Accelerated iTBS Treats Bipolar Depression in 5 Days
Yvette Sheline, of the University of Pennsylvania Perelman School of Medicine, reported that 10 intermittent theta burst stimulations (iTBS) per day for 5 days yielded dramatic improvement in patients with bipolar depression – both immediately after the iTBS as well as at 4 weeks.
Resting-state functional MRI was used to individually target the left dorsolateral prefrontal cortex (dlPFC), the region most anticorrelated with the subgenual anterior cingulate cortex (sgACC).
THE PATHOPHYSIOLOGY OF SCHIZOPHRENIA IS BECOMING CLEARER
David Lewis of U. Pittsburgh showed that the glutamate neurons in the prefrontal cortex of patients with schizophrenia are deficient in the gamma (30-50 Hz) oscillations that are responsible for normal working memory.
Not only are dendrites and spines deficient in these neurons in layer 3 of the cortex, but there is a deficit in parvalbumin GABA inhibitory neurons. The GABA enzyme GAD 67 is lower, producing less inhibition. The frontal neurons are hypoactive and there is less BDNF and oxidative phosphorylation present, yielding decreases in mitochondrial function.
Adolescent Cannabis Use is Associated with Regional Decreases in Cortical Volume and Greater Decreases in Males than Females
Mona Darvishi of The Ohio State University reported that adolescent cannabis use is associated with regional decreases in cortical volume in 10 of 42 brain regions.
In two of these regions, the superior frontal gyrus and the caudal middle frontal gyrus, there was a significant drug-by-sex interaction with males having significantly greater volume reductions. They conclude “Our findings, combined with existing research on marijuana users, suggest that marijuana use is associated with brain structure, with potential sex-specific effects”
Bipolar I patient show dramatic reductions in white matter integrity
Thiel et al in Neuropsychopharmacology (2024) reported that “Compared with HC [healthy controls], BD-I patients exhibited lower FA [fractional anisotropy] in widespread clusters (ptfce-FWE?< 0.001), including almost all major projection, association, and commissural fiber tracts. BD-II patients also demonstrated lower FA compared with HC, although less pronounced (ptfce-FWE?=?0.049).”
Editors Note: These data once more emphasize the importance of using lithium (Li) in bipolar disorder as it can ameliorate the deficits in white matter integrity that are so prominent in the illness. Li also improve the loss of cortical grey matter volume that evolves with illness progression. Li prevents episodes of depression and mania and reduces the incidence of suicides. That Li can reverse or ameliorate brain abnormalities in bipolar disorder is one more piece of evidence that Li should be considered a disease modifying drug (DMD) and started early in the course of illness in almost all bipolar patients. The new mantra for patients and clinicians is: Use more lithium and prevent illness progression.
Smoking Pot While Pregnant is a No-No
Mom, Don’t Think Smoking Pot When Pregnant is Harmless for your Child
In a new article in Science, Jasmine Hurd reports on a large sample of mothers who smoked pot while pregnant. Their offspring were more anxious, hyperactive, and aggressive and had higher levels of the stress hormone cortisol in their hair at ages 3-6.
When Superstorm Sandy hit, mothers who were stressed and smoked pot while pregnant had children 31 times more like to have oppositional defiant disorder and 7 times more likely to have an anxiety disorder. Stress may interact negatively with the effects of pot.
In fetuses aborted after being exposed to pot while in utero had decreased dopamine receptors in the their amygdala and n. accumbens, a reward center in brain. In animal studies, pregnant mother rodents who were exposed to THC had offspring more likely to use heroin.
DADS’ BEHAVIOR COUNTS TOO. Dad’s exposure to THC as an adult also led to offspring who preferred opiates. This was based on epigenetic changes passed on in the sperm. To the extent that this also happens in humans, one could ask how much of the current opiate epidemic is based on parental use of marijuana. Mom’s and dad’s smoking pot could make their offspring more vulnerable to opiate addiction.
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.
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.”
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.
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.
Both Obesity and Bipolar Disorders in 2249 Individuals Show White Matter Microstructure Abnormalities
Lorielle Dietze of Dalhousie University “obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) values from 930 individuals with bipolar disorders (BD), and 1319 control individuals from 20 cohorts in the ENIGMA-BD Working Group.”
They “found that lower FA was associated with both BD and BMI, in five white matter tracts, including the corpus callosum and thalamic radiation. Nine ROIs were correlated with only BD, while higher BMI was uniquely correlated with lower FA in four white matter ROIs.”
They concluded: “For the first time we showed that both obesity and BD demonstrated lower FA in some of the same regions. The impact of obesity may be greater in some tracts in BD individuals.”
