Understanding Dopamine's Role in Schizophrenia: Dr. Vikaas Sohal

Psychosis can be both terrifying and debilitating. Blocking dopamine receptors is an effective drug mechanism to reduce psychotic symptoms, hence dopamine must be involved in psychotic diseases like schizophrenia. But how? This question remains open even after 50 years of doctors prescribing such drugs. If it can be answered, better, safer therapies can start to be developed.

One scientist beginning to connect the dots is Vikaas Sohal, M.D., Ph.D, IMHRO Assistant Professor of Psychiatry at UCSF. Not to give too much away, but his recent findings pinpoint a specific type of neuron whose overstimulation by dopamine generates the kind of elevated prefrontal cortical activity that might be the neural substrate for the disorganized behavior seen in schizophrenia.

Dr. Sohal is an ace at explaining anything about the brain, and loves to do so, as you can see below. Comments are now closed.

  • If you find you like what Dr. Sohal is doing, please consider a donation to IMHRO. Caring people like you make it happen, enabling scientists like Dr. Sohal to make crucial discoveries for better mental health care.

Have fun! -Brandon

Comments

rpetheram's picture

My son, Thomas, has suffered with schizoaffective disorder and assorted "features" for over 10 years.  In that time, he has been "treated" by a number of psychiatrists. The bureaucracy in our county totally failed him.  (They are a waste of funds, in my opinion, based upon our experiences.) Ultimately, Thomas became involved in the court system who sent him to Western State Hospital.  He has remained there for over a year.             Why is it that he is NOW getting better? One thing that helped is that through repeated bloodwork, they found his body metabolizes his meds VERY differently.  But more than that, the environment seems to have helped. What about the stay in the state mental hospital has made him bettter than he has been in years?  And how long should he stay?  He is terrified to come out. 

Hi there.  First off let me commend you on taking an active role in your son's care.  Strong family support is more important than any treatment we as psychiatrists can currently offer.  Unfortunately it's incredibly difficult to provide that kind of support because 1) you are often met with resistance from the family member who is sick, 2) as you correctly point out, the mental health care system we have right now is bueracratic, limited, and often woefully inadequate, and 3) it can be incredibly frustrating to provide support for long periods of time when it seems like nothing is getting better.  Why then is your son finally doing better?  Obviously, I have not met your son so I can only speculate and please take what I say with a grain of salt.  But there are a few general factors that I would like to mention.
 
First, stress plays a HUGE part in schizophrenia -- stress hormones act on many of the same receptors on the brain that our medicines target, and stress frequently causes the onset of episodes of illness.  Thus, being in a stable, predictable environment, even one that might at first seem undesirable like a state hospital, can be very beneficial for patients.
 
Second, being in a hospital for a long period of time gives doctors the opportunity to try lots of different medications and doses to find the right one.  Different patients respond differently to various medications, but unfortunately, we do not have any test that tells us what the "right" medicine or dose is for any patient.  This can be incredibly frustrating for patients and their families because it might feel like a doctor is simply "experimenting" on the patient when he or she is going through a trial and error process to find the right medicine and dose.  This requires a lot of patience, but it sounds like in your case it has paid off, because they've figured out that he metabolizes drugs differently, and this may have helped them find the right medicine / dose.
 
Third, and this is not necessarily the case for your son but I want to point it out for the benefit of other families, sometimes being in the hospital can keep a family member away from drugs that worsen symptoms of schizophrenia, e.g. cannabis, cocaine, or methamphetamine.
 
Fourth, sometimes it is just luck -- we know that symptoms get better and worse over time, so it is possible that your son's improvement has just coincided with the time he is in the hospital.  This isn't the most likely explanation, but I wanted to mention it to be complete.
 
As for how long your son should stay -- it's very complex.  On the one hand, if he's terrified to leave, you don't want to push him to leave just to leave.  Sometimes families view leaving the hospital as a goal like graduating from high school, and understandably try to push for it to happen more quickly.  But if it happens too quickly, it could push your son right back into being worse again.  On the other hand sometimes there's no "perfect" time to leave, i.e. a patient will never be 100% comfortable or ready to leave, but you have to try to leave the hospital just to see what happens.  I wish I could tell you something more specific here, but all I can say is to consult with everyone -- you, your son, and his caregivers, to come up with a plan which is reasonable and safe even if it's not perfect.  Good luck and hang in there!

