Tag: mental health

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Genetic Basis for Why Lithium is Effective for Only Some

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Lithium was the first effective mood stabiliser for bipolar disorder (BD) and still the first-line treatment, but it is effective only in about 30% of patients, while the remainder are unresponsive. A new study implicates the decreased activation of a certain gene.

The study shows that decreased activation of a gene called LEF1 disrupts ordinary neuronal function and promotes hyperexcitability in brain cells—a hallmark of BD. The findings could lead to development of a new drug target for BD as well as a biomarker for lithium nonresponsiveness.

“Only one-third of patients respond to lithium with disappearance of the symptoms,” says Renata Santos, co-first author on the study. “We were interested in the molecular mechanisms behind lithium resistance, what was blocking lithium treatment in nonresponders. We found that LEF1 was deficient in neurons derived from nonresponders. We were excited to see that it was possible to increase LEF1 and its dependent genes, making it a new target for therapeutic intervention in BD.”

The study built on a previous one which discovered differences in the neurons of those with lithium unresponsiveness.

Using stem cell technology, the team grew neurons sampled from patients’ blood, who had BD and were responsive or unresponsive to lithium, and from normal patients. They compared the genetic characteristics and behaviour of those neurons.Lithium enables beta-catenin to pair with LEF1 to promote neural regulation in the normal controls and lithium responders.

Administration of valproic acid, a typical treatment for non-responders, increased LEF1 levels as well as activation of related genes. Silencing the LEF1 gene also deactivated related genes.”When we silenced the LEF1 gene, the neurons became hyperexcitable,” says Shani Stern, co-first author on the study. “And when we used valproic acid, expression of LEF1 increased, and we lowered the hyperexcitability. That shows there is a causative relationship, and that’s why we think LEF1 may be a possible target for drug therapy.”

The team wants to look at other types of cells, such as astrocytes, to better understand the role of LEF1 in the bipolar neural network.”LEF1 works in various ways in different parts of the body, so you can’t just turn it on everywhere,” said  co-corresponding author Carol Marchettor. “You want to be more specific, either activating LEF1 on a targeted basis or activating downstream genes that are relevant for lithium nonresponsiveness.”

Source: Medical Xpress

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Unmedicated Autism Associated With Substance Abuse

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A Taiwanese study has shown that individuals diagnosed with untreated autism spectrum disorder (ASD) have higher rates of substance abuse compared to those on treatment.

The researchers used inpatient and outpatient data of 6 599 individuals with ASD who had at least 3 outpatients visits for ASD, drawn from the Taiwan National Health Insurance Research Database. They found an increased risk of substance use disorder (SUD) among those who were not receiving medication for ASD (adjusted hazard ratio 2.33, 95% CI 1.89-2.87). The risk for drug abuse was three times higher, and the risk for alcohol abuse was two times higher.

Additionally, those with comorbid SUD had over a three times greater risk of death over a follow-up period of 8.1 years.Those taking psychotropic agents had a 40% reduction for SUD risk when taking one agent, and a 63% reduction with a multiagent.

There were several comorbidities of psychiatric disorders seen in patients with ASD, such as intellectual disability, attention deficit hyperactivity disorder, tic disorder, epilepsy, obsessive-compulsive disorder, mood disorder, anxiety disorder, and impulse control disorder. However, individuals with ASD had a higher risk of SUD even compared with matched controls with the same comorbidities. SUD risk was highest with certain comorbidities; untreated ASD with comorbid tic disorder was 6 times higher; with a comorbid impulse control disorder, it was five times higher.

The researchers stated that these are critical findings, but of limited use due to the “umbrella term” of substance use disorder, and further studies will be needed to examine the specific types of drug use amongst individuals with ASD. Future research could investigate whether non-pharmaceutical treatments such as behavioural therapy had the same effect.They conclude that screening  individuals with ASD for SUD is important, given the findings of the study.

