In the open-access journal PLOS Biology, researchers present the first evidence of 12-hour cycles of gene activity in the human brain. Led by Madeline R. Scott, the study also reveals that some of those 12-hour rhythms are missing or altered in the postmortem brains of patients with schizophrenia.
Schizophrenia patients are known to have disturbances in several types of 24-hour bodily rhythms, including sleep/wake cycles, hormone levels, and gene activity in the prefrontal cortex of the brain. However, virtually nothing is known about gene activity in the brain for cycles that are shorter than the usual 24-hour circadian rhythm. A few years ago, researchers discovered that certain genes in the body were associated with 12-hour bodily rhythms, which may have an origin in the 12-hour cycle of ocean tides.
As it is not possible to measure gene transcript levels in living brains, the new study instead used a time-of-death analysis to search for 12-hour rhythms in gene activity within postmortem brains. They focused on the dorsolateral prefrontal cortex as it is associated with cognitive symptoms and other abnormalities in gene expression rhythms that have been observed in schizophrenia.
Numerous genes in the normal dorsolateral prefrontal cortex were found to have 12-hour rhythms in activity. Among them, gene activity levels related to building connections between neurons peaked in the afternoon/night, while those related to mitochondrial function (and therefore cellular energy supply) peaked in the morning/evening.
In contrast, postmortem brains from patients with schizophrenia contained fewer genes with 12-hour activity cycles, and those related to neural connections were missing entirely. Additionally, although the mitochondria-related genes did maintain a 12-hour rhythm, their activity did not peak at the normal times. Whether these abnormal rhythms underlie the behavioural abnormalities in schizophrenia, or whether they result from medications, nicotine use, or sleep disturbances should be examined in future studies.
Co-author Colleen A. McClung adds: “We find that the human brain has not only circadian (24 hour) rhythms in gene expression but also 12-hour rhythms in a number of genes that are important for cellular function and neuronal maintenance. Many of these gene expression rhythms are lost in people with schizophrenia, and there is a dramatic shift in the timing of rhythms in mitochondrial-related transcripts which could lead to suboptimal mitochondrial function at the times of day when cellular energy is needed the most.”
Scientists have worked out why selective serotonin reuptake inhibitors (SSRIs), a common antidepressant class, cause around a half of users to feel emotionally ‘blunted’. In a study published in Neuropsychopharmacology, they show that the drugs interfere with reinforcement learning, which allows humans to adapt to their environment.
As their name implies, SSRIs target the neurotransmitter serotonin, and are commonly used to treat more resistant depression and anxiety. One of their widely-reported side effects is ‘blunting’, where patients report feeling emotionally dull and no longer finding things as pleasurable as they used to. Between 40–60% of patients taking SSRIs are believed to experience this side effect.
To date, most studies of SSRIs have only examined their short term use, but, for clinical use in depression these drugs are taken chronically, over a longer period of time. Researchers sought to address this by recruiting healthy volunteers and administering one of the best tolerated SSRIs, escitalopram, over several weeks and assessing the impact the drug had on their performance on a suite of cognitive tests.
In total, 66 volunteers took part in the experiment, 32 of whom were given escitalopram while the other 34 were given a placebo. Volunteers took the drug or placebo for at least 21 days and completed a comprehensive set of self-report questionnaires and were given a series of tests to assess cognitive functions including learning, inhibition, executive function, reinforcement behaviour, and decision-making.
No differences were found in ‘cold’ cognition – such as attention and memory, nor any differences found in most tests of ‘hot’ cognition – cognitive functions that involve our emotions.
However, the key novel finding was that there was reduced reinforcement sensitivity on two tasks for the escitalopram group compared to those on placebo. Reinforcement learning is how we learn from feedback from our actions and environment.
