Trace lithium levels in drinking water reduce the risk of dementia: a systematic review
International Journal of Bipolar Disorders volume 12, Article number: 32 (2024)
The sample size varied in the studies from 37,597 to 35,000,000. Lithium levels ranged from 0.002 to 0.027 (mg/L).
“We systematically reviewed five available studies, which reported associations between trace-Li in water and incidence [of] or mortality from dementia. Association between trace-Li levels and a lower risk or mortality from dementia were observed at concentrations of Li in drinking water as low as 0.002 mg/L and 0.056 mg/L. Meanwhile, levels below 0.002 mg/L did not elicit this effect. Although three of the five studies found dementia protective properties of Li in both sexes, a single study including lower Li levels (0.002 mg/l) found such association only in women.
Conclusion
The reviewed evidence shows that trace-Li levels in the water are sufficient to lower the incidence or mortality from dementia. Considering the lack of options for the prevention or treatment of dementia, we should not ignore these findings. Future trials of Li should focus on long term use of low or even micro doses of Li in the prevention or treatment of dementia.
No HIV Infections After Twice-a-Year PrEP
Lenacapavir, a twice-yearly injectable HIV-1 capsid inhibitor, has shown 100% efficacy in preventing HIV in women at a high risk for infection, according to an interim analysis of the phase 3 PURPOSE 1 trial.
The results were so promising that the independent data monitoring committee recommended that Gilead Sciences stop the blinded phase of the trial and offer open-label lenacapavir to all participants.
The results were both unexpected and exciting. “I’ve been in the HIV field for a really long time, and there’s no other phase 3 PrEP trial that found zero infections,” said Moupali Das, MD, PhD, executive director of clinical development at Gilead Sciences, Foster City, California.
Editors Note: It would be nice if we knew anything about primary prophylaxis of bipolar disorder for high risk children.
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.
A DESEASE MODIFYING DRUG, LECANEMAB, IS NOW AVAILABLE FOR ALZHEIMER’S DISEASE
C. H. van Dyck from Yale talked about the diagnosis and treatment of Alzheimer’s dementia.
New brain imaging data have revealed that Lecanemab cannot only highly significantly delay memory decline but also improve PET measures of amyloid and tau. Early illness in those with mild cognitive impairment (MCI) can be detected; results indicate better effects of treatment Lecanemab in those with earlier and milder illness compared to those with more severe illness.
Influence of Childhood Maltreatment on Morphometry and Brain Network Architecture in Bipolar Disorder
Martin Teicher of McLean Hospital, Harvard Medical School, reported on the influence of childhood maltreatment on morphometry and brain network architecture in Bipolar Disorder.
“Childhood maltreatment (MAL) is common in individuals with bipolar disorder (BP) and is associated with earlier onset, more severe course, and more comorbidities.” They found that reduced hippocampal volume and white matter alterations were present in those with a history of childhood maltreatment. They concluded that “MAL may act as a sensitizer promoting the emergence of bipolar symptoms in individuals with less severe network abnormalities” than in BP patients with no MAL.
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”
Antidepressant Use and Risk of Manic Episodes in Children and Adolescents With Unipolar Depression
Suvi Virtanen, PhD; et al in JAMA Psychiatry. September 27, 2023. report a low risk of switching in youngsters with unipolar depression. However, the odds ratio for a switch were significantly elevated when there was concomitant use of anticonvulsants and antipsychotics, and there was a four fold increased risk if a parent had bipolar disorder. Thus one should be particularly careful about treating depression with antidepressants (AD) when there is a positive parental history of bipolar disorder and one should think of other options, such as lamotrigine, an atypical with good AD effects, or lithium.
NEW DATA ON EXTENDING THE EFFFECTS OF IV KETAMINE: Implications for countering the effects of stigma.
John Krystal of Yale U. in an article in Proceedings of the National Academy of Sci. (2023) gave new information about the anatomical and physiological effects of ketamine and about how to extend its effects. Ketamine in animals acutely (in a matter of hours) increases spines, synapses, and dendrites and physiological connectivity in neurons in the prefrontal cortex. Data now support these findings in humans with depression, but AD effects of ketamine tend to dissipate over a period of 3 to 5 days and require repeated infusions to maintain the improvement. Synaptic density can be measured with SV2A and this can be enhanced with a Navitor Pharmaceuticals drug acting on mTORC1. Surprisingly low doses of rapamycin, an inhibitor of mTOR1, extends the duration of AD effects of ketamine, increasing the response rate at 2 weeks of 13% to 41%. Ketamine restores only the spines that have been reduced in depression and rapamycin is thought to extend the duration of the restored spines. It may do this by increasing the neurotropic effects of microglia. The tripartite synapse of pre and post synaptic neurons and astrocytes, may now be better described as the tetrapartite synapse with the inclusion of microglial.
Adding psychotherapy to the effects of ketamine in PTSD increases and extends efficacy.
AD effects of ketamine can be extended with cognitive behavioral therapy. Thus, ketamine increases synaptic efficacy, synaptic density, glutamate homeostasis, and experience-dependent neuroplasticity. Extending the persistence of these effects by various chemical and psychotherapeutic mechanisms may give new ways of enhancing and prolonging the therapeutic effects of this rapidly acting agent.
Interestingly, Kaye at Yale U. reports that in contrast to transient effects of ketamine, the AD effects of therapy-assisted psilocybin appear to be very long lasting and the associated increases in spines persist for longer than 37 days. Another psychedelic MDMA that is effective in PTSD causes large increases in spines, although they are less persistent and are gone by 34 days.
Editors Note: As we have previously highlighted in the BNN, these data on ketamine and other psychedelics reversing the anatomical and physiological deficits in prefrontal neurons of depressed animals and humans (spines, dendrites, synapses and intercellular communication), give a new view of the real, reliable, and replicable neurological defects accompanying depression. The rapid correction of these neural abnormalities in conjunction with the rapid induction of antidepressant effects are not only paradigm shifting from a treatment perspective, but have major implications for the assertion that there is a neurobiological basis of depression and its treatment.
As such, these data should do much to counter the continuing stigma too often accompanying the term “mental” illness that it is somehow not as real as other medical and neurological conditions, and as it is often asserted that “it is just all in one’s head.” This picks up on the unfortunate associations and definitions of “mental” as imaginary, all in the mind, and evanescent and that mental illness can readily be countered with effort and will power such as “pulling oneself up by the bootstraps,” (the latter of which is in itself a logical impossibility.)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.
