Older Antipsychotic Drugs Linked to Breast Cancer


Source: National Cancer Institute

A number of commonly prescribed older antipsychotic drugs, and some newer ones, are associated with a significant increase in risk of breast cancer. 

Previous research uncovered the link between antipsychotic drug use, prescribed for a wide array of mental health problems, and breast cancer risk. This study compared newer antipsychotics to older drugs, and examined how the drugs affect prolactin levels, which have been associated with breast cancer. However, many antipsychotics elevate prolactin levels and can produce side effects such as menstrual cycle irregularities, abnormal breast milk production and abnormal breast tissue growth.

The findings are published online in the Journal of Clinical Psychopharmacology.

“Many women with psychiatric illnesses such as schizophrenia and bipolar disorder will take antipsychotics for decades, and they are essential to keeping symptoms in check,” said first author Tahir Rahman, MD. “But both older antipsychotic medicines and some newer drugs raise levels of prolactin and increase the risk of breast cancer, which is concerning. Our study confirms findings from a smaller European study that advised women and their doctors to first try drugs that don’t affect prolactin levels. We agree with that advice and believe psychiatrists should start to monitor prolactin levels in their patients taking antipsychotics.”

Antipsychotic drugs were classified into three categories, based on their established effects on prolactin. Category 1 included drugs associated with high prolactin levels, such as haloperidol, paliperidone and risperidone. Category 2 had mid-range effects and included iloperidone, lurasidone and olanzapine. Category 3 had low-effect drugs such as aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, quetiapine and ziprasidone.

Comparing the three drug categories to anticonvulsant drugs and lithium, the relative risk of breast cancer was 62% higher for women who took Category 1 drugs and 54% higher for those taking Category 2 drugs, whereas Category 3 antipsychotics were not associated with any increase in breast cancer risk.

“Certain drugs are known to elevate prolactin, and the women taking those drugs were more likely to have breast cancer,” Dr Rahman said. “But we didn’t detect any increased risk in women taking antipsychotics that don’t raise prolactin levels.”

In mouse models, prolactin can help weaken systems keeping precancerous lesions from becoming breast cancer. In humans, prolactin levels tend to be lower in women who have had more children at a younger age than in women who have fewer children or wait until they are older to do so.

In this study using data collected from 2012 through 2016, the research team performed a retrospective, observational study of breast cancer risk in women ages 18 through 64 who took antipsychotics.

The researchers identified which patients were treated for breast cancer during a 12-month period and matched that information to patients taking antipsychotic drugs. Of the 540 737 women in the database taking antipsychotics, only 914 were identified as having breast cancer – a significant number of whom were taking drugs known to increase prolactin.

“Antipsychotic medications can be lifesaving for patients who have psychotic episodes where they experience symptoms such as hallucinations and delusions,” Dr Rahman said. “In recent years, the drugs have been approved to treat other conditions, too, including depression and bipolar disorder. As those high-prolactin agents are used more widely, the number at risk could increase. We’ve been advising against using these high-prolactin agents in women who already have breast cancer, but we’d like to investigate whether keeping prolactin levels lower even might prevent some of these cancers.”

In another recent study, the antipsychotic drug aripiprazole did not increase prolactin levels in women and that a few women who began the study with high prolactin levels experienced decreases in prolactin levels after 12 weeks of treatment.

Those findings, combined with preclinical evidence of the anticancer effects of some antipsychotics, have inspired Dr Rahman and colleagues to propose repurposing some antipsychotic drugs in the fight against breast cancer.

“We don’t want to alarm patients taking antipsychotic drugs for life-threatening mental health problems, but we also think it is time for doctors to track prolactin levels and vigilantly monitor their patients who are being treated with antipsychotics,” Dr Rahman said.

Source: Washington University School of Medicine

Tick Saliva Yields Powerful Anticoagulants

Source: Wikimedia CC0

A novel study has isolated powerful anticoagulants from the saliva of ticks, which may have reduced potential for bleeding .

Blood-feeding animals rely on specific molecules in their saliva to overcome defence mechanisms of their mammalian hosts for successful survival. The saliva of ticks, for example, contains molecules that can prevent blood from clotting, and which can also suppress inflammation or immune response to enable continuous feeding on the same bite site for days, sometimes undetected by the host. The harmful effects of these parasites can actually be harnessed for medical treatments.