In order to assess reinforcement sensitivity, the researchers used a ‘probabilistic reversal test’. In this task, a participant would typically be shown two stimuli, A and B. If they chose A, then four out of five times, they would receive a reward; if they chose B, they would only receive a reward one time out of five. Volunteers would not be told this rule, but would have to learn it themselves, and at some point in the experiment, the probabilities would switch and participants would need to learn the new rule.
The team found that the escitalopram group was less likely to use the positive and negative feedback to guide their learning of the task compared to the placebo group. This suggests that the drug affected their sensitivity to the rewards and their ability to respond accordingly.
The finding may also explain the one difference the team found in the self-reported questionnaires, that volunteers taking escitalopram had more trouble reaching orgasm when having sex, a side effect often reported by patients.
Professor Barbara Sahakian, senior author, from the Department of Psychiatry at the University of Cambridge and a Fellow at Clare Hall, said: “Emotional blunting is a common side effect of SSRI antidepressants. In a way, this may be in part how they work – they take away some of the emotional pain that people who experience depression feel, but, unfortunately, it seems that they also take away some of the enjoyment. From our study, we can now see that this is because they become less sensitive to rewards, which provide important feedback.”
Dr Christelle Langley, joint first author also from the Department of Psychiatry, added: “Our findings provide important evidence for the role of serotonin in reinforcement learning. We are following this work up with a study examining neuroimaging data to understand how escitalopram affects the brain during reward learning.”
Researchers have found that a class of older antipsychotic drugs could be a promising new therapeutic option for people with type 2 diabetes, helping fill a need among patients who aren’t able to take other currently available treatments. The drugs interact with the metabolic enzyme succinyl CoA:3-ketoacid CoA transferase (SCOT), preventing the muscles from using ketones for fuel.
“There is a growing need to find new therapies for type 2 diabetes,” says John Ussher, professor in the Faculty of Pharmacy & Pharmaceutical Sciences and lead author of the recent study published in the journal Diabetes.
Metformin is one of the most common therapeutics for type 2 diabetes, but about 15% of patients aren’t able to take it. Iinsulin secretagogues, another commonly used drug class, isn’t as effective for later-stage patients.
“For the patients who can’t take metformin, patients with late-stage diabetes where their beta cells aren’t working as well, when you’re trying to find new therapies or new combination therapies as the disease progresses, it becomes more important to find new drug classes that target new mechanisms so then you have more options to try and lower blood sugar in those individuals,” Ussher explains.
The mechanism Ussher and his team turned their attention to is SCOT, which is an enzyme involved in the body’s process of making energy from ketones. Using computer modelling to find drugs that could potentially interact with SCOT, they landed on an older generation of antipsychotic drugs, a drug class called diphenylbutylpiperidines, or DPBP for short.
Ussher and his team had previously found that a specific drug within this class called pimozide could be repurposed to help treat diabetes, but they’ve since expanded their focus to see whether more of the DPBP class could also be useful for treating the disease.
“We’ve tested three drugs now, and they all interact with this enzyme,” says Ussher. “They all improve blood sugar control by preventing the muscle from burning ketones as a fuel source.”
“We believe this SCOT inhibition is the reason these antipsychotics might actually have a second life for repurposing as an anti-diabetic agent,” he adds.
Developing a drug is a complicated, time-consuming and expensive process. It involves clinical trials to test the safety and efficacy of the drug, and can easily cost hundreds of millions of dollars. Not to mention, it can take years to go from development in the laboratory to use in the clinic or hospital. Repurposing an existing drug may help fast-track the process, Ussher notes.
“With something that’s an older drug which we used historically in humans that we no longer use, we know what the adverse effects are, we know in general that it’s safe,” he says.
Though clinical trials are still needed, repurposing a drug allows researchers to focus specifically on the efficacy and safety of the new intended use, offering a quicker and cheaper path to a new therapy.
“As you already have safety data, it somewhat accelerates the process,” says Ussher. “And from an economic standpoint, often because a lot of these drugs being pursued for repurposing are older, they’re off patent and cheaper.”