Source: MedPage Today

Journal information: Huang J, Yang F, Chien W, et al. Risk of Substance Use Disorder and Its Associations With Comorbidities and Psychotropic Agents in Patients With Autism. JAMA Pediatr. Published online January 04, 2021. doi:10.1001/jamapediatrics.2020.5371

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Impact of COVID Lockdown on Soweto Residents’ Mental Health

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A new study reported by Health-e has revealed the mental health toll that COVID and the lockdown to control it took on residents of Soweto, with 957 participants interviewed before the lockdown and then six weeks into the lockdown.

The interviews revealed that some 14% of those surveyed were at risk of depression, which was worsened by factors such as childhood trauma as well as their level of knowledge about COVID. Feeling unable to take precautions against the virus caused anxiety levels to skyrocket. 

“While participants believed that the pandemic did not affect their mental health or their ‘mind,’ the strong relationship between perceived risk and depressive symptoms raises the concern that they may not be aware of the potential threats to their mental health during Covid-19,” said Dr Andrew Wooyoung Kim, co-director of the study. “This discrepancy may be due to different ideas of mental health, including mental health stigma.”

Kim acknowledges that the challenging South African environment of poverty and poor services may also have had significant impacts.
“Our study re-emphasises the importance of prioritising and provisioning accessible mental health resources for resource-limited communities in Soweto and across South Africa,” Kim added. 

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Anti-anxiety Drug Repurposed to Boost Cancer Therapies

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University of Cincinnati clinician-scientist Soma Sengupta, MD, PhD, says that new findings from a study conducted by her and Daniel Pomeranz Krummel, PhD, showed promising results towards enhancing the effectiveness of traditional cancer treatments with a simple anti-anxiety drug, repurposed and proven effective against melanomas.

Sengupta said, “While physicians can often quickly find and treat melanoma of the skin, metastatic melanoma, or melanoma that has spread to other parts of the body, often the brain, is a lethal cancer. Often, patients who receive immunotherapy, which uses the patient’s own immune system to treat the condition, do not have good responses. They also experience many uncomfortable side effects that impact their quality of life.”

By using a new class of sedatives (related to diazepam) to target GABA receptors, radiation or immune therapy could be enhanced, with reduced side effects. Animal study results showed that the drug allowed better infiltration of immune cells into the tumour cells, causing them to shrink, or in some cases even disappear.

“Our long-term goal is to add this new class of drugs to a patient’s radiation and immunotherapy treatment,” said Sengupta. “We hope this will help patients avoid side effects, and that by adding this drug to the regimens, we will reduce costs, since we think the treatments will become more effective, and in turn, doses of standard treatments can be lowered. More studies are needed, but this is a promising new approach using a non-toxic drug from a class of compounds that have already been approved for anxiety, but now used for a serious condition that claims lives every day.”

Source: News-Medical.Net

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‘Flight or Flight’ Brain Region Linked to Heart Disease

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Research on marmosets as reported in The Conversation has revealed the role that a region of the brain called sgACC plays in emotional arousal. Over-activity of sgACC was already associated with the dampening of pleasure and reward stimulus, seen in depression. 

A threat was presented to the marmosets in the form of a rubber snake and the marmosets were conditioned with a tone to create an association. The tone was later made without the snake to de-associate it from threat. The experimental group had over-activity induced in sgACC, the control group did not.

They found that marmosets who had not had sgACC over-stimulated responding normally to the de-association, calming down more quickly, but the over-activity group displayed fear and elevated blood pressure for much longer.

The over-activity of sgACC was also linked to abnormal heart function – increased heart rate and reduced variability in heart rate even at rest, without the presence of a threat.

Such changes reflect the presence of anxiety. The abnormal heart rates suggests that sgACC promotes the “flight or fight” response.
Brain imaging showed, with over-activity in sgACC, concurrent increased activity in the amygdala and hypothalamus, and reduced activity in the lateral prefrontal cortex, which is also seen in depression. Ketamine, a drug being investigated to treat depression, was shown to treat the depression aspects of sgACC over-activity, but in this case not anxiety – the marmosets remained fearful to stimulus.