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(https://www.psypost.org/scientists-explore-molecular-links-between-stress-brain-function-and-personality-disorders/) Scientists explore molecular links between stress, brain function, and personality disorders
Apr 15th 2025, 10:00

A new scientific review published in (https://www.sciencedirect.com/science/article/pii/S0028390825000280) Neuropharmacology explores how the environment interacts with brain biology in shaping personality disorders. By examining molecular, neurochemical, and metabolic pathways, the authors highlight promising directions for developing more personalized treatments. The review underscores how early life stress and environmental influences may lead to persistent changes in brain circuits responsible for emotion regulation and social behavior.
Personality disorders are a group of mental health conditions defined by long-lasting patterns of behavior, emotional response, and thinking that differ significantly from societal expectations. These patterns typically emerge in adolescence or early adulthood and can disrupt a person’s relationships, work, and self-image. The causes of personality disorders are complex, involving both inherited traits and life experiences. The authors of the review set out to explore how environmental exposures, such as childhood trauma and chronic stress, might alter the brain at a molecular level, increasing the risk for these disorders.
“The way the human brain adapts to the environment is of great interest in the neuroscience field, especially when exploring new avenues to treat mental health conditions that are currently poorly understood,” said the corresponding authors of the paper, (https://www.lancashire.ac.uk/academics/dr-lorenzo-more) Lorenzo More (a senior lecturer in neuroscience at the University of Central Lancashire), (https://unipv.unifind.cineca.it/resource/person/1221568) Ilaria Morella (assistant professor in pharmacology at Pavia University), and Andrew Shaw, (a lecturer in biomedical science at Glasgow University).
One of the central themes of the review is how environmental stress can shape the brain’s development through biological changes, a process known as environmental embodiment. The authors examine how specific molecular signaling pathways—namely Ras-ERK, p38, and mTOR—respond to external stimuli. These pathways regulate important brain functions like memory, stress responses, and social behavior. When disrupted, they may contribute to the kinds of emotional instability, impulsivity, and interpersonal difficulties seen in many personality disorders.
The review also discusses how certain chemicals in the brain, including serotonin, dopamine, noradrenaline, oxytocin, and vasopressin, are involved in the development and expression of personality disorder traits. For instance, reduced serotonin activity has been linked to increased impulsivity and emotional instability, while altered dopamine function may affect how people respond to rewards or frustration. Imbalances in oxytocin and vasopressin, which influence bonding and aggression, are believed to underlie some of the social and emotional challenges seen in people with disorders such as borderline or antisocial personality disorder.
The authors draw particular attention to the brain’s energy systems, especially the role of mitochondria—tiny structures within cells that generate energy. These energy-producing systems are not just about keeping neurons running; they also help regulate the production of neurotransmitters like serotonin and dopamine. Studies in both humans and animal models have found that disruptions in mitochondrial function may be associated with traits like impulsivity and aggression. Additionally, the review highlights the role of oxidative stress—when harmful molecules called reactive oxygen species build up in the brain—in influencing how people react to stress and social situations.
Because personality disorders are difficult to model in animals, researchers have turned to studying smaller behavioral traits known as endophenotypes. These include behaviors such as heightened aggression or reduced social interaction. For example, one widely used test involves observing how mice respond to intruders, which gives insight into aggression levels. Although these models cannot capture the full complexity of human personality disorders, they help researchers identify biological mechanisms that might contribute to symptoms.
The review highlights “that antisocial traits — such as disproportionate aggression — which are characteristic of a clinical condition called antisocial personality disorder, result from imbalances in certain brain molecular pathways within cells,” the researchers told PsyPost. “These pathways can be influenced by one’s environment. For example, environments marked by high social competition increase the activity of p38, a ‘pro-stress’ molecular pathway, while reducing the activity of the Ras-ERK ‘anti-stress’ pathway.”
A key innovation discussed in the review is the potential development of “enviromimetic” drugs—medications that mimic the positive effects of healthy environmental experiences. These drugs would not treat symptoms in isolation, but instead activate the same molecular pathways that are engaged by nurturing social experiences or supportive environments. The goal is to reset or strengthen the biological systems involved in emotion regulation and social functioning.
“Targeting key components of the Ras-ERK pathway could enhance its cellular anti-stress effects and potentially reduce aggressive behaviors,” the researchers explained.
Some early examples of such interventions include ampakines—compounds that enhance the activity of specific brain receptors and may improve memory, plasticity, and sociability. Ampakines work by stimulating the Ras-ERK pathway, which is involved in learning and synaptic growth. Similarly, certain nutraceuticals, such as omega-3 fatty acids or saffron extract, may reduce inflammation and oxidative stress, which are increasingly recognized as contributors to emotional instability and aggression. These dietary supplements could complement existing therapies by supporting brain health at a cellular level.
The review also introduces a novel experimental compound called RB5, a cell-penetrating peptide that enhances ERK signaling in the brain. By mimicking certain deficiencies in ERK regulation, RB5 increases the activity of pathways involved in synaptic function and gene expression. This type of targeted molecular intervention might eventually help reduce aggressive or antisocial behaviors by recalibrating brain responses to social stimuli.
Looking ahead, the authors stress the need for more precise models of personality disorders that go beyond single traits like aggression. Many features of these disorders—such as a fragile sense of self, chronic feelings of emptiness, or fears of abandonment—are difficult to study in animals, leaving significant gaps in current knowledge. Future research may focus on combining genetic, molecular, and behavioral data to identify biomarkers that can guide personalized treatment strategies.
In particular, more work is needed “to better understand how the human brain encodes the valence of environmental stimuli, and how we can harness this knowledge to develop treatments for affective mental health conditions such as anxiety, depression, and schizophrenia,” the researchers said.
The review, “(https://doi.org/10.1016/j.neuropharm.2025.110322) Neurobiology, molecular pathways, and environmental influences in antisocial traits and personality disorders,” was authored by Patryk M. Adamczyk, Andrew Shaw, Ilaria M. Morella, and Lorenzo More.

(https://www.psypost.org/expressing-negativity-improves-support-from-romantic-partners-new-research-finds/) Expressing negativity improves support from romantic partners, new research finds
Apr 15th 2025, 08:00