Repurposing is effective because it capitalises on a main characteristic of most drugs, ie not being restricted to just one target in the body. As Ussher explains, most drugs actually have numerous targets they can influence.
“That’s where repurposing comes in,” he says. “Can we identify the other targets that a drug may interact with, and by identifying those other targets, can this drug serve a purpose for a different disease?”
This is what Ussher’s lab did in recognising the DPBP drug class could target SCOT activity as well as the dopamine receptors it targets in its original intended use to treat psychosis.
Knowledge of these original targets can also provide valuable context when refining and improving the repurposed drug. Since DPBP drugs were originally antipsychotics, many of their potential side-effects such as drowsiness, dizziness or fatigue arise from their effects on their original target: the dopamine receptors in the brain. Ussher’s lab is planning to try creating a modified version of the drug class that doesn’t reach the brain and has fewer potential adverse effects.
“For us, the excitement is that it looks like the entire family of these compounds interacts with this protein [SCOT] and can improve blood sugar control in type 2 diabetes.”
Neuroimaging technologies hold great promise in helping clinicians link specific symptoms of mental health disorders to abnormal patterns of brain activity. But a new study published in the American Journal of Psychiatry shows there are still kinks to be ironed out before doctors can translate images of the brain to psychiatric disorders such as post-traumatic stress disorder (PTSD).
Several years ago, The National Institutes of Mental Health launched a multi-billion-dollar research effort to locate biomarkers of brain activity that point to the biological roots of a host of mental health diseases, which today are typically identified by clinical evaluation of a constellation of often overlapping symptoms reported by patients.
“The idea is to forget classification of disease by symptoms and find underlying biological causes,” said Yale’s Ilan Harpaz-Rotem, professor of psychiatry and psychology and senior author of the study.
For the new study, the Yale-led team attempted to replicate the findings of an earlier nationwide neuroimaging study, in which scientists linked clusters of brain activity to a variety of outcomes among patients who had arrived at US emergency departments following traumatic events. Specifically, when researchers measured patients’ brain activity during the performance of simple tasks such as mapping responses to threats and rewards, they detected a cluster of brain activity that showed high reactivity to both threat and reward signals and seemed to predict more severe symptoms of PTSD later on.
However, when Yale researchers analysed similar neuroimaging data collected from recent trauma survivors in Israel, they were not able to replicate these findings. While they did identify the different clusters of brain activity observed in the earlier study, they found no association with prospective PTSD symptoms.
“That is not to say one set of data is right and the other is wrong, just that there is a lot of fundamental work that needs to be done to develop reliable models that could generalise across different studies,” said Yale’s Ziv Ben-Zion, a postdoctoral associate at Yale School of Medicine and the corresponding author of the study.
In fact, Yale researchers are currently working with the investigators of the original study to merge datasets “to search for common underlying patterns of brain activity associated with different responses to trauma,” Ben-Zion said.
“It took about 100 years to come up with current classifications of mental illness, but we’ve only been exploring refining psychiatric diagnoses using biomarkers for the last 10 years,” said Harpaz-Rotem. “We still have a long way to go.”
Antidepressants and psychotherapy typically are the preferred treatment options for anxiety and depression, although benzodiazepines can be helpful in treating acute or persistent anxiety that does not respond to first-line therapy. In “Walking the Benzodiazepine High Wire,” published in Psychiatric Services, two experts advocate advocate a multipronged strategy for the cautious prescribing of this class of anxiety medications rather than a stringent and exclusively regulatory approach to their use.
Kurt Kroenke, MD, of the Regenstrief Institute and Indiana University School of Medicine, and Matthew E. Hirschtritt, MD, MPH, of Kaiser Permanente Northern California and University of California, San Francisco,
Noting that the number of benzodiazepine prescriptions in the US has substantially increased over the past decade, leading to a parallel rise in rates of misuse and overdose, Dr Kroenke and Dr Hirschtritt counsel that to stem this disquieting tide, provider and patient education, coupled with prescribing surveillance, may be preferable to overly strict governmental regulation of benzodiazepines.