In their paper, published in Nature Communications, the authors explain how the cardiovascular team developed a series of thrombin inhibitors to be potent anticoagulants based on sequences of inhibitors of blood coagulation enzyme thrombin found in the tropical bont tick Amblyomma variegatum.

The team developed a series of thrombin inhibitors to be powerful anticoagulants.

Anticoagulants are used in conditions where there is an increased propensity to form blood clots in our body depriving blood supplies to important tissues and organs, otherwise known as thrombosis. These drugs are needed in many diseases caused by blood clots including heart attacks, strokes, deep vein thrombosis, pulmonary embolism and even some severe complications caused by SARS-CoV-2 infection.

These next-generation anticoagulants will now need to be tested in human trials to determine if they can effectively counteract clotting without the bleeding side effects of currently available anticoagulants.

Source: EurekAlert!

The Secret of ‘Rejuvenating’ Blood Transfusions Between Mice

Photo by Kanasi on Unsplash

Researchers have identified an important mediator of youthfulness in mouse muscle, which explains the ‘rejuvenating’ blood transfusions effect between young and old mice. The discovery could also lead to new therapies for age-related muscle loss.

Published in Nature Aging, the study showed that circulating shuttles called extracellular vesicles, or EVs, deliver genetic instructions for the longevity protein known as Klotho to muscle cells. Reduced muscle function and repair in old mice may be driven by aged EVs, which carry fewer instructions than those in young animals.

The findings help further as to understanding why muscle regeneration capacity diminishes with age.

“We’re really excited about this research for a couple of reasons,” said senior author Dr Fabrisia Ambrosio. “In one way, it helps us understand the basic biology of how muscle regeneration works and how it fails to work as we age. Then, taking that information to the next step, we can think about using extracellular vesicles as therapeutics to counteract these age-related defects.”

Decades of research have shown that when old mice are given blood from young mice, youthful features are restored to many cells and tissues. But until now, it was unclear which components of young blood confer these rejuvenating effects.

“Amrita Sahu releaseWe wondered if extracellular vesicles might contribute to muscle regeneration because these couriers travel between cells via the blood and other bodily fluids,” said lead author Dr Amrita Sahu. “Like a message in a bottle, EVs deliver information to target cells.”

Ambrosio and her team collected serum from young mice and injected it into aged mice with injured muscle. Mice that received young serum showed enhanced muscle regeneration and functional recovery compared to those that received a placebo treatment, but the serum’s restorative properties were lost when EVs were removed, indicating that it is these vesicles which deliver the beneficial effects of young blood.

The researchers then found that EVs deliver genetic instructions, or mRNA, encoding the anti-ageing protein Klotho to muscle progenitor cells, important stem cells for muscle regeneration. EVs collected from old mice carried fewer copies of Klotho instructions than those from young mice, causing muscle progenitor cells to produce less of this protein.

With advancing age, muscle doesn’t recover from damage as well because scar tissue is laid down. In earlier work, Ambrosio and her team showed that Klotho is an important regulator of regenerative capacity in muscle progenitor cells and that this protein declines with age.

The new study shows for the first time that age-related shifts in EV cargo contribute to depleted Klotho in aged stem cells, suggesting that EVs could be developed into novel therapies for healing damaged muscle tissue.

“EVs may be beneficial for boosting regenerative capacity of muscle in older individuals and improving functional recovery after an injury,” said Ambrosio. “One of the ideas we’re really excited about is engineering EVs with specific cargoes, so that we can dictate the responses of target cells.”

Beyond muscles, EVs also could help reverse other effects of ageing. Previous work has demonstrated that young blood can boost cognitive performance of aged mice.


Source: University of Pittsburgh

Eating More Avocados Edges Out Unhealthy Foods

Photo by Dirk Ribbler on Unsplash

In a novel study, researchers conducted a randomised controlled trial comparing the potential health effects between families of Mexican descent that consumed a low allotment of avocados (three per week) and families that consumed a high allotment (14 per week).

They found that the high avocado allotment families self-reported lower caloric consumption, reducing their intake of other foods, including dairy, meats and refined grains and their associated negative nutrients, such as saturated fat and sodium.

The findings, published in Nutrients, may offer insights into how to better address the burgeoning public health issues of obesity and related diseases, particularly in high-risk communities, said the authors.