When people face stressful situations, reaching out to a partner for emotional support is a common response. But not all support is created equal—and not everyone receives it in the same way. New research published in (https://doi.org/10.1177/01461672241273142) Personality and Social Psychology Bulletin suggests that the way people express their emotions, particularly negative emotions, can influence the quality of support they receive from romantic partners. Across three studies, the researchers found that expressing more negativity—through sadness, worry, or frustration—tended to elicit higher-quality support, even when the stressor was relatively minor.
Although receiving emotional support from close partners is linked to better coping and psychological well-being, research has mostly focused on the person giving support. Less is known about how support-seekers might influence the kind of help they receive. The authors, Kirby Sigler and Amanda Forest from the University of Pittsburgh, wanted to understand whether expressing negative emotions helps people receive better emotional support.
“I was interested in this topic because social support is an important contributor to individual and relational well-being and I wanted to begin to understand how people can effectively garner support when they experience negative events. One way to do that was to examine how people are discussing these stressful events with their partner and how they may communicate,” explained study author Kirby Sigler, a graduate student at the University of Pittsburgh and member of the (https://www.pittrelationshipprocesseslab.com/) Pitt Relationship Processes Lab.
The researchers conducted three separate studies to explore the link between emotional expression and partner support. Each study used different methods and types of interaction to ensure the findings were robust.
Study 1 involved 386 participants in romantic relationships who were recruited online. Each person was shown a simulated text message from a partner asking for support. The message varied in two key ways: the severity of the stressor (either serious, like a home burglary, or trivial, like ruined plans due to bad weather) and the level of negative emotional expression (low versus high). After reading the message, participants wrote a response as if they were replying to their partner. These responses were then evaluated by independent coders for support quality—specifically, how caring and helpful they seemed.
Study 2 was a preregistered follow-up with 314 participants using a similar design but a different communication format. Instead of reading and writing messages, participants listened to a voicemail from their partner describing a stressful event and recorded an audio reply. Again, the severity of the stressor and level of negative expressivity were manipulated. Coders rated the quality of each response, and participants also answered questions about their impressions of the partner’s need and their own motivations for responding.
Study 3 extended the research into real conversations. The researchers brought 104 couples into a virtual lab setting and asked one partner to talk about a real-life stressor from the past year. The other partner acted as the support-provider. Both partners then reported how much negativity was expressed, how much support was needed, and how responsive or helpful the conversation was. This study allowed the team to observe how natural emotional expression and real-world stressors influenced support behaviors.
Across all three studies, expressing more negative emotion consistently led to better-quality support from romantic partners. In Studies 1 and 2, participants gave more caring and helpful responses when the support-seeking message contained higher levels of emotional distress, regardless of whether the stressor was serious or minor. The support responses were both more responsive (showing understanding and care) and more effective at helping the partner manage the problem.
In Study 3, similar patterns emerged in real-life conversations. Partners who expressed more negativity were seen as needing more support and received more effective help in return. This held true even after accounting for other types of emotional expression, like positive or neutral comments.
One of the key mechanisms driving these effects appeared to be the way negative expressivity influenced the partner’s perception of need. When a support-seeker expressed strong emotions, their partner was more likely to think they genuinely needed help. This perception of need predicted greater effort to be supportive, especially in ways that were practically useful—such as offering perspective or helping with problem-solving.
The researchers also tested whether the seriousness of the problem made a difference. They initially expected that negative expression might backfire when the issue was trivial, but this was not supported. Across all three studies, the effects of emotional expression were not moderated by how severe the stressor was. That is, expressing negative emotions about even minor issues still prompted better support from partners.
“We were surprised to find that negativity predicted high-quality support, even for relatively trivial stressors,” Sigler told PsyPost.
Interestingly, while negativity helped elicit more support overall, it was not without some downsides. In Study 1, support-providers sometimes interpreted highly negative messages as complaining, which slightly reduced their responsiveness. In Study 2, highly negative expression led some partners to feel that the support-seeker was too dependent. And in Study 3, perceiving the support-seeker as coping poorly was linked to lower responsiveness. These findings suggest that while negative expressivity helps communicate need, it can also generate judgments that slightly dampen the support response.
Nonetheless, in all three studies, the overall effect of expressing more negative emotion was positive: partners provided better, more helpful support when they thought the person was genuinely upset.
“One key takeaway is that expressing one’s negative emotions, such as sadness, about stressful events may help communicate to others that you need support (even though this might feel vulnerable!),” Sigler explained. “However, we are not suggesting that people should express negativity inauthentically or to everyone they meet, all of the time, as expressing negativity in these ways may have different effects than what we observed.”
As with all research, there are some limitations to consider. The findings focused on short-term support interactions, long-term patterns of negative expression could lead to different results. In addition, the samples were largely composed of mixed-gender, long-term couples, which may limit generalizability. It’s not clear whether similar effects would be seen in friendships, newer relationships, or professional settings.
“One caveat to be aware of is that the negativity we investigated here was in short communications — either a hypothetical text or voicemail, or in a discussion we asked people to have for seven minutes,” Sigler said. “Another is that we studied negative expressivity’s effects on support provided by a close relationship partner. There are many situational and relational features to consider with expressions of negativity, so we would not definitively say that expressing negativity will always predict receiving high-quality support. Understanding when and for whom it does so is an important direction for future work.”
The researchers noted that future work could explore how people express their needs more clearly—whether through emotions, words, or both—and whether this changes the kind of support they receive. Another area to investigate is how cultural norms or personal histories influence responses to emotional disclosure.
“In our lab we hope to continue to examine how people can garner support when they need it, and to examine the types of stressors people are talking about and how they’re talking about them,” Sigler said.
The study, “(https://doi.org/10.1177/01461672241273142) Expressing Negativity Enhances Support From Romantic Partners, Even for Trivial Stressors,” was authored by Kirby N. Sigler and Amanda L. Forest.

(https://www.psypost.org/probiotic-supplements-may-reduce-negative-emotions-in-healthy-adults/) Probiotic supplements may reduce negative emotions in healthy adults
Apr 15th 2025, 06:00

