NEW FINDINGS BY COLVIN AWARD WINNER ROGER MCINTYRE

There is a convergence of finding of the occurrence of cognitive dysfunction in diabetes, obesity, and bipolar and unipolar mood disorders. This is based on new evidence of insulin resistance in the CNS found in examination of exosomes. Insulin is neuroprotective and neurotrophic much like lithium. People on lithium do not have evidence of loss of grey and white matter that other’s with bipolar disorder who are not on lithium have. Intra-nasal insulin can improve cognition. The widely used insulin sensitizers GLP-1s for diabetes and weight loss appear to also decrease cognitive decline. The GLP-1 liraglutide improves cognition in mood disordered patients, and increases brain NAA in obesity. The GLP-1 semaglutide appears to increase motivation, cognition and overcome reward deficits. These agents could have anti-depressant and depression preventing properties which remain to be further confirmed in ongoing clinical trials.

McIntyre finds that 80% of Alzheimer’s patients are insulin resistant and the GLP-1s are being studied for this illness as well. There is also a convergence of deficits in cognition, motivation, normal mood in Alzheimer’s patients.

Cannabis Contributes to 15% of Case of Schizophrenia

A study in Psychological Medicine (May 2, 2023) reported on ” Danish registry data spanning five decades and representing more than 6.9 million people in Denmark to estimate the population-level percentage of schizophrenia cases attributable to (cannabis use disorder) CUD. A total of 60,563 participants were diagnosed with CUD. Three quarters of cases were in men; there were 45,327 incident cases of schizophrenia during the study period. The researchers estimate that in 2021, about 15% of schizophrenia cases among males aged 16 to 49 could have been avoided by preventing CUD, compared with 4% among females in this age range. For young men aged 21 to 30, the proportion of preventable schizophrenia cases related to CUD may be as high as 30%, the authors report.

Editors Note: Other data also support an increased risk for bipolar disorder in those abusing cannabis. The notion that cannabis use carries few risks is baloney. Making pot legal does not make it safe.

Changes in brain structure in remitted bipolar patients

Macoveanu et al reported in the Journal of Affective Disorders (2023) that compared to controls that remitted bipolar patients had “a decline in total white matter volume over time and they had a larger amygdala volume, both at baseline and at follow-up time. Patients further showed lower cognitive performance at both times of investigation with no significant change over time….Cognitive impairment and amygdala enlargement may represent stable markers of BD early in the course of illness, whereas subtle white matter decline may result from illness progression.”

A Case Report: Good Effect of Psilocybin Even with No Psychedelic Effects

Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023

Marisa Leon-Carlyle reported on a 43 yr. old man with chronic treatment refractory depression who was given psilocybin 25mg (a 5HT2A agonist) at 8:00 AM after receiving trazodone 200mg HS (which should be enough to block 80% of 5HT2A receptors). He had an excellent antidepressant response, was able to feel emotion and new love for his wife, and finally felt that doing one’s best is good enough. Obviously further systematic study is needed.

Assets of Exercise

Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023

Ben Goldstein of the University of Toronto gave a plenary talk on the benefits of exercise.

He found poor aerobic fitness in 19 of 20 young bipolar patients. They had low cerebral blood flow in proportion to the severity of their exhaustion after exercise. He noted the importance of stressing an endpoint of fitness for exercise rather than weight loss. Using an exercise coach and running with family and friends was helpful in motivating patients for consistent exercise.

Long COVID ‘Brain Fog’ Confounds Doctors, but New Research Offers Hope

James C. Jackson, PsyD, a licensed psychologist specializing in neuropsychology and rehabilitation, at Vanderbilt University School of Medicine and author of a new book, Clearing the Fog: From Surviving to Thriving With Long COVID ? A Practical Guide, reports in Medscape July, 2023 : “There’s not a lot of imprecision in the term (brain fog) because it might mean different things to different patients,”

Jackson, who began treating [a patient] in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.

An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.

Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.
Thus, new data suggest that long COVID is associated with inflammation and both reduced volume of several brain structures and decreases in white matter. These data suggest several novel approaches to therapy that require further study. One is low dose lithium which both increases gray matter volume and white matter integrity. Lithium also has some antiviral properties. This could be combined with anti-inflammatories that could be bought over the counter such as N-acetylcysteine (NAC), acetyl-L-carnitine, and celecoxib.

Note of caution. This is only an untested hypothesis and would need to be discussed with one’s physician before any of these options are considered.

High Response Rate to Psilocybin in Bipolar II Depression

Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023

Scott Aaronson gave 15 medication-free BP II patients (off all medications) 25mg of psilocybin with extensive therapeutic support. He saw rapid onset and persistent AD effects, such that at the end of 12 weeks 12 of the 15 patients were still in remission. Quality of life increased and suicidal ideation decreased. He indicated that others found that serum BDNF increased 1000 fold greater than baseline.

Antidepressant Effects of Psilocybin in Unipolar Depression

Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023

Alan Young reported on 233 patients with treatment refractory depression who were given 10mg then 25mg of psilocybin, 1 week apart.

There was intensive therapeutic support before, during, and after the ingestions. Patients experienced it as a waking dream. Response was rapid in onset and 20% response persisted at least through week 12.

Metabolic Changes in Brain of Bipolar at Autopsy

Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023

Graeme Preston reported on the brain of autopsied bipolar patients having increases aspartate and citrulline, while those with unipolar depression had decreases in the TCA cycle.

He saw increases in acetyl carnitine in manic bipolar patients versus bipolar depressed patients, which is of interest in relationship to the putative antidepressant effects of acetyl-L-carnitine in animal models of depression and in humans.

Preliminary data on ketogenic diet

Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023

Georgia Ede gave a talk on the first results of 12 bipolar patients using a ketogenic diet (composed of 75% fat; 5% carbohydrates; 20% protein) as a adjunct to about 5 medications that were insufficiently effective. She saw improvement by week 3, 58% remitted, and some lost weight. She indicated that some could revert to a regular diet after the improvement achieved by children, but not in adults.

Sebari Sethi talked about 26 of 27 bipolar patients who achieved 1.3 mmole/L ketones and lost weight and showed increases in glutamate in brain measured by Glx and decreases of 11.2% in the ACC

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