“Benzodiazepines should not be tried first or probably even second, but as with opiates which can be appropriate for acute pain at end of life or following a severe injury or major surgery, there are appropriate reasons for prescribing benzodiazepines for severe anxiety,” said Dr Kroenke.
He is a pioneer in the field of medical symptomology and international leader in the interpretation and treatment of psychological and physical symptoms. He has co-developed brief survey measures in worldwide clinical use to track symptoms of anxiety (GAD-7); depression (PHQ-9); suicide risk (P-4); and other conditions. These tools have been translated into more than 100 languages and assist clinicians around the world in selecting treatments and evaluating their effectiveness.
The authors conclude: “The tightrope between the benefits and risks of prescribing a medication that may be useful for some patients and harmful for others exists not only for controlled drugs but also for treatments such as antibiotics, which continue to be overprescribed, leading to antibiotic resistance. A multipronged strategy for BZD [benzodiazepine] use that includes ongoing education of providers, patients, and the general population; surveillance to optimise selective and appropriate use; and closer oversight of outlier prescribing patterns is preferable to a stringent and exclusively regulatory approach.”
While guilt is usually an appropriate emotional reaction, usually in response to doing something negative or hurtful, sometimes it can be unwarranted and persistent. Researchers at the University of Basel have shown that placebos can help assuage feelings of guilt, even when the placebo is administered openly, ie the participants are aware of the treatment being a placebo.
Guilt is considered an important moral emotion, as long as it is adaptive – in other words, appropriate and in proportion to the situation. “It can improve interpersonal relationships and is therefore valuable for social cohesion,” says Dilan Sezer, researcher at the Division of Clinical Psychology and Psychotherapy at the University of Basel. Previous research had demonstrated that placebos – even given openly – can still be effective in provoking a beneficial response.
In order to arouse feelings of guilt, healthy participants were recruited and asked to write about a time when they had disregarded important rules of conduct, or treated someone close to them unfairly, hurt or even harmed them. The idea was that the study participants should still feel bad about the chosen situation.
Participants were then randomised to three conditions: Participants in one group received placebo pills with being deceptively told that this was a real medication while participants in another group were told that they are given a placebo. Both groups were told that what they had been given will be effective against feelings of guilt. The control group received no treatment at all. The results, published in Scientific Reports, showed that feelings of guilt were significantly reduced in both placebo groups compared with those without medication.
This was also the case when the subjects knew they had been given a placebo. “Our study therefore supports the intriguing finding that placebos work even when they are administered openly, and that explanation of the treatment is key to its effectiveness,” states the study’s lead author, Dilan Sezer.
Where feelings of guilt are irrational and continue for longer periods of time, they are considered maladaptive – in other words, disproportionate. These emotions can affect people’s health and are also, among other things, a common symptom of depression.
Scientific studies have shown that placebo effects can be powerful in treating depression. But the finding that open-label placebos can also be useful for such strong emotions as guilt is new. It stands to reason, says Dilan Sezer, that we should try to harness these effects to help those affected. “The administering of open-label placebos, in particular, is a promising approach, as it preserves patient autonomy by allowing patients to be fully aware of how the intervention works.” The results of the study are an initial promising step in the direction of symptom-specific and more ethical treatments for psychological complaints using open-label placebos, Sezer continues.
Further research will need to be done into whether it is possible to treat maladaptive guilt with placebos. And it is still not known whether similar effects are also possible with other feeling states. For Dilan Sezer, one thing is certain: “Using open-label placebos would be an inexpensive and straightforward treatment option for many psychological and physical complaints.”