A new study published in (https://www.nature.com/articles/s44184-025-00123-z) npj Mental Health Research suggests that taking (https://www.psypost.org/probiotic-supplements-may-improve-working-memory/) probiotics can reduce negative mood in healthy adults—but only if you know where to look. While standard psychological questionnaires failed to detect meaningful changes, participants who tracked their emotional state each day showed a clear and consistent decline in negative feelings after taking probiotics for two weeks. The findings suggest that daily monitoring may offer a more sensitive way to measure subtle improvements in mood and could help resolve conflicting results from past probiotic studies.
The study was motivated by (https://www.psypost.org/gut-feeling-can-probiotics-lift-your-mood-new-research-provides-insight/) growing scientific interest in the “microbiome–gut–brain axis,” the idea that gut bacteria may influence mental health. While some evidence supports this connection, especially in people with clinical depression, research on healthy populations has produced mixed results. Probiotics—supplements containing live bacteria thought to benefit gut health—have been studied as a potential way to improve mental well-being, but findings have been inconsistent. This study aimed to clarify whether probiotics can influence emotion in healthy people and whether certain individuals might benefit more than others.
“The burgeoning field of the gut microbiome is revealing the numerous effects that bacteria in the gut may have on the brain and behaviour – and in the future this field may be able to offer novel solutions when it comes to treating mental health,” explained study author (https://www.katerinajohnson.co.uk/) Katerina Johnson of Leiden University. “We know that the gut–brain connection provides various routes through which bacteria in the gut can influence how we feel and behave, including via the vagus nerve, immune system and hormones. So here we used a combination of methods to capture how probiotics might influence the ability to regulate our emotions and affect our mood.” 
For their study, the researchers recruited 88 healthy adults and randomly assigned them to receive either a probiotic supplement or a placebo each day for four weeks. The study used a double-blind design, meaning neither the participants nor the researchers knew who received which treatment. The probiotic used in the study was a commercially available product containing nine bacterial strains commonly found in the human gut. Participants mixed the probiotic or placebo powder into lukewarm water and drank it once daily.
Unlike many previous studies, which relied solely on questionnaires administered before and after the intervention, this research included several types of measurements. Participants completed a wide range of psychological questionnaires both before and after the four-week period to assess traits such as anxiety, depression, stress, and emotional regulation. They also took part in cognitive tasks designed to measure how they processed emotional stimuli, such as identifying facial expressions or responding to emotionally charged images.
In addition to these standard assessments, participants were asked to report their mood and digestive symptoms each day using a smartphone link. Each day, they rated how positive and how negative they felt on a scale from 0 to 100, along with reporting on stool consistency. This daily tracking was a novel aspect of the study, providing much more detailed insight into changes in emotional state over time.
The main finding was that probiotics reduced negative mood in the probiotic group, and this effect became noticeable after two weeks of use. Participants who took the probiotic supplement consistently reported a gradual decline in negative feelings, such as sadness or irritability, compared to those who took the placebo. Interestingly, there was no change in reported positive feelings, suggesting that probiotics may specifically buffer against negative emotional states without affecting positive mood.
“Our research has promising implications in terms of the effect of probiotics on mood, although science still doesn’t have a good understanding of precisely how probiotics work and all the various effects they may have on our physiology,” Johnson told PsyPost. “More studies would have to be conducted first, but it’s possible that in the future probiotics could be used in a targeted way to help prevent low mood progressing to mental health conditions like depression.”
On the other hand, the more traditional psychological questionnaires did not detect significant differences between the two groups. In fact, in some cases, scores on measures like anxiety and stress improved more in the placebo group. However, these changes were small, and given the number of comparisons made, the authors caution against overinterpreting these findings. The questionnaires might simply not be sensitive enough to detect subtle emotional shifts in healthy individuals who are not experiencing clinical symptoms.
The researchers also examined whether certain traits made individuals more likely to benefit from probiotics. They found that people who scored higher on measures of risk aversion—a trait linked to vulnerability to depression—tended to show the largest reductions in negative mood. This suggests that even within a healthy population, some people may be more sensitive to the psychological effects of probiotics than others. If confirmed in future studies, this insight could help target probiotic interventions to those who are most likely to benefit.
“Another novel aspect of our research is that we then looked at whether we could predict who would best respond to probiotics based on their psychological traits,” Johnson said. “We found that various traits, particularly people who tended to be more risk averse, were the ones whose mood benefited most from taking probiotics. This is interesting because there is some evidence that people who are more risk avoidant may be more vulnerable to developing depression.”
The study did not find meaningful changes in cognitive processing of emotional information, such as recognizing facial expressions or shifting attention to emotional faces. This is notable because other research has suggested that probiotics can influence emotional processing at the cognitive level, especially in people with depression. The absence of such effects here may be due to the healthy status of the participants or the relatively short intervention period.
One of the most interesting aspects of the study is the comparison with antidepressants. The researchers noted that the mood improvements from probiotics began around two weeks into the intervention—the same time frame in which many people begin to feel the effects of antidepressants. 
“The comparable timescales are an interesting aspect of our findings,” Johnson explained. “It may be a sign that both antidepressants and probiotics can affect our mood through shared pathways. “In fact we know that both can signal to the brain via the vagus nerve (the main nerve connecting the gut and brain) and also that they both have anti-inflammatory effects.”
The authors also emphasize that their study helps explain why past research on probiotics has yielded conflicting results. Many studies use only pre- and post-treatment questionnaires, which may overlook important changes that develop gradually over time.
“It’s particularly notable that by tracking how people felt on a daily basis, we could detect the beneficial effects of probiotics on mood, whereas the standard psychological questionnaires that are commonly used in the field weren’t sensitive enough to pick up these changes,” Johnsonnoted. “By monitoring people daily, rather than just assessing them before and after, it gives us much better resolution of changes over time when taking probiotics.”  
“This is the first study to implement daily mood monitoring to assess the effects of probiotics and in fact, by the end of the month-long study, their negative mood still appears to be improving. One disadvantage with psychological questionnaires is that they attempt to dissect how people are feeling into discrete categories e.g. stress, anger, anxiety or depressive tendencies. In contrast, asking how positive or negative someone is feeling can holistically capture a change in any emotional state.”
Despite the promising findings, the study has some limitations. The participants were healthy young adults, so the results may not apply to older individuals or those with clinical conditions. The sample size, while adequate for detecting medium effects, may not capture smaller differences. Also, the daily mood ratings were based on simple questions rather than validated clinical measures. However, the researchers argue that this simplicity might be a strength, capturing subjective emotional experience more directly than structured questionnaires.
The study opens several avenues for future research. Longer intervention periods might reveal larger or more lasting effects, especially since mood improvements were still increasing at the end of the four-week study. Future studies could also compare different probiotic formulations, explore the role of diet, or use biological markers to track changes in inflammation or gut bacteria. 
“Although this study was using probiotic supplements, it’s relevant to note that there are natural sources of probiotics in our diet (e.g. fermented cheese, sauerkraut, kimchi) and also prebiotic fiber which helps promote the growth of beneficial gut bacteria and is found in various foods (e.g. bananas, legumes, whole grains),” Johnson explained. “In fact, (https://www.sciencedirect.com/science/article/pii/S2452231719300181) some of my other research on the human microbiome found that eating naturally occurring sources of probiotics and prebiotics was linked to a more diverse microbiome, typically a marker of a healthy gut.”
The study, “(https://www.nature.com/articles/s44184-025-00123-z) Probiotics reduce negative mood over time: the value of daily self-reports in detecting effects,” was authored by Katerina V.-A. Johnson and Laura Steenbergen.

(https://www.psypost.org/als-breakthrough-ashwagandha-derived-drug-shows-promise-in-slowing-progression-of-amyotrophic-lateral-sclerosis/) ALS breakthrough: Ashwagandha-derived drug shows promise in slowing progression of amyotrophic lateral sclerosis
Apr 15th 2025, 02:00

