Psychiatry's Challenges and Future: From Words to Circuits with Dr. Karl Deisseroth

This episode features Dr. Karl Deisseroth, who delves into the fundamental distinctions between neurology and psychiatry, highlighting psychiatry's unique challenge of diagnosing and treating disorders without clear physical measurables. Unlike neurology, which relies on visible brain scans or EEG activity, psychiatry primarily uses words and rating scales to navigate the complex and often mysterious landscape of the human mind. Deisseroth emphasizes that despite this inherent difficulty, psychiatric treatments, including both talk therapy and medications, can be remarkably effective, citing examples like Cognitive Behavioral Therapy for panic disorder and antipsychotics for psychosis, as well as the potent, albeit less understood, electroconvulsive therapy for severe depression.\n\nA significant portion of the discussion addresses the biggest challenge facing psychiatry today: the pervasive stigma associated with mental illness. This stigma often prevents individuals from seeking timely treatment, leading to worsening symptoms, such as untreated anxiety progressing to depression. Deisseroth also explores the subjective nature of human feelings, acknowledging the difficulty in truly knowing another person's internal state or even one's own. He advocates for moving beyond colloquial jargon in psychiatric interviews to elicit precise, unambiguous descriptions of a patient's experiences, such as their capacity for future planning or hope, to better understand their condition.\n\nThe conversation then shifts to the future of psychiatric intervention, particularly the potential of advanced neurotechnologies. Deisseroth envisions a future where quantitative tests, possibly involving external EEG measurements, could aid diagnosis. He discusses the promise of optogenetics (channelrhodopsins) for highly precise brain stimulation, contrasting it with current methods like vagus nerve stimulation, which, while accessible, lacks specificity and causes side effects. The ultimate goal is to understand brain circuits at a level analogous to understanding the heart as a pump, allowing for targeted interventions to correct atypical behaviors.\n\nFinally, the episode touches on ADHD, distinguishing between hyperactive and inattentive presentations, and the ongoing debate about its diagnosis and treatment, including the potential for EEG-based diagnostics. Deisseroth also offers a nuanced perspective on psychedelic medicine, acknowledging both its therapeutic potential for altering the experience of reality and the inherent perils of addiction and lasting negative changes. He conceptualizes the brain's cortex as a "hypothesis generation and testing machine," suggesting that psychedelics might work by lowering the threshold for conscious awareness of unlikely or incomplete hypotheses, which could be beneficial in reframing depressive thought patterns.

Psychiatry focuses on disorders where we can't see something that's physically wrong, where we don't have a measurable, where there's no blood test that makes the diagnosis, there's no brain scan that tells us this is schizophrenia, this is depression for an individual patient.

Ultimately, what's going on in the brain in psychiatric disease is physical. And it's due to the circuits and the connections and the projections and the brain that are not working as they would in a typical situation.

I think we have-- we're making progress on what the biggest challenge, which I think there's still such a strong stigma for psychiatric disease that patients often don't come to us.

I never really know what's going on inside the mind of the other person. I get some feedback, and I get words. I get behaviors. I get actions. But I never really know.

In psychiatry, despite the depths of the mystery we struggle with, many of our treatments are actually-- we may be doing better than some other specialties in terms of actually causing therapeutic benefit for patients.

The heart is-- we now know it's a pump, it's pumping blood. And so you can look at everything about how it's working or not working in terms of that frame. It's clearly a pump. We don't really have that level of what is the circuit really there for in psychiatry.

To your initial question, could a more precise stimulation method like optogenetics help in this setting? In principle, it could, because that if you would target the light sensitivity to just the right kind of cell... then you're in business.

Literally every psychiatric diagnosis requires that it has to be disrupting someone's social or occupational functioning.

The brain and in particular, our cortex, I think, is a hypothesis generation and testing machine.

What the psychedelics seem to do is they change the threshold for us to become aware of these incomplete hypotheses or wrong hypotheses or concepts that might be noise but are just wrong.