6 Minutes of Intense Cycling Produces Major Increases in BDNF
Brain derived neurotrophic factor (BDNF) is necessary for new synapses and call survival. A new study in J. Physiology (2023) reports that the increases in BDNF from short intense cycling exercise are much greater than from prolonged (90-minute) light cycling. The authors think that this is cause by the increases in lactate produced which helps up regulate BDNF production. This could be good for fighting depression and Alzheimer’s disease, where BDNF levels are low.
Bottom line: If you don’t have much time, bust your buns.
Chronic Fatigue, Depression and Anxiety Symptoms in Long COVID Are Strongly Predicted by Neuroimmune and Neuro- Oxidative Pathways Which Are Caused by the Inflammation during Acute Infection
HK Al-Hakeim et al in Michael Maes’ lab report in J. Clinical Medicine (2023) on very important findings about immune and oxidative changes in long COVID with “physio- somatic (chronic fatigue syndrome and somatic symptoms) and affective (depression and anxiety) symptoms. The severity of the long COVID physio-affective phenome is largely predicted by increased peak body temperature (BT) and lowered oxygen saturation (SpO2) during the acute infectious phase….. We recruited 86 patients with long COVID (3–4 months after the acute phase) and 39 healthy controls and assessed serum C-reactive protein (CRP), caspase 1, interleukin (IL) 1?, IL-18, IL-10, myeloperoxidase (MPO), advanced oxidation protein products (AOPPs), total antioxidant capacity (TAC), and calcium (Ca), as well as peak BT and SpO2 during the acute phase. Results: Cluster analysis revealed that a significant part (34.9%) of long COVID patients (n = 30) show a highly elevated NT (neurotoxicity) index as computed based on IL-1?, IL-18, caspase 1, CRP, MPO, and AOPPs. Partial least squares analysis showed that 61.6% of the variance in the physio-affective phenome of long COVID could be explained by the NT index, lowered Ca, and peak BT/SpO2 in the acute phase and prior vaccinations with AstraZeneca or Pfizer. The most important predictors of the physio-affective phenome are Ca, CRP, IL-1?, AOPPs, and MPO. Conclusion: The infection–immune–inflammatory core of acute COVID-19 strongly predicts the development of physio-affective symptoms 3–4 months later, and these effects are partly mediated by neuro-immune and neuro-oxidative pathways.”
Editors Note: These finding are important as they may lead to new treatment interventions. BNN readers are reminded of a previous BNN article by investigators from Yale (written by by Isabella Backman on Dec. 13, 2022) that in a new case study, they found that guanfacine plus N-acetylcysteine (which is an anti-inflammatory, anti-oxidant, and glutathione precursor) “mitigated and sometimes eliminated the cognitive impairment known as “brain fog” that often accompanies long COVID.
Cannabidiol Reduces the Anxiety Induced by Simulated Public Speaking in Treatment-Naïve Social Phobia Patients
M M Bergamaschi, et al reported in Neuropsychopharmacology volume 36, pages 1219–1226 (2011) that the one of the ingredient in cannabis, the diol or cannabidiol (CBD), containing none of the usual THC which make up the vast majority of plant-based marijuana, reduces the anxiety Induced by simulated public speaking in treatment-naïve social phobia patients. They used “CBD (600?mg) in powder, ?99.9% pure (kindly supplied by STI-Pharm, Brentwood, UK and THC-Pharm, Frankfurt, Germany),… dissolved in corn oil.” This CBD has shown efficacy in other anxiety disorders and is FDA approved for one form of seizure disorder. This pure form of CBD is very expensive and usual preparations of available cannabis contain mostly THC and only minute amounts of CBD. Thus, the generalizability of these results to people using the widely available preparations of cannabis is extremely unlikely.
U.S. FDA Approves VRAYLAR® (cariprazine) as an Adjunctive Treatment for Major Depressive Disorder
“A Phase 3 Study 3111-301-001 showed a clinically and statistically significant change from baseline to week six in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score for patients treated with cariprazine at 1.5 mg/day + ADT compared with placebo + ADT. A second registration-enabling study, RGH-MD-75, showed a clinically and statistically significant change from baseline to week eight in the MADRS total score for patients treated with cariprazine at 2-4.5 mg/day (mean dose 2.6 mg) + ADT compared with placebo + ADT.
Cariprazine was generally well tolerated in 6- and 8-week studies. Mean weight change was < 2lbs and ? 3% of patients had a weight increase of ? 7%.
The starting dosage of VRAYLAR is 1.5 mg once daily. Depending upon clinical response and tolerability, the dosage can be increased to 3 mg once daily on Day 15. In clinical trials, dosage titration at intervals of less than 14 days resulted in a higher incidence of adverse reactions. The maximum recommended dosage is 3 mg once daily.
Most common adverse reactions observed in the adjunctive MDD studies (? 5% and at least twice the rate of placebo) were:
Akathisia, nausea, and insomnia at the recommended doses in 6-week, fixed-dose trials
Akathisia, restlessness, fatigue, constipation, nausea, increased appetite, dizziness, insomnia, and extrapyramidal symptoms in one 8-week flexible-dose trial at a titration of less than 14 days”
Potential Treatment for “Brain Fog” in Long COVID Patients: Guanfacine plus NAC
As announced in Yale on December 13, 2022 by Isabella Backman “A new Yale case study finds that two medications used for treating traumatic brain injuries, when taken together, can mitigate and sometimes eliminate the cognitive impairments known as “brain fog,” common among people with persistent COVID-19 symptoms….Individuals with long COVID, sometimes referred to as “long-haulers,” experience symptoms that may persist for weeks, months, or even years after their acute viral infection. While symptoms vary widely, a common complaint among patients is “brain fog”—a colloquial term for significant, persistent cognitive deficits, with consistent impairment of executive functioning and working memory. Long-haulers may experience a lack of mental clarity, poor focus and concentration, memory problems, difficulty with multi-tasking, and more. Brain fog can be debilitating, but there currently are no treatment options that are approved for the condition.