Every year roughly 1,000 Canadians are diagnosed with amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease). Some (https://als.ca/) 4,000 Canadians are currently living with the disease.
There are few effective treatments available to slow the progression of ALS and, unfortunately, most sufferers die within two to five years of being diagnosed.
As neuroscience researchers, we are dedicated to finding ways to reduce the symptoms of ALS. In this article, we discuss the promising results of one of our recent studies.
ALS, a complex disease
ALS is a neurodegenerative disease. Sufferers gradually lose the ability to perform voluntary movements due to loss of communication between the nervous system and muscles.
Our scientific understanding of ALS has evolved considerably since the disease was first described by the neurologist Jean-Martin Charcot, in 1874.
Today it is widely recognized that ALS affects several types of cells, including immune cells, muscle cells, glial cells (those that surround and insulate neurons) and neurons. However, for reasons that are still unknown, motor neurons, the cells responsible for controlling voluntary and involuntary movement, (https://doi.org/10.1016/B978-0-323-98817-9.00031-4) are particularly vulnerable.
Targeting motor neurons
Motor neurons have a complex morphology with projections that transmit information, resembling the branches of a tree. The neurons connect the brain and spinal cord to the muscles. These neuronal connections with the muscles are responsible for voluntary movements such as walking, speaking and eating.
(https://doi.org/10.3389/fncir.2023.1208876) In ALS, motor neurons degenerate and die, which leads to muscle weakness and, ultimately, paralysis. Because ALS is a complex disease with few effective therapies, there is an urgent need to better understand it in order to develop more therapeutic strategies.
Our research team in the Department of Psychiatry and Neuroscience at Université Laval is dedicated to understanding the early pathological changes that occur in motor neurons before they die. Our aim is to identify and develop therapeutic interventions that can reverse these early changes and slow the progression of the disease.
How do neurons lose their connectivity?
Using the mouse as a model, we carried out genetic modifications to recreate the motor and cognitive disability brought about by ALS.
In doing so, (https://doi.org/10.1186/s40478-023-01671-1) we discovered that changes in the morphology of motor neurons in the brain occur early in the disease process. This happens even before any changes in motor function have been seen.
We also discovered that a decline in motor functions was associated with the degeneration of motor neurons and the loss of synapses. Synapses are the places where motor neurons communicate, thus connecting the brain and spinal cord to the muscles.
Our study also found that astrocytes and microglia, the immune cells of the brain and spinal cord, were highly activated while synapse loss was underway and motor function was declining.
The over-activation of astrocytes and microglia, which can be described as neuroinflammation, changes the morphology of motor neurons and impairs their interconnectivity. These changes affect the neuronal network and disrupt the transmission of information.
Can we restore motor neuron connectivity?
We then wondered whether, by blocking neuroinflammation (for example, the activation of astrocytes and microglia), it would be possible to restore the morphology and connectivity of motor neurons.
In an attempt to answer this question, we tested the efficacy of a (https://doi.org/10.1007/s00018-015-2012-1) semisynthetic drug based on withaferin A, an extract of the ashwagandha plant which has been used for thousands of years in traditional Indian medicine.
The results of our study show that by blocking the activation of astrocytes and microglia, and thereby preventing inflammation, the morphology of motor neurons and their synaptic connections could be restored.
These promising results coincide with cognitive and motor improvements observed in our ALS mouse model.
Inflammation and loss of synapses are common to several neurodegenerative diseases, including ALS, Alzheimer’s and Parkinson’s disease.
As a result, therapeutic approaches that block inflammation and encourage the restoration of neuronal morphology and synaptic connections could have a wider application in the treatment of neurodegenerative diseases.
Future work by our team will aim to further develop treatment strategies that target inflammation and restore synaptic function in ALS sufferers.
 
This article is republished from (https://theconversation.com) The Conversation under a Creative Commons license. Read the (https://theconversation.com/a-promising-new-study-could-lead-to-a-reduction-in-symptoms-of-amyotrophic-lateral-sclerosis-als-228463) original article.

(https://www.psypost.org/brain-imaging-method-detects-genetic-markers-of-autism-with-over-90-accuracy/) Brain imaging method detects genetic markers of autism with over 90% accuracy
Apr 15th 2025, 00:15

A new study published in (https://doi.org/10.1126/sciadv.adl5307) Science Advances introduces a powerful brain imaging technique that can detect autism-linked genetic variations with up to 95% accuracy. This approach, developed by researchers from multiple universities, including Johns Hopkins and Carnegie Mellon, analyzes structural brain images to identify specific genetic patterns associated with autism, potentially offering a way to detect the condition earlier and more objectively than current behavior-based methods.
Autism spectrum disorder is a neurodevelopmental condition characterized by differences in social communication, interaction, and the presence of restricted interests or repetitive behaviors. It is understood to result from a complex interplay of genetic predispositions and environmental influences. Currently, autism is diagnosed based on observing an individual’s behavior, a process that can take time and may not occur until certain developmental milestones are missed. 
However, research increasingly points to a strong genetic component in autism. Understanding this genetic basis offers a potential pathway to better comprehend the condition’s origins, potentially leading to more personalized approaches and earlier support. This study explored a “genetics-first” avenue, focusing on specific genetic alterations known as copy number variations. These variations involve segments of a person’s genetic code being deleted or duplicated. Certain copy number variations are known to substantially increase the likelihood of developing autism. 
The researchers aimed to see if unique patterns in brain structure, visible through imaging, could be directly linked to these specific genetic variations, providing a potential biological marker, sometimes called an endophenotype, that connects genes to observable traits.
To investigate this possibility, the research team, involving experts from Carnegie Mellon University, the University of California San Francisco, and the Johns Hopkins University School of Medicine, utilized a specialized computer modeling technique they developed called transport-based morphometry. This method stands apart from many other image analysis techniques because its mathematical underpinnings are based on modeling the movement and distribution of mass, akin to how substances move within biological tissues. It essentially quantifies the shape and form (morphometry) of the brain based on these modelled transport processes. 
The researchers applied this technique to analyze brain scans from a group of 206 individuals sourced from the Simons Variation in Individuals Project. This cohort included 48 individuals with a deletion in a specific genetic region known as 16p11.2, 40 individuals with a duplication in the same region (both variations are strongly associated with increased autism risk), and 118 control participants without these specific genetic changes. 
The control group was carefully selected to match the other participants in terms of age, sex, handedness, and non-verbal intelligence scores, and they were screened to exclude individuals with related neurological conditions or family histories of autism. High-resolution structural brain images (T1-weighted magnetic resonance imaging scans) were obtained for all participants using standardized procedures across different imaging sites. 
The images underwent preprocessing steps to isolate brain tissue (gray matter and white matter), adjust for overall brain size differences, and normalize the data before the transport-based morphometry analysis was performed separately on gray matter and white matter distributions. The system was trained using machine learning principles to distinguish the brain structure patterns characteristic of the deletion group, the duplication group, and the control group.
The analysis revealed distinct patterns in brain structure associated with the 16p11.2 copy number variations. The transport-based morphometry system was highly effective at identifying which genetic group an individual belonged to based solely on their brain scan. When analyzing white matter structure, the system achieved an average accuracy of 94.6% in correctly classifying individuals into the deletion, duplication, or control group on previously unseen test data. Analyzing gray matter structure yielded an average accuracy of 88.5%. These results significantly outperformed classification attempts using only basic information like age, gender, or overall brain volume.
A key capability of the transport-based morphometry technique is that it is generative, meaning it allowed the researchers not just to classify the scans but also to visualize the specific brain structure differences driving the classifications. The analysis indicated that the 16p11.2 variations were associated with widespread, or diffuse, changes across the brain, rather than being confined to just one or two small areas. 
There was a dose-dependent relationship observed: individuals with the 16p11.2 deletion tended to have larger overall brain volumes and relatively more gray matter tissue compared to controls, while those with the duplication tended to have smaller brain volumes and relatively less gray matter tissue. The visualization also revealed specific regional patterns. 
For instance, areas involved in language processing, emotional regulation, visuospatial skills, and integrating information from multiple senses showed distinct patterns of relative tissue expansion or contraction depending on whether an individual had the deletion or duplication. Often, the effect was reciprocal, meaning a region might show relative expansion in the deletion group and relative contraction in the duplication group compared to controls. Some differences were also noted between the left and right sides of the brain.
Importantly, the researchers explored associations between these identified brain structure patterns and participants’ behavioral or cognitive characteristics. They found a strong association between one specific brain pattern (identified along what the researchers termed discriminant direction 1) and the presence of articulation disorders – difficulties producing speech sounds correctly. 
This pattern was particularly prominent in individuals with the 16p11.2 deletion. Another distinct brain pattern (associated with discriminant direction 2) showed a significant association with participants’ intelligence quotient scores, explaining roughly 17-20% of the variation in full-scale, verbal, and nonverbal intelligence quotient measures across the groups. These findings suggest that the structural brain differences linked to the 16p11.2 copy number variations are related to observable functional outcomes.
The researchers acknowledge some limitations to their study. The participants were recruited through clinical genetics centers and patient networks, which might mean the sample doesn’t represent the full spectrum of individuals with these genetic variations, potentially missing those with milder or different presentations (ascertainment bias). The study focused on one specific genetic region, 16p11.2, and didn’t explore interactions with other genes. 
While the study included individuals from childhood through adulthood, assuming relative stability of these brain patterns, further research focusing on early development is warranted. Also, while associations between brain structure patterns and behavioral measures like articulation or intelligence quotient were found, this type of study cannot establish a cause-and-effect relationship. 
Future research could apply this transport-based morphometry approach to investigate other genetic variations linked to autism and related neurodevelopmental conditions. Larger studies involving more diverse populations and prospective studies tracking individuals over time are needed to validate these findings and explore their potential clinical utility for early detection, prognosis, or monitoring responses to interventions. Such work could significantly advance a genetics-first approach to understanding and supporting individuals with autism.
The study, “(https://doi.org/10.1126/sciadv.adl5307) Discovering the gene-brain- behavior link in autism via generative machine learning,” was authored by Shinjini Kundu, Haris Sair, Elliott H. Sherr, Pratik Mukherjee, and Gustavo K. Rohde.

