodopsins) using light – used to understand and manipulate sensation, cognition, action
Protocol of gene injection: channel rhodopsinsare are put into a vector (adeno-associated virus (AAV)) packaged with DNA and injected into a specific part of the body depending on the desired outcome
Protocol of light delivery: inject ½ mm light-emitting photon under the skin
Early barriers to overcome: channelrhodopsins don’t move many ions because they have a small current so have to pack a lot in without damaging cells
2007 put channelrhodopsins in mice to control actions in mice
2021 put channelrhodopsins in the eyes of human beings and made a blind person see
The broader significance of optogenetics is understanding because once you know how circuitry works and what matters, treatment options become more grounded
In principle, channelrhodopsins will enable treatments to turn on or off specific regions of the brain which lead to depression, anxiety, etc.
Optogenetics would allow for more precise stimulation methods without affecting other parts of the body
The specificity of optogenetics is only useful if you have an understanding of how to use that information
The eyes are rich in information – eye contact can be intense, mistimed, avoided, absent
The pairing of what’s going on in eyes with body language, verbal cues provides additional information
Psychiatrists learn to hone in on whatever data stream is given and can detect changes in tone of voice, eyes, etc. to inform diagnoses
Brain-machine interface: devices that will stimulate patterns of activity of neurons
Using electrodes to gather information from neurons will allow us to understand what’s going on in the brain but still has risks
Could allow information collection and stimulation only when needed and with greater specificity
Identify patterns to target psychiatric interventions and timepoints
ADHD: symptoms of hyperactive or inattentive states; the key thing is that it’s present across different domains of life and isn’t specific to one setting
There is debate about what percentage of the population with symptoms should be treated with medicine
Working on quantitative EEG diagnosis
It’s debatable whether behaviors and interactions with the sensory world could induce or activate ADD or ADHD – it must be disrupting social or occupational functioning in non-adaptive ways
Psychedelics create both an opportunity for therapeutic benefit and a risk
This is not the first time there has been a movement of psychedelics for medicinal purpose
Psychedelics alter the experience of reality in precise ways and there is an opportunity
There is a risk with all treatment, but it doesn’t appear the risks in psychedelics exceed the risks tolerated in other branches of medicine
Patients with depression are often stuck and can’t look to the future so they discount the value of their own action – psychedelics may improve this symptom by opening new paths or representations of seeing future or altered state
MDMA increases brain levels of dopamine and serotonin modulator which can be useful for the treatment of trauma
The brain learns from the experiences of psychedelics: psychedelics elicit experience at the moment and lasting impact after
Carve out protected time to just think – can even be while driving – any time to sit still
Make time for yourself without a phone, checking email, notifications, etc.
Learn to be physically still
Embrace that different stages of life come with unique needs