Cold Water Immersion Can Have Benefits
From:
Medscape Staff, December 08, 2022
“Bathing in cold water or ice may cut “bad” body fat and reduce the risk of disorders such as diabetes, but other claims of health benefits are less defined, according to researchers from the Arctic University of Norway and the University Hospital of North Norway.
WHAT TO KNOW:
- Immersion in cold water has a major impact on the body. It elevates the heart rate and has positive effects on brown adipose tissue, a type of “good” body fat that is activated by cold and may protect against obesity and cardiovascular disease.
- Exposure to cold water or cold air also appears to increase the production of the protein adiponectin by adipose tissue. Adiponectin plays a key role in protecting against insulin resistance, diabetes, and other diseases.
- Repeated cold-water immersions by inexperienced as well as experienced swimmers during the winter months significantly increased insulin sensitivity and decreased insulin concentrations.
- Numerous health and well-being claims from regular exposure to the cold, such as weight loss, better mental health, and increased libido, may be explained by other factors, including an active lifestyle, trained stress handling, social interactions, as well as a positive mindset.
- Those seeking to voluntarily practice cold-water emersion need to be educated about possible health risks associated with taking a dip in icy water, which include the consequences of hypothermia, and of heart and lung problems, which are often related to the shock from the cold.”
Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma
Gapp, K. et al. wrote about the “Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma” in Neuropsychopharmacol 41, 2749–2758 (2016).
They “used a mouse model of unpredictable maternal separation combined with unpredictable maternal stress (MSUS) to examine the consequences of traumatic stress on coping behaviors in adulthood and across generations, and the potential contribution of (glucocorticoid receptors) GR. We show that MSUS affects avoidance behaviors and learning in aversive environments in exposed fathers and their male offspring. This is associated with an increase in GR expression in the hippocampus, and with decreased DNA methylation of GR promoter in the hippocampus and in germ cells. We show that transmission of the effects of paternal trauma can be prevented by paternal (environmental enrichment) EE, suggesting a reversibility of these effects.”
Editors Note: Dad’s early environmental adversity alter his response to traumatic stress as an adult, and this can be passed to the next generation via epigenetic changes in DNA methylation, histone and microRNA chemical changes persisting in sperm. If the dad with early life adversity is housed in an enriched environment, he does not have the altered response to stress or the changes in GR, and his offspring do not have the transgenerational alterations in stress responsively. This could probably happen in people if we could only figure out to super good environmental enrichment in those having early life adversity. Having lots of stress as a neonate and then being adopted out to wonderful foster family could be the basis for a naturalistic study of this sort of result.
Lithium is a Lifesaver in Bipolar Disorder
Batya Swift Yasgur MA, LSW reported in Medscape Medical News on November 28, 2022 that “Mood stabilizers protect against suicide and all-cause mortality in patients with bipolar disorder (BD), including natural mortality, with lithium emerging as the most protective agent, new research suggests.
Investigators led by Pao-Huan Chen, MD, of the Department of Psychiatry, Taipei Medical University Hospital, Taiwan, evaluated the association between the use of mood stabilizers and the risks for all-cause mortality, suicide, and natural mortality in over 25,000 patients with BD and found that those with BD had higher mortality.
However, they also found that patients with BD had a significantly decreased adjusted 5-year risk of dying from any cause, suicide, and natural causes. Lithium was associated with the largest risk reduction compared with the other mood stabilizers.“
Intermittent theta burst magnetic stimulation (iTBS) is FDA approved.
As reported in Psych. News:?The Food and Drug Administration (FDA) has cleared the SAINT Neuromodulation System for the treatment of refractory depression in adults, Magnus Medical Inc. (the manufacturer of the product)?announced?Tuesday. SAINT is a?modified form of transcranial magnetic stimulation?(TMS) that compresses weeks of conventional TMS therapy into just five days”. ?Regular TMS takes 20-30 minutes per daily session while iTBS takes about 5 minutes and thus can be applied many times in a single day. ?”As demonstrated in a clinical trial?published?in?The American Journal of Psychiatry, Montgomery-Åsberg Depression Rating Scale (MADRS) scores dropped by 62% among participants following five days of SAINT stimulation compared with a 14% drop among participants receiving sham stimulation. These improvements were sustained over a four-week follow-up.” ?The method was developed by Nolan Williams and he used MRI to best target the site of stimulation
Cannabidiol (CBD) does not make cannabis safer
Amir Englund et al reported in Neuropsychopharmacology in A randomised, double-blind, cross-over trial of cannabis with four different CBD:THC ratios that CBD did not protect against the adverse effect of THC. These included impaired delayed verbal recall ( p?=?0.001) and induced positive psychotic symptoms on the PANSS ( p?=?2.41?×?10–5).
Editors Note: Not only does marijuana impair memory, it is a risk factor the onset of bipolar disorder and schizophrenia. When pot is used by a person with a unipolar or bipolar mood disorder, there are increases in depression and anxiety and an overall less favorable course of illness. If a person with a mood disorder uses heavy amounts of marijuana, they could consider buying N-acetylcysteine (NAC) 500mg and increasing the dose to 1,000mg twice a day within a week as this has been shown to decrease drug use compared to placebo in adolescents and young adults using and abusing pot. Most people who sell pot, are not well-informed about its dangers and just want to make money.