(https://www.psypost.org/food-insecurity-is-associated-with-cognitive-disengagement-in-adolescents/) Food insecurity is associated with cognitive disengagement in adolescents
Apr 14th 2025, 20:00

Adolescents who live in food-insecure households may be more likely to experience symptoms of cognitive disengagement, such as excessive daydreaming, confusion, and sluggish thinking, according to new research published in (https://link.springer.com/article/10.1007/s10802-024-01226-5) Research on Child and Adolescent Psychopathology. In contrast, the study found no clear relationship between food insecurity and symptoms of attention-deficit/hyperactivity disorder (ADHD), despite some previous studies suggesting a link. These findings suggest food insecurity may affect mental health in subtle and under-recognized ways, particularly through its relationship with cognitive disengagement syndrome, a condition closely related to but distinct from ADHD.
ADHD is one of the most common mental health conditions in childhood, typically involving high levels of inattention, impulsivity, and hyperactivity. Researchers have long studied how environmental stressors might contribute to these symptoms, and nutrition has emerged as a key area of interest. Food insecurity — defined as limited or uncertain access to adequate food — is one such stressor, affecting nearly 14 million households in the United States.
More than half of these households include children. Although earlier studies have linked food insecurity to behavioral and emotional problems in children, few have investigated how it relates to ADHD. Even fewer have looked at how food insecurity might relate to symptoms of cognitive disengagement syndrome, a condition marked by mental confusion, hypoactivity, and persistent daydreaming. This study aimed to address these gaps.
Researchers at Cincinnati Children’s Hospital Medical Center conducted the study with a group of 136 adolescents between the ages of 10 and 12. Participants and their caregivers were recruited through social media, community postings, and hospital networks. Roughly half of the participants had a formal diagnosis of ADHD. To be included in the study, children had to meet basic criteria including a minimum score on a vocabulary test and the ability to complete study tasks in English. Adolescents with more severe developmental or psychiatric disorders were excluded.
To measure food insecurity, parents answered two questions from a national screening tool assessing whether their household had worried about running out of food or had experienced food shortages over the past year. These responses were combined into a single score, with higher scores indicating more severe food insecurity. About 15 percent of the sample met the criteria for experiencing food insecurity, a rate nearly identical to national averages.
To measure symptoms of ADHD and cognitive disengagement syndrome, the researchers used standardized questionnaires filled out by three informants: parents, teachers, and the adolescents themselves. These surveys asked about specific behaviors related to attention problems, hyperactivity, and cognitive disengagement symptoms like frequent daydreaming, getting lost in thought, or seeming mentally confused. The team also accounted for factors like age, sex, race, ethnicity, psychiatric medication use, and family income.
Initial statistical analyses showed that food insecurity was significantly related to higher levels of cognitive disengagement symptoms across all three reporting sources: parents, teachers, and the adolescents themselves. These associations held up even after accounting for differences in age, sex, race, ethnicity, and medication use. However, once family income was included in the models, only the teacher- and adolescent-reported cognitive disengagement symptoms remained significantly associated with food insecurity. Parent-reported symptoms no longer showed a unique association.
Importantly, none of the ADHD symptom scores were significantly linked to food insecurity when all other factors were taken into account. This held true for both dimensions of ADHD: inattentiveness and hyperactivity/impulsivity. The only exception was a modest correlation between teacher-reported inattention and food insecurity, which did not hold up in the full statistical models. Similarly, food insecurity was not associated with symptoms of anxiety or depression reported by any informant.
These results suggest that food insecurity may be more strongly associated with internal, withdrawn forms of mental disengagement than with the outwardly visible behaviors typical of ADHD. One possibility is that food insecurity, through its effects on diet quality and stress, may impair cognitive functions like focus and attention in subtle ways that manifest as daydreaming or mental fog. Research shows that proper nutrition is important for brain development and cognitive functioning, and hunger or poor diet could contribute to the kinds of slow, internally focused thinking seen in cognitive disengagement syndrome.
Another explanation may involve how children psychologically respond to the stress of food insecurity. Adolescents are more aware of family hardships than younger children and may cope with distress by turning inward. Qualitative research suggests that some children respond to hunger by retreating into imagination, even creating imaginary friends or fantasizing about food to comfort themselves. Such coping strategies could increase the likelihood of behaviors that resemble the symptoms of cognitive disengagement.
Sleep could also be an important link. Studies in adults and young children have found that food insecurity can disrupt sleep, and other research has shown that poor sleep quality is associated with more pronounced symptoms of cognitive disengagement. In this view, food insecurity may impact adolescents’ mental functioning by interfering with sleep, which in turn contributes to greater cognitive sluggishness and disconnection from the external world.
Despite these insights, the study had several limitations. The research design was cross-sectional, meaning that all data were collected at one time. This limits the ability to determine whether food insecurity causes cognitive disengagement symptoms or whether another underlying factor explains both. The food insecurity measure was brief and based solely on caregiver reports, which may differ from how adolescents themselves perceive and are affected by food-related hardship. Moreover, the study sample came from relatively well-educated and higher-income families, with only a small proportion reporting food insecurity. This means the findings might not fully apply to more economically vulnerable populations, where the effects of food insecurity may be more pronounced.
Even so, the study makes an important contribution by identifying a potential relationship between food insecurity and a form of mental disengagement that has received little attention in the context of socioeconomic hardship. The findings suggest that cognitive disengagement syndrome may be especially sensitive to environmental stressors like food insecurity, even when accounting for family income and ADHD symptoms.
The study, “(https://doi.org/10.1007/s10802-024-01226-5) Examining ADHD and Cognitive Disengagement Syndrome Symptoms in Relation to Food Insecurity in Early Adolescents,” was authored by Cathrin D. Green, Andrew C. Martinez, and Stephen P. Becker.