“Data regarding the effects of avocado intake on family nutritional status has been non-existent,” said senior author Matthew Allison, MD, professor at UC San Diego School of Medicine.

“Recent trials have focused on individuals, primarily adults, and limited to changes in cardiometabolic disease blood markers. Our trial’s results provide evidence that a nutrition education and high avocado allotment reduces total caloric energy in Mexican heritage families.”

The soft and buttery insides of the avocado are rich in vitamins C, E, K and B6, plus riboflavin, niacin, folate, pantothenic acid, magnesium, potassium, lutein, beta carotene and omega-3 fatty acids.

Half of a medium-sized fruit provides up to 20% of the recommended daily fibre, 10% potassium, 5% magnesium, 15% folate and 7.5 grams of monounsaturated fatty acids.

For the study, researchers enrolled 72 families (231 individuals) consisting of at least three members each over the age of five, residing in the same home, free of severe chronic disease, not on specific diets, and of Mexican heritage. The families were randomised into two groups for six months, during which time both groups also received bi-weekly nutrition education sessions.

Researchers wanted to assess if increased but moderated consumption of a single, nutrient-dense food might measurably improve overall health and decrease diet-related disparities.

While no change in BMI or waist circumference was seen between the two groups during the trial, researchers noted that consuming more avocados appeared to speed satiety. Fats and some dietary fibres, such as those found in avocados, can impact total energy intake by influencing gastrointestinal functions, such as introducing bulk that slows gastric emptying, regulating glucose and insulin reactions, prolonging nutrient absorption and modifying key peptide hormones that signal fullness.

Interestingly, the study found that families consuming more avocados correspondingly reduced their consumption of animal protein, specifically chicken, eggs and processed meats, the latter of which are typically higher in fat and sodium. Current nutrition guidelines recommend reduced consumption of both fat and sodium.

But surprisingly, high avocado consumers also recorded decreased intake of calcium, iron, sodium, vitamin D, potassium and magnesium, which researchers said might be associated with eating less.

“Our results show that the nutrition education and high avocado intake intervention group significantly reduced their family total energy intake, as well as carbohydrate, protein, fat (including saturated), calcium, magnesium, sodium, iron, potassium and vitamin D,” said first author Lorena Pacheco.

“In secondary energy-adjusted analyses, the nutrition education and high avocado allotment group significantly increased their intake of dietary fibre, monounsaturated fatty acids, potassium, vitamin E and folate.”

Source: EurekAlert!

Should Unvaccinated-by-choice COVID Patients Get Less Priority?

Credit: ATS

A new opinion piece provides an exhaustive examination of the ethics of using hospital resources on unvaccinated-by-choice COVID patients with pneumonia, versus patients with other serious but slower illnesses.

In his article published online in the Annals of the American Thoracic Society, William F. Parker, MD, PhD, looked at cases in which hospitals delayed time-sensitive and medically necessary procedures for vaccinated adults when they were overwhelmed with unvaccinated patients who had severe, life-threatening COVID pneumonia and suggested an ethical framework for triaging these patients.

“These vaccinated patients are directly harmed when hospitals use all their resources to care for the many unvaccinated patients with COVID,” he wrote.  “For example, delaying breast cancer surgery by just four weeks increases the relative risk of death from the disease by 8%.”

Dr Parker argues for a contingency care standard prioritising emergency life-support, regardless of vaccination status, in order to save the most lives.  “Simply rejecting the use of vaccination in prioritisation of medical resources without analysis ignores the very real tradeoffs at play during a pandemic.  The pain and suffering of the vaccinated from deferred medical care require a deeper defense of caring for the unvaccinated.”

Eliminating double standards
He stated: “Even though the vast majority of patients who develop life-threatening COVID pneumonia are unvaccinated, hospitals still have ethical obligations to expand capacity and focus operations on caring for them—even if it means making vaccinated patients wait for important but less urgent care like cancer and heart surgeries.”

“If tertiary care centers turn inward and stop taking transfers of COVID patients from overwhelmed community hospitals, this will result in de facto triage in favor of lower benefit care and cause systematic harm to both the vaccinated and unvaccinated in vulnerable communities,” he adds.  “Hospitals must justify their nonprofit status by accepting transfers and prioritizing life-saving care during a pandemic surge.”