Research published in the journal Molecular Psychiatry suggest that clonidine, a 50-year-old blood pressure drug, could provide immediate treatment to the significant number of people emerging from the current pandemic with PTSD, as well as from longer-established causes like wars and other violence.
Clonidine is commonly used as a hypertension medication and for ADHD. It’s also already been studied in PTSD because clonidine works on adrenergic receptors in the brain, likely best known for their role in “fight or flight,” a heightened state of response that helps keep us safe.
These receptors are thought to be activated in PTSD and to have a role in consolidating a traumatic memory. Clonidine’s sister drug guanfacine, which also activates these receptors, also has been studied in PTSD. Conflicting results from the clinical trials have clonidine, which has shown promise in PTSD, put aside along with guanfacine, which has not.
Laboratory evidence shows that while the two drugs bind to the same receptors, they do different things there, says Qin Wang, MD, PhD, neuropharmacologist and founding director of the Program for Alzheimer’s Therapeutics Discovery at MCG.
Large-scale clinical trials of clonidine in PTSD are warranted, the scientists write. Their studies also indicate that other new therapies could be identified by looking at the impact on activation of a key protein called cofilin by existing drugs.
The new studies looked in genetically modified mice as well as neurons that came from human stem cells, which have the capacity to make many cell types.
In the hippocampus, they found that a novel axis on an adrenergic receptor called ɑ2A is essential to maintaining fear memories which associate a place or situation, like the site of a horrific car accident, with fear or other distressing emotions that are hallmarks of PTSD.
In this axis, they found the protein spinophilin interacts with cofilin, which is known to control protrusions on the synapses of neurons called dendritic spines, where memories are consolidated and stored.
A single neuron can have hundreds of these spines which change shape based on brain activity and whose changing impacts the strength of the synapse, the juncture between two neurons where they swap information.
“Normally whenever there is a stimulation, good or bad, in order to memorize it, you have to go through a process in which the spines store the information and get bigger,” Wang says, morphing from a slender profile to a more mushroom-like shape.
“The mushroom spine is very important for your memory formation,” says corresponding author Wang. For these mushroom shapes to happen, levels of cofilin must be significantly reduced in the synapse where the spines reside. That is where clonidine comes in.
The scientists found clonidine interferes with cofilin’s exit by encouraging it to interact with the receptor which consequently interferes with the dendritic spine’s ability to resume a mushroom shape and retain the memory. Guanfacine, on the other hand, had no effect on this key player cofilin.
The findings help clarify the disparate results in the clinical trials of these two similar drugs, Wang says. In fact, when mice got both drugs, the guanfacine appeared to lessen the impact of clonidine in the essential step of reconsolidating – and so sustaining – a traumatic memory, indicating their polar-opposite impact at least on this biological function, Wang says.
There was also living evidence. In their studies that mimicked how PTSD happens, mice were given a mild shock then treated with clonidine right after they were returned to the place where they received the shock and should be recalling what happened earlier. Clonidine-treated mice had a significantly reduced response, like freezing in their tracks, compared to untreated mice when brought back to the scene. In fact, their response was more like the mice who were never shocked. Guanfacine had no effect on freezing behaviour.
Obviously, Wang says, they cannot know for certain how much the mice remember of what previously happened, but clearly those treated with clonidine did not have the same overt reaction as untreated mice or those receiving guanfacine.
“The interpretation is that they don’t have as strong a memory,” she says, noting that the goal is not to erase memories like those of wartime, rather diminish their disruption in a soldier’s life.
When a memory is recalled, like when you return to an intersection where you were involved in a horrific car wreck, the synapses that hold the memory of what happened there become temporarily unstable, or labile, before the memory restabilises, or reconsolidates. This natural dynamic provides an opportunity to intervene in reconsolidation and so at least diminish the strength of a bad memory, Wang says. Clonidine appears to be one way to do that.
Adrenergic drugs like clonidine bind to receptors in the central nervous system to reduce blood levels of the stress hormones you produce like epinephrine (adrenaline) and norepinephrine, which do things like increase blood pressure and heart rate.