(https://www.psypost.org/scientists-tested-three-wake-up-routines-one-type-of-bedroom-lighting-clearly-stood-out/) Scientists tested three wake-up routines. One type of bedroom lighting clearly stood out.
Apr 14th 2025, 18:00

Many people struggle with grogginess in the morning, a common experience known as sleep inertia. A new study published in (https://doi.org/10.1016/j.buildenv.2025.112733) Building and Environment suggests that a simple change to your bedroom lighting might help. Researchers from Osaka Metropolitan University found that exposing sleepers to a moderate amount of natural morning light—specifically starting 20 minutes before waking—led to improved alertness and reduced sleepiness compared to no light or longer light exposure starting at dawn. The findings suggest that carefully timed exposure to natural light could be a practical, energy-efficient way to enhance morning wakefulness.
The researchers were interested in finding better ways to help people transition from sleep to wakefulness, especially in modern environments where many sleep indoors with limited exposure to natural light. While previous research has focused heavily on artificial lighting—such as dawn simulation devices that mimic sunlight—this team wanted to explore whether natural light might offer more effective or more realistic benefits in everyday life. Given that people’s biological clocks evolved under natural lighting conditions, the team hypothesized that natural light, when appropriately timed and controlled, could improve the process of waking up.
To test this, the researchers designed a controlled laboratory experiment that mimicked an ordinary bedroom environment. The study was led by Xiaorui Wang, a graduate student in the School of Human Life and Ecology, and Professor Daisuke Matsushita. Nineteen university students aged 20 to 30 participated in the study. Each participant stayed in a specially outfitted sleep lab on three separate nights. The researchers used motorized curtains to expose participants to different types of natural light before waking.
The experiment tested three conditions. In one condition (called IA), participants were exposed to natural light for 20 minutes before their scheduled wake-up time. In another condition (IB), participants received natural light from dawn (when the sun was just below the horizon) until waking. In the third condition (CC), participants received no natural light before waking. The same participants experienced all three conditions, one each night, in a rotating order to reduce bias. This design allowed the researchers to compare the effects of the lighting conditions on the same individuals, which helps control for personal differences in sleep habits or physiology.
After waking, the researchers measured participants’ sleepiness, alertness, and fatigue using both self-report and biological tools. Subjective sleepiness was assessed using the Karolinska Sleepiness Scale, and alertness was measured with a reaction time test known as the Psychomotor Vigilance Test. For objective data, the researchers recorded brainwave activity with electroencephalograms (EEGs), and heart rate variability with wearable sensors to assess physiological fatigue.
The results showed that natural light exposure had a measurable effect on awakening quality. Both light exposure conditions (IA and IB) were associated with less subjective sleepiness than the no-light condition. However, the 20-minute pre-wake exposure (IA) was most effective overall. Participants in the IA condition had significantly lower objective and subjective sleepiness and responded faster in the alertness test compared to when they received no light. The IB condition, which exposed participants to light starting at dawn and potentially for a longer period, also helped reduce subjective sleepiness and improve alertness—but to a lesser extent than IA.
Interestingly, the longer duration of light exposure in the IB condition did not enhance wakefulness and in some cases may have been less helpful. The researchers suggested that early or prolonged light exposure might lead to more frequent awakenings during sleep, reducing total sleep time and affecting how refreshed participants felt. Indeed, participants in the IA condition slept slightly longer in the final 90 minutes before waking compared to those in the IB condition.
Fatigue levels, as measured through heart rate variability and self-report, did not show consistent differences across the three conditions. This suggests that while light can help people feel more awake and alert, it may not directly reduce feelings of physical tiredness or physiological fatigue in the short term. However, there was some indication that increased natural light exposure was associated with lower fatigue-related indicators, though these findings were not statistically strong enough to draw firm conclusions.
The study also explored how the amount and timing of natural light exposure influenced outcomes. Measurements of illuminance—the brightness of the light—confirmed that the IA and IB conditions both significantly increased light levels in the bedroom compared to the CC condition. However, there was no meaningful difference in brightness between IA and IB, highlighting that duration and timing, rather than brightness alone, may be more important for waking quality.
While the findings suggest practical benefits of morning natural light, the researchers noted several limitations. The participants were young adults with relatively consistent sleep patterns, and all had late bedtime habits typical of college students. These results may not generalize to older adults, people with sleep disorders, or individuals with different routines. In addition, while the controlled lab environment helped isolate the effects of light, it does not capture the full complexity of real-world sleep environments, which vary in terms of noise, temperature, and distractions.
The researchers also pointed out that the study did not include a washout period between conditions, which might have affected the results slightly. Although the crossover design helped minimize individual differences, some carryover effects from the previous night’s condition could not be completely ruled out.
Despite these limitations, the study makes an important contribution to understanding how natural light can support better sleep-wake transitions. By showing that just 20 minutes of light exposure before waking can improve how people feel and function in the morning, the research points to practical changes that could be implemented in everyday bedrooms using automated curtains or smart lighting systems.
Future research will need to explore how these findings apply across different age groups, housing types, and seasons. The team also hopes to examine how other properties of light, such as spectrum and direction, interact with timing and intensity to affect waking. These insights could help guide the development of more responsive and personalized lighting systems that support human health and well-being.
The ultimate goal is to help people wake up feeling better by working with, rather than against, the rhythms of the natural environment. By aligning light exposure with the body’s internal clock, simple changes to how morning light is managed in the bedroom may offer a low-cost, energy-efficient way to ease the daily transition from sleep to wakefulness. “In the future, we hope to control natural light in the sleep environment as it changes with the seasons and time of day, and to clarify how to introduce natural light that is suitable for a more comfortable awakening,” Matsushita said.
The study, “(https://doi.org/10.1016/j.buildenv.2025.112733) Natural light control to improve awakening quality,” was authored by Xiaorui Wang, Yangcheng Gu, Jihui Yuan, and Daisuke Matsushita.