He cited the example of a surge in Los Angeles, when the public health department had to issue an order forcing elite hospitals to stop doing financially lucrative elective procedures and accept patient transfers from community hospitals with ICUs overwhelmed by COVID.

Reciprocity and proportionality
The principle of reciprocity supports a possible tiebreaker role for vaccination status when two patients have equivalent survival benefit from a scarce health care resource. However, a universal exclusion of the unvaccinated from life support during a pandemic surge fails the test of proportionality for reciprocity, according to Dr Parker.

Reciprocity is rewarding one positive action with another. One example of this principle is giving vaccinated people access to sporting or entertainment events that are off limits to the unvaccinated (even if negative for COVID). Proportionality is the principle that ‘payback’ should be proportional to the magnitude of the act.  For example, living kidney donors get moved way up the waitlist- the equivalent of four years of waiting time on dialysis.  This satisfies the proportionality principle.

Dr Parker points out that while the increased relative risk of death of 8% from deferring breast cancer surgery is awful, the absolute increase in risk is only one per 100, and perhaps only one per 200 for a two-week deferral.
“After the surge is over, the hospital can catch up on deferred elective surgeries,” he wrote. “The harm from a coronary artery bypass or cancer surgery delayed two weeks is real, but tiny in comparison to certain death from denying life support for respiratory failure.”

He concluded that: “There is a defensible role for vaccination status in triage as a limited tiebreaker, not as a categorical exclusion, but only in the context of a well-defined and transparent triage algorithm.  Despite the enormous financial pressure to do otherwise, elite academic centres are obligated to prioritise life support for emergency conditions to save as many lives as possible during COVID surges.”    

Source: EurekAlert!

Just Ten Minutes of Running Boosts Cognitive Function

Photo by Ketut Subiyanto on Pexels

Researchers have found that a mere ten minutes of running at moderate intensity boosts blood flow to the bilateral prefrontal cortex, improving cognitive function and mood. These findings, published in Scientific Reports, may contribute to the development of a wider range of treatment recommendations to benefit mental health.

Physical activity has many benefits as noted by a great body of evidence, such as the ability to lift mood, but in previous studies, cycling was often the form of exercise studied. However, running has always played an important role in the well-being of humans. Human running’s unique form and efficiency, which includes the ability to sustain this form of exertion (ie, by jogging as opposed to sprinting), and human evolutionary success are closely linked.

Despite this fact, researchers had not yet looked closely at the effects of running on brain regions that control mood and executive functions. “Given the extent of executive control required in coordinating balance, movement, and propulsion during running, it is logical that there would be increased neuronal activation in the prefrontal cortex and that other functions in this region would benefit from this increase in brain resources,” explained senior author Professor Hideaki Soya at the University of Tsukuba, Japan.

To test their hypothesis, the research team used the well-established Stroop Colour–Word Test and measured haemodynamic changes associated with brain activity while participants were engaged in each task. For example, in one task, incongruent information is shown, eg the word ‘red’ is written in green, and the participant must name the colour rather than read out the word. To do so, the brain must process both sets of information and inhibit the extraneous information. The Stroop interference effect was quantified by the difference in response times for this task and those for a simpler version of the task – stating the names of colour swatches.

The results show that, after ten minutes of moderate-intensity running, there was a significant reduction in Stroop interference effect time. Furthermore, bilateral prefrontal activation had significantly increased during the Stroop task and participants also reported being in a better mood. “This was supported by findings of coincident activations in the prefrontal cortical regions involved in mood regulation,” noted first author Chorphaka Damrongthai.

Given that many characteristics of the human prefrontal cortex are uniquely human, this study not only sheds light on the present benefits of running but also on the possible role that these benefits may have played in the evolutionary past of humans.

Source: EurekAlert!

Air Pollution Linked to Hypertension

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Chronic exposure to air pollution in the form of particulate matter contributes to the risk of cardiovascular and respiratory diseases, and in particular has been linked to hypertension, according to a study published in Scientific Reports.

Air pollution, accounting for more than 4.2 million deaths annually, is a significant health risk. The study assessed the impact of particulate pollution on the long-term incidence of hypertension in Spain, supporting the need to improve air quality to the extent possible in order to reduce the risk of cardiometabolic diseases among the population.