Studies like one that came out 15 years ago, which only looked at guanfacine, indicated it was of no benefit in PTSD. But then in 2021, a retrospective look at a cohort of 79 veterans with PTSD treated with clonidine, for example, indicated 72% experienced improvement and 49% were much improved or very much improved with minimal side effects.
Previous basic science studies also have indicated that manipulating the adrenergic receptor can impact fear memory formation and memory, but how has remained unknown.
PTSD has emerged as a major neuropsychiatric component of the COVID-19 pandemic, affecting about 30% of survivors, a similar percentage of the health care workers who care for them and an estimated 20% of the total population, Wang says, which means the impact on human health and health care systems could be “profound.”
Psychotherapy is generally considered the most effective treatment for PTSD, and some medications, like antidepressants, can also be used, but there are limited drug options, with only two approved specifically for the condition, she says. The lack of approved drugs has led to off-label uses of drugs like clonidine.
Cofilin is a key element in helping muscle cells and other cell types contract as well as the flexibility of the cytoskeleton of the dendritic spine. A single neuron can have thousands of dendritic spines which change shape based on brain activity and whose changing shape impacts the strength of the synapse.
Making an intentional effort to mark positive life events and achievements while gathering for food and drink will leave people feeling more socially supported, according to new research published in the Journal of Public Policy & Marketing.
The researchers found that celebrations with three conditions – social gathering, eating or drinking, and intentionally marking a positive life event – will increase perceived social support. Perceived social support, according to prior studies, is the belief that having a social network will provide support in case of future, negative life events. That belief is associated with health and well-being outcomes, including increased life-span and decreased anxiety and depression.
“Many celebrations this time of year include two of the three conditions — eating and drinking while gathering together,” said study co-author Kelley Gullo Wight, assistant professor at the Indiana University Kelley School of Business. “Adding the third condition, making an intentional effort to recognise other’s positive achievements, is key. For example, take the time to congratulate someone for getting accepted to their first-choice university, or a work project that went well, or a new job offer. This will maximise the benefits to your well-being and the well-being of all the attendees at that holiday party.”
Wight and her co-authors used behavioural experiments to survey thousands of participants over several years.
The findings showed that even if gatherings are virtual, if everyone has food and drink (no matter if it’s healthy or indulgent) and they’re celebrating positive events, this also increases a person’s perceived social support, and they can receive the same well-being benefits from it.
It also has implications for marketing managers or anyone looking to raise funds for a good cause.
“We found that when people feel supported socially after a celebration, they’re more ‘pro-social,’ and more willing to volunteer their time or donate to a cause,” said co-author Danielle Brick, assistant professor of marketing at the University of Connecticut. “This would be a good time for non-profits to market donation campaigns, around the time many people are celebrating positive life events, like holidays or graduations.”
The researchers note that hosting celebrations that increase perceived social support can be especially beneficial at places serving populations at greater risk of loneliness and isolation, like nursing homes or community centres.
They also note the importance of understanding the well-being benefits of celebrations for policymakers looking to implement regulations or measures that could impact social gatherings, like COVID lockdowns, to avoid negative consequences to mental health. They recommend that if organisers need to have virtual celebrations, they should involve some type of consumption and the marking of a separate, positive life event, so people leave the celebration feeling socially supported.
Problems with managing anger can have severe consequences for the afflicted individual and their loved ones. A new study from Karolinska Institutet shows a four-week therapy course delivered over the internet can help people to deal with their anger and aggression. The results have been published in the Journal of Consulting and Clinical Psychology.
The study, which the researchers have chosen to call the “anger study”, is the first to compare different internet-mediated emotion regulation strategies against anger. The results are expected to be important for understanding emotion regulation and for the dissemination of evidence-based methods.
