How To Use Metabolic Psychiatry To Heal Your Anxiety & Depression | Stanford Psychiatrist

Cerebral glucose hypometabolism is a central characteristic of neurodegenerative conditions and is present in schizophrenia and bipolar disorder before the diagnosis of psychosis or administration of medications.

"So cerebral glucose hypometabolism in the brain globally is a central pathological characteristic of neurodegenerative conditions and also present in schizophrenia and bipolar in particular. And that's really when certain areas of the brain cannot use glucose for energy. Even though glucose is present, it can't process the glucose well, and you develop insulin resistance as well. And when you have insulin resistance centrally, there's a problem with insulin signaling and glucose signaling in the brain, and we see this even before the diagnosis of psychosis, before medications are given and before the diagnosis it's present." (said at 0:15:18)

While cerebral glucose hypometabolism is a well-established feature of neurodegenerative diseases such as Alzheimer's disease, and peripheral insulin resistance is frequently observed in drug-naïve psychiatric patients, the claim that global brain glucose hypometabolism is present in schizophrenia prior to medication or diagnosis overstates the evidence. A systematic review and meta-analysis of 36 FDG-PET imaging studies (PMID 35730361) found that glucose hypometabolism in schizophrenia is regional (confined primarily to the frontal cortex, termed hypofrontality) rather than global. Critically, absolute frontal metabolism was significantly reduced in chronic and medicated patients, whereas drug-free and first-episode psychosis patients did not differ significantly from healthy controls.

contradicts: Brain glucose metabolism in schizophrenia: a systematic review and meta-analysis of 18 FDG… (Psychological medicine 2023) · cited 70x in the literature
"Absolute frontal metabolism was lower in chronic (g = -1.18 ± 0.73) v. first-episode patients (g = -0.09 ± 0.88) and controls. Medicated patients showed frontal hypometabolism relative to controls (-1.04 ± 0.26) while metabolism in drug-free patients did not differ significantly from controls. There were no differences in parietal, temporal or occipital lobe or thalamic metabolism in schizophrenia v. controls." (abstract, results)
pubmed full study (doi)
context: Variability of glucose, insulin, and lipid disturbances in first-episode psychosis: a meta… (Psychological medicine 2023) · cited 28x in the literature
"Mean glucose, glucose post-OGTT, fasting insulin, insulin resistance, and triglycerides were greater in patients; mean total-cholesterol and HDL-cholesterol were reduced in patients." (abstract, results, passage verified)
pubmed full study (doi)

0:19:25 Mark Hyman (host)overstatedmoderate

Mitochondria in type 2 diabetics function at half the rate of mitochondria in people without type 2 diabetes.

"And when you look at type 2 diabetics, their mitochondria function at half the rate as regular people who don't have type 2 diabetes." (said at 0:19:25)

Studies evaluating in vivo mitochondrial function (oxidative phosphorylation and substrate oxidation rates in skeletal muscle) in individuals with type 2 diabetes or insulin resistance show an impairment compared to healthy controls, but typically in the range of approximately 30% to 40%, not a 50% reduction ('half the rate'). Furthermore, much of this difference is linked to reduced mitochondrial content and physical fitness rather than a halving of intrinsic mitochondrial function.

contradicts: Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2… (The New England journal of medicine 2004) · cited 2196x in the literature
"This increase in intramyocellular lipid content was most likely attributable to mitochondrial dysfunction, as reflected by a reduction of approximately 30 percent in mitochondrial phosphorylation (P=0.01 for the comparison with controls)" (abstract, results, passage verified)
pubmed full study (doi)
contradicts: Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of typ… (Diabetes 2007) · cited 456x in the literature
"Using this approach, we found that rates of muscle mitochondrial substrate oxidation were decreased by 30% in lean, insulin-resistant offspring (59.8 +/- 5.1 nmol x g(-1) x min(-1), P = 0.02) compared with insulin-sensitive control subjects (96.1 +/- 16.3 nmol x g(-1) x min(-1))." (abstract, results, passage verified)
pubmed full study (doi)

How To Use Metabolic Psychiatry To Heal Your Anxiety & Depression | Stanford Psychiatrist

Overstated

Cerebral glucose hypometabolism is a central characteristic of neurodegenerative conditions and is present in schizophrenia and bipolar disorder before the diagnosis of psychosis or administration of medications.

Mitochondria in type 2 diabetics function at half the rate of mitochondria in people without type 2 diabetes.