(https://www.psypost.org/psychology-study-political-overconfidence-worsens-polarization-in-online-debates/) Political overconfidence worsens polarization in online debates
Apr 14th 2025, 16:00

A new study published in (https://journals.sagepub.com/doi/10.1177/00936502241301174) Communication Research suggests that people who overestimate their political knowledge are more likely to react negatively during online conversations with those who hold opposing views—and as a result, become more emotionally polarized over time. The researchers found that this “overconfidence effect” helps explain why cross-cutting discussions, or exchanges between people with different political views, often fail to reduce hostility between political groups and may even backfire.
The study explores two psychological patterns that may be undermining efforts to reduce political polarization through dialogue. One is affective polarization—the tendency to dislike or distrust those from the opposing political side. The other is the Dunning-Kruger effect, a well-documented bias in which people with low ability or knowledge in a domain tend to overestimate their competence. The researchers proposed that individuals who overestimate their political knowledge are more likely to respond to disagreements with hostility, especially in online spaces where social norms are weaker. This oppositional behavior, in turn, deepens affective polarization.
To test this idea, the researchers conducted a two-wave online survey in South Korea during early 2022. They recruited a nationally representative sample through a professional survey firm, yielding 1,175 responses in the first wave and 948 in the second. Participants answered questions about their political beliefs, behaviors on social media, and attitudes toward people with opposing views. Crucially, the study measured both perceived and actual political knowledge, allowing the researchers to assess overconfidence—how much individuals overestimated their knowledge relative to their performance on a factual quiz.
Cross-cutting discussion was measured by asking participants how often they talked about public affairs with people who held different political opinions on their most-used social media platform. Oppositional responses to disagreement were assessed one month later by asking how often participants engaged in negative behaviors on social media, such as clicking “dislike,” posting critical content, or making hostile comments in response to opposing views. Affective polarization was also measured in the second wave using a composite score of how warmly or coldly participants felt toward candidates and supporters from opposing political parties.
The results showed several key patterns. First, the Dunning-Kruger effect was clearly present in the political domain. Participants who scored the lowest on objective political knowledge tended to believe they were more knowledgeable than average. In contrast, those who performed well were more likely to underestimate their knowledge. This misalignment between actual and perceived knowledge helped identify who was politically overconfident.
Second, the study found that cross-cutting discussions were not directly associated with either an increase or decrease in affective polarization. However, the relationship changed when looking at behavioral responses. People who more frequently engaged in conversations with political opponents were also more likely to respond with oppositional behaviors, such as publicly criticizing the other side or reacting negatively to their posts. These behaviors, in turn, predicted higher levels of affective polarization over time. In other words, cross-cutting exposure alone did not reduce hostility—but when it led to antagonistic reactions, polarization worsened.
Most importantly, political overconfidence influenced this chain of effects. Among participants who overestimated their political knowledge, cross-cutting discussions were significantly more likely to produce oppositional reactions, which then predicted increased polarization. For those who underestimated their knowledge, this pathway was not statistically significant. In other words, overconfident individuals were more prone to interpreting disagreement as a threat or challenge, responding with hostility, and becoming more emotionally polarized as a result.
These findings help clarify why conversations across political divides on social media often do not lead to greater understanding. Rather than reflecting an honest effort to engage, such exchanges may become battlegrounds for self-affirmation, particularly among those who falsely believe they have superior political knowledge. When people feel certain they are right, they may become less willing to listen and more inclined to attack, reinforcing existing divisions.
The study has several implications for how we think about political dialogue and polarization in the digital age. First, it highlights the importance of metacognition—people’s ability to accurately assess their own knowledge—in shaping the tone and outcome of political conversations. Second, it suggests that interventions aimed at reducing polarization should not only focus on improving political knowledge, but also on addressing overconfidence. Helping individuals recognize the limits of their knowledge may reduce the likelihood of hostile responses to disagreement.
But there are limitations to consider. The study relied on self-reported data, which may be influenced by biases or inaccuracies in how participants recall their behavior. The researchers also focused exclusively on online interactions, particularly on social media platforms where anonymity and low accountability may encourage more extreme behavior. It remains unclear whether the same patterns would hold in face-to-face conversations.
Additionally, the study used only two waves of data, which limits the ability to draw conclusions about long-term effects or the direction of causality. For instance, it is possible that those who are already polarized may be more likely to behave negatively and misjudge their knowledge.
Future research could build on these findings by incorporating more waves of data, examining how overconfidence develops over time, and testing interventions designed to reduce it. Experimental studies could also help clarify how specific features of online platforms—such as anonymity, comment visibility, or feedback mechanisms—shape the relationship between overconfidence and hostility. Another promising direction would be to explore how individual traits like intellectual humility influence responses to disagreement and whether cultivating such traits can help counteract polarization.
The study, “(https://doi.org/10.1177/00936502241301174) How Political Overconfidence Fuels Affective Polarization in Cross-cutting Discussions,” was authored by Han Lin and Yonghwan Kim.

(https://www.psypost.org/new-study-suggests-musical-aptitude-is-multifaceted-not-general/) New study suggests musical aptitude is multifaceted, not general
Apr 14th 2025, 14:00

A study of healthy older adults in Switzerland and Germany found that they were able to acquire various musical skills over the course of one year of practice. This finding suggests that musical ability comprises a broad spectrum of distinct competencies, rather than a single, general musical aptitude. The study was published in (https://doi.org/10.1186/s12877-024-05600-2) BMC Geriatrics.
Musical skills encompass a range of abilities required to perform, comprehend, and create music, including pitch recognition, rhythmic timing, instrumental technique, musical expression, and the ability to read and interpret musical notation. Musical proficiency is thus a complex combination of diverse skills and capacities.
These skills include both technical aspects—such as finger dexterity for playing an instrument—and interpretive elements, such as emotional expression and stylistic phrasing. They require development through both formal training and personal practice, indicating that exposure, education, and environment play significant roles in musical development.
Study author Hannah Losch and her colleagues set out to examine the acquisition of musical skills in musically naïve older adults over the span of one year. They assessed changes in musical skills in two groups: one engaged in piano practice, and another participating in music sensitization activities. The latter included analytical listening and learning theoretical information about music, such as musical styles and structure. The researchers were particularly interested in whether musical abilities develop as a single general skill or as a set of independent abilities.
The data came from the “Train the Brain with Music” project, which involved 156 healthy retirees aged 64–76 from Hannover and Geneva. All participants were native German or French speakers. To qualify for the study, they had to be musically naïve—that is, they could not have had more than six months of musical practice in their lives.
Participants were randomly assigned to either the piano practice group or the musical culture group. The piano group attended weekly 60-minute piano lessons in pairs with an instructor. The music culture group participated in weekly 60-minute seminars in groups of three to six students, where they learned about music, listened to musical pieces, and discussed them. Both interventions lasted for one year.
The researchers assessed participants’ musical and cognitive abilities at four time points: at the beginning of the study, at the six-month mark, at the end of the interventions (12 months), and six months after the interventions ended (follow-up). Participants completed the Cognitive Reserve Index Questionnaire and several musical ability assessments, including the Goldsmiths Musical Sophistication Index, the Beat Alignment Test, the Melodic Discrimination Test, and the MIDI Scale Analysis. They also took music quizzes, and the researchers evaluated recordings of their piano performances.
Twenty-one participants dropped out before the end of the study, and 35 additional participants did not take part in the six-month follow-up.
The results showed that each group improved in the areas they had practiced. The piano group showed moderate improvements in piano articulation and dynamics, while the musical culture group achieved higher scores on the music quiz. Participants with better cognitive functioning and greater musical sophistication performed better on the melody discrimination test. Changes in different musical aptitude scores were not correlated, indicating that these were independent abilities rather than expressions of a single general musical aptitude.
“Musically naïve older adults can acquire diverse musical abilities, which progress independently, suggesting a broad spectrum of musical abilities rather than a single general musical aptitude,” the study authors concluded.
The study contributes to the scientific understanding of the nature of music abilities. However, it should be noted that the musical abilities tested in this study represent only a subset of the full range of musical abilities that can be measured.
The paper, “(https://doi.org/10.1186/s12877-024-05600-2) Acquisition of musical skills and abilities in older adults—results of 12 months of music training,” was authored by Hannah Losch, Eckart Altenmüller, Damien Marie, Edoardo Passarotto, Clara R. Kretschmer, Daniel S. Scholz, Matthias Kliegel, Tillmann H. C. Krüger, Christopher Sinke, Kristin Jünemann, Clara E. James, and Florian Worschech.