To this end, researchers have carried out a study, di@bet.es, which recruited 1103 participants aged 18–83. None of the participants presented with hypertension at the start of the study (2008–2010), and they were monitored until 2016–17. Participants were assigned air pollution concentrations for particulate matter, obtained through modeling and air quality readings. During this period, 282 cases of incident hypertension were recorded.

The study was carried out in collaboration with the air pollution department of the Research Centre for Energy, Environment and Technology (CIEMAT).

As explained by endocrinologist Sergio Valdés, “Several previous studies have described the short- and long-term association of ambient air pollutants with hypertension and blood pressure levels, but few studies have addressed the association between long-term exposure to these particles and the incidence of hypertension in a prospective manner. Therefore, the di@bet.es study has offered us the opportunity to do so in the Spanish population.”

Participants underwent a medical examination and had blood samples taken. They also answered questionnaires to obtain demographic information and variables such as smoking, exercise and diet.

Gemma Rojo, last study author, stated that “our data is consistent with a large body of evidence suggesting that air pollution may contribute to the pathogenesis of hypertension. It also supports the idea that the particulate component of air pollution is the greatest threat to the cardiovascular system.”

In this regard, she noted, “Although previous associations between exposure to gaseous pollutants and hypertension have shown some discrepancies, most studies reporting long-term exposure to particulate matter and incident high blood pressure have reported positive associations consistent with our findings.”

As Sergio Valdés explained, “our results support the need to improve air quality to the extent possible in order to reduce the risk of high blood pressure among our population, as even moderate levels such as those we report here increase the risk significantly.”

Source: Consorcio Centro de Investigación Biomédica en Red MP

Vaccine Mandate Battle Looms as Omicron Cases Surge

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As President Cyril Ramaphosa warns that the long-expected fourth wave is upon the country, a legal battle against mandatory vaccination is brewing even as Omicron rates create an unprecedented surge, likely driven through re-infections.  

Omicron, detected by South African scientists only two weeks ago, is now dominating in most provinces. However, he stressed that the country had been prepared for a fourth wave, having long been predicted by modellers. He reiterated the call for more vaccinations and to observe social distancing as much as possible over the festive season.

Vaccine mandates are now on the cards, which are expected to be introduced in early 2022. Civil rights groups including Afriforum and Sakeliga have threatened legal action if the government moves ahead on its plans to introduce vaccine mandates.

Afriforum called vaccine mandates a violation of personal freedoms, and cited Ramaphosa’s statement February this year saying that nobody in the country would be forced to take a vaccination.

As of Monday evening, reported test positivity rate now stands at 26.4%, which is well above the 10% ‘level of concern’ which had been reached a week ago.. In the third wave, it took about a month to go from this level to 25%

At this stage, there is only anecdotal evidence around Omicron’s severity which suggests milder disease.

Prof Dame Sarah Gilbert, one of the creators of the Oxford/AstraZeneca vaccine, echoed the warning that vaccine effectiveness may be reduced against Omicron, noting its spike protein contained mutations known to increase the transmissibility of the virus. She cautioned that “there are additional changes that may mean antibodies induced by the vaccines, or by infection with other variants, may be less effective at preventing infection with Omicron.

“Until we know more, we should be cautious, and take steps to slow down the spread of this new variant.”

Preliminary results published in a preprint paper awaiting peer review suggest that the re-infection hazard ratio for Omicron is 2.39, with a possible range of  1.88–3.11 falling within the 95% confidence interval. By contrast, they found that the Beta and Delta variants proliferated primarily as a result of increased transmissibility, not immune escape.

Can Seven Questions Measure Wisdom and Resilience?

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In a new study published in International Psychogeriatrics, researchers report that a shortened, seven-item scale can help determine a person’s level of wisdom, a potentially modifiable personality trait shown to be strongly associated with well-being.

Previously, the researchers had developed the 28-item San Diego Wisdom Scale (SD-WISE-28), which has been used in large national and international studies, biological research and clinical trials to evaluate wisdom.

But researchers found that an abbreviated seven-item version (SD-WISE-7 or Jeste-Thomas Wisdom Index), was comparable and reliable.

“Wisdom measures are increasingly being used to study factors that impact mental health and optimal aging. We wanted to test if a list of only seven items could provide valuable information to test wisdom,” said senior author Dilip V. Jeste, MD.