Easy to recruit participants
“It is usually very difficult to recruit participants for treatment studies. For the anger study, however, it was very easy, and we had to close the recruitment site after a few weeks due to the high number of applicants. This suggests that there is a pent-up need for the psychological treatment of anger. Many people who have problems with anger feel ashamed, and we think the internet format suits this group particularly well because they don’t have to wait in a reception room or sit face-to-face with a therapist and talk about their anger,” says lead researcher Johan Bjureberg, assistant professor at Karolinska Institutet.
The anger study evaluated the effect of two emotion regulation strategies: mindful emotionawareness; and cognitive reappraisal. Mindful emotion awareness focuses on the ability to notice and accept one’s feelings and thoughts without judging or acting on them. Cognitive reappraisal, on the other hand, focuses on the ability to reinterpret thoughts and situations and identify alternative thoughts that do not trigger difficult feelings.
The 234 participants, all with significant anger problems, were randomly assigned to four weeks of either mindful emotion awareness, cognitive reappraisal, or a combination of these two strategies. All treatments were of approximately the same length and were associated with decreased self-reported anger and aggressiveness at the end of the treatment.
Combination therapy most effective
The combined treatment resulted in significantly lower levels of outward anger expression, aggression, and anger rumination, but not anger suppression, compared to mindful emotion awareness or cognitive reappraisal alone. The combination was particularly effective for participants who were experiencing very high levels of anger at the start of the study. The results strengthen research and theories suggesting that difficulties in regulating emotions and interpreting events and situations can be a major contributing factor to problems in managing anger.
“Our results suggest that a very short treatment of only four weeks administered over the internet with minimal therapist support is effective in reducing anger problems. Our hope is that follow-up studies support this finding and that the treatment can be offered broadly within regular care,” explains Johan Bjureberg.
Florida State University College of Medicine researchers have linked aspartame, an artificial sweetener found in nearly 5000 diet foods and drinks, to anxiety-like behaviour in mice.
Along with producing anxiety in the mice who consumed aspartame, the effects extended up to two generations from the males exposed to the sweetener. The study is published in the Proceedings of the National Academy of Sciences.
“What this study is showing is we need to look back at the environmental factors, because what we see today is not only what’s happening today, but what happened two generations ago and maybe even longer,” said co-author Pradeep Bhide, the Jim and Betty Ann Rodgers Eminent Scholar Chair of Developmental Neuroscience in the Department of Biomedical Sciences.
The study came about, in part, because of previous research from the Bhide Lab on the transgenerational effects of nicotine on mice. The research showed temporary, or epigenetic, changes in mice sperm cells. Unlike genetic changes (mutations), epigenetic changes are reversible and don’t change the DNA sequence; however, they can change how the body reads a DNA sequence.
“We were working on the effects of nicotine on the same type of model,” Bhide said. “The father smokes. What happened to the children?”
Aspartame received FDA approval as a sweetener in 1981. Today, nearly 5000 tonnes are produced each year. When consumed, aspartame becomes aspartic acid, phenylalanine and methanol, all of which can have potent effects on the central nervous system.
Led by doctoral candidate Sara Jones, the study involved providing mice with drinking water containing aspartame at approximately 15% of the FDA-approved maximum daily human intake. The dosage, equivalent to six to eight cans of diet fizzy drink a day for humans, continued for 12 weeks in a study spanning four years.
Pronounced anxiety-like behaviour was observed in the mice through a variety of maze tests across multiple generations descending from the aspartame-exposed males.
“It was such a robust anxiety-like trait that I don’t think any of us were anticipating we would see,” Jones said. “It was completely unexpected. Usually you see subtle changes.”
When given diazepam, a drug used to treat anxiety disorder in humans, mice in all generations ceased to show anxiety-like behaviour.
Researchers are planning an additional publication from this study focused on how aspartame affected memory. Future research will identify the molecular mechanisms that influence the transmission of aspartame’s effect across generations.
