Thermoregulation dysfunction and association with depression and schizophrenia. | Charles Raison
Get the full length version of this episode as a podcast.
This episode will make a great companion for a long drive.
The BDNF Protocol Guide
An essential checklist for cognitive longevity — filled with specific exercise, heat stress, and omega-3 protocols for boosting BDNF. Enter your email, and we'll deliver it straight to your inbox.
People experiencing depression or schizophrenia tend to have impaired thermoregulation, causing difficulties with sweating and cooling themselves off. Using heat exposure, investigators were able to sensitize pathways important to thermoregulatory cooling that also affect brain regions implicated in the regulation of mood. In this clip, Dr. Charles Raison explains the relationship between thermoregulatory dysfunction and how periodic exposure to high heat may aid with treating depression and schizophrenia.
- Charles: So you would think if the world was simple, that if you’re depressed and cold, I should heat you up, and if you’re depressed and hot, I should cool you down. But in fact, the opposite is true. So in the European study, we actually very successfully measured core body temperature the day before they got to treatment, and five days after. What we found was that the hotter you were before you got into the box, the better antidepressant response you got.
- Rhonda: I was going to ask you about.
- Charles: Right. What we found from five days after being in the box, everybody’s core body temperature was really lower over 24 hours. So the box didn’t make people hotter, it made them cooler. What we were actually inducing was hypothermia. We used hyperthermia to induce hypothermia.
- Rhonda: Long term, you mean?
- Charles: Longer term.
- Rhonda: Which would be like a, almost like a hormetic effect.
- Charles: Yeah, it is. We toughened the system. We toughened up the system. We recalibrated. And this is really the work of my colleague, Christopher Lowry, at UC Boulder, in Colorado. What we think we’ve done, is sensitized thermal regulatory cooling pathways so that the heat actually exercised them in some way, or shocked them into being more sensitive. There is a giant literature on this fact that thermoregulation is impaired as we said in depression. Depressed people can’t cool off. They can’t sweat. They can’t cool off. So what we think we’ve done is sensitized the pathways of the brain and the body that mediate those effects and that that’s a marker for that sort of...we’ve also then strengthened anti-depressants levels.
- Rhonda: It’d be interesting to look at dynorphin, that whole system. Because that is involved in this.
- Charles: I know. Because it’s also, what do they call it, a cryogen, it cools.
- Rhonda: Yeah. Don’t schizophrenics also have a similar problem in terms of thermal regulation?
- Charles: They do. They’ve got really, really crazy thermal regulatory challenges, right? So that means when you see folks out, you know, it’s a tragedy, when you see them out on the street, one of the things you notice about schizophrenics is it can be hot, and they’re wearing three or four coats. So they really, really have thermal regulatory problems. If I think about it for a minute, I’ll be able to tell you there’s a study where they found that they do better...so what do they do better? They do worse with cold and better with heat, or they do worse with heat? One of the two. But it’s interesting that it’s not all bad.
- Rhonda: The thermal regulation. Yeah.
- Charles: But their thermal regulation is absolutely whacked, right.
- Rhonda: Yeah.
- Charles: I mean, you see these guys, you know, and women, right? So it’s not just depression.
A mood disorder characterized by profound sadness, fatigue, altered sleep and appetite, as well as feelings of guilt or low self-worth. Depression is often accompanied by perturbations in metabolic, hormonal, and immune function. A critical element in the pathophysiology of depression is inflammation. As a result, elevated biomarkers of inflammation, including the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, are commonly observed in depressed people. Although selective serotonin reuptake inhibitors and cognitive behavioral therapy typically form the first line of treatment for people who have depression, several non-pharmacological adjunct therapies have demonstrated effectiveness in modulating depressive symptoms, including exercise, dietary modification (especially interventions that capitalize on circadian rhythms), meditation, sauna use, and light therapy, among others.
A potent endogenous opioid peptide. Dynorphin acts on the kappa-opioid receptor and is associated with a transient feeling of dysphoria. It has many different physiological actions, depending upon its site of production, and is involved in addiction, temperature regulation, appetite, circadian rhythm, pain, stress, and depression. Dynorphin may also be involved in the body’s thermoregulatory response to hyperthermia.[1]
Biological responses to low-dose exposures to toxins or other stressors such as exercise, heat, cold, fasting, and xenohormetics. Hormetic responses are generally favorable and elicit a wide array of protective mechanisms. Examples of xenohormetic substances include plant polyphenols – molecules that plants produce in response to stress. Some evidence suggests plant polyphenols may have longevity-conferring effects when consumed in the diet.
Hypothermia is a medical emergency that occurs when your body loses heat faster than it can produce heat, causing a dangerously low body temperature. Normal body temperature is around 98.6 F (37 C). Hypothermia occurs as your body temperature passes below 95 F (35 C)
A mental disorder characterized by abnormal social behavior and failure to understand what is real. Common symptoms include false beliefs, unclear or confused thinking, hearing voices that others do not, reduced social engagement and emotional expression, and a lack of motivation. People with schizophrenia often have additional mental health problems such as anxiety disorders, major depressive illness, or substance use disorders.
Member only extras:
Learn more about the advantages of a premium membership by clicking below.
Hear new content from Rhonda on The Aliquot, our member's only podcast
Listen in on our regularly curated interview segments called "Aliquots" released every week on our premium podcast The Aliquot. Aliquots come in two flavors: features and mashups.
- Hours of deep dive on topics like fasting, sauna, child development surfaced from our enormous collection of members-only Q&A episodes.
- Important conversational highlights from our interviews with extra commentary and value. Short but salient.
Depression News
- Exercise improves depression through positive modulation of brain-derived neurotrophic factor (BDNF).
- Association of serum interleukin-6 and C-reactive protein in childhood with depression and psychosis in young adult life. (2014)
- Mouse study suggests that blocking the action of interleukin-6 may reduce symptoms of depression. (2010)
- Mouse study suggests that interleukin-6-releasing immune cells outside the brain influence the propensity to develop depression. (2013)
- Microglial interleukin-6 signaling and prostaglandin synthesis may regulate depressive symptoms in neurological disorders. (2021)