Past studies have shown that wisdom is comprised of seven components: self-reflection, pro-social behaviours (such as empathy, compassion and altruism), emotional regulation, acceptance of diverse perspectives, decisiveness, social advising (such as giving rational and helpful advice to others) and spirituality.

The latest study surveyed 2093 participants online, ages 20 to 82. The seven statements, selected from SD-WISE-28, relate to the seven components of wisdom and are rated on a 1 to 5 scale, from strongly disagree to strongly agree. Examples of the statements include “I remain calm under pressure” and “I avoid situations where I know my help will be needed.”

“Shorter doesn’t mean less valid,” said Dr Jeste. “We selected the right type of questions to get important information that not only contributes to the advancement of science but also supports our previous data that wisdom correlates with health and longevity.”  

In addition, the SD-WISE-7 was found to strongly and positively correlate with resilience, happiness and mental well-being and strongly and negatively correlate with loneliness, depression and anxiety.

“There are evidence-based interventions to increase levels of specific components of wisdom, which would help reduce loneliness and promote overall well-being,” said Dr Jeste.

“Like the COVID vaccine protects us from the novel coronavirus, wisdom can aid in protecting us from loneliness. Thus, we can potentially help end a behavioural pandemic of loneliness, suicides and opioid abuse that has been going on for the last 20 years.”

Next steps include genetic, biological, psychosocial and cultural studies of large numbers of diverse populations to assess wisdom, as well as various factors related to mental, physical and cognitive health in people across the lifespan.

“We need wisdom for surviving and thriving in life. Now, we have a list of questions that take less than a couple of minutes to answer that can be put into clinical practice to try to help individuals,” said Dr Jeste. 

Source: University of California San Diego School of Medicine

Why Antidepressants Take Weeks to Provide Relief

A healthy neuron.
A healthy neuron. Credit: NIH

The findings of a study published in Science Translational Medicine paint a new picture of how current antidepressant drugs work and suggest a new drug target in depression. As with most drugs, antidepressants were developed through trial and observation. Some 40% of patients with the disorder don’t respond adequately to the drugs, and when they do work, antidepressants take weeks to provide relief. Why this is has remained largely a mystery.

To figure out why these drugs have a delayed onset, the team examined a mouse model of chronic stress that leads to changes in behaviours controlled by the hippocampus. The hippocampus is vulnerable to stress and atrophies in people with major depression or schizophrenia. Mice exposed to chronic stress show cognitive deficits, a hallmark of impaired hippocampal function.

“Cognitive impairment is a key feature of major depressive disorder, and patients often report that difficulties at school and work are some of the most challenging parts of living with depression. Our ability to model cognitive impairment in lab mice gives us the chance to try and understand how to treat these kinds of symptoms,” said Professor Dane Chetkovich, MD, PhD, who led the study.

The study focussed on an ion transporter channel in nerve cell membranes known as the HCN channelPrevious work has shown HCN channels have a role in depression and separately to have a role in regulation of cognition. According to the authors, this was the first study to explicitly link the two observations.

Examination of postmortem hippocampal samples led the team to establish that HCN channels are more highly expressed in people with depression. HCN channel activity is modulated by a small signaling molecule called cAMP, which is increased by antidepressants. The team used protein receptor engineering to increase cAMP signaling in mice and establish in detail the effects this has on hippocampal HCN channel activity and, through that connection, on cognition.

Turning up cAMP was found to initially increase HCN channel activity, limit the intended effects of antidepressants and negatively impact cognition (as measured in standard lab tests).

However, a total reversal took place over a period of some weeks. Previous work by the researchers had established that an auxiliary subunit of the HCN channel, TRIP8b, is essential for the channel’s role in regulating animal behaviour. The new study shows that, over weeks, a sustained increase in cAMP starts to interfere with TRIP8b’s ability to bind to the HCN channel, thereby quieting the channel and restoring cognitive abilities.

“This leaves us with acute and chronic changes in cAMP, of the sort seen in antidepressant drug therapy, seen here for the first time to be regulating the HCN channel in the hippocampus in two distinct ways, with opposing effects on behaviour,” Prof Chetkovich said. “This appears to carry promising implications for new drug development, and targeting TRIP8b’s role in the hippocampus more directly could help to more quickly address cognitive deficits related to chronic stress and depression.”

Source: Vanderbilt University