Gayle A's picture

Hi-Thank you so much for your contribution to schizophrenia research.  I was wondering if you could explain the difference between typical and atypical antipsychotic drugs.  Do they impact dopamine systems differently? My daughter (schizoaffective disorder) is on clozapine (after four years of trials with other medications) and we are seeing improvement with crippling auditory hallucinations.  Does clozapine impact dopamine systems differently than other atypical antipsychotic drugs?  Thank You!

Hi there.  Thank you for your interest in our work.  First off, I am happy to hear that your daughter is doing better on clozapine.  Here's what we do and do not know about this subject.  First, we know that clozapine definitely works better than other antipsychotic drugs.  In particular, there are some individuals (perhaps like your daughter) who don't improve much on any other antipsychotic drugs, but do improve on clozapine.  Clozapine also seems to moderately improve cognition in individuals with schizophrenia, whereas other antipsychotics have effects that are limited at best.  And clozapine seems to reduce the risk of suicide in schizophrenia more than other antipsychotics.

 
Second, we know that there are many differences between clozapine and other antipsychotics.  First, clozapine affects different receptors for brain chemicals than other antipsychotics.  In particular, clozapine has less of an effect on dopamine receptors than did the older ("typical") antipsychotics.  Clozapine also has many effects on receptors for other brain chemicals, particularly serotonin.  This difference -- more of an effect on serotonin receptors and less of an effect on dopamine receptors -- was one of the first things that researchers focused on, and was the basis for calling some drugs like clozapine "atypical" antipsychotics.  There is also evidence that when clozapine does affect dopamine receptors, it might affect them in different ways than typical antipsychotics.  Specifically, typical antipsychotics tend to target dopamine receptors in a part of the brain called the striatum, which plays a key role in movement and Parkinson's disease.  By contrast, clozapine might have less of an effect on dopamine receptors in the striatum and more of an effect on dopamine receptors in the cortex -- the part of the brain that mediates many higher cognitive functions and includes the prefrontal cortex.  This might be why clozapine causes fewer Parkinson's like side effects than typical antipsychotics.  It might also be one reason why clozapine works differently than typical antipsychotics.

 
Unfortunately, we don't know which of the many differences between clozapine and other antipsychotics make it "special," i.e. make it a more effective treatment.  Since the clozapine came to attention in the 1980s, many other "atypical" antipsychotics have been developed which, like clozapine, bind to receptors for serotonin and brain chemicals besides dopamine .  However, none of these have fully duplicated the remarkable effectiveness of clozapine.  This is important because clozapine can cause intolerable side effects, making it impossible for many people to take it.  Of course, many other people are doing amazingly well on clozapine.

 
The goal of some work in my laboratory is to understand how to create new treatments that might capture the benefits of clozapine but not have as many side effects.  Whereas many scientists began studying antipsychotics like clozapine by identifying which receptor they target, we are trying to understand how all the different effects on different receptors "add up" to change the way that the brain works.  It's kind of like this: if you were a traffic reporter, you could either try to find where all the individual accidents are located, or you could look at the big picture, i.e. how do all these accidents add up to change the amount of time it takes to get from point A to point B.  We're very lucky because new technologies have made these kinds of studies possible, and we're hoping that in several years, they will finally lead us to better treatments for your daughter and many others like her.
 

Gayle A's picture

I learned so much from your response.  Thank you for explaining the role of antipsychotics in a way that is so clear to understand.  I am very grateful to hear that you are doing additional research focused on capturing the benefits of clozapine as well as the additional research you've discussed.   I am also impressed by your approach to research (mentioned in your final paragraph) as it is such a great way to access a complicated obstacle/issue/challenge.  Thank you so much.

brandon.staglin@staglinfamily.com's picture

Thanks for participating in this week's segment, rpetheram. I am so glad to hear your son is getting better. DaffodilMom, it is always a pleasure to see your posts on Brain Waves. Thanks to you both for asking your very relevant questions--I hope the answers help you and your families, and I believe they help others to understand the nature of mental health care better--I know I learned something this time.

And, thank you, Vikaas, for being on Brain Waves again. Your compassion and expertise have been wonderful to see on the program and I know you will continue to help many people.

I am now closing comments. Tune in again in October for a feature with Dr. Susan Bookheimer and the Staglin/IMHRO Center for Cognitive Neuroscience at UCLA. Bye for now!

-Brandon

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