(https://www.psypost.org/caffeine-metabolite-1-mx-boosts-memory-and-brain-health-study-finds/) Caffeine metabolite 1-MX boosts memory and brain health, study finds
Apr 14th 2025, 12:00

A new study published in (https://doi.org/10.1371/journal.pone.0313486) PLOS ONE suggests that a lesser-known metabolite of caffeine, called 1-methylxanthine (1-MX), may help improve memory and support brain health in both young and aged animals. The researchers found that rats given 1-MX for 12 days performed better on a memory task and showed increases in key brain chemicals linked to learning, neuroprotection, and antioxidant defenses.
Caffeine is one of the most widely consumed psychoactive substances in the world, known for its stimulating effects and ability to enhance attention and short-term memory. However, much of caffeine’s activity in the body results from how it is broken down into other compounds. One of the primary byproducts of caffeine metabolism is paraxanthine, which has been shown to boost memory and brain activity in both humans and animals. Another compound that forms as caffeine is further metabolized is 1-MX.
Despite the prevalence of 1-MX in the body after caffeine consumption, its potential effects on cognition and brain health had never been directly tested. The authors of the new study aimed to fill this gap by investigating whether daily supplementation of 1-MX could improve memory performance and affect various brain chemicals associated with learning, aging, and neurodegeneration.
To explore the effects of 1-MX, researchers used 32 male Swiss albino rats divided evenly by age: 16 young rats (8 weeks old) and 16 aged rats (16 months old). Each age group was further divided into a control group and a group that received 1-MX. The supplemented animals were given a human-equivalent daily dose of 100 milligrams of 1-MX, delivered orally for 12 consecutive days.
On the 15th day, the rats completed a widely used memory test known as the Morris water maze. In this task, animals are placed in a pool of water and must locate a hidden platform using spatial cues from the environment. The main measure of learning is escape latency, or how long it takes the animal to find the platform. A shorter escape time suggests better memory performance.
After the final testing day, the rats were euthanized, and their brains were examined for several biological markers. The researchers measured levels of neurotransmitters including acetylcholine, dopamine, and gamma-aminobutyric acid (GABA), as well as other brain chemicals associated with memory, antioxidant activity, and aging. These included brain-derived neurotrophic factor (BDNF), glutathione, catalase, cyclic GMP, and amyloid beta.
Rats that received 1-MX supplementation performed significantly better on the memory task. Young rats in the 1-MX group showed a 39% reduction in escape latency compared to controls, while aged rats improved by 27%. Although younger animals tended to learn the task more quickly overall, both age groups benefited from the supplement.
The biological analyses revealed that 1-MX had widespread effects on brain chemistry. Rats given 1-MX had higher levels of acetylcholine, dopamine, and GABA. These neurotransmitters play key roles in attention, motivation, inhibition, and learning. The increase in cyclic GMP, a molecule involved in signal transmission within cells, suggested improved synaptic communication.
The supplemented animals also showed signs of enhanced brain health. BDNF, a protein that supports the growth and survival of neurons, was elevated in the 1-MX group. Levels of glutathione and catalase—two important antioxidants—were also higher, especially in aged animals. This suggests that 1-MX may help defend against oxidative stress, a process that contributes to cognitive decline during aging.
Importantly, the study also found a reduction in amyloid beta 1–40, a protein fragment that can accumulate in the brain and is associated with the development of Alzheimer’s disease. The presence of lower amyloid beta levels suggests that 1-MX may have a protective effect against age-related neurological changes.
These findings suggest that 1-MX is more than just a metabolic byproduct of caffeine—it may play an active role in supporting cognitive function and brain health. The memory improvements observed in both young and old animals indicate that 1-MX could enhance learning regardless of age. The associated increases in neurotransmitters and neuroprotective compounds point to a possible mechanism for these cognitive benefits.
Although caffeine and its better-known metabolite paraxanthine have been studied extensively, this research is the first to directly examine 1-MX’s physiological effects. The fact that 1-MX improved memory and boosted brain markers similar to or beyond those seen with caffeine and paraxanthine suggests it may be a promising candidate for future cognitive enhancement research.
While the results are promising, several limitations should be noted. First, the study was conducted on rats, and the findings may not directly translate to humans. Animal brains differ in important ways from human brains, and the complex nature of human cognition requires additional investigation.
Second, the study used only one behavioral test to measure memory. Escape latency in the water maze provides insight into spatial learning, but it does not capture other aspects of cognitive function such as attention, problem-solving, or long-term memory. Future studies could include a broader range of cognitive tests to determine the full impact of 1-MX.
Third, only male rats were used in this experiment. There is growing recognition that sex differences can influence how drugs and supplements affect the brain, so future research should include female animals to better understand whether the observed benefits extend across sexes.
In addition, the researchers measured brain chemical levels from the entire brain, rather than isolating specific regions such as the hippocampus or prefrontal cortex, which are directly involved in memory and learning. Measuring neurotransmitter changes in specific brain regions could provide a more detailed understanding of how 1-MX affects cognitive processes.
Lastly, the duration of the study was relatively short. While 12 days of supplementation was enough to detect changes in memory and brain chemistry, it remains unclear whether these effects would persist over time or whether different doses would be more or less effective. Long-term studies and dose-response trials will be needed to explore the safety and sustained impact of 1-MX supplementation.
“In conclusion, the caffeine metabolite 1-MX is physiologically active and increases memory, neurotransmitter levels, neuroplasticity and several markers of neuronal health. Our study demonstrates that 1-MX is a new nootropic dietary ingredient supporting brain health and performance,” the researchers wrote.
The study, “(https://doi.org/10.1371/journal.pone.0313486) 1-Methylxanthine enhances memory and neurotransmitter levels,” was authored by Ralf Jäger, Sidney Abou Sawan, Marco Orrú, Grant M. Tinlsey, Martin Purpura, Shawn D. Wells, Kylin Liao, and Ashok Godavarthi.

Forwarded by:
Michael Reeder LCPC
Baltimore